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R Kato

Publications and source records attributed to R Kato.

At least 343 records · Page 19Linked to original sources
PubMed1991

Formation of inositol polyphosphates in cultured adrenal chromaffin cells.

Formation of inositol polyphosphates has been characterized in cultured bovine adrenal chromaffin cells in terms of calcium dependency and isomers of inositol polyphosphates. There are two distinct pathways of generation of InsP3. Stimulants such as high K+ induce InsP3 accumulation by a calcium uptake-dependent mechanism. Stimulants such as Ang II induce InsP3 accumulation by a calcium uptake-independent mechanism. Both mechanisms are involved in nicotinic stimulation. These results suggest that calcium entry as well as receptor-mediated mechanisms play a significant role in phosphoinositides hydrolysis through phospholipase C in adrenal chromaffin cells. Nicotinic receptor stimulation induces a rapid and transient increase in Ins(1,4,5)P3 accumulation followed by a slower accumulation of Ins(1,3,4)P3. Moreover, nicotine induces a large and rapid increase in Ins(1,3,4,5,6)P5 accumulation with an extent and time course similar to Ins(1,4,5)P3, which peaks at 15 sec after stimulation. Nicotine also induced Ins(1,3,4,5)P4 and InsP6 accumulation with a slower time course and a lesser magnitude than Ins(1,3,4,5,6)P5. These results indicate that adrenal chromaffin cells possess fine regulation of inositol polyphosphates metabolism and that inositol polyphosphates are involved with the control of cellular function in these cells.

Adrenal Medulla↗
PubMed1991

Suppressive effect of SUN1165 on supraventricular tachycardia.

The electrophysiologic properties of SUN1165 and its suppressive effect on supraventricular tachycardia were assessed in 14 patients, nine with atrioventricular reentrant tachycardia (AVRT) and five with atrioventricular nodal reentrant tachycardia (AVNRT). This new agent prolonged the PR interval and QRS duration but did not alter the QT interval or the corrected QT interval. It did not alter the sinus cycle length or sinus node recovery time. The drug prolonged the AH interval, HV interval, and intraatrial conduction time but did not change the effective refractory periods of the right atrium or right ventricle. SUN1165 prevented the induction of tachycardia in six of nine patients with AVRT by a complete retrograde block of the accessory pathway and prevented AVNRT in four of five patients by a complete retrograde block of the fast atrioventricular nodal pathway as well. We conclude that SUN1165 is very effective in preventing AVRT or AVNRT. Larger studies with more patients are warranted.

Administration, Oral↗
PubMed1991

Improved technique for inserting a T tube in patients with subglottic stenosis.

An improved method for inserting a silicone T tube through a tracheostomy stoma in patients with subglottic stenosis is presented. A silicone T tube is pulled into the trachea with a catheter that is inserted into the tracheostomy stoma, advanced through the stenotic subglottic space, and pulled out the mouth. A cone-shaped dilator is placed beforehand at the proximal end of the vertical limb of the T tube to facilitate the passage of that end through the stenotic subglottic space. This method was used in 4 patients with good results. We suggest this technique be tried when attempts to insert a T tube by the usual method fail, as it can be performed under local anesthesia without special instruments and is technically easy.

Catheterization, Peripheral↗
PubMed1991

Potentiation by a sodium channel activator of effects of lithium ion on cyclic AMP, cyclic GMP and inositol phosphates.

The effects of the lithium ion (Li+) on receptor-mediated synthesis of second messengers were determined, when cellular sodium channels were quiescent or excited, using the murine neuroblastoma clone (N1E-115). In this clone, lithium inhibited the receptor-mediated synthesis of cyclic AMP and cyclic GMP and it also increased the accumulation of inositol phosphates by a receptor-mediated process. When veratridine (20 microM) excited the sodium channel, the effects of lithium were potentiated. However, tetrodotoxin, a sodium channel blocker, completely prevented this potentiation. These results suggest that when neurons are depolarizing actively and intraneuronal levels of lithium increase by entry through the sodium channel, lithium has a more potent intracellular effect. As a result, lithium would have more potent and selective effects in those pathologically-active neurons underlying manic-depressive disorder.

