Isolated choroidal leukemic infiltration during complete remission.
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Adolescent↗
Biomedical subjects
N Ohno
Publications and source records attributed to N Ohno.
Effects of a highly selective synthetic inhibitor of plasma kallikrein on disseminated intravascular coagulation in rats.
We found a new, highly selective plasma kallikrein inhibitor, trans-4-aminomethyl-cyclohexanecarbonylphenylalanine 4-carboxymethylanilide hydrochloride, called PKSI-527 in our laboratories. This study was conducted to evaluate PKSI-527, on thromboplastin (TP)- and endotoxin (LPS)-induced disseminated intravascular coagulation (DIC) in rats. PKSI-527 was infused intravenously at 0.1 mg/kg/min for 250 min. Three of the parameters of the coagulation and fibrinolysis system, fibrinogen level, platelet counts and fibrin(ogen) degradation products (FDP) level were assayed. PKSI-527 prevented the change in the coagulation and fibrinolysis system in LPS-induced DIC, however it was not clearly effective in TP-induced DIC. The parameters of organ failure, such as serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), creatine phosphokinase (CPK), lactate, blood urea nitrogen and beta-glucuronidase, were assayed. Although the changes in the fibrinogen level, platelet counts and FDP level were almost the same in both models, the parameters of organ failure apparently increased in LPS-induced DIC more so than in TP-induced DIC. PKSI-527 significantly suppressed the increases in GOT and GPT in LPS-induced DIC. These results indicate that plasma kallikrein may play a significant role in LPS-induced DIC. Therefore, PKSI-527, as a synthetic plasma kallikrein inhibitor may be a valuable tool to explore the mechanism of DIC and the accompanying organ failure.
Animals↗
Use of an active center-directed plasmin inhibitor elucidates the multiplicity of plasmin actions.
In our studies, designed to synthesize an active center-directed plasmin (PL) inhibitor, N-(4-aminomethylbenzoyl)-4-(3-picolyloxy)-L-phenylalanine n-hexylamide dihydrochloride (PASI-535) was found. We characterized PASI-535 and analyzed the actions of PL, comparing with those of PASI-535 and tranexamic acid (t-AMCHA). (1) PASI-535 strongly inhibited not only fibrinolysis (IC50: 2.9 x 10(-6) M) but also amidolysis (Ki value: 2.9 x 10(-6) M) and fibrinogenolysis (IC50: 4.5 x 10(-6) M) induced by PL. While t-AMCHA which strongly inhibited fibrinolysis (IC50: 6.0 x 10(-5) M), rarely inhibited amidolysis (Ki value: 4.0 x 10(-2) M) and fibrinogenolysis (IC50: 1.0 x 10(-2) M). (2) PL is able to liberate kinins by degrading kininogen. This kinin-generation by PL was inhibited by 2 x 10(-5) M PASI-535. However, it was little inhibited even by 1 x 10(-3) M t-AMCHA. (3) The inhibitory effect of PASI-535 and t-AMCHA on tumor growth was studied. In sarcoma-180 bearing mice, ascites retention and the increase of tumor cells were markedly suppressed by subcutaneous injection of PASI-535, either 30 mg/kg/day or 50 mg/kg/day, for 5 days, and the inhibitory effect was dose-dependent. Although t-AMCHA also reduced both ascites retention and the increase of tumor cells, it needed approximately 40 times (2 g/kg/day) the amount of PASI-535 to exert these effects. PASI-535 may be a useful tool in analyzing the multiplicity of PL actions. Moreover, PASI-535 can be used as an antifibrinolytic drug which has a mechanism of function different from that of t-AMCHA.
Amino Acid Sequence↗
Pathologic aspects of polytetrafluoroethylene sutures in human heart.
BACKGROUND: Polytetrafluoroethylene (PTFE) sutures have been widely used as a mitral chord substitute. We present the cases of 4 patients who underwent mitral valve repair with chordal replacement by PTFE sutures and these required another operation. This gave us the chance to examine the PTFE sutures. METHODS: Structural analysis of the PTFE sutures was performed 26 to 378 days postoperatively. The specimens were examined grossly, microscopically, and by scanning or transmission electron microscopy or both. RESULTS: The PTFE suture in 1 patient was found to be completely covered with endothelial cells 154 days postoperatively. There was no calcification, and the flexibility and pliability of the PTFE sutures was preserved. Even though the PTFE sutures seemed uncovered on visual inspection, there was a thin lining of collagen and fibrin on the surface. Endothelial cells were seen in areas that looked clear in one specimen 26 days postoperatively. CONCLUSIONS: We think that the new layer of collagen could be promising in terms of durability and that the endothelial layer wil resemble normal tissue in its anticoagulant properties.
