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Biomedical subjects

T Ariga

Publications and source records attributed to T Ariga.

At least 37 records · Page 2Linked to original sources

Immunohistochemical detection of verotoxin receptors in nervous system.

Verotoxin receptor is a globotriaosylceramide (Gb3) present on vascular endothelial cells, in which the toxin causes hemolytic uremic syndrome. We established a sensitive method of immunohistochemical staining in serial sections using monoclonal antibodies (mAbs) against verotoxin and glycolipids that includes Gb3 and galactosylGb3 (GalGb3). With it, we showed co-localization of the verotoxin receptor and Gb3 in dorsal root ganglia (DRG) of humans, rabbits, rats and mice. We also used a very simple method to identify the presence of lipofuscin-like autofluorescence which complicates fluorescence microscopy observation of aged human nervous tissues.

Animals↗

Characterization of a phospholipid antigen reacting with serum antibody in patients with peripheral neuropathies and paraproteinemia.

A phospholipid antigen that reacted with the serum antibody from a patient with peripheral neuropathy and paraproteinemia with both impaired sensory and motor functions, but not with sera from patients with only impaired sensory functions and healthy controls, was purified from bovine cauda equina as a minor component with a concentration of about 0.6 microg per gram wet-weight tissue. The structure of the phospholipid was characterized as lysophosphatidylinositol by means of thin-layer chromatography, gas-liquid chromatography, and negative-ion fast-atom-bombardment mass spectrometry. The major fatty acid component of this phospholipid was stearic acid (> 81%). Our data suggest the possible involvement of a lysophospholipid antigen in the immunopathogenesis of peripheral neuropathies with severe motor and sensory dysfunctions. There is an intriguing possibility that the difference in immunoreactivity of serum antibodies may underlie the differential clinical manifestations in patients with peripheral neuropathy and paraproteinemia.

Animals↗

Gangliosides inhibit the release of interleukin-1beta in amyloid beta-protein-treated human monocytic cells.

Amyloid-beta protein (A beta) is known to induce microglial activation with concomitant release of cytokines. Gangliosides have documented neuritogenic and neurotrophic properties. We determined the effects of A beta on the release of interleukin-1beta (IL-1beta) from the human monocytic cell line, THP-1 cells. A beta 1-42 significantly induced the release of IL-1beta from the cells. A beta 1-40, A beta 40-1, A beta 1-38, and A beta precursor protein (beta-APP) analogs also released a small amount of IL-1beta. A beta 1-42-activated cells demonstrated approx an 18-fold higher IL-1beta release than that for control cells or A beta 1-40 (soluble; S) treated cells. The release of IL-1beta from A beta 1-42-activated cells was significantly inhibited (33-48% of activated cells; p < 0.05 for the control value) by addition of gangliosides, suggesting that gangliosides inhibit the continuous cycle of the IL-1beta production in THP-1 cells.

Amyloid beta-Peptides↗

[Gene therapy for adenosine deaminase (ADA) deficiency: review of the past, the present and the future].

ADA deficiency is the first disease being treated by gene therapy. Since the first trial of gene therapy performed ten years ago, more than 10 patients including our case with ADA deficiency have been treated by the gene therapy with different clinical protocols. In contrast to the recent successful report for X-SCID patients, however, no curative effect of gene therapy for ADA deficiency has been achieved at the moment. In this chapter, I would like to review the past, the present and the future of gene therapy for ADA deficiency, and discuss an issue, especially PEG-ADA therapy, regarding the prospect for stem cell gene therapy for the disease.

Antigens, CD34↗

Establishment of a swine monocyte cell line.

A swine monocyte cell line was established from peripheral blood sample collected from a healthy adult male pig. The cloned cells grow actively in forming monolayers in both glass and plastic cell culture flasks with the growth medium reported previously (Kadoi, 2000) at 36.5 degrees C incubation. The plating efficiency is more than 95%. Densely grown cells in flasks show an epithelioid morphology. The fundamental properties of the cells were examined for cytological definition as monocytes. A positive property detected was guinea pig complement receptor, porcine IgG receptor, non-specific esterase, and acid phosphatase. A significant phagocytic activity proved by the inoculation of Saccharomyces cerevisiae is also one of the characteristics observed in the LPS-activated cells.

Animals↗

Garlic and onion oils inhibit proliferation and induce differentiation of HL-60 cells.

Phytochemicals present in the genus Allium have potential pharmacological effects, such as antimicrobial, antithrombotic, antitumor, hypolipidaemic and hypoglycemic activities. In this present study, we examined the effects of garlic and onion oils on human promyelocytic leukemia cells, HL-60. Incubation of HL-60 with garlic or onion oil (20 microg/ml) caused a marked suppression of HL-60 proliferation; the suppression was almost identical with those obtained by all-trans-retinoic acid (ATRA) or dimethyl sulfoxide (DMSO) used as positive controls. These oils induced the generation of nitroblue tetrazolium (NBT)-reducing activity, and about 20% of the HL-60 cells became NBT positive. CD11b, another marker of the differentiation of these cells, was also significantly induced by garlic oil or onion oil. The combination of garlic or onion oil with ATRA was more effective than either alone. These data suggest that garlic and onion oils have the ability to induce differentiation of HL-60 cells into those of the granulocytic lineage.

