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Biomedical subjects

N Inagaki

Publications and source records attributed to N Inagaki.

At least 199 records · Page 11Linked to original sources

Nine phenethyl alcohol glycosides from Stachys sieboldii.

Three new phenethyl alcohol glycosides together with six known compounds have been isolated from the leaves of Stachys sieboldii. On the basis of chemical and spectral analyses, the structures of three new compounds named stachysosides A, B and C have been established as 2-(3,4-dihydroxyphenyl)ethyl O-alpha-L-arabinopyranosyl-(1----2)-alpha-L-rhamnopyranosyl- (1----3)-4-O-E-caffeoyl-beta-D-glucopyranoside, 2-(3,4-dihydroxyphenyl)ethyl O-alpha-L-arabinopyranosyl-(1----2)-alpha-L-rhamnopyranosyl- (1----3)-4-O-E-feruloyl-beta-D-glucopyranoside and 2-(3-hydroxy-4-methoxyphenyl)ethyl O-alpha-L-arabinopyranosyl-(1----2)-alpha-L-rhamnopyranosyl- (1----3)-4-O-E- feruloyl-beta-D-glucopyranoside, respectively.

Carbohydrate Sequence↗

The effect of ONO-3708, a novel TxA2 receptor antagonist, on U-46619-induced contraction of guinea pig and human tracheal strips in vitro and on bronchoconstriction in guinea pigs in vivo.

The effect of (9, 11), (11, 12)-didedoxa-9 alpha, 11-alpha-dimethylmethano-11,12-methano-13,14-dihydro-13-aza-14-oxo -15-cyclo-pentyl-16, 17, 18, 19, 20-pentanor-15-epi-TxA2 (ONO-3708) on 9,11-methanoepoxy-prostaglandin H2 (U-46619)-induced contraction of airway smooth muscle in the guinea pigs and human in vitro and bronchoconstriction in guinea pigs in vivo was investigated. In in vitro experiments, ONO-3708 inhibited the U-46619-induced contraction of isolated guinea pig and human tracheal smooth muscle in a dose related fashion (guinea pig; pA2=7.78, human; pA2 = 7.43). The contractions of guinea pig tracheal muscle caused by histamine and leukotriene D4 (LTD4) were not inhibited by ONO-3708. In in vivo experiments, intravenous injection of ONO-3708 at doses between 1 and 20 mg/kg inhibited the U-46619-induced increase of airway insufflation pressure as measured by Konzett-Rössler method. In addition, ONO-3708 inhibited the U-46619-induced increase in airway reactivity to acetylcholine. These data suggest that ONO-3708 has possible therapeutic utility for asthma in which TxA2 participates.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Is the histaminergic neuron system a regulatory center for whole-brain activity?

Recent immunocytochemical studies have demonstrated the existence of histaminergic neurons in the brain, which are concentrated in the tuberomammillary nucleus of the posterior hypothalamus, and which project efferent fibers to almost all parts of the brain. Three subtypes of histamine receptors are widely distributed in the brain, not only on neurons but also on astrocytes and blood vessels. Consistent with its wide-ranging output, the histaminergic neuron system regulates various activities of the brain, such as the arousal state, brain energy metabolism, locomotor activity, neuroendocrine, autonomic and vestibular functions, feeding, drinking, sexual behavior, and analgesia--this regulation is possibly achieved by the histaminergic system as a whole.

Animals↗

In vitro development and functions of human mast cells.

A long-term co-culture of mononuclear cells of human umbilical cord blood with mouse embryo-derived 3T3 fibroblasts resulted in the development of human mast cells. These mast cells are morphologically and functionally mature cells, containing 1.4-2.8 micrograms histamine per 10(6) cells and bear approximately 10(5) Fc epsilon RI per cell. The mast cells sensitized with human IgE released histamine upon challenge with anti-IgE. Electron-microscopic analysis of the cells showed that these cells were mature human mast cells, and clearly different from basophilic granulocytes. Most of the mast cells contained some granules with regular crystalline arrays and both tryptase and chymase, resembling human skin mast cells. When mononuclear cells of cord blood were seeded in a millicell insert which was placed on 3T3 fibroblasts monolayer, the number of mast cells developed in the millicell inserts was comparable to those developed in the co-culture of the same cord blood cells with 3T3 fibroblasts. Recent observations that mast cells developed in the presence of concentrated culture supernatants of 3T3 fibroblasts without fibroblasts feeder layers, confirmed that soluble factors released from 3T3 fibroblasts are essential and sufficient for the differentiation of human mast cell progenitors in vitro. Analysis of functional characteristics of cultured mast cells revealed that they respond to anti-IgE, Ca2+ ionophore A23187 and substance P for histamine release, but failed to respond to compound 48/80 and FMLP. Upon anti-IgE challenge, sensitized mast cells generated approximately 80 ng PGD2 per 10(6) cells, and approximately 50 ng of LTC4 per 10(6) cells but no detectable generation of LTB4.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗

Extracellular phospholipase A2 and histamine release from rat peritoneal mast cells.