Female↗
Conformation dependency of nitric oxide synthesis of murine peritoneal macrophages by beta-glucans in vitro.
We have already demonstrated that various activities including NO (nitric oxide) synthesis in vivo were significantly different between triple helical (SPG) and single helical (alkaline-treated SPG, SPG-OH) beta-glucans, and that beta-glucan-mediated NO synthesis was associated with increased gene expression of IFN-gamma. In this study, we analyzed beta-glucan-mediated NO production in vitro with the concomitant use of IFN-gamma. Proteose peptone-elicited peritoneal macrophages (PM) were collected from male C3H/HeJ mice and cultured with beta-glucans in the presence or absence of IFN-gamma for 24 h. It was found that SPG-OH, but not SPG, enhanced NO synthesis in vitro, especially in the presence of IFN-gamma. Concentrations of interleukin-1 alpha, -6 and TNF-alpha in the culture supernatant of SPG-OH were significantly higher than those in that of SPG. Membrane-associated IL-1 alpha was also high with SPG-OH. Cytokine productivity of PMs, as well as NO synthesis, was elevated in the presence of IFN-gamma. These facts intensely suggest that the single helical conformer of beta-glucan (SPG-OH) is dominant in cytokine production and subsequent NO synthesis.
Animals↗
Conformation dependency of nitric oxide synthesis of murine peritoneal macrophages by beta-glucans in vitro.
We have already demonstrated that various activities including NO (nitric oxide) synthesis in vivo were significantly different between triple helical (SPG) and single helical (alkaline-treated SPG, SPG-OH) beta-glucans, and beta-glucan-mediated NO synthesis was associated with increased gene of IFN-gamma. In this study, we analyzed beta-glucan-mediated NO production in vitro with the concomitant use of IFN-gamma. Proteose peptone-elicited peritoneal macrophages (PM) were collected from male C3H/HeJ mice and cultured with beta-glucans in the presence or absence of IFN-gamma for 24 h. It was found that SPG-OH, but not SPG, enhanced NO synthesis in vitro, especially in the presence of IFN-gamma. Concentrations of interleukin-1 alpha, -6 and TNF-alpha in the culture supernatant of SPG-OH were significantly higher than those in that SPG. Membrane-associated IL-1 alpha was also high with SPG-OH. Cytokine productivity of PMs, as well as NO synthesis, was elevated in the presence of IFN-gamma. These facts intensely suggest that the single helical conformer of beta-glucan (SPG-OH) is dominant in cytokine production and subsequent NO synthesis.
Animals↗
A water-soluble antitumor glycoprotein from Chlorella vulgaris.
An active substance with antitumor activity (ARS2) was purified from the culture media of Chlorella vulgaris and found to be a glycoprotein with a molecular weight of 63,100 amu, as determined by matrix-assisted laser desorption/ ionization (MALDI) mass spectrometry. ARS2 contains 66.9% carbohydrate, mainly D-galactose, and 35.2% protein. The carbohydrate moiety has a beta-1,6-D-galactopyranose backbone, as determined by methylation analysis and 13C-NMR. Apparently, the protein moiety, whose 15 amino acid sequence at the NH2-terminus, we determined as DVGEAFPTVVDALVA, is necessary for the antitumor activity, as assessed by hydrazinolysis, periodate oxidation, and proteolysis.
Amino Acid Sequence↗
Properties of the inhibitory junction potential in smooth muscle of the guinea-pig gastric fundus.
1. In circular smooth muscle of the guinea-pig gastric fundus, transmural nerve stimulation evoked a cholinergic excitatory junction potential (e.j.p.), and blockade of the e.j.p. by atropine revealed a non-adrenergic non-cholinergic (NANC) inhibitory junction potential (i.j.p.). 2. The amplitude of the e.j.p. was increased by apamin, suramin or NGnitro-L-arginine (L-NOARG), with no significant change in the membrane potential. 3. The i.j.p. consisted of two components (fast and slow); apamin inhibited the former, nitroarginine inhibited the latter, and suramin inhibited both components. 4. Apamin inhibited the hyperpolarization produced by adenosine 5'-triphosphate (ATP) but not by vasoactive intestinal polypeptide (VIP). Suramin inhibited the hyperpolarization produced by VIP but not by ATP. The sodium nitroprusside (SNP)-induced hyperpolarization was not blocked by apamin or suramin. L-NOARG or tetrodotoxin did not inhibit the hyperpolarization produced by ATP, VIP or SNP. 5. The data did not support the hypothesis that ATP, VIP or nitric oxide (NO) is the main transmitter responsible for generation of the NANC i.j.p. in the fundus. 6. Actions of L-NOARG suggest that endogenous NO may be involved in junctional transmission, mainly as an inhibitory modulator of cholinergic transmission.
