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C Sato

Publications and source records attributed to C Sato.

At least 19 recordsLinked to original sources
PubMed1992

Proposed tertiary structure of the sodium channel.

On the basis of our recent results of the complete amino acid sequence of the squid Loligo bleekeri sodium channel deduced by cloning and sequence analysis of the complementary DNA (Sato, C. and Matsumoto, G. Biochem. Biophys. Res. Comm. 186, 1), we have proposed a tertiary structure model of the sodium channel where the transmembrane segments are octagonally aligned and the four linkers of S5-6 between segments S5 and S6 play a crucial role in the activation gate, voltage sensor and ion selective pore, which can slide, depending on membrane potentials, along inner walls consisting of segments S2 and S4 alternately. The proposed model is contrasted with that of Noda et al. (Nature 320; 188-192, 1986).

Amino Acid Sequence↗
PubMed1992

Primary structure of squid sodium channel deduced from the complementary DNA sequence.

The complete amino acid sequence of a sodium channel from squid Loligo bleekeri has been deduced by cloning and sequence analysis of the complementary DNA. The deduced sequence revealed an organization virtually identical to the vertebrate sodium channel proteins; four homologous domains containing all six membrane-spanning structures are repeated in tandem with connecting linkers of various sizes. A unique feature of the squid Na channel is the 1,522 residue sequence, approximately three fourths of those of the rat sodium channels I, II and III.

Amino Acid Sequence↗
PubMed1992

c-myc expression is down-regulated by cell-cell and cell-extracellular matrix contacts in normal hepatocytes, but not in hepatoma cells.

Primary culture of adult rat hepatocytes resulted in marked increase of c-myc expression within a few hours. The high level of c-myc mRNA was maintained throughout culture on collagen-coated dishes, but decreased greatly with time during culture on collagen-gel or matrigel. Expression of c-myc was also down-regulated at high cell density. The decrease in its expression appeared closely related to inhibitions of DNA synthesis and cell spreading. In contrast, hepatoma H4TG cells showed a high level of c-myc expression which was not affected by culture on any extracellular matrices examined or by the cell density. These results suggest that up-regulation of expression of the c-myc gene is linked to G0 to G1 transition during cell cycle progression, which in normal hepatocytes is strictly regulated by cell-cell and cell-extracellular matrix interactions, but that this control mechanism is defective in malignant hepatic tumor cells.

Animals↗
PubMed1992

Clinical significance of elevated plasma endothelin concentration in patients with cirrhosis.

Endothelin is a newly discovered potent vasoconstrictor peptide. To explain the clinical significance of endothelin in patients with chronic liver diseases, we measured the plasma concentration of endothelin in patients with chronic hepatitis (n = 15), cirrhosis with ascites (n = 8) and cirrhosis without ascites (n = 12), and we compared the findings with the plasma concentration of endothelin in normal controls (n = 14). The plasma endothelin concentration was significantly higher in patients with cirrhosis with ascites than in normal controls (8.3 +/- 2.3 pg/ml vs. 3.3 +/- 1.4 pg/ml, mean +/- S.D., p less than 0.001), whereas no significant difference was observed between normal controls and the other groups of patients (cirrhosis without ascites = 5.0 +/- 1.3 pg/ml; chronic hepatitis = 3.8 +/- 1.2 pg/ml). In patients with cirrhosis, the plasma endothelin concentration showed a significant negative correlation with creatinine clearance (r = -0.73, p less than 0.01), but no significant correlation was observed between plasma endothelin concentration and fractional excretion of filtered sodium. Furthermore, plasma endothelin levels were significantly higher in patients with endotoxemia than in those without (10.1 +/- 2.1 pg/ml vs. 4.9 +/- 1.2 pg/ml, p less than 0.001). From these results, elevated plasma endothelin, which has a close relation to endotoxemia, may play a contributory role in kidney dysfunction in patients with cirrhosis.

Aldosterone↗
PubMed1992

V1-receptor mediated GSH efflux by vasopressin from rat hepatocytes.

