Biomedical subjects

T Inukai

Publications and source records attributed to T Inukai.

At least 91 records · Page 5Linked to original sources

PubMed1996

Triphenyltin chloride induces glucose intolerance by the suppression of insulin release from hamster pancreatic beta-cells.

UNLABELLED: We performed an intravenous glucose tolerance test (IVGTT) after the administration of triphenyltin chloride (TPTCl-Ad) in hamsters in order to confirm the presence of glucose intolerance and to clarify the pathogenesis of TPTCl-induced glucose intolerance. On the 1st, 2nd, 3rd, 4th and 7th days after TPTCl-Ad or the administration of sesame oil alone as a control, glucose was injected at a dose of 0.05 g glucose/100 g B.W., and then PG, IRI and TG were measured on 0, 1, 2, 3, 5 and 10 min after IVGTT. The TPT concentration in the pancreas was measured by gaschromatography and the morphological findings with a transmission electron microscope were compared between the TPTCl-Ad and the control hamsters. FPG on the 1st and the 2nd days after TPTCl-Ad were significantly higher than those in control, but those on the 4th and the 7th day recovered up to the control level. In contrast, basal IRI levels showed reciprocal results compared to the FPG levels. delta IRI/ delta PG on the 1st day after TPTCl-Ad was significantly reduced compared to the control. Fasting TG on the 1st day after TPTCl-Ad was much higher than the control. TPT-concentration on the 1st day after TPTCl-Ad showed peak values and its concentration gradually decreased. Electron microscopic findings in the pancreas after TPTCl-Ad indicated neither destruction nor lymphocyte infiltration of the pancreas. CONCLUSIONS: The present data suggest that the administration of TPTCl in hamsters induces a functional transient damage on islet cells but not a morphological disorder, which shows an essentially different nature from the change in the pancreas induced by viral infection or by a large amount of streptozotocin.

Animals↗

PubMed1996

Mechanisms of glucocorticoid resistance in human leukemic cells: implication of abnormal 90 and 70 kDa heat shock proteins.

The unliganded glucocorticoid receptor is a multi-oligomer complex consisting of a ligand-binding protein with which two 90 kDa heat shock proteins (hsp90s) are associated. Upon binding of glucocorticoid to the receptor, the ligand-binding protein, which dissociated from hsp90s, enters the nucleus, binds to a specific site in DNA, and thus transmits signal(s). The 70 kDa heat shock protein (hsp70) also works as a molecular chaperone when the ligand-binding protein enters the nucleus. Regarding the mechanisms of glucocorticoid resistance, a decreased expression of glucocorticoid receptor and a mutant protein with low ligand binding affinity have been reported. In the present study, to address other mechanisms of glucocorticoid resistance, we examined the expression of hsp90 and hsp70 in addition to the number of glucocorticoid-binding sites and their affinity using glucocorticoid-sensitive and -resistant human leukemic cell lines. We showed that two of nine resistant cell lines with normal glucocorticoid-binding proteins express aberrant hsp90 and extremely low hsp70, while another seven resistant cell lines had decreased binding sites with normal hsps. These results suggest that there are at least two independent mechanisms of glucocorticoid resistance in human leukemic cell lines: the decreased ligand-binding sites and the abnormal hsps expression.

Antineoplastic Agents, Hormonal↗

PubMed1995

Expression of granulocyte colony-stimulating factor receptor on CD10-positive human B-cell precursors.

We examined the expression of CD10 and G-CSF receptor (G-CSFR) on the lymphoid population of mononuclear cells obtained from bone marrow (BM) using two-colour analysis. In the BM of children with ALL in remission, the CD10+ population was significantly increased (20.6 +/- 5.1% compared with that of controls (2.5 +/- 0.5%). More than half (61.3 +/- 2.9%) of the CD10+ cells co-expressed G-CSFR, but not CD13. These results indicate G-CSFR+ B-cell precursors are markedly increased in BM of ALL in remission, suggesting the probable involvement of G-CSF in the human early B-cell ontogeny.

Adolescent↗

PubMed1994

Evidence that Ca(2+)-activated K+ channels participate in the regulation of pituitary prolactin secretion.