Animals↗
PubMed1991

Inhibition by prostacyclin and carbacyclins of endothelin-induced DNA synthesis in cultured vascular smooth muscle cells.

Effects of prostacyclin and carbacyclins on endothelin-induced DNA synthesis were investigated in vascular smooth muscle cells. DNA synthesis was estimated by [3H]thymidine incorporation. Five carbacyclins used in this report were 5-[(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(S)-3-hydroxy-1-octenyl]bicyclo [3.3.0]oct-2-en-3-yl) pentanoic acid (TEI-7165), methyl 5-[(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(S)-3-hydroxy-1-octenyl]bicyclo[3.3.0]oct-2-en-3- yl]pentanoate (TEI-9090), 5-[(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(3S, 5S)-3-hydroxy-5-methyl-1-nonenyl]bicyclo[3.3.0]oct-2-en-3-yl)penta noic acid (TEI-9063), methyl 5-[(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(3S, 5S)-3-hydroxy-5-methyl-1- nonenyl]bicyclo[3.3.0]oct-2-en-3-yl)pentanoate (TEI-1324), 5-[(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(S)-4-hydroxy-4-methyl-1- octenyl]bicyclo[3.3.0]oct-2-en-3-yl] pentanoic acid (TEI-3356). Prostacyclin and the carbacyclins inhibited the endothelin-induced DNA synthesis within the nanomolar range. These results suggest that prostacyclin and carbacyclins are possibly effective in inhibiting the proliferation of vascular smooth muscle cells under some situations in vivo.

Animals↗
PubMed1991

Differential transnasal pressure in anterior and posterior rhinomanometry.

Transnasal differential pressures during spontaneous breathing through an artificial nasal model were measured using anterior and posterior types of rhinomanometry by Rhinorheograph MPR-1100 manufactured by Nihon Kohden Co., Ltd. for comparing postnasal pressures at the nasopharynx with those at the nostril. No significant differences between postnasal pressures at the nasopharynx and at the nostril were found at 0.25, 0.5 liter/s, or the peak flow point on the pressure/flow relation curve. Application of the Ohm's Law equation for parallel resistors to nasal airflow resistance seems to be a more important problem than the differences resulting from the postnasal pressure sampling procedures in the anterior and posterior methods.

Adult↗
PubMed1991

The effect of L-menthol stimulation of the major palatine nerve on nasal patency.

Objective and subjective measurements of nasal patency were made before and after L-menthol stimulation of the palatal mucosa (supplied with the trigeminal nerve) in 15 normal adult subjects. The stimulation exerted indirect effect on the nasal cavity in that all subjects mentioned a cold sensation in their nose and a sensation of increased nasal patency, but no influence on nasal resistance to airflow was detected.

Adult↗
PubMed1991

The potent anti-tumor-promoting agent isoliquiritigenin.

A topical application of a chalcone derivative, 4,2',4'-trihydroxychalcone (isoliquiritigenin) inhibited epidermal ornithine decarboxylase (ODC) induction and ear edema formation, i.e. inflammation, caused by a topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) in CD-1 mice. In addition, isoliquiritigenin potently inhibited 7,12-dimethylbenz[alpha]anthracene (DMBA)-initiated and TPA-promoted skin papilloma formation. This inhibitory effect of isoliquiritigenin was not due to any damage inflicted on the initiated cells but due to its anti-tumor-promoting action. Isoliquiritigenin also inhibited epidermal ODC induction and skin tumor promotion caused by 7-bromomethylbenz[alpha]anthracene (BrMBA), a non-TPA type of tumor-promoting agent, in DMBA-initiated mice. Isoliquiritigenin inhibits neither 12-lipoxygenase nor cyclooxygenase in epidermal subcellular fractions. This compound, however, inhibited TPA-stimulated prostaglandin E2 (PGE2) production in intact epidermal cells. ODC induction caused by TPA was inhibited by a topical application of cyclooxygenase inhibitor, indomethacin. Inhibition of ODC induction by indomethacin was counteracted by a topical application of PGE2, while inhibition caused by isoliquiritigenin was not overcome by PGE2. The results suggest that a mechanism other than the inhibition of PGE2 production is involved in the anti-tumor-promoting action of isoliquiritigenin. Isoliquiritigenin failed to inhibit phospholipase A2 activity of platelet sonicates, but inhibited platelet 12-lipoxygenase and 5-lipoxygenase in polymorphonuclear leukocytes. Therefore, it might be possible that isoliquiritigenin exerts its anti-tumor-promoting action through the lipoxygenase inhibition by acting on cells other than the target epidermal cells. Our present results, in combination with our previous data, demonstrate that some chalcone derivatives and flavonoids which show a potent lipoxygenase inhibitory action act on a common step in the skin tumor promotion caused by two different types of tumor-promoting agents, i.e. TPA and BrMBA, and suggest that these compounds show promise as drugs to prevent tumor promotion.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Involvement of prostaglandin E2 in the tumor promoter phorbol ester-caused increase in epidermal cholesterol sulfotransferase activity.

