Paradoxical worsening of tuberculosis after anti-TB therapy in a kidney transplant recipient.
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Adult↗
Biomedical subjects
T Tanimoto
Publications and source records attributed to T Tanimoto.
Polygonum tinctorium extract suppresses nitric oxide production by activated macrophages through inhibiting inducible nitric oxide synthase expression.
Despite its beneficial role in host defense mechanisms, excessive nitric oxide (NO) production by activated macrophages has been implicated in several inflammatory diseases. To clarify the mechanisms of anti-inflammatory activities of Polygonum tinctorium, we evaluated whether extracts of P. tinctorium could modulate the production of NO by activated macrophages. An AcOEt extract of P. tinctorium markedly inhibited NO synthesis by interferon-gamma (IFN-gamma)/lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages and the macrophage-like cell line RAW 264.7 in a dose-dependent manner. Inhibition of NO synthesis was achieved by reducing inducible NO synthase (iNOS) expression at protein and mRNA levels. However, the AcOEt extract of P. tinctorium failed to inhibit NO synthesis when iNOS was already expressed following stimulation with IFN-gamma and LPS. The AcOEt extract also exhibited inhibitory activity on iNOS expression in human lung epithelial A549 cells stimulated with a combination of IFN-gamma, TNF-alpha and IL-1 beta without affecting the expression of constitutive isoforms of NOS. Furthermore, in vivo injection of the AcOEt extract of P. tinctorium into LPS-treated mice significantly reduced NO synthesis by peritoneal exudate cells under ex vivo conditions. These results suggest that P. tinctorium extract may be a potential therapeutic modulator of NO synthesis in various pathological conditions.
Animals↗
Serum interferon-gamma-inducing factor/IL-18 levels in primary biliary cirrhosis.
Primary biliary cirrhosis is an autoimmune disease of the liver in which T helper 1 cytokines predominate over those of T helper 2 in the pathogenesis. Interleukin- 18 (IL-18), for which the gene was recently cloned, is a novel T helper 1 cytokine, which augments interferon-gamma production. We designed this study to clarify the role of IL-18 in primary biliary cirrhosis and to examine whether serum IL-18 level can be a prognostic indicator for the disease. Serum IL-18 levels were measured using an enzyme linked immuno sorbent assay with mouse monoclonal antibodies. Twenty-two healthy volunteers, 31 patients with primary biliary cirrhosis (Scheuer's stage I, 13; II, 10; and IV, 8), 20 patients with autoimmune hepatitis, 11 patients with virus-related liver cirrhosis and six patients with obstructive jaundice were enrolled. Significant differences of serum IL-18 levels were observed between patients with Scheuer's stage IV and those with stage I, or II, virus-related liver cirrhosis and obstructive jaundice (P < 0.05). The IL-18 levels in primary biliary cirrhosis increased according to the disease progression, and fell promptly after living-related liver transplantation. Moreover, serum IL-18 levels in primary biliary cirrhosis were correlated with serum bilirubin concentrations and the Risk scores of the Mayo Clinic prognostic model for the disease. The IL-18 levels observed in patients with autoimmune hepatitis were also elevated, and correlated with the activity of the disease. These results indicate that serum interleukin-18 levels reflect the severity of primary biliary cirrhosis, the activity of autoimmune hepatitis, and may be an additive prognostic indicator in primary biliary cirrhosis.
Autoimmune Diseases↗
Interleukin-18 in combination with IL-2 enhances natural killer cell activity without inducing large amounts of IFN-gamma in vivo.