We evaluated the role of Ca(2+)-activated K+ channels in the regulation of prolactin (PRL) secretion with a perifusion system using acutely dispersed rat anterior pituitary cells. Apamin, which blocks Ca(2+)-activated K+ channels, induced PRL secretion in a dose-dependent fashion between 1 and 300 nM (r = 0.99, P < 0.01). Charybdotoxin, another Ca(2+)-activated K+ channel-blocker, also induced PRL secretion at 20 nM concentration. These were not non-specific toxic effects, since stimulation of PRL secretion by 10 nM thyrotropin-releasing hormone (TRH) was not different before and after applying the channel-blockers. Both 10 microM dopamine and 2 microM nifedipine significantly, but incompletely, depressed PRL secretion induced by 100 nM apamin; 10 microM dopamine completely blocked PRL secretion induced by 20 nM charybdotoxin. Our data indicate that Ca(2+)-activated K+ channels may play an important role in the regulation of PRL secretion.

Animals↗

PubMed1994

Vasoactive intestinal polypeptide stimulates cyclic AMP production in mouse N1E-115 neuroblastoma cells: modulation by a protein kinase C activator and ionomycin.

In this study, we investigated the vasoactive intestinal polypeptide (VIP)-stimulated cAMP production and its interaction with protein kinase C activation and elevation of intracellular Ca2+ in N1E-115 neuroblastoma cells. VIP treatment caused a 55-fold increase in cAMP accumulation. Addition of 4 beta-phorbol 12-myristate 13-acetate reduced VIP- but not forskolin-stimulated cAMP response. In comparison, ionomycin potentiated both VIP- and forskolin-induced cAMP accumulation. Our results indicate that VIP stimulates cAMP accumulation in N1E-115 cells, and that although activation of protein kinase C inhibits the VIP-stimulated cAMP response, elevation of intracellular Ca2+ potentiates this signaling pathway.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1994

Analysis of cytoplasmic and surface antigens in childhood T-cell acute lymphoblastic leukaemias: clinical relevance of cytoplasmic TCR beta chain expression.

Expression of surface and cytoplasmic antigens on the blasts from 42 cases of childhood T-cell acute lymphoblastic leukaemia (T-ALL) were analysed. All with childhood T-ALL, except for one case expressing cytoplasmic TCR delta chain, were classified on the basis of differential expression of cytoplasmic CD3 (cCD3), TCR beta chain (cTCR beta) and surface CD3 (sCD3) into the following three groups: group I (cCD3+, cTCR beta-, sCD3-), eight cases (19.5%); group II (cCD3+, cTCR beta +, sCD3-), 23 cases (56.1%); group III (cCD3+, cTCR beta +/-, sCD3+), 10 cases (24.4%). Each group defines the stepwise maturational stage of the CD3/TCR complex along the intrathymic T-cell differentiation. Group I had the lowest initial WBC count among the three groups (P < 0.05) and showed significantly (P < 0.05) a higher event-free survival (0.75) than those of group II (0.33). There was no significant difference in both the initial WBC count and the event-free survival between groups II and III. Thus, the absence of cTCR beta in sCD3-negative T-ALL appears to be a good prognostic factor, suggesting that this classification provides a useful tool to predict the prognosis of childhood T-ALL. This is the first report, to our knowledge, studying the relationship between the expression of cytoplasmic CD3/TCR antigens and the clinical features in T-ALL.

Adolescent↗

PubMed1994

Rat Prl and TSH secretion are regulated differently by K(+)-channel blockers.

All four different K(+)-channel blockers [tetraethylammonium (TEA), a nonselective K(+)-channel blocker; tolbutamide, an ATP-sensitive K(+)-channel blocker; quinine and 4-aminopyridine, both primarily voltage-dependent K(+)-channel blockers] stimulated prolactin (Prl) secretion by acutely dispersed anterior pituitary cells but had no effect on thyroid-stimulating hormone (TSH) secretion. TEA stimulated Prl secretion in a dose-dependent manner between 1 microM and 20 mM, but even as high as 20 mM, TEA did not induce TSH secretion. Valinomycin (2 microM), a K+ ionophore, inhibited both basal and TEA-induced Prl secretion. TEA-stimulated Prl secretion was abolished by using a Ca(2+)-depleted medium or adding 10 microM dopamine. TEA did not reverse the inhibitory effect of dopamine on thyrotropin-releasing hormone-induced Prl secretion. Our data indicate that K+ channels may play a role in the secretion of adenohypophysial hormones that is idiosyncratic for each hormone. Differences in the role of K+ channels may reflect differences between the various pituitary cell types in plasma membrane ion channel composition, membrane potential, or the mechanism of exocytosis.