Vasopression increases sinusoidal efflux of GSH in the perfused rat liver. The mechanism of this effect was studied in the perfused rat liver and in isolated rat hepatocytes. Vasopressin stimulated GSH efflux in both systems and a V1-receptor antagonist (OPC-21268) significantly inhibited the effect of vasopressin suggesting that vasopressin stimulates GSH efflux from rat hepatocytes via V1-receptor.

Angiotensin Receptor Antagonists↗
PubMed1992

Possible involvement of protein kinase C and calcium in GSH efflux from Hep G2 cells.

We investigated the effects of protein kinase C modulations and calcium mobilization on GSH efflux in Hep G2 cells. GSH efflux from Hep G2 cells was increased by a phorbol ester. Staurosporine, an inhibitor of protein kinase C, diminished phorbol ester-stimulated GSH efflux from the cells. GSH efflux was negatively correlated with extracellular calcium concentrations. Verapamil enhanced GSH efflux, whereas ATP decreased GSH efflux. The latter effect was diminished in the absence of extracellular calcium. Protein kinase C and calcium mobilization may be crucial factors in GSH efflux from human hepatocytes.

Adenosine Triphosphate↗
PubMed1992

Radiosensitization by 2-nitroimidazole nucleoside analog RP-170: radiosensitizing effects under both intravenous and oral administration.

The radiosensitizing activity, pharmacokinetics and toxicity of RP-170, 2-nitroimidazole nucleoside analog, were investigated and compared with those of etanidazole (SR-2508). An intravenous administration (i.v.) of 100 mg/kg of RP-170 or the same dose of etanidazole showed an equal sensitizer enhancement ratio (SER) of about 1.4 to solid EMT6 tumor under in vivo-in vitro assay and a virtually equal SER of 1.4-1.5 to solid SCC VII tumor under tumor growth delay assay. As predicted from the low partition coefficient, lower drug levels in neural tissue and more rapid serum elimination of RP-170 and etanidazole produced lower acute toxicity than lipophilic sensitizers (e.g., misonidazole). The major advantage of RP-170 over etanidazole is that it has a second route of administration. In contrast to etanidazole, in which the administration route is limited to intravenous injection, with RP-170 oral administration also exhibited effective distribution to tumors, sensitizing radiation activity to solid EMT6 and SCC VII tumors. Moreover, LD50 in mice of RP-170 (4.3 g/kg on i.v.) was increased to 5.2 g/kg by oral administration. This availability of two routes of administration indicates RP-170 as a promising hypoxic cell radiosensitizer for clinical use.

Administration, Oral↗
PubMed1992

Inhibition of acetaminophen hepatotoxicity by acetaldehyde in the rat.

Since we have observed that acetaldehyde, an oxidative metabolite of ethanol, inhibits acetaminophen activation in rat liver microsomes, the in vivo effect of acetaldehyde on acetaminophen hepatotoxicity was tested. In vivo experiments in 3-methylcholanthrene-pretreated male Sprague-Dawley rats showed that administration of cyanamide (20 mg/kg, i.p.) and acetaldehyde (600 mg/kg, s.c.) given 3 and 1 h, respectively, prior to acetaminophen (500 mg/kg, i.p.) but not cyanamide alone prevented acetaminophen hepatotoxicity as assessed by serum transaminases and histology. Acetaldehyde may partly be responsible for the inhibitory effect of ethanol on acetaminophen hepatotoxicity.

Acetaldehyde↗
PubMed1992

Identification of human blood in mosquitoes (Diptera: Culicidae) using nonradioactive DNA dot blot hybridization.

A dot blot hybridization procedure was developed to detect human blood meals in engorged mosquitoes. A biotinylated DNA probe allowed the detection of 10-100 ng of human DNA, discriminated well between human and nonhuman sources of blood, and cross-reacted only with monkey DNA. Results showed that this method was a specific and sensitive technique for the identification of blood meals up to 100 h after ingestion. The nonisotopic label offers easy handling without the problems inherent in the use of radioisotopes, and it can be adapted for use in routine field tests.

Animals↗
PubMed1992

Stimulation of keratinocyte migration by growth factors.