Interleukin-18 (IL-18) is known to synergistically enhance murine natural killer (NK) cell activity in vitro when combined with either IL-12 or IL-2. However, it has also been demonstrated that simultaneous administration of IL-18 and IL-12 to mice induces extraordinarily large amounts of interferon-gamma (IFN-gamma) in the serum. In this study, we examined the effects of a combination of IL-18 and IL-2 on in vivo NK cell activation in parallel with the induction of toxicity. In contrast to the IL-18 and IL-12 combination, the combined administration of IL-18 and IL-2 to BALB/c mice for 3 days induced neither high levels of IFN-gamma production nor other visible side effects. When compared with treatment with IL-18 or IL-2 alone, the combined treatment resulted in a significant increase in the number of DX-5 (pan-NK cells marker)-positive cells in spleens and a marked enhancement of splenic NK activity, as determined by standard cytotoxicity assays. Enhanced splenic cytotoxicity generated in the mice treated with both IL-18 and IL-2 was also observed against syngeneic Colon 26 adenocarcinoma cells. Consistent with this in vitro observation, combined treatment produced a significantly stronger inhibitory effect on the pulmonary metastases following i.v. injection of Colon 26 tumor cells than treatment with either cytokine alone. These results suggest that IL-18 combined with IL-2 potentiates in vivo NK cell activity and contributes to inhibition of tumor metastasis without inducing significant toxicity.
Animals↗
Effect of polymer excipients on the enzyme activity of lyophilized bilirubin oxidase and beta-galactosidase formulations.
The effects of excipients on the protein stability during lyophilization as well as the storage stability of lyophilized bilirubin oxidase (BO) and beta-galactosidase (GA) formulations were studied using four polymer excipients: dextran, polyvinylalcohol (PVA), poly(acrylic acid) (PAA), and alpha, beta-poly(N-hydroxyethyl)-L-aspartamide (PHEA). Denaturation of BO and GA during lyophilization largely depended on the excipient used. Dextran appeared to cause severe damage to proteins, whereas PHEA protected proteins effectively from denaturation. Storage stability of BO and GA formulations also depended on the excipients, such that the formulations containing dextran and PAA were relatively unstable. Storage stability was improved by absorption of a small amount of water for all the formulations studied. Absorption of a larger amount of water, however, decreased the storage stability of the formulations containing PVA, PAA or PHEA. In contrast, the storage stability of formulations containing dextran did not decrease noticeably with increasing water. This may be because formulations containing dextran have a higher glass transition temperature than formulations containing PVA, PAA or PHEA when a large amount of water is absorbed.
Acrylic Resins↗
Synthesis of novel heterobranched beta-cyclodextrins from 4(2)-O-beta-D-galactosyl-maltose and beta-cyclodextrin by the reverse action of pullulanase, and isolation and characterization of the products.
From the mixture of 4(2)-O-beta-D-galactosyl-maltose (Gal-G2) and beta-cyclodextrin (betaCD), novel heterobranched betaCDs, (Gal-G2)-betaCD and (Gal-G2)2-betaCDs, were synthesized by the reverse action of debranching enzyme. The optimum conditions for the production of (Gal-G2)2-betaCDs were examined. A mixture of (Gal-G2)2-betaCDs was produced in about 4% yield when Aerobacter aerogenes pullulanase (64 units per 1 g of Gal-G2) was incubated with 1.6 M Gal-G2 and 0.16 M betaCD at 50 degrees C for 4 days. The reaction products, (Gal-G2)2-betaCDs, were separated into three peaks by HPLC analysis on a Hypercarb S column. Their structures were analyzed by fast atom bombardment mass spectroscopy and NMR spectroscopies, and confirmed by comparison of their hydrolyzates by beta-galactosidase with the authentic (G2)2 -betaCDs. The structures of (Gal-G2)-betaCD and three components of (Gal-G2)2-betaCDs were identified as 6-O-(GalG2)-betaCD, 6(1),6(2)-, 6(1),6(3)- and 6(1),6(4)-di-O-(Gal-G2)2-betaCD, respectively.
Carbohydrate Sequence↗
Synthesis of novel heterobranched beta-cyclodextrins from alpha-D-mannosylmaltotriose and beta-cyclodextrin by the reverse action of pullulanase, and isolation and characterization of the products.