Animals↗

PubMed1993

Tetraethylammonium blockade of K+ channels in GH4C1 cells regulates prolactin secretion by inducing Ca2+ influx.

Tetraethylammonium (TEA), a K+ channel blocker, induced PRL secretion and an increase in cytosol Ca2+ concentration [Ca2+]i in a dose-dependent manner between 5-20 mM in GH4C1 rat pituitary tumor-derived cells. Removal of medium Ca2+ or the addition of 1 microM nifedipine abolished both the induced [Ca2+]i increment and PRL secretion. TEA augmented the TRH-induced rise in [Ca2+]i and inhibited the rise in [Ca2+]i induced by 30 mM K+. The dynamics of TEA-, TRH- and K(+)-induced PRL secretion were different, with the TEA-induced secretory peak occurring at about 10 min compared to 2-3 min for TRH and K+. Tolbutamide, which blocks ATP-sensitive K+ channels, induced PRL secretion without causing a rise in [Ca2+]i. The results suggest that: (a) K+ channels have a complex interaction with the PRL secretory process in GH4C1 cells; (b) TEA induces PRL secretion by causing Ca2+ influx through dihydropyridine-sensitive Ca2+ channels; and (c) K+ channels play a different role in the [Ca2+]i rise induced by TRH than in that induced by depolarizing K+.

Animals↗

PubMed1993

Adenosine 3',5'-cyclic monophosphate-mediated prolactin secretion in GH4C1 cells involves Ca2+ influx through L-type Ca2+ channels.

In normal anterior pituitary cells adenosine 3',5'-cyclic monophosphate (cAMP)-mediated prolactin (PRL) secretion requires Ca2+ influx. However, the role of Ca2+ in cAMP-induced secretion in the clonal rat pituitary tumor-derived GH4C1 cells remains uncertain. We examined in GH4C1 cells the effects of forskolin (FSK), an adenylate cyclase activator, and dibutyryl cAMP (DB-cAMP) on PRL secretion and intracellular Ca2+ ([Ca2+]i) dynamics. Ca2+ depletion of the medium inhibited FSK and DB-cAMP stimulated PRL secretion approximately 50%. Both FSK and DB-cAMP increased [Ca2+]i in a dose-dependent fashion. The peak amplitude in [Ca2+]i in response to each concentration of these stimuli was achieved in 3 min, corresponding to the peak PRL response to the same stimuli. Either Ca2+ depletion of the medium or addition of 2 microM nifedipine (NF) abolished the increase in [Ca2+]i caused by FSK or DB-cAMP. Our data indicate that an increase in intracellular c-AMP in GH4C1 cells produces an elevation of [Ca2+]i by opening L-type Ca2+ channels and that c-AMP-mediated PRL secretion is augmented by Ca2+ influx in GH4C1 cells as in normal pituitary cells.

Adenylyl Cyclases↗

PubMed1993

A novel 203 kD aberrant BCR-ABL product in a girl with Philadelphia chromosome positive acute lymphoblastic leukaemia.

We report a girl with Ph1-positive ALL with the aberrant BCR-ABL product. In this case, bcr exon 3 jointed not to ordinal abl exon 2 but to exon 3 resulting in the production of a 203 kD BCR-ABL fusion protein with marked tyrosine kinase activity. To our knowledge, this is the first report of an aberrant BCR-ABL product in childhood. This case was characterized with younger age and low leucocyte count at the onset, but relapsed early like the typical Ph1-positive ALL, suggesting the diversity in the clinicopathogenesis of Ph1-positive ALL.

Base Sequence↗

PubMed1993

Isotonic but not hypertonic ethanol stimulates LHRH secretion from perifused rat median eminence.

We utilized luteinizing hormone-releasing hormone (LHRH) secretion by perifused minced rat hypothalamic median eminence (ME) tissue to evaluate whether isotonic ethanol would stimulate neurosecretion as it does secretion from pituitary cells. Isotonic ethanol induced a dose-dependent burst of LHRH secretion which was maximal at 2-3 min and returned to near baseline by 10 min. In Ca(2+)-depleted media (< 2 microM Ca2+), stimulation of secretion by isotonic ethanol was enhanced, but secretion induced by depolarizing 30 mM K+ was abolished. Hypertonic ethanol was ineffective in stimulating LHRH secretion in either normal or Ca(2+)-free media. The secretory response of hypothalamic LHRH-secreting cells to ethanol and its negative modulation by medium Ca2+ is thus identical to that of normal anterior pituitary cells and presumably is caused by cell swelling resulting from influx of permeant ethanol molecules across the plasmalemma.