Cell Count↗

Determination of carrier status for the Wiskott-Aldrich syndrome by flow cytometric analysis of Wiskott-Aldrich syndrome protein expression in peripheral blood mononuclear cells.

The Wiskott-Aldrich syndrome (WAS) is caused by defects in the WAS protein (WASP) gene on the X chromosome. Previous study disclosed that flow cytometric analysis of intracellular WASP expression (FCM-WASP analysis) in lymphocytes was useful for the diagnosis of WAS patients. Lymphocytes from all WAS patients showed WASPdim instead of WASPbright. Here we report that FCM-WASP analysis in monocytes could be a useful tool for the WAS carrier diagnosis. Monocytes from all nine WAS carriers showed varied population of WASPdim together with WASPbright. None of control individuals possessed the WASPdim population. In contrast, lymphocytes from all the carriers except two lacked the WASPdim population. The difference of the WASPdim population in monocytes and lymphocytes observed in WAS carriers suggests that WASP plays a more critical role in the development of lymphocytes than in that of monocytes. The present studies suggest that a skewed X-chromosomal inactivation pattern observed in WAS carrier peripheral blood cells is not fixed at the hemopoietic stem cell level but progresses after the lineage commitment.

Female↗

Rapid tyrosine phosphorylation and activation of Bruton's tyrosine/Tec kinases in platelets induced by collagen binding or CD32 cross-linking.

Stimulation of the platelet nonintegrin collagen receptor, glycoprotein VI, evokes a signaling response similar to that induced by antigen receptor activation in B and T lymphocytes. A key transducer of the lymphocyte signaling pathways is the Bruton's tyrosine kinase (Btk)/Tec kinase family, which connects receptors to the elevation of intracellular-free calcium levels. An important signaling function for Btk in collagen-induced platelet activation in vitro was recently demonstrated by other researchers using Btk-deficient platelets from patients with X-linked agammaglobulinemia (XLA). Since Btk-deficiency does not induce an overt platelet-based bleeding disorder in vivo, collagen receptor responses may include other Btk/Tec kinase family members in normal platelets. Both Btk and Tec had increased tyrosine following stimulation of collagen receptors or CD32 cross-linking. Data from kinetic analyses and inhibitor studies and the use of phosphopeptide-specific antibodies recognizing 2 Btk regulatory phosphorylated tyrosine residues suggest a mechanism for coordinate recruitment of Btk and Tec through the immunoreceptor tyrosine-based activation motif, Src family kinases, and phosphatidylinositol 3-kinase. In XLA platelets, collagen treatment increased tyrosine phosphorylation of Tec and several other signaling proteins, including Lyn, Fyb, Slp-76, and the Wiskott-Aldrich syndrome protein. This indicates that important elements of the collagen signaling pathway proximal and distal to Btk and Tec are preserved despite the lack of functional Btk. The results are consistent with the conclusion that activation of Tec may sustain XLA platelet function in vivo, while some in vitro assays of nonintegrin collagen receptor signaling through the Btk/Tec kinase family reflect the additive dosage of the transducers. (Blood. 2000;95:1663-1670)

Agammaglobulinaemia Tyrosine Kinase↗

Antithrombotic and antineoplastic effects of phyto-organosulfur compounds.

The antiplatelet activity of methyl allyltrisulfide (MATS), a component commonly present in steam-distilled garlic oil, has been demonstrated by the authors. MATS inhibits arachidonic acid cascade at the reaction site with PGH synthase. However, this enzyme catalyzes two successive reactions, from arachidonic acid to PGG2, and from PGG2 to PGH2. The present study revealed that MATS inhibited the latter reaction. In addition, our recent findings that to a promyelocytic leukemia cell HL60, Allium oils shows marked anti-neoplastic effects representing both growth suppression and differentiation activities are described. The garlic oil and onion oil showed almost equal ability in inducing the proliferation, which measured either by nitroblue-tetrazolium reducing activity assay or by flow cytometry for detecting CD11b expression. The combination use of one of these oils with all-trans retinoic acid or with dimethyl sulfoxide lead to the marked differentiation of the cells, and their effects were estimated to be synergistic.

Allium↗

Thermochemical transformation of sulfur compounds in Japanese domestic Allium, Allium victorialis L.