Phospholipase A2 (PLA2) from cobra (Naja naja) venom and PLA2 from porcine pancreas accelerated IgE antibody-mediated histamine release from rat peritoneal mast cells. These enhancements were clearly abrogated by heating the enzymes and pretreatment with parabromophenacyl bromide, mepacrine and antiflammin. Indomethacin (cyclooxygenase inhibitor) and AA-861 (lipoxygenase inhibitor) did not affect the enhancement by PLA2. These results indicate that extracellular PLA2 enhances the IgE antibody-mediated histamine release from rat peritoneal mast cells without the participation of arachidonate.

Animals↗

Over-expression of facilitative glucose transporter genes in human cancer.

The expression of five facilitative glucose transporter genes, GLUT1 (erythrocyte type), GLUT2 (liver type), GLUT3 (brain type), GLUT4 (muscle/fat type), and GLUT5 (small intestine type), was examined in human cancer tissues of the digestive system by RNA blotting analysis. The amounts of the GLUT1, GLUT2, and GLUT3 transcripts were elevated in most cancer tissues studied, although the expression of the GLUT2 gene is primarily restricted to the liver. On the other hand, mRNA levels of GLUT4 and GLUT5 were below sensitivity in all cancer tissues examined. These results suggest that over-expression of GLUT1 and GLUT3 might be closely related with tissue development and that the acceleration of glucose uptake by transformed cells may result, at least in part, from the increase in the expression of these two glucose transporters.

Digestive System Neoplasms↗

Organization of the histaminergic system in the brain of the turtle Chinemys reevesii.

To accumulate phylogenetic information on the central histaminergic system, we investigated the histaminergic system in the brain of the Reeves turtle, Chinemys reevesii, using the indirect immunofluorescent method with antiserum against histamine. Histaminergic neuronal cell bodies were found exclusively in the posterior part of the ventral hypothalamus. Histaminergic varicose fibers innervated almost all parts of the turtle brain, but tended to be concentrated in several areas. Very dense innervation was observed in the medial part of the telencephalon, ventrolateral part of the hypothalamus, nucleus habenularis lateralis, and ventromedial part of the tegmentum. Medium density of innervation was seen in the olfactory bulb, nucleus medialis amygdalae, and tectum. Only a few fibers were detected in the lateral part of the telencephalon, dorsal part of the hypothalamus, thalamus, rhombencephalon, and spinal cord. The main ascending fibers were observed in the lateral part of the hypothalamus, sending dense fiber bundles to the cortices dorsomedialis and medialis and nucleus habenularis lateralis. Descending fibers appeared to run in the ventral tegmental area, passing through the dorsal and ventral parts of the midline of the brain stem to the spinal cord. These findings indicate that the general morphological features of the histaminergic system in the turtle brain are similar to those in the mammalian and frog brains.

Animals↗

Increase in liver glucose transporter mRNA levels during rat liver regeneration.

Gene expression of liver facilitated glucose transporter was rapidly induced during the liver regenerating process in rats. It reached maximum of 2.7 times at 8 hr of the regenerating course and returned to normal by 48 hr. The protein synthesis inhibitor, cycloheximide, did not interfere with the increased gene expression of liver facilitated glucose transporter. By contrast, erythrocyte/brain-type glucose transporter mRNA could not be detected in the livers of partially hepatectomized rats and sham-operated rats. The plasma glucose levels were transiently increased within 2 hr of the regenerative course and then decreased to a nadir at 4 hr. These results suggest that the increased gene expression of liver facilitated glucose transporter contributes to the decrease in plasma glucose levels.

Animals↗

An analysis of histaminergic efferents of the tuberomammillary nucleus to the medial preoptic area and inferior colliculus of the rat.