Animals↗

PubMed1992

Cell swelling induced by medium hyposmolarity or isosmolar urea stimulates gonadotropin-releasing hormone secretion from perifused rat median eminence.

Medium hyposmolarity between 10 and 50% and isotonic urea between 22.5 and 90 mM induced a dose-dependent burst of gonadotropin-releasing hormone (GnRH) secretion from perifused median eminence tissue which was maximal at 2-3 min and returned to near baseline by 5 min in spite of continued exposure to the stimulus. If Ca(2+)-free medium was used, osmotic stimulation of secretion was increased or unchanged, but secretion induced by 30 mM K+ was markedly reduced. Our data indicate that cell swelling induced by medium hyposmolarity or permeant molecules stimulates GnRH secretion from median eminence cells or cell processes as it does secretion from normal endocrine cells containing hormone stored in intracellular vesicles. In both, Ca2+ influx is not required or has a negative modulating influence on cell swelling-induced secretion.

Animals↗

PubMed1992

Both cyclooxygenase and lipoxygenase inhibitor partially restore the anorexia by interleukin-1 beta.

Since the peripheral prostaglandin synthetizing system may at least partly involved in the anorexia that follows central interleukin-1 beta (IL-1) administration, this study was undertaken to investigate the effect of ibuprofen (ip), selective cyclooxygenase blocker and AA 861, selective lipoxygenase inhibitor, on changes of food and water intake by a single injection of IL-1 (2 micrograms/rat, ip). We demonstrated that food and water intake were suppressed by peripheral administration of IL-1. Throughout the entire observation periods, suppressed food intake was partially restored to control levels by ibuprofen, while water intake completely restored. In addition, no significant differences about water/food intake were observed in the IL-1 + ibuprofen-treated groups, respectively. In the next experiment, IL-1 induced anorexia was also partially restored to the control level following pretreatment with AA 861. These results may suggest that other mechanism including lipoxygenase blocker besides prostaglandin production may be involved in IL-1 induced anorexia.

Analysis of Variance↗

PubMed1992

The suppression of olfactory bulbectomy-induced muricide by antidepressants and antihistamines via histamine H1 receptor blocking.

The effects of antidepressants [(+)-oxaprotiline, (-)-oxaprotiline, imipramine, maprotiline, and trazodone] and antihistamines (mepyramine, dimethindene, ketotifen, methapyrilene, and antazoline) on muricidal behaviour in olfactory bulbectomized rats were investigated. All drugs except for dimethindene, which only minimally passes across the blood-brain barrier, suppressed muricide. The drugs which have high affinity for histamine H1 receptor showed potent suppressive effect on muricide. It is suggested that the central histaminergic system is involved via H1 receptors in the expression of muricide in olfactory bulbectomized rats.

Aggression↗

PubMed1992

Alpha-adrenergic inhibition of thyrotropin-releasing hormone-induced prolactin secretion in GH4C1 cells is associated with a depressed rise in intracellular Ca2+.

alpha-Adrenergic receptors are present on the plasma membrane of normal anterior pituitary cells and alpha-adrenergic agonists may play a role in the secretion of corticotropin (ACTH) and thyrotropin (TSH). However, alpha-adrenergic involvement in prolactin (PRL) secretion is uncertain. We have therefore examined this question in the PRL-secreting clonal rat pituitary tumor-derived GH4C1 cells. Norepinephrine (NE), an alpha-adrenergic agonist, had no effect on basal PRL secretion but abolished thyrotropin-releasing hormone (TRH)-induced PRL secretion in a dose-dependent manner (EC50 100 nM). NE also significantly suppressed the TRH-stimulated rise in [Ca2+]i. Phentolamine (PA), a non-selective alpha-adrenergic antagonist, reversed the inhibitory effect of NE on both the TRH-stimulated PRL secretion and [Ca2+]i rise. NE did not inhibit the rise in PRL secretion or [Ca2+]i induced by depolarizing 30 mM K+, 30% hyposmolarity or BAY K-8644, a specific L-type Ca2+ channel agonist. The inhibitory effect of NE on TRH-induced PRL and [Ca2+]i changes was also present when Ca2+ influx was prevented by removing medium Ca2+ or by blocking L-type Ca2+ channels with 2 microM nifedipine. The TRH-stimulated first-phase rise in [Ca2+]i in GH4C1 cells is believed to result primarily from release of sequestered Ca2+ from an intracellular pool through the activation of inositol 1,4,5-trisphosphate (IP3) and this [Ca2+]i spike stimulates PRL secretion. Our data thus suggest that GH4C1 cells have alpha-adrenergic receptors and that alpha-adrenergic agonists either suppress IP3 generation or block IP3 release of sequestered intracellular Ca2+.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1992