Adenosine Triphosphate↗
Kupffer cells play important roles in the metabolic degradation of a soluble anti-tumor (1-->3)-beta-D-glucan, SSG, in mice.
Metabolic degradation of a soluble highly branched (-->3)-beta-D-glucan, SSG, was examined in mice using a macrophage blocker, gadolinium chloride (GdCl3). Intraperitoneally administered SSG distributed in the liver was slowly degraded, and after 5 weeks about 30% of the SSG became anionic. In addition, it is suggested that the metabolites would contain fewer branching points as assessed by the reactivity to limulus factor G. On the other hand, in the spleen, the molecular weight and the degree of branching of SSG were not changed for at least 5 weeks. Blockade of Kupffer cells by GdCl3 did not significantly change the distribution ratio of SSG in the liver. However, the treatment significantly delayed the degradation of SSG. These results suggested that Kupffer cells play important roles, not in the distribution, but in the oxidative degradation of SSG in the liver. In addition, splenic macrophages did not significantly contribute to the metabolic degradation of SSG.
Animals↗
Blood clearance of (1-->3)-beta-D-glucan in MRL lpr/lpr mice.
(1-->3)-beta-D-Glucans have a variety of biological and immunopharmacological properties, and they are used clinically as biological response modifiers (BRMs). Clinically, these glucans have often been used for long periods by multiple dosing. During studies on the clearance and metabolism of the glucans in mice, we have found that, in the case of a single dose, the glucan was cleared from blood eventually, and remained constant in the organs for at least one month. Here, we investigated the clearance of glucans from the blood following multiple dosing using MRL lpr/lpr mice with an autoimmune disease. Two kinds of glucans, GRN from Grifola frondosa and SSG from Sclerotinia sclerotiorum, were administered to the mice once a week for more than 35 weeks (250 micrograms/week/mouse by the intraperitoneal route). Examination of the blood clearance of the glucans in these mice revealed that the glucan concentrations were always high (about 20 micrograms/ml for GRN and 200 micrograms/ml for SSG). It is also shown that the glucans were significantly deposited in the liver and spleen of these mice. These findings suggest that administration of a large quantity of the glucan saturated the reticuloendothelial system, resulting in circulation of the glucan in the blood.
Animals↗
Effects of murine lysozyme on lipopolysaccharide-induced biological activities.
We have demonstrated that egg-white lysozyme (EW-LZM) bound to lipopolysaccharide (LPS), reduced the lethal toxicity and the biological activity of LPS. In this study, the interaction of LPS with murine lysozyme (M-LZM) and the modulation of biological activities were investigated. M-LZM was prepared from the culture supernatant of the murine macrophage cell line RAW264.7 by ion-exchange and gel filtration chromatographies and dialysis. Two types of M-LZM, murine M lysozyme (MM-LZM) and murine P lysozyme (MP-LZM), were purified from the supernatant. The enzymatic activities of both MM-LZM and MP-LZM were inhibited by LPS and their effects were affected by the temperature and the ionic strength. TNF-alpha production from RAW264.7 by LPS was inhibited by mixing with MM-LZM and MP-LZM. MP-LZM inhibited TNF-alpha production stronger than MM-LZM. Considering these facts, we suggested that M-LZM, like EW-LZM, make a complex with LPS to reduce the toxicity of LPS together with inhibiting the enzymatic activity.
Amino Acid Sequence↗
Immunopharmacological activity of the purified insoluble glucan, zymocel, in mice.