Alpha-D-mannosyl-maltotriose (Man-G3) were synthesized from methyl alpha-mannoside and maltotriose by the transfer action of alpha-mannosidase. (Man-G3)-betaCD and (Man-G3)2-betaCD were produced in about 20% and 4% yield, respectively when Aerobacter aerogenes pullulanase (160 units per 1 g of Man-G3) was incubated with the mixture of 1.6 M Man-G3 and 0.16 M betaCD at 50 degrees C for 4 days. The reaction products, (Man-G3)-betaCD were separated to three peaks by HPLC analysis on a YMC-PACK A-323-3 column and (Man-G3)2-betaCD were separated to several peaks by HPLC analysis on a Daisopak ODS column. The major product of (Man-G3)-betaCDs was identified as 6-O-alpha-(6(3)-O-alpha-D-mannosylmaltotriosyl)-betaCD by FAB-MS and NMR spectroscopies. The structures of (Man-G3)2-betaCDs were analyzed by TOF-MS and NMR spectroscopies, and confirmed by comparison of elution profiles of their hydrolyzates by alpha-mannosidase and glucoamylase on a graphitized carbon column with those of the authentic di-glucosyl-betaCDs. The structures of three main components of (Man-G3)2-betaCDs were identified as 6(1),6(2)-, 6(1),6(3)- and 6(1),64-di-O-(63-O-alpha-D-mannosyl-maltotriosyl)-betaCD.
Cyclodextrins↗
Interleukin 18 induces a synergistic enhancement of interferon gamma production in mixed murine spleen cell-tumor cell cultures: role of endogenous interleukin 12.
Interleukin 18 (IL-18) reportedly synergizes with IL-12 and IL-10 for interferon gamma (IFN-gamma) synthesis and natural killer (NK) cell activity, respectively. Here we show that IL-18 alone induces low level IFN-gamma production by unstimulated Balb/c mouse spleen cells, but production is enhanced synergistically in cocultures of spleen cells and allogeneic living or fixed Yac-1 cells. Spleen cells could be primed with IL-18 prior to coculture with Yac-1 cells for IFN-gamma production, which also was observed in cocultures containing either syngeneic or xenogeneic tumor cells. IFN-gamma production in stimulated cocultures was abrogated almost completely by anti-IL-12 antibody and was unrelated to spleen cell lytic activity. IL-10 moderately inhibited IFN-gamma production induced by IL-18. Therefore, in spleen cell and tumor cell cocultures exposed to IL-18, high levels of IFN-gamma are produced by the spleen cells arising from a synergistic interaction between the exogenous IL-18 and endogenous IL-12; however, this activity is unrelated to the spleen cell lytic activity.
Animals↗
[Thiamine Hydrochloride Solution Reference Standard (Control 991) of National Institute of Health Sciences].
The raw material of thiamine hydrochloride solution was examined for preparation of the "Thiamine Hydrochloride Solution Reference Standard (Control 991)". The analytical data obtained were: assay by HPLC, 101.0%; spectrophotometric assay, 100.4%. Based on the above results, the raw material was authorized as the Thiamine Hydrochloride Solution Reference Standard (Control 991) of the National Institute of Health Sciences.
Government Agencies↗
[Tocopherol Acetate Reference Standard (Control 001) of National Institute of Health Sciences].
The raw material of tocopherol acetate was examined for the preparation of the "Tocopherol Acetate Reference Standard (Control 001)". Analytical data obtained were: IR spectrum, same as that of the Tocopherol Acetate Reference Standard (Control 974); specific absorbance, E/cm% (284 nm) = 43.7; thin-layer chromatography, no impurities were detected until 50 micrograms of the loaded raw material; high-performance liquid chromatography (HPLC), total amount of impurities estimated to be less than 0.6%; assay by HPLC, 101.7%. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Reference Standard (Control 001).
Chromatography, High Pressure Liquid↗
[Tocopherol Reference Standard (Control 001) of National Institute of Health Sciences].
The raw material of tocopherol was tested for the preparation of "Tocopherol Reference Standard (Control 991)". Analytical data obtained were: IR spectrum, same as the Tocopherol Reference Standard (Control 941); specific absorbance, E/cm% (292 nm) = 72.9; thin-layer chromatography, no impurities were detected until 50.0 micrograms; high-performance liquid chromatography (HPLC), trace amounts of five impurities were detected and the total amount was estimated to be less than 1.4%; assay by HPLC, 99.9%. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Standard (Control 991).
Chromatography, High Pressure Liquid↗
[Prednisolone Sodium Phosphate Reference Standard (Control 001) of National Institute of Health Sciences].
