Biomedical subjects

T Tanimoto

Publications and source records attributed to T Tanimoto.

At least 37 records · Page 2Linked to original sources

PubMed2001

Bisabosquals, novel squalene synthase inhibitors. I. Taxonomy, fermentation, isolation and biological activities.

In the course of screening for yeast squalene synthase inhibitors, bisabosqual A was isolated from the culture broth of Stachybotrys sp. RF-7260. The related compounds bisabosquals B, C and D were also isolated from Stachybotrys ruwenzoriensis RF-6853. Bisabosquals inhibited squalene synthases. IC50 values of bisabosqual A against the microsomal squalene synthases from Saccharomyces cerevisiae, Candida albicans, HepG2 cell and rat liver were 0.43, 0.25, 0.95 and 2.5 microg/ml, respectively. Bisabosqual C exhibited inhibitory activities similar to bisabosqual A. Bisabosqual A showed broad spectrum antifungal activity in vitro.

Animals↗

PubMed2001

The process of cardiorespiratory autoresuscitation in intact newborn rats.

To examine the process of spontaneous autoresuscitation and the recovery of the hypoxic ventilatory response (HVR) after prolonged anoxia, we monitored respiratory frequency (f, by body plethysmography) and heart rate (HR, by ECG) in intact newborn rats (n = 12, day 2-4) before, during, and after 100% N2 exposure. The rat before anoxia showed signs of HVR: f changes at acute hypoxia (10% O2) and hyperoxia (100% O2). During anoxia, the spontaneous respiratory movement "gasping" appeared for 21 min (mean). At O2 restoration (with 100% O2), gasping stopped and no respiratory flow was detected for 1 min. One rat failed to autoresuscitate and had heart arrhythmia during the transient apnea, but 11 rats recovered respiration after the HR acceleration. Despite the successful autoresuscitation, the rats did not show HVR at 10 min into the recovery period and the recovery of HVR required more than 30 min. The results indicate that O2 inhalation is useful to trigger autoresuscitation even when the rat has already been in a state of profound hypoxic depression, but the rat becomes transiently insensitive to HVR after autoresuscitation. We estimate that reform of the respiratory control system in newborn rats is not yet firmly established to track HVR early in the recovery phase after prolonged anoxia.

Animals↗

PubMed2001

[Ergocalciferol Reference Standard (Control 001) of National Institute of Health Sciences].

The raw material of ergocalciferol was examined for the preparation of "Ergocalciferol Reference Standard (Control 001)". Analytical data obtained were: melting point, 114.8 degrees C; UV and infrared spectra, the same as those of JP Ergocalciferol Reference Standard (Control 971); specific absorbance, E1ca1% = 471(265 nm); optical rotation, [alpha]D20 = +102.4 degrees; thin-layer chromatography, no impurities were detected until 100 micrograms; high-performance liquid chromatography (HPLC), total amount of impurities estimated to be less than 0.1%. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Ergocalciferol Reference Standard (Control 001).

Chemical Phenomena↗

PubMed2001

[Alprostadil Reference Standard (Control 001) of National Institute of Health Sciences].

The raw material of Alprostadil was examined for the preparation of "Alprostadil Reference Standard (Control 001)". Analytical data obtained were: IR spectrum, same as that of the Alprostadil Reference Standard (Control 923); thin-layer chromatography, no impurities were detected until 20 micrograms; high-performance liquid chromatography (HPLC), total amount of impurities estimated to be less than 0.2%. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Alprostadil Reference Standard (Control 001).

Alprostadil↗

PubMed2001

[Cholecalciferol Reference Standard (Control 001) of National Institute of Health Sciences].

The raw material of cholecalciferol was examined for the preparation of "Cholecalciferol Reference Standard (Control 001)". Analytical data obtained were: melting point, 83.2 degrees C; UV and infrared spectra, the same as those of JP Cholecalciferol Reference Standard (Control 971), respectively; specific absorbance at 265 nm, E1ca1% = 478; optical rotation, [alpha]D20 = +108.6 degrees; thin-layer chromatography, no impurities were detected until 100 micrograms; high-performance liquid chromatography (HPLC), total amount of impurities estimated to be less than 0.05%. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Cholecalciferol Reference Standard (Control 001).