Sulfur compounds contributed to the health promotion in Allium species are produced via enzymic and thermal reactions. Potent antithrombotic agents which have been identified as allyl trisulfides, dithiins, and ajoene in garlic (A. sativum) and caucas (A. victorialis) are thermochemically transformed from allicin (allyl 2-propenethiosulfinate). The leaves and stems of Japanese domestic Allium plant, A. victorialis L. which is widely distributed in the northern part of Japan, under the name "Gyoja-ninniku" is a nutritious vegetable. The significant flavor compounds of caucas are methyl allyl disulfide (Chinese chive odor), diallyl disulfide (garlic-like odor), and dimethyl disulfide and methyl allyl trisulfide (pickles-like odor) among more than 85 peaks on the gas chromatogram. 2-Vinyl-4H-1,3-dithiin and 3,4-dihydro-3-vinyl-1,2-dithiin as platelet aggregation inhibitors were found eliminated in dichloromethane extract of caucas. The significant health promoting factors, allyl trisulfides and dithiins were relatively increased when caucas was cooked on a frying pan.

Allium↗

Protective effects of murine recombinant interferon-beta administered by intravenous, intramuscular or subcutaneous route on mouse hepatitis virus infection.

The significance of the route for administration of murine recombinant interferon-beta (IFN-beta) for inducing its therapeutic effects has been studied. BALB/c mice were daily injected intravenously, intramuscularly or subcutaneously with 1.5x10(3), 1. 5x10(4), or 1.5x10(5) IU of IFN-beta, from one day before to 8th day after mouse hepatitis virus (MHV-2) challenge. All mice received IFN-beta survived significantly longer than those without IFN. In the liver of those IFN-treated mice, viral growth and the histopathological damages were extremely alleviated. These results suggest that, irrespective of the differences in the route of administration, IFN-beta markedly suppressed viral activity when its administration was started prior to viral infection. For clinical use, however, further studies are needed on the optimal route for administration if IFN-beta is given after viral infection.

Animals↗

Antioxidative and anti-glycation activity of garcinol from Garcinia indica fruit rind.

Garcinol, a polyisoprenylated benzophenone derivative, was purified from Garcinia indica fruit rind, and its antioxidative activity, chelating activity, free radical scavenging activity, and anti-glycation activity were studied. Garcinol exhibited moderate antioxidative activity in the micellar linoleic acid peroxidation system and also exhibited chelating activity at almost the same level as citrate. It also showed nearly 3 times greater DPPH (1, 1-diphenyl-2-picrylhydrazyl) free radical scavenging activity than DL-alpha-tocopherol by weight in aqueous ethanol solution. In a phenazine methosulfate/NADH-nitroblue tetrazolium system, garcinol exhibited superoxide anion scavenging activity and suppressed protein glycation in a bovine serum albumin/fructose system. Thus, garcinol might be beneficial as a potent antioxidant and a glycation inhibitor under specified conditions.

Animals↗

Free radical scavenging activity and antiulcer activity of garcinol from Garcinia indica fruit rind.

Garcinol, a polyisoprenylated benzophenone derivative, was purified from Garcinia indica fruit rind, and its free radical scavenging activity was studied using electron spin resonance (ESR) spectrometry. In the hypoxanthine/xanthine oxidase system, emulsified garcinol suppressed superoxide anion to almost the same extent as DL-alpha-tocopherol by weight. In the Fenton reaction system, garcinol also suppressed hydroxyl radical more strongly than DL-alpha-tocopherol. In the H(2)O(2)/NaOH/DMSO system, garcinol suppressed superoxide anion, hydroxyl radical, and methyl radical. It was thus confirmed that this derivative is a potent free radical scavenger and able to scavenge both hydrophilic and hydrophobic ones including reactive oxygen species. Orally administered garcinol prevented acute ulceration in rats induced by indomethacin and water immersion stress caused by radical formation. These results suggested garcinol might have potential as a free radical scavenger and clinical application as an antiulcer drug.

Animals↗

Genetic studies of three Japanese patients with p22-phox-deficient chronic granulomatous disease: detection of a possible common mutant CYBA allele in Japan and a genotype-phenotype correlation in these patients.

Chronic granulomatous disease (CGD) is a disorder caused by defects in the NADPH oxidase responsible for superoxide generation in phagocytes. Cytochrome b558, an essential component of this enzyme, is a heterodimer formed by a 91 kDa glycoprotein (gp91-phox) and a 22 kDa polypeptide (p22-phox). Mutations in the p22-phox gene (CYBA) locus in 16q24 result in one of the rare autosomal recessive forms of CGD. We performed mutation analysis in three female CGD patients suspected of having this form of the disease and found two novel mutations in CYBA. Whereas patient 1 with severe phenotype had a homozygous nonsense mutation in exon 1 (C-35 --> T, Gln-3 --> stop), patients 2 and 3 with mild phenotype shared the same homozygous missense mutation in exon 2 (G-98 --> A, Gly-24 --> Arg). None of the parents of patients 2 and 3 is related. Therefore, this mutation could be a hot-spot or a common mutation in the Japanese population. Patients 2 and 3, but not patient 1, were demonstrated to have detectable p22-phox expression and significant granulocyte respiratory burst (ROB) activity. In this study, we were able to demonstrate an excellent correlation between genotype, p22-phox expression, ROB activity and clinical phenotype in these patients.

Adult↗