A single topical application of 10 nmol TPA to mouse skin caused an increase in epidermal cholesterol sulfotransferase activity, a squamous differentiation associated enzyme. A topical application of indomethacin (1.2 mumol), a cyclooxygenase inhibitor, 10 min before TPA application markedly inhibited the above TPA action. Concurrent application of prostaglandin E2 (PGE2) with indomethacin reversed the inhibitory effect of indomethacin. PGF2 alpha, however, failed to reverse the inhibition caused by indomethacin. Both indomethacin and PGE2 alone did not change epidermal cholesterol sulfotransferase activity significantly. These results indicate that PGE2 plays a significant role in the mechanism of TPA-caused increase in cholesterol sulfotransferase activity in mouse epidermis.

Animals↗
PubMed1991

Cytochrome P-450 human-2 (P-450IIC9) in mephenytoin hydroxylation polymorphism in human livers: differences in substrate and stereoselectivities among microheterogeneous P-450IIC species expressed in yeasts.

The cDNA of a P-450 human-2 and the two other closely related cDNAs, MP-8 (two deduced amino acids substituted) and lambda hPA6 (two deduced amino acids deleted) were expressed in Saccharomyces cerevisiae cells, and their catalytic and chemical properties were compared to identify which cDNA encodes a major S-mephenytoin 4'-hydroxylase in human livers. In immunoblots, P-450 human-2 cDNA-derived protein in yeasts was stained at the position identical with P-450 human-2 purified from liver and a major protein in microsomes of 19 Japanese livers. MP-8- and lambda hPA6-derived proteins were immunostained at positions near, but distinct from P-450 human-2, and were not detected in those 19 livers. All three proteins expressed in yeasts catalyzed hydroxylation of mephenytoin, hexobarbital, benzo[a]pyrene and tolbutamide, although the rates of the hydroxylation of most of the drugs by P-450 human-2 were higher than those of the two others. In addition, these expressed proteins showed clear differences in the hydroxylation of chiral substrates: P-450 human-2 catalyzed the hydroxylation of S-mephenytoin five times faster than that of the R-enantiomer. Similar high enantioselectivities were also observed on the hydroxylation of R- and S-hexobarbital. However, MP-8- and lambda hPA6-derived proteins catalyzed hydroxylation of these two drugs with less or almost no stereoselectivity. These results indicate that only a few amino acid alterations cause dramatic changes in both the chemical and catalytic properties of P-450 human-2.

Base Sequence↗
PubMed1991

Purification of hepatic N-hydroxyarylamine sulfotransferases and their regulation by growth hormone and thyroid hormone in rats.