Chemical Phenomena↗

PubMed2001

[Betamethasone Sodium Phosphate Reference Standard (Control 001) of National Institute of Health Sciences].

The raw material of betamethasone sodium phosphate was examined for the preparation of the "Betamethasone Sodium Phosphate Reference Standard (Control 001)". The analytical data obtained were: melting point, 207.2 degrees C; pH, 8.1; optical rotation, [alpha]D20 = +104.4 degrees; UV spectrum, lambda max of 242 nm and specific absorbance in water at 242 nm = 272.9; IR spectrum, specific absorptions at 3386.9, 1721.7, 1663.3, 1620.4, 1605.0, 1094.3, 985.8, 889.8 cm-1; free phosphoric acid, 0.3%; thin-layer chromatography, one impurity was detected until 200 micrograms; high-performance liquid chromatography, total amount of impurities estimated to be less than 0.5%; water, 9.2%. Based on the above results, the raw material was authorized as the Betamethasone Sodium Phosphate Reference Standard (Control 001) of the National Institute of Health Sciences.

Betamethasone↗

PubMed2001

[Hydrocortisone Sodium Phosphate Reference Standard (Control 001) of National Institute of Health Sciences].

The raw material of hydrocortisone sodium phosphate was examined for the preparation of the "Hydrocortisone Sodium Phosphate Reference Standard (Control 001)". The analytical data obtained were: pH, 8.3: optical rotation, [alpha]D20 = +126.2 degrees; UV spectrum, lambda max of 248 nm and specific absorbance in water at 248 nm = 338.6; IR spectrum, same as that of the Hydrocortisone Sodium Phosphate Reference Standard (Control 891); free phosphoric acid, 0.2%; free hydrocortisone, 0.01%; thin-layer chromatography, no impurity was detected until 200 micrograms; high-performance liquid chromatography, total amount of impurities estimated to be less than 0.2%; residual solvent, 0.0% (acetone) and 0.02% (ethanol); loss on drying, 1.5%. Based on the above results, the raw material was authorized as the Hydrocortisone Sodium Phosphate Reference Standard (Control 001) of the National Institute of Health Sciences.

Chromatography, High Pressure Liquid↗

PubMed2001

[Beclometasone Dipropionate Reference Standard (Control 011) of National Institute of Health Sciences].

The raw material of beclometasone dipropionate was examined for the preparation of the "Beclometasone Dipropionate Reference Standard (Control 011)". The analytical data obtained were: melting point, 208.8 degrees C; optical rotation, [alpha]D20 = +91.7 degrees; IR spectrum, same as that of the Beclometasone Dipropionate Reference Standard (Control 865); thin-layer chromatography, one impurity was detected until 40 micrograms; high-performance liquid chromatography, total amount of impurities estimated to be less than 0.5%; loss on drying, 0.6%. Based on the above results, the raw material was authorized as the Beclometasone Dipropionate Reference Standard (Control 011) of the National Institute of Health Sciences.

Beclomethasone↗

PubMed2001

[Dexamethasone Sodium Phosphate Reference Standard (Control 001) of National Institute of Health Sciences].

The raw material for dexamethasone sodium phosphate was examined for the preparation of the "Dexamethasone Sodium Phosphate Reference Standard (Control 001)". The analytical data obtained were: pH, 8.0; optical rotation, [alpha]D20 = +79.6 degrees; UV spectrum, lambda max of 242 nm and specific absorbance in water at 242 nm = 313.6; IR spectrum, same as that of the Dexamethasone Sodium Phosphate Reference Standard (Control 893); free phosphoric acid, 0.06%; free dexamethasone, 0.07%; thin-layer chromatography, no impurities were detected until 100 micrograms; high-performance liquid chromatography, total amount of impurities estimated to be less than 0.2%; residual solvent, 4.3% (ethanol); water, 7.3%. Based on the above results, the raw material was authorized as the Dexamethasone Sodium Phosphate Reference Standard (Control 001) of the National Institute of Health Sciences.

Chromatography, High Pressure Liquid↗

PubMed2001

[Glycyrrhizinic Acid Reference Standard (Control 001) of National Institute of Health Sciences].