Migration of keratinocytes from the wound edge is thought to be one of the critical features of reepithelialization. A quantitative migration assay was carried out using normal human keratinocytes. Keratinocytes, seeded on 12 well plates, were grown in serum free, keratinocyte growth medium (KGM, Curabo Co) with 0.08 mM Ca2+. The medium was switched from KGM to keratinocyte basal medium (KBM) 6 h prior to the wounding. Half of the plate's confluent monolayer of keratinocytes was removed with razor blade, and the remaining keratinocytes were incubated in KBM for 16 hrs in the presence of indicated growth factors. After incubation, the cells were fixed and counted at 100 magnification. Migration was quantitated by counting the number of cells in ten successive 125-microns zones. Transforming growth factor alpha (TGF-alpha), acidic and basic fibroblast growth factor (aFGF, bFGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), and insulin-like growth factor-I (IGF-I) stimulated the migration of keratinocytes, while TGF-beta suppressed it.

Cell Movement↗
PubMed1992

[Effects of adrenergic drugs injected into the nucleus tractus solitarius region on the baroreceptor reflex in rabbits].

It has been presumed that a primary site of termination of the baroreceptor afferent was in the nucleus tractus solitarii (NTS). The intermediate region of the nucleus, located at the level of the obex, contains a large number of catecholamine neurons. The principal noradrenergic innervation of the NTS appears to arise from neurons of the so-called A2 group. It has been proposed that catecholamines released by A2 neurons serve to lower blood pressure and heart rate. We performed experiments to determine the effects of alpha-adrenoceptor agonists and antagonists on the baroreceptor reflex and alpha-adrenoceptor. Rabbits anesthetized with chloralose-urethane were injected with an alpha-adrenoceptor agonist, such as noradrenaline, phenylephrine or clonidine, into the NTS. An adrenoceptor-antagonist, such as yohimbine, phentolamine, prazosin or corynanthine was injected into the NTS of other anesthetized rabbits. Clonidine markedly lowered the blood pressure and heart rate, and it inhibited the baroreceptor reflex responses. Noradrenaline or phenylephrine did not lower the blood pressure and heart rate and scarcely inhibited the baroreceptor reflex. Yohimbine remarkedly inhibited the baroreceptor reflex responses; on the other hand, prazosin, corynanthine and phentolamine produced little inhibition of the responses. It is concluded that there are alpha 1- and alpha 2-receptors in the NTS of the rabbits, and the alpha 2-receptors play an important role in the neurotransmission in the NTS.

Animals↗
PubMed1992

Effects of caffeine on paracetamol activation in rat and mouse liver microsomes.

1. The effects of caffeine on the NADPH-dependent production of paracetamol-glutathione conjugate were studied in rat and mouse liver microsomes. 2. In the presence of caffeine, glutathione conjugate production in rat microsomes was enhanced, whereas that in mouse microsomes was not affected significantly, showing an apparent species difference. 3. The data partly explain the species difference in the effects of caffeine on paracetamol hepatotoxicity.

Acetaminophen↗
PubMed1991

Hyperreactivity of alpha 1-adrenoceptors, but not of P2X-purinoceptors, in vas deferens of spontaneously hypertensive rats.

We evaluated the contractile reactivity to various stimuli, and the content and release of noradrenaline (NA) from a non-vascular tissue, the vas deferens, isolated from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The concentration-contraction curves for NA in tissue from animals of two ages (10-25 weeks and 30-45 weeks) were shifted to the left in SHR as compared with in age-matched WKY, with significant differences at 1.0 and/or 10 microM of NA. Similarly, the amplitude of contraction produced by electrical stimulation at 4, 8 and 16 Hz in the tissue was much larger in SHR than in WKY. However, ATP (10-100 microM) evoked contractions of the tissue to a similar extent in both SHR and WKY. The electrically evoked contractions of vas deferens from both strains were inhibited by isoprenaline in an approximate dose-dependent and equipotent manner. The tissue NA content, determined by HPLC-ECD, was nearly same in both SHR and WKY. In addition, the same amount of NA was released from the vas deferens of both strains by electrical stimulation in the presence of 4-aminopyridine. The present findings indicate that the contractile response of vas deferens to stimulation of alpha 1-adrenoceptors, but not of beta-adrenoceptors or P2X-purinoceptors, is more pronounced in SHR than in WKY and that a response indicative of hypertension may also occur in non-vascular tissue as it does in vascular tissue.