Although it has been established that soluble glucan in fungi is important to host defence against infection, the importance of insoluble glucans is not clear. We have examined the in-vivo immunopharmacological activity of the insoluble glucan, zymocel. Administration of zymocel increased peritoneal exudate cell number and spleen weight, and enhanced: phagocytic activity, hydrogen peroxide production, and nitric oxide production of peritoneal exudate cells; the extravascular release of Evans blue (which might reflect vascular permeability); lipopolysaccharide-triggered synthesis of tumour necrosis factor (TNF); and recovery of white blood cell number in cyclophosphamide-induced leukopenia. Zymocel also showed anti-tumour activity against sarcoma 180 in mice and also enhanced TNF synthesis and hydrogen peroxide production by macrophage-like cell line in-vitro, i.e. resulted in direct macrophage activation. These results show that zymocel shows varied immunopharmacological activity; it is suggested that the administration of insoluble glucan induces the inflammatory response, the subsequent activation of the immune systems via the cytokine network, and direct macrophage activation.
Animals↗
Signal transduction pathway on beta-glucans-triggered hydrogen peroxide production by murine peritoneal macrophages in vitro.
It has been reported that the biological activities of several beta-glucans vary due to differences in their physicochemical properties. In this study we investigated the ability of beta-glucans to trigger H2O2 production and activate signaling pathway on peritoneal macrophages. The most effective beta-glucan tested on H2O2 production was zymocel which was a particulate preparation from the yeast cell wall. In contrast, gel-forming beta-glucans which are known as immunoenhancers did not trigger the H2O2 production by macrophages at all. To identify the related signaling pathway for the particulate beta-glucans-triggered H2O2 production, several inhibitors were applied. Hydrogen peroxide production triggered with phorbol myristate acetate was inhibited by pretreatment of macrophages with H-7, a protein kinase C inhibitor. However, beta-glucans-triggered H2O2 production was not affected by H-7. The results suggested that genistein-sensitive tyrosine kinase and bromophenacyl bromide-sensitive phospholipase A2 participated in the particulate beta-glucans-triggered H2O2 production, although the phagocytosis of particulate beta-glucans was not inhibited by either reagents. In conclusion, gel-forming (1-->3)-beta-D-glucans-induced activation was not sufficient to trigger H2O2 on macrophages, and pathways for particulate beta-glucans-triggered H2O2 production were regulated differently from those for phagocytosis of beta-glucans.
Animals↗
Effect of beta-glucans on the nitric oxide synthesis by peritoneal macrophage in mice.
Nitric oxide (NO) is an important effector molecule on antimicrobial and antitumor effects of macrophages. (1 -> 3)-beta-D-Glucan (beta-glucan) is well known to show various immunopharmacological effects such as antimicrobial effect and antitumor effect by activating various points of host defense mechanisms. This paper deals with NO synthetic activity of peritoneal macrophage (PM) induced by beta-glucan administration in mice. The activity was determined by measuring NO concentration in PM culture by Griess reagent after 24 or 48 h in vitro culture. Administration (i.p. or i.v.) of a branched soluble (1 -> 3)-beta-D-glucan, grifolan (GRN), from Grifola frondosa enhanced NO synthesis of PM dose and time dependently. The activity was abrogated by the addition of N(G)-monomethyl-L-arginine (L-NMMA) in vitro. The most significant activity was observed at 3-7 d after the administration of GRN (250 mu g/mouse). PM from all strains of ICR, C3H/HeN, C3H/HeJ, BALB/c, BALB/c nu/nu, C57BL, and AKR mice showed significant activity by GRN administration. Among beta-glucans tested, SSG and OL-2, highly branched soluble glucans, and a particulate beta-glucan, zymosan, showed similar activity. Addition of GRN directly to in vitro RAW 264.7 or proteose peptone induced peritoneal macrophage (PP-PEC) culture could not enhance NO synthesis. However, NO synthesis of PP-PEC was enhanced in vitro by addition of GRN in the presence of interferon gamma (IFN gamma). Gene expression of IFN gamma mRNA in the liver and PEC were enhanced in GRN administered mice assessed by reverse transcriptase assisted PCR (RT-PCR) method. These facts strongly suggested that beta-glucan has capacity to enhance NO synthesis of PM in vivo through IFN gamma mediated mechanism.
Adjuvants, Immunologic↗
Characterization of sodium hypochlorite degradation of beta-glucan in relation to its metabolism in vivo.