The raw material of glycyrrhizinic acid was examined for preparation of the "Glycyrrhizinic Acid Reference Standard". The analytical data obtained were: UV spectrum: lambda max, 251 nm; and specific absorbance (E1ca1%) in ethanol at 251 nm, 146; IR spectrum, specific absorptions at 1714, 1655, 1215, and 1170 cm-1; and the spectrum of raw material was consistent with that of Standard (Control 991). Also, thin-layer chromatography, no impurity was detected; high-performance liquid chromatography, several impurities were detected. The amount of each impurity was estimated at less than 0.2% and total amount of impurities was less than 0.4%. Based on the above results, the candidate material was authorized as the Glycyrrhizinic Acid Reference Standard (Control 001) of the National Institute of Health Sciences.

Chromatography, High Pressure Liquid↗

PubMed2001

[Berberine Hydrochloride Reference Standard (Control 001) of National Institute of Health Sciences].

The raw material of Berberine Hydrochloride was examined for preparation of the "Berberine Hydrochloride Reference Standard". The analytical data obtained were: UV spectrum: lambda max, 420, 345, 263 and 228 nm and specific absorbance (E1ca1%) in ethanol at each lambda max, 155, 724, 796 and 820, respectively; IR spectrum, specific absorptions at 2844, 1635, 1569, and 1506 cm-1; and the spectrum of raw material was consistent with that of Standard (Control 941). Also, thin-layer chromatography, an impurity was detected; high-performance liquid chromatography, several impurities were detected. The amount of each impurity was estimated at less than 0.1% and the total amount of impurities was less than 0.2%. Based on the above results, the candidate material was authorized as the Berberine Hydrochloride Reference Standard (Control 001) of the National Institute of Health Sciences.

Berberine↗

PubMed2000

Mantle dynamics and seismic tomography.

Three-dimensional imaging of the Earth's interior, called seismic tomography, has achieved breakthrough advances in the last two decades, revealing fundamental geodynamical processes throughout the Earth's mantle and core. Convective circulation of the entire mantle is taking place, with subducted oceanic lithosphere sinking into the lower mantle, overcoming the resistance to penetration provided by the phase boundary near 650-km depth that separates the upper and lower mantle. The boundary layer at the base of the mantle has been revealed to have complex structure, involving local stratification, extensive structural anisotropy, and massive regions of partial melt. The Earth's high Rayleigh number convective regime now is recognized to be much more interesting and complex than suggested by textbook cartoons, and continued advances in seismic tomography, geodynamical modeling, and high-pressure-high-temperature mineral physics will be needed to fully quantify the complex dynamics of our planet's interior.

Journal Article↗

PubMed2000

Inhibitory mechanism of slowly adapting pulmonary stretch receptors after release from hyperinflation in anesthetized rabbits.

In anesthetized, artificially ventilated rabbits with vagus nerve section, release from 10 consecutive hyperinflations (inflation volume = 3 tidal volume) caused an inhibition of the slowly adapting pulmonary stretch receptor (SAR) activity for 16-22 sec. Intravenous administration of tetraethylammonium (TEA, 10 and 20 mg/kg), a K+ channel blocker, did not significantly alter either basal SAR discharge or tracheal pressure (PT). Although TEA treatment at 10.0 mg/kg had no significant effect on the magnitude and duration of inhibited SAR activity seen after release from hyperinflation, the increasing dose of this K+ channel blocker up to 20 mg/kg inhibited these effects of the receptor activity but this inhibition was small. The Na+ -K+ ATPase inhibitor ouabain (5 and 10 microg/kg) that had no significant effect on SAR activity and P(T) in the control abolished or attenuated the inhibitory action of SARs in a dose-dependent manner. Furthermore, the changes in dynamic lung compliance (Cdyn) and P(T) in response to post-hyperinflation were not significantly influenced by pretreatment with either TEA or ouabain. These results suggest that the inhibitory action of receptors seen during post-hyperinflation corresponded with the induction of slow afterhyperpolarization (sAHP), and that the mechanism of generating the sAHP of SARs is mainly mediated by the activation of Na+ -K+ pump activity.

Adaptation, Physiological↗

PubMed2000

Inhibition of lipoprotein lipase activity by sphingomyelin: role of membrane surface structure.