The raw material for prednisolone sodium phosphate was examined for the preparation of the "Prednisolone Sodium Phosphate Reference Standard (Control 001)". The analytical data obtained were: pH, 7.9; optical rotation, [alpha]D20 = +98.0 degrees; UV spectrum, lambda max of 248 nm and specific absorbance in ethanol at 248 nm = 306.7; IR spectrum, same as that of the Prednisolone Sodium Phosphate Reference Standard (Control 892); thin-layer chromatography, five impurities were detected at 200 micrograms; high-performance liquid chromatography (HPLC), total amount of impurities estimated to be less than 3.7%; residual solvent, 0.0% (ethanol) and 0.0% (hexane); loss on drying, 2.7%. Based on the above results, the raw material was authorized as the Prednisolone Sodium Phosphate Reference Standard (Control 001) of the National Institute of Health Sciences.
Chromatography, High Pressure Liquid↗
[Estradiol Reference Standard (Control 001) of National Institute of Health Sciences].
The raw material of tocopherol was tested for the preparation of "Estradiol Reference Standard (Control 991)". Analytical data obtained were: melting point, 178.5 degrees C: UV spectrum, lambda max of 281 nm and specific absorbance in ethanol at lambda max = 77.7; IR spectrum, same as that of the Estradiol Reference Standard (Control 964); optical rotation, [alpha]D20 = +79.5 degrees; thin-layer chromatography, one impurity was detected; high-performance liquid chromatography (HPLC), total amount of impurities estimated to be less than 0.6%; loss on drying, 3.3%; assay, 100.2% by UV spectrophotometry and 99.9% by HPLC. Based on the above results, the raw material was authorized as the Estradiol Reference Standard (Control 001) of the National Institute of Health Sciences.
Chromatography, High Pressure Liquid↗
[Heparin Sodium Reference Standard (Control 991) of National Institute of Health Sciences].
The National Institute of Health Sciences Reference Standard for Heparin Sodium (Control 991) was prepared. The potency of heparin sodium for the candidate reference standard was assayed against "Heparin Sodium Reference Standard (Control 871)" by JP Method in collaboration with 4 laboratories, and estimated as 1,453 +/- 25 units per ampoule. The filling amounts of heparin sodium in ampoule was estimated as 7.46 +/- 0.15 mg per ampoule, and the precision of filling into ampoule was about 2.0% as C.V. Based on the above results, the candidate was defined as 1450 units per ampoule, and was authorized as the Heparin Sodium Reference Standard (Control 991) of the National Institute of Health Sciences.
Government Agencies↗
Coalescence of Lipid Emulsions in Floating and Freeze-Thawing Processes: Examination of the Coalescence Transition State Theory.
Lipid emulsions, triacylglycerol droplets covered with single surface monolayers of phospholipid in aqueous medium, were prepared by high-pressure emulsification and successive ultracentrifugation. Egg yolk phosphatidylethanolamine did not stabilize triolein (TO) droplets in aqueous medium. Phosphatidylcholine (PC) of various long fatty acyl chains dispersed TO and tricaprylin (TC) well in aqueous medium as emulsion droplets of 110 nm. After ultracentrifugation, however, oil separation was observed in the floating creamy layer of TO/dioleoyl-PC emulsions. Dioleoyl-PC contains two bulky unsaturated fatty acyl chains, as well as oleoyl chains, and it has a lower spontaneous curvature than egg PC. Egg PC and dipalmitoyl-PC gave stably dispersed emulsion droplets of TO even after the freeze-thawing (F-T) procedure. On the other hand, TO/egg PC emulsion droplets containing cholesterol of 83 mol% PC and TC/egg PC emulsion droplets coalesced after the F-T procedure. Cholesterol and a medium chain triacylglycerol, TC, were distributed into the surface PC monolayers and occupied an appreciable fraction of the surface area. These neutral lipids have small polar groups and thus decrease the mean spontaneous curvature of surface lipids. The relationship between the droplet coalescence and the spontaneous curvature was discussed on the basis of the coalescence transition state theory recently developed by Kabalnov et al. in 1996. In addition, effects of maltose on the emulsion coalescence in the freeze state were briefly discussed. Copyright 1999 Academic Press.