Soluble (SSG, beta-1,3-D-glucan obtained from the culture filtrates of a fungus, Sclerotinia sclerotiorum IFO 9395) and particulate (zymosan) beta-glucans were oxidized by sodium hypochlorite (NaClO), and the oxidized products were analyzed by gel filtration and ion-exchange chromatographies and by limulus G-test to study the metabolism of beta-glucans in vivo. By oxidative degradation, SSG was gradually oxidized to anionic polymers, which decreased the molecular weight and reduced the content of the sidechain at the same time. Zymosan, a particle from fungi cell wall, was easily solubilized to a high molecular weight polysaccharide by oxidative degradation. The elution profiles on ion exchange columns and the limulus G-test reactivity of the products were similar to those of polysaccharides obtained by in vivo experiments using SSG and zymosan. These results suggest that oxidative degradation is the main metabolic pathway of beta-glucans in vivo, and that the sidechains would be oxidized faster than the main chain.
Ascomycota↗
Immunochemical characterization of alkaline-soluble polysaccharide, P-1, from the kernels of Prunus mume Sieb. et Zucc.
Polyclonal antibodies against P-1, a pectic polysaccharide fraction extracted with 0.5 M NaOH from the kernels of Prunus mume and consisted of arabino-galacturonan, and I-3, the partial acid (0.1 M trifluoroacetic acid) hydrolysate of P-1, were prepared in Japanese white rabbits. Competitive ELISA experiments strongly suggested that anti P-1 and anti I-3 antibodies were different but P-1 and I-3 cross-reacted with each other to recognize a partly similar epitope structure. The reactivities of polysaccharide fractions from the raw flesh of P. mume, and the kernels of apricot and peach extracted with either water or sodium hydroxide were examined using both antisera by the indirect competitive ELISA method. The polysaccharide fractions extracted with sodium hydroxide solutions had the reactivities but not those extracted with cold and hot water. These facts suggested that the similar structure of polysaccharides to P-1 was present in the flesh of P. mume and the kernels of apricot and peach. However, neither pectin of apple nor citrus had reactivity with each antiserum. P-1 would be different in chemical structure from a commercially available pectin, a water-soluble polysaccharide from apple and citrus.
Animals↗
Architecture of alkaline-soluble and bioactive polysaccharide from the kernels of Prunus mume Sieb. et Zucc. assessed by anti P-1 antibody.
P-1 was partially hydrolyzed with 0.01, 0.05, and 0.1 M trifluoroacetic acid (TFA), successively, and the dialyzable (E-1, E-2, and E-3) and non-dialyzable (I-1, I-2, and I-3) fractions were prepared and analyzed chemically and immunochemically. Either I-1 or E-1 reacted with anti P-1 serum as strongly as P-1 and were mitogenic. The cross-reactivity of I-2 and I-3 was less than I-1 with anti P-1 serum. However, they were as mitogenic as I-1. The cross-reactivity of E-2 and E-3 to anti P-1 serum was also very weak, and they were not mitogenic. The E-1 fraction had a similar sugar composition to I-1 and P-1. E-2 was a monosaccharide, all of Ara, and would be from the linkage of furanosyl residues in P-1. The composition of E-3 was free from Ara and the structure of E-3 was similar to that of I-3. E-3 would be considered to be deleted arabinofuranose from E-1. These results suggest that the mitogenic activity measured by the alkaline phosphatase assay is a property of the core part, I-3, but that P-1 contains several epitopes other than the core part by the immunochemical analysis.
Animals↗
Effects of fungal beta-glucan and interferon-gamma on the secretory functions of murine alveolar macrophages.
We investigated the effect of a fungal component, soluble beta-glucan, on secretory functions of murine alveolar macrophages (AMs) in vitro. Stimulation by beta-glucan (500 microg/mL) or interferon-gamma (IFN-gamma; 100 U/mL) alone had a slight effect on AM functions, but when AMs were incubated together with beta-glucan and IFN-gamma, the production and secretion of some immune mediators, such as nitric oxide, interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-alpha), were markedly augmented. This combined effect of beta-glucan and IFN-gamma was based on a priming effect of IFN-gamma, because prestimulation with IFN-gamma followed by beta-glucan induced high nitric oxide production of AMs, but reversal of the sequence of treatments had only a slight effect. We also found that preincubation of AMs with IFN-gamma enhanced the binding of fluorescein-labeled beta-glucan on the AM surface, and this increased binding was abrogated to the control level by the addition of three species of soluble unlabeled (1-->3)-beta-D-glucans but not by soluble alpha-glucan. These data imply that the priming effect of IFN-gamma on the AM response to beta-glucan was dependent, at least in part, on the enhancement of beta-glucan specific binding sites on the AM surface. It was suggested that IFN-gamma is one of the principal factors controlling the pulmonary immune system against both severe fungal infection and inflammation via AM activation at the alveoli.
Animals↗