From liver cytosols of male Sprague-Dawley rats, two N-hydroxyarylamine sulfotransferases (HASTs) which sulfate N-hydroxy-2-acetylaminofluorene and a phenolsulfotransferase (PST-I) have been purified about 290-, 690-, and 210-fold, respectively, by the use of DEAE-anion exchange, Blue-Sepharose CL-6B, DEAE-HPLC, and ATP-agarose affinity chromatography. All three enzymes showed almost the same molecular weight of 33 kDa on SDS-polyacrylamide gel electrophoresis. In Western blots using antibody raised against HAST I, the two HASTs, but not PST-I, were detected. The content of total HAST in male rats was estimated as 4-5 micrograms/mg cytosolic protein, about 4 times higher than that in female rats. Direct comparison of the DEAE-HPLC elution profiles of cytosol showed that HAST I and HAST II were male-dominant and male-specific, respectively, in their expression in the livers. Hypophysectomy decreased the level of HAST by 60% in male rats, but had no obvious effect in female rats. Intermittent injection of growth hormone to mimic the male secretory pattern raised the content in hypophysectomized rats of both sexes close to that in intact male rats, while the continuous infusion of growth hormone to mimic the female secretory pattern showed limited effects. In addition, the administration of triiodothyronine stimulated HAST in hypophysectomized rats of both sexes, and the extent of stimulation was nearly the same as observed in the male-type growth hormone treatment. PST-I, in contrast to HAST, showed no clear sex-related difference in hepatic content, and was not apparently affected by growth hormone or triiodothyronine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Inhibition of endothelin-1-induced DNA synthesis by prostacyclin and its stable analogues in vascular smooth muscle cells.

The effects of prostacyclin and its stable analogues on endothelin-induced DNA synthesis were investigated in cultured vascular smooth muscle cells. Aortic smooth muscle cells were obtained from male Wistar rats. In order to eliminate endothelial cells, the cells were cloned. DNA synthesis in intact cells was estimated by [3H]thymidine incorporation. Prostacyclin and its stable analogues (TEI-7165, TEI-9090, TEI-1324, TEI-3356, and TEI-9063) inhibited the endothelin-induced DNA synthesis with an IC50 of 1-30 nM. These results indicate that prostacyclin and its stable analogues are possibly effective in preventing the proliferation of vascular smooth muscle cells under some pathological situations, including atherosclerosis.

Animals↗
PubMed1991

Two possibly distinct prostaglandin E1 receptors in N1E-115 clone: one mediating inositol trisphosphate formation, cyclic GMP formation, and intracellular calcium mobilization and the other mediating cyclic AMP formation.

Prostaglandin E1 (PGE1)-mediated transmembrane signal control systems were investigated in intact murine neuroblastoma cells (clone N1E-115). PGE1 increased intracellular levels of total inositol phosphates (IP), cyclic GMP, cyclic AMP, and calcium ([Ca2+]i). PGE1 transiently increased inositol 1,4,5-trisphosphate formation, peaking at 20 s. There was more than a 10-fold difference between the ED50 for PGE1 at cyclic AMP formation (70 nM) and its ED50 values at IP accumulation (1 microM), cyclic GMP formation (2 microM), and [Ca2+]i increase (5 microM). PGE1-mediated IP accumulation, cyclic GMP formation, and [Ca2+]i increase depended on both the concentration of PGE1 and extracellular calcium ions. PGE1 had more potent intrinsic activity in cyclic AMP formation, IP accumulation, and cyclic GMP formation than did PGE2, PGF2 alpha, or PGD2. A protein kinase C activator, 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, had opposite effects on PGE1-mediated IP release and cyclic GMP formation (inhibitory) and cyclic AMP formation (stimulatory). These data suggest that there may be subtypes of the PGE1 receptor in this clone: a high-affinity receptor mediating cyclic AMP formation, and a low-affinity receptor mediating IP accumulation, cyclic GMP formation, and intracellular calcium mobilization.

Animals↗
PubMed1991

Inhibitory regulation of serum factor(s)-caused ornithine decarboxylase induction by the protein kinase C system in A431 human epidermoid carcinoma cells.