We have recently shown that sphingomyelin (SM) strongly inhibits lipoprotein lipase (LPL)-mediated lipolysis in monolayers and emulsion particles. To further evaluate how SM modulates LPL activity on the emulsion surface, the relationship between membrane surface structure and LPL activity was investigated. We measured fluorescence anisotropy of 1-palmitoyl-2-[3-(diphenylhexatrienyl)propionyl]-sn-3-phosphati dylcho line, probing surface acyl chain fluidity, and fluorescence lifetime of N-(5-dimethylaminonaphthalene-1-sulfonyl)dipalmitoylphosphatidylethan olamine in H(2)O and D(2)O buffer, assessing the degree of hydration in the head group region. The results revealed that incorporation of egg SM into triolein-egg phosphatidylcholine emulsions markedly increased acyl chain order and decreased head group hydration of the surface monolayers. In contrast, cholesterol was shown to increase head group hydration despite a strong increase in acyl chain order. The close correlation between the apparent K(m) values of LPL and the degree of head group hydration indicated that LPL interacts with the head group region rather than with the hydrophobic interior of the surface monolayers. However, apparent V(max) did not show a simple correlation with any surface structure, and the finding in which SM had no effect on apparent V(max) of medium-chain triglyceride emulsions suggested that the hydrophobic interaction between acyl chains of SM and triglyceride at the emulsion surface is important for determining the apparent V(max). These results showed conclusively that SM inhibits LPL activity mainly by changing the emulsion surface structure and not by a specific interaction between SM and LPL.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2000

IL-18 prevents the development of chronic graft-versus-host disease in mice.

The development of chronic graft-versus-host disease (GVHD), which is induced by the transfer of DBA/2 spleen cells into (C57BL/6 x DBA/2)F1 (BDF1) mice, is closely related to diminished donor anti-host CTL activity and host B cell hyperactivation. Therefore, an approach which activates donor CD8+ T cells or suppresses donor CD4+ T cell-host B cell interaction may have clinical utility in the treatment of chronic GVHD. We have previously demonstrated that IL-18 induces the development of naive CD8+ T cells into type I effector cells in DBA/2 anti-BDF1 MLC. In this paper we examined the effect of IL-18 administration on the development of chronic GVHD in mice. The treatment was started before or after the onset of clinical evidence of the disease. Regardless of the treatment schedule, IL-18 significantly decreased immunological parameters indicative of chronic GVHD, such as elevated serum IgG antinuclear Abs, IgG1, and IgE levels, and host B cell numbers and their activation. Importantly, IL-18-treated mice did not show the same acute GVHD-like symptoms reported for IL-12 treatment, because there was no weight loss, death, or severe immunodeficiency as indicated by a decrease in IL-2 and IFN-gamma production by Con A-stimulated spleen cells. In contrast, IL-18 treatment partially but significantly restored the production of these cytokines. Data further suggested that these IL-18-mediated therapeutic effects may be due to the induction of donor CD8+ CTL, the decrease in donor CD4+ T cell numbers, and a down-regulation of host B cell MHC class II expression. Thus, our results suggest that IL-18 has beneficial effects in the prevention and treatment of chronic GVHD.

Acute Disease↗

PubMed2000

Change in mechanical receptive field properties induced by GABA(A) receptor activation in the trigeminal spinal nucleus caudalis neurons in rats.

The purpose of the present study was to characterize the effect of a local GABAergic inhibitory mechanism on the mechanical receptive field properties of trigeminal spinal nucleus caudalis (SpVc) neurons by iontophoretic application of a gamma-aminobutyric acidA (GABA(A))-antagonist and -agonist. A total of 24 SpVc neurons that responded to orofacial mechanical stimulation were extracellularly recorded by means of multibarrel microelectrodes in urethane-anesthetized rats. The GABA(A) antagonist bicuculline (30 nA, 5 min) enhanced the activities of SpVc neurons (20/24) induced by both touch/pressure and pinch stimuli and also lowered the mechanical stimulation threshold (touch/pressure). Spontaneous discharges in these neurons (20/24) were significantly increased after bicuculline application. Eighteen out of 24 SpVc neurons showed signs of expansion of the receptive field size after iontophoretic application of bicuculline. These changes showed a current-dependent manner and were reversed in approximately 15-20 min. Iontophoretic application of the GABA(A) agonist muscimol induced a current-related inhibition of neuronal activity elicited by touch/pressure and pinch stimuli as well as a decrease in the size of receptive fields. The facilitation of evoked responses and receptive field expansion of SpVc neuron induced by bicuculline application were blocked by coapplication of muscimol (50 nA, 5 min). These results suggest that a local mechanism acting via GABA(A) receptors normally exerts a tonic inhibition of mechanoreceptive transmission in the trigeminal spinal nucleus neurons and this effect may limit responsiveness and size of receptive fields.