The efferent projections of the five histaminergic neuronal subgroups in the tuberomammillary nucleus to the medial preoptic area (MPO) and inferior colliculus (IC) were examined by immunocytochemistry with antihistidine decarboxylase (HDC) antibodies combined with retrograde axonal tracing with Fast Blue (FB). The term "E groups" were used for the histaminergic neuronal subgroups. About 10% of the HDC-immunoreactive (HDCI) neurons were retrogradely labeled after FB injection into the MPO. The labeled neurons were not concentrated in any particular area, but were diffusely distributed bilaterally in all the subgroups. About two-thirds of the labeled neurons were observed on the side ipsilateral to the injection site and one-third on the contralateral side. The percentages of labeled neurons (double-labeled neurons/HDCI neurons) in the five subgroups were not significantly different with each other. The percentages in group E1 and E2 were particularly close, while that in group E4 resembled that in group E5. About 4% of the HDCI neurons were retrogradely labeled after the dye injections into the IC, and about half of the labeled neurons were detected on the ipsilateral side. The percentage of the double-labeled neurons in the five groups were not significantly different. Furthermore, those in E1 and E2, and in E4 and E5 were almost identical, respectively, to the situation following injection of FB into the MPO. These results indicate that each subgroup of histaminergic neurons in the tuberomammillary nucleus has similar efferent projections to the MPO and IC.

Animals↗

A method for evaluating anti-allergic drugs by simultaneously induced passive cutaneous anaphylaxis and mediator cutaneous reactions.

Homologous passive cutaneous anaphylaxis (PCA) was induced by IgE antibody and, simultaneously, cutaneous reactions were induced by some allergic mediators such as histamine, serotonin and leukotriene (LT) C4 on rat back skin. Disodium cromoglycate and tranilast with inhibitory actions on mediator release inhibited PCA specifically, whereas antihistaminics, including ketotifen, azelastine, mequitazine and diphenhydramine, inhibited histamine- and serotonin-induced cutaneous reactions as well as PCA. Anti-slow-reacting substance of anaphylaxis drugs, KC-404 and FPL-55712, significantly inhibited PCA and histamine- and serotonin-induced reactions, but at the same doses they did not produce significant inhibition of the LTC4-induced reaction. All reactions tested were strongly inhibited dose dependently with the beta stimulants, salbutamol and isoproterenol, and a xanthine derivative, theophylline, which are known to increase the intracellular cyclic AMP level. We think that this method enables the determination of the properties of anti-allergic drugs.

Albuterol↗

Effect of CV-3988, a specific antagonist against platelet activating factor, on homologous passive cutaneous anaphylaxis in the mouse ear.

Effect of CV-3988, a specific antagonist against platelet activating factor (PAF), on homologous passive cutaneous anaphylaxis (PCA) elicited in the mouse ear was investigated. PAF caused a potent increase in vascular permeability in the mouse ear. The potency was slightly lower than that of serotonin but higher than those of histamine, leukotriene (LT) C4, LTD4, prostaglandin (PG) E1 and PGE2 on a weight basis. The increased vascular permeability caused by PAF was inhibited by CV-3988 in a dose-dependent manner. CV-3988 did not affect the increase in vascular permeability caused by histamine or serotonin. IgG1 antibody-mediated PCA in the mouse ear was inhibited by CV-3988, although it did not affect IgE antibody-mediated PCA. These results suggest a possibility that PAF might be involved in IgG1 antibody-mediated PCA in the mouse.

Alprostadil↗

The immunotoxicity of triphenyltin chloride in mice.

The immunotoxicity of triphenyltin chloride (TPTC) in mice was investigated. 1) When TPTC was injected intraperitoneally (i.p.) into mice at doses between 1 and 10 mg/kg for 14 d, a reduction in the weights of thymus and spleen was noticed, however, the body weight was not changed significantly. 2) The production of hemolytic plaque forming cells in the spleen of mice immunized with sheep red blood cells (SRBC) was inhibited by the administration of 10 mg/kg of TPTC. 3) The i.p. injection of TPTC at a dose of 10 mg/kg for 5 d after the primary immunization of mice with dinitrophenylated ascaris antigen resulted in suppression of immunoglobulin E antibody formation in primary immune response, but did not affect the secondary immune response. 4) The production of antibody against polyvinylpyrrolidone (T cell independent antigen) was not affected by the administration of TPTC. 5) The production of effector T cells which are able to cause SRBC- or tuberculin-induced footpad reaction in mice and the induction of cytotoxic T cell in local graft versus host reaction in mice were also inhibited by TPTC. These results indicate that TPTC inhibits both the T cell dependent humoral and cellular immune responses in mice.