Replacement of the culture medium with fresh medium containing 10% fetal calf serum caused ornithine decarboxylase (ODC) induction in A431 human epidermoid carcinoma cells. Two peaks of ODC activity were observed at 5 and 14 hr after the medium replacement. The peak activity observed at 5 hr was more prominent than that at 14 hr. The first peak of ODC induction was suppressed by a potent protein kinase C activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), in a concentration-dependent manner. The second peak, however, was not suppressed by TPA. Other potent protein kinase C activators, such as mezerein and 12-O-retinoylphorbol-13-acetate, also suppressed the first peak of ODC induction. Synthetic diacylglycerols, 1,2-dioctanoyl-sn-glycerol and 1-oleoyl-2-acetylglycerol, did not inhibit the serum factor(s)-caused ODC induction. Phorbol-13-acetate, an inactive phorbol ester, also failed to inhibit the ODC induction. The growth of A431 cells was slightly suppressed by TPA. In protein kinase C down-regulated cells, TPA failed to inhibit the serum factor(s)-caused ODC induction. These results suggest that the serum factor(s)-caused ODC induction in A431 cells is negatively regulated by the protein kinase C system, which may not be activated by exogenous diacylglycerols.

Blood↗
PubMed1991

Regulations of male-dominant P-450Md mRNA in rat liver by hormonal factors and xenobiotics.

Male-dominant P-450Md mRNA was undetectable in the livers of newborn rats. In female rat livers, the mRNA appeared at 17 days of age and then decreased to very low levels in the adult periods. The level of P-450Md mRNA in female rats was increased by phenobarbital or dexamethasone treatment, whereas the level in the males was depressed by methylcholanthrene. Hypophysectomy decreased the level of P-450Md mRNA in male rat livers, and continuous infusion or twice-daily injections of growth hormone to hypophysectomized rats caused further suppression or clear restoration, respectively, of the mRNA level.

Animals↗
PubMed1991

Synergistic stimulation of prostaglandin E2 release by epidermal growth factor and a tumor promoter anthralin from primary cultures of mouse epidermal cells.

The tumor promoter anthralin stimulated prostaglandin E2 (PGE2) and arachidonic acid release from primary cultures of mouse epidermal cells. Epidermal growth factor (EGF) hardly stimulated PGE2 release by itself; however, a combination of anthralin and EGF synergistically stimulated PGE2 release. Neither anthralin, EGF nor EGF plus anthralin affected the incorporation of arachidonic acid into cellular phospholipids at least up to 2 hr after the stimulation by these agents. In the presence of EGF, however, [3H]arachidonic acid in the medium decreased substantially 4-8 hr after the addition of this agent, indicating that EGF suppresses [3H]arachidonic acid release and stimulates the incorporation of [3H]arachidonic acid into the cells during this time period. Cellular cyclooxygenase activity was increased by treating the cells either with anthralin or EGF, and it was synergistically increased by EGF plus anthralin. Both cycloheximide and actinomycin D inhibited the increase in cyclooxygenase activity caused by EGF plus anthralin. These results indicate that the synergistic stimulation of PGE2 release caused by EGF plus anthralin is due to a synergistic stimulation of arachidonic acid release (in the early phase of stimulation) and a synergistic increase in cyclooxygenase activity, probably a synergistic induction of cyclooxygenase, by these agents.

Animals↗
PubMed1991

Serum free triiodothyronine to free thyroxine ratio enables early prediction of the outcome of antithyroid drug therapy in patients with Graves' hyperthyroidism.

This study scrutinizes the correlation between serum free triiodothyronine (FT3) to free thyroxine (FT4) ratios and the eventual outcome of antithyroid drug (ATD) therapy in patients with Graves' disease. Forty-four patients with Graves' thyrotoxicosis were treated with methylmercaptoimidazole (methimazole). During the follow-up, 16 patients relapsed in the short period of one to five months after cessation of the drug (relapse group), and 28 patients remained in remission when checked at 12 to 20 months after treatment (remission group). Serum FT3 to FT4 ratios [(pg/ml/ng/dl) x 10] were less than 55 throughout ATD therapy in 27 of the 28 remission patients whereas the ratios of the relapse group exceeded 55 from the early phase of methimazole treatment in 10 of 16 patients. In eight of these 10 patients the increased ratios were detected within three months of therapy (1 month, 3 patients; 2 months, 4 patients; 3 months, 1 patient). The ratios for the remaining two patients rose above 55 at the fifth and sixth months. There was no statistical difference between the remission and relapse groups in the FT3 to FT4 ratios either before nor at the completion of the treatment. However, a clear difference could be measured at a point during the therapy. Those in whom this difference was pronounced later underwent relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