Adenosine Triphosphate↗
PubMed1991

Phenotypic modulation in lipocytes in experimental liver fibrosis.

The presence of a-smooth muscle actin (smA)-positive cells has recently been reported in the fibrotic liver. Lipocytes have been considered to play important roles in hepatic fibrosis. However, the relation of the a-smA-positive cells and lipocytes has not been determined. The biological implication of a-smA expression remains unknown. To study these questions, we carried out double immunofluorescent staining of a-smA and desmin (a marker for lipocytes), or a-smA and collagen, and double immunohistochemical staining of a-smA and 5-bromo-2'-deoxyuridine (BrdUrd) in carbon tetrachloride-induced fibrotic rat livers. In normal and control livers, a-smA-positive cells were not seen in the lobules, whereas scattered desmin-positive cells were present. With the development of hepatic fibrosis, a-smA was expressed only in a portion of desmin-positive cells located predominantly around collagen bundles. A number of a-smA-positive cells in the lobules were labelled with BrdUrd. These results suggest phenotypic modulation in lipocytes and differentiation of lipocytes towards myofibroblast-like cells, since a-smA is expressed with desmin in myofibroblasts in scar tissue. The expression of a-smA may be related to events of the fibrotic process, such as tissue contraction or fibrogenesis per se.

Actins↗
PubMed1991

Somatosensory evoked potentials following stimulation of median and tibial nerves in patients with localized intracerebral hemorrhage: correlations with clinical and CT findings.

Median and tibial somatosensory evoked potentials (SEPs) were performed on 38 patients with localized intracerebral hemorrhage, 23 with thalamic hemorrhage and 15 with putaminal hemorrhage. Of 65 arms and 62 legs examined, cerebral evoked responses of 60 arms and 50 legs were diagnosed as abnormal. The abnormal findings in scalp-recorded SEPs consisted of a reduction in amplitude, loss of waves and delay in peak latencies. The SEP abnormalities were not indicative of location of hemorrhage. Absence of SEPs was more frequently observed in large hemorrhages and at the early stage. Substantial improvement in SEPs was observed over several months after stroke in many limbs. Motor function as evaluated with Brunnstrom staging of the upper limbs whose SEPs were absent was lower than that whose SEPs were evoked, but that was not observed in the lower limbs because in some cases absence of SEPs coexisted with good motor function. Loss of SEP waves had a significant correlation with disturbed deep sensation. The median and tibial SEPs provided an excellent clinical correlation with the patients' improvement over several months.

Adult↗
PubMed1991

Existence of ATP-evoked ATP release system in smooth muscles.

Effects of stable ATP analogs such as alpha,beta-methylene ATP (alpha,beta-mATP) and beta,gamma-methylene ATP (beta,gamma-mATP) on ATP release and contractile response were evaluated in the vas deferens and ileal longitudinal muscles of guinea pig. In these smooth muscles, administration of alpha,beta-mATP (10, 30 or 100 microM) produced an ATP release accompanied by a transient contraction, but alpha,beta-methylene ADP (30 or 100 microM) or adenosine (30 microM) failed to elicit both the ATP release and the contraction. However, the peak responses of ATP release and contraction to alpha,beta-mATP (100 microM) in the vas deferens appeared around 2 min and 2.62 sec, respectively, after the injection of the drug. Beta,gamma-mATP (10 or 100 microM) caused an ATP release from the vas deferens. The ATP release as well as the contraction evoked by alpha,beta-mATP or beta,gamma-mATP were effectively inhibited by 300 microM suramin, a P2 purinoceptor antagonist. By contrast, ATP release and contractile response to norepinephrine in the vas deferens and those to bethanechol in the ileum were virtually unaffected by this antagonist. Veratridine and ouabain at (30 or 100 microM) caused markedly acetylcholine release from the ileum and norepinephrine release from the vas deferens, respectively. However, alpha,beta-mATP, even in a high concentration of 100 microM, did not elicit any release of acetylcholine or norepinephrine. These findings suggest that alpha,beta-mATP and probably beta,gamma-mATP evoke ATP release from not neuronal but mainly smooth muscular sites by activating suramin-sensitive P2x receptors, implying that "ATP-evoked ATP release system" exists.

Acetylcholine↗