Animals↗

[Clinical effects of oxybutynin hydrochloride (Pollakis)--especially in the treatment of pollakisuria, urgency and urinary incontinence].

The effects and the safety of oxybutynin hydrochloride were investigated in 52 patients, 17 male and 35 female, with the chief complaints of pollakisuria, urgency and urinary incontinence. Clinical responses to the drug were assessed mainly by the subjective symptoms of the patients. The diagnoses of these patients were neurogenic bladder in 17, unstable bladder in 16 and others in 19 patients. The average administration period was 66.8 days. The rate of global improvement (excellent and good) was 55% in the 2 mg dose given 3 times daily group, 68.2% in the 3 mg dose given 3 times daily group. Side effects, such as dry mouth, were observed in 2 of the 52 patients (3.8%), but no serious side effects were observed. The rate of global utility (remarkable and moderate) was 67.3%. These data indicate that oxybutynin hydrochloride seems to be useful and safe for the treatment of pollakisuria, urgency and urinary incontinence.

Administration, Oral↗

[Percutaneous drainage of renal and perinephric abscesses].

Two patients with renal or perinephric abscess were successfully managed by percutaneous drainage under ultrasonic guidance. We recommend percutaneous drainage as the first choice of treatment for a renal or perinephric abscess instead of traditional open surgery, especially in a high risk patient.

Abscess↗

[The therapeutic effect of norfloxacin on chronic prostatitis].

The clinical efficacy of norfloxacin (NFLX) was evaluated on 40 patients. They had subjective symptoms suggestive of prostate inflammations and more than five white blood cells (WBC)/hpf in their prostatic secretions (EPS) or VB3. Of these, gram negative rods were isolated from the EPS in 3 patients and gram positive cocci were obtained in 26 patients. The overall clinical efficacy was determined at the second week. The effectiveness rate of the subjective symptoms was 82.5%. The effectiveness rate of the WBC in the EPS was 47.4%. The effectiveness rate of the bacteria in the EPS was 64.3%. The overall clinical effectiveness rate was 77.8%. A subjective side effect was observed only in one patient who had skin eruption like urticaria. Mild liver dysfunction of blood chemistry analysis was shown only in two patients but they had had long standing chronic hepatitis. We conclude that NFLX is an effective drug for the patients with chronic prostatitis.

Adult↗

Characterization of histamine H1-receptors on astrocytes in primary culture: [3H]mepyramine binding studies.

The characteristics of histamine H1-receptors on astrocytes from the cerebral cortex of newborn rats in primary culture were analyzed with a [3H]mepyramine binding assay, and compared with those in the cerebral cortex. The apparent dissociation constant (KD) of [3H]mepyramine binding, the apparent inhibition constants (Ki) of various H1-ligands for [3H]mepyramine binding and the stereoselectivity of d- and l-chlorpheniramine for the inhibition of [3H]mepyramine binding to receptors on cultured astrocytes and to receptors in the brain tissue were very similar, indicating that these receptors are identical. The apparent density of H1-receptors (Bmax) on astrocytes was 262 +/- 60 fmol/mg protein, which was comparable to that in the brain tissue (194 +/- 24 fmol/mg protein). The development of H1-receptors on cultured astrocytes resembled the postnatal development of the receptors in the rat brain. These results suggest that astrocytes could be one of the main targets of the central histaminergic system.

Aminopyridines↗

Cleavage of a synthetic COOH-terminal oligopeptide of D1 precursor protein by a purified processing enzyme.

A synthetic COOH-terminal oligopeptide of D1 protein deduced from the spinach psbA gene (Asn-325-Gly-353) was subjected to proteolytic digestion by purified processing enzyme of D1 protein [(1989) FEBS Lett. 246, 218-222] and the following two fragments were obtained as cleavage products: a COOH-terminal 9-amino-acid fragment (Ala-345-Gly-353) and an NH2-terminal 10-amino-acid fragment (Asn-325-Arg-334). It was concluded that: (i) the oligopeptide consisting of the COOH-terminal 29-amino-acid sequence deduced from the spinach psbA gene provides the recognition domain for the processing enzyme; (ii) the cleavage takes place at the predicted processing site of native D1 precursor protein (COOH side of Ala-344); and (iii) another cleavage takes place at an additional site (COOH side of Arg-334) for the synthetic substrate, but not for the native D1 precursor protein.

Amino Acid Sequence↗