Animals↗

PubMed2000

Elevation of serum interleukin-18 levels and activation of Kupffer cells in biliary atresia.

BACKGROUND/PURPOSE: Interleukin-18 (IL-18)/interferon-gamma-inducing factor (IGIF) is a novel proinflammatory cytokine that can induce interferon gamma (IFN-gamma). In addition, IL-18 enhances intracellular adhesion molecule-1 (ICAM-1) expression as well as Fas ligand (FasL) expression, and induces apoptosis in hepatic injury. The aim of this study was to clarify the potential role of IL-18 in the pathogenesis of the progressive inflammation and fibrosis in biliary atresia (BA). METHODS: Six children with BA before hepatic portoenterostomy (HPE), 13 with BA including 7 without jaundice and 6 with persistent jaundice after HPE, and 16 healthy controls were examined. Blood samples were obtained preoperatively from 6 patients, after HPE from 13, and after liver transplantation from 4. The IL-18 level was determined by an enzyme-linked immunosorbent assay (ELISA). Immunohistochemically, liver specimens from BA patients were studied using a monoclonal antibody to macrophage-associated antigen (CD68). RESULTS: IL-18 levels were elevated in the patients before HPE compared with those of the controls (349+/-54 pg/mL v. 138+/-13 pg/mL, P<.0001). After HPE, extremely high concentrations of IL-18 were observed in patients with persistent jaundice (532+/-95 pg/mL, P<.0001), and the IL-18 levels were significantly high even in the patients without jaundice (249+/-29 pg/mL, P<0.005). The high IL-18 level lasted for a long time even in the patients without jaundice after HPE. In contrast, the IL-18 levels immediately decreased after liver transplantation. Immunohistochemically, the number of CD68-positive Kupffer cells was significantly higher, and the size was larger in the livers of the patients than in the controls. The proliferation of CD68-positive cells was much more conspicuous in the liver specimens obtained during liver transplantation than in those at the time of HPE. CONCLUSIONS: Our findings showed elevation of serum IL-18 levels and activation of Kupffer cells in BA. IL-18 released from activated Kupffer cells might play an important role in the pathophysiology of the progressive inflammation and fibrosis in BA. Furthermore, IL-18 level may be related to the prognosis in patients with BA.

Antigens, CD↗

PubMed2000

Effects of ouabain and flecainide on CO(2)-induced slowly adapting pulmonary stretch receptor inhibition in the rabbit.

The inhibitory effect of CO2 on slowly adapting pulmonary stretch receptors (SARs) was examined before and after administration of ouabain, a Na+-K+ ATPase inhibitor, and flecainide, a Na+ channel blocker. The experiments were performed in anesthetized, artificially ventilated rabbits after vagus nerve section. CO2 inhalation (maximal tracheal CO2 concentration ranging from 9.2 % to 10.4%) for about 60 sec decreased the receptor activity during both inflation and deflation. The magnitude of decreased SAR activity during deflation was greater than that seen during inflation. Administration of ouabain (25 microg/kg) initially stimulated SAR activities during inflation and deflation, and after 20 min, the SAR response was still kept excitatory in both inflation and deflation phases. Under these conditions, CO2 inhalation inhibited SAR activities during inflation and deflation. Flecainide treatment (3 mg/kg) that abolished veratridine (30 microg/kg)-induced SAR excitation had no significant effect on the inhibitory responses of SAR activity to CO2. These results suggest that the inhibitory effect of CO2 occurs when ouabain results in intracellular Na+ concentration ([Na+]i) increases in the SAR endings, and that CO2-induced SAR inhibition may not be related to the reduction of influx of Na+ through voltage-gated Na+ channels.

Adaptation, Physiological↗