[Antihypertensive effect of felodipine, a new calcium antagonist].

The antihypertensive effect of felodipine was examined in various hypertensive animal models. In spontaneously hypertensive rats, felodipine administered singly at 0.1-1.0 mg/kg (p.o.) had a dose-dependent antihypertensive effect. Nifedipine was effective at 1 mg/kg. In the repeated oral administration experiment, both the maximum decrease in blood pressure and duration of the effect increased gradually and reached steady levels at 3 weeks of administration, which were maintained thereafter. Similar results were noted with nifedipine, but felodipine was longer-acting (4-6 hr) in the steady state than nifedipine (1-2 hr). No development of tolerance was observed during the administration period. In DOCA-salt and renal hypertensive (2K1C) rats, felodipine at 0.1-0.5 mg/kg (p.o.) was superior to nifedipine in the maximum decrease in blood pressure and duration of the effect. Felodipine up to 1 mg/kg (p.o.) caused no significant heart rate increase in any rat model. In renal hypertensive (2K2C) dogs given felodipine at 0.2-0.5 mg/kg (p.o.), the effect lasted for 2 hr after injection. This felodipine effect was stronger and longer lasting than the nifedipine one. At 0.5 mg/kg of felodipine, the heart rate was transiently increased. The present results show that felodipine has a stronger and long-lasting antihypertensive effect than nifedipine in the hypertension models.

Administration, Oral↗

PubMed1992

Repeated treatment with levoprotiline, a novel antidepressant, up-regulates histamine H1 receptors and phosphoinositide hydrolysis response in vivo.

The effects of repeated administration of levoprotiline, a novel type of tetracyclic antidepressant on histamine H1, muscarinic acetylcholine and alpha 1-adrenergic receptors and the response of phosphoinositide hydrolysis (PI) stimulated by histamine in the cortex of the rat brain were investigated. Histamine H1 receptors were up-regulated to 120% and PI response stimulated by histamine was enhanced to 160%-200% after repeated treatment with levoprotiline (20 mg/kg, i.p., once a day for 28 days) when compared to that of the saline-treated group. No significant alterations of muscarinic acetylcholine and alpha 1-adrenergic receptors were observed. This demonstrates that the repeated treatment with levoprotiline has prominent action on the regulation of histamine H1 receptors and PI response coupling to histamine H1 receptors in vivo.

Animals↗

PubMed1992

Effect of pamidronate in a rat hypercalcemia model induced by cholecalciferol.

Pamidronate (disodium 3-amino-1-hydroxypropylidene-1,1-bisphosphonate pentahydrate, CGP 23339A, CAS 57248-88-1) has been show to provide a potent antihypercalcemic effect through the inhibition of calcium release from the bone. The time course study on the antihypercalcemic effect of pamidronate was performed using a rat hypercalcemia model induced by orally administered cholecalciferol. The onset of the antihypercalcemic effect was observed within 48 h after a single i.v. injection of pamidronate at 1 mg/kg and this effect was sustained for 19 days. The time course of the antihypercalcemic effect of pamidronate in combination with calcitonin was also examined in the same model. The onset of the antihypercalcemic effect was observed within 4 h after combination therapy with a single i.v. injection of pamidronate at 1 mg/kg and successive i.m. injections of calcitonin at 3.2 IU/kg and the effect was of sufficient duration. These results suggest that pamidronate has a pronounced effect in controlling hypercalcemia and provides a long-lasting effect by a single i.v. administration. Moreover, the use of pamidronate in combination with calcitonin may be useful when a quicker onset of action is required clinically.

Animals↗