Journal Article↗
Development of CD8+ effector T cells is differentially regulated by IL-18 and IL-12.
We investigated the effects of IL-18 on the development of CD8+ effector T cells in DBA/2 anti-BDF1 whole spleen cell MLC and compared the results with those of IL-12. Addition of IL-18 to the MLC resulted in a twofold increase in CD8/CD4 ratios compared with the control cultures when cells were expanded in IL-2-containing medium following MLC. Purified CD8+ T cells recovered from the IL-18-stimulated MLC produced 20- to 30-fold more IFN-gamma after secondary stimulation with C57BL/6 spleen cells or anti-CD3 mAb, and exhibited strong allospecific CTL activity. Neither IL-18 nor IL-18-supplemented culture supernatants from DBA/2 anti-BDF1 MLC induced type I CD8+ effector T cells when purified CD8+ T cells were used as responder cells in primary MLC. Furthermore, CD4+ T cell depletion from the responder cells abrogated the IL-18-induced increase in secondary IFN-gamma production by CD8+ T cells, suggesting that IL-18-induced type I effector CD8+ T cell development was CD4+ T cell dependent. In marked contrast, adding IL-12 to primary MLC decreased CD8/CD4 ratios by 50% and suppressed secondary IFN-gamma production and CTL activity by CD8+ T cells regardless of concentration, whereas Th1 development was promoted by IL-12. Moreover, both IL-12 and IL-18 efficiently induced type I CD8+ effector T cells in C57BL/6 anti-BDF1 MLC. These findings show that IL-18 plays an important role in the generation of type I CD8+ effector T cells, and further suggest that functional maturation of CD8+ T cells is differentially regulated by IL-18 and IL-12.
Animals↗
Cloning and expression of interleukin-18 binding protein.
Interleukin-18 binding protein is a novel glycoprotein that we successfully cloned and expressed. First, murine interleukin-18 binding protein was purified from the sera of mice with endotoxin shock using ligand affinity chromatography. The murine interleukin-18 binding protein cDNA was cloned after RT-PCR using mixed primer pair sequences based on partial murine interleukin-18 binding protein amino acid sequence analysis. Subsequently, human interleukin-18 binding protein cDNA was cloned from cDNA libraries of normal human liver using murine interleukin-18 binding protein cDNA as a probe. Next, we transiently expressed recombinant human and murine interleukin-18 binding proteins in COS-1 cells and purified them from culture supernatants. Both recombinant interleukin-18 binding proteins did not exhibit species specificity and prevented interleukin-18 binding to its receptor. In addition, they inhibited interleukine-18 dependent IFN-gamma production from KG-1 cells effectively. These results suggest that the interleukin-18 binding protein may possess interleukine-18 antagonist activity.
Amino Acid Sequence↗
Effects of electrical stimulation of the tooth pulp and phrenic nerve fibers on C1 spinal neurons in the rat.
Effects of electrical stimulation of the ipsilateral tooth pulp (TP) on C1 spinal neurons were determined in 33 anesthetized rats. One hundred and seven neurons responded to TP stimulation. In 10 rats, the activity of 18 C1 spinal neurons and the amplitude of a digastric electromyogram (dEMG, n = 10) increased proportionally during the TP stimulation at an intensity of 1-3 times the threshold for jaw-opening reflex (JOR). Excitatory receptive somatic fields were examined in 61 neurons. Somatic field locations of many neurons (67.2%) involved the ipsilateral face, neck, and jaw. The activity of 45 neurons was increased by both noxious pinch and brushing hair. Of the 107 C1 spinal neurons responding to TP stimulation, 55 were tested to determine the effects of electrical stimulation of the ipsilateral phrenic nerve (PN) above the heart. Twenty-eight of 55 neurons tested were excited; no change in activity was seen for the remaining 27 neurons. The activity of six neurons increased as the intensity of PN stimulation was increased. Excitatory receptive somatic fields were determined in 28 neurons, and somatic field locations of 17 neurons (60.7%) included the ipsilateral face, neck, and jaw. Both noxious pinch and brushing hair excited all 28 neurons. These results suggest that there may be the convergence of face, neck, jaw, TP, and PN afferents on the same C1 spinal neurons in the rat.
Animals↗