Search PubMed⌕ Search

Biomedical subjects

M Satoh

Publications and source records attributed to M Satoh.

At least 559 records · Page 31Linked to original sources

Mutations of the APC gene occur during early stages of gastric adenoma development.

Mutations of the adenomatous polyposis coli (APC) gene have recently been shown to play an important role in colorectal tumorigenesis. We investigated mutations of the APC gene in 30 gastric adenomas obtained endoscopically. Mutations of the APC gene were examined by polymerase chain reaction-single-strand conformation polymorphism analysis followed by sequencing of the polymerase chain reaction products. Mutations were detected in 20% (6 of 30) of gastric adenomas. In addition, deletion of the remaining allele that subsequently led to complete inactivation of the APC gene was confirmed in one-half (3 of 6) of the tumors with APC gene mutations. Sequencing analysis confirmed that the mutations resulted in truncation of the gene products or in an amino acid change. The incidences of mutations of the APC gene remained constant regardless of the size or degree of histological atypia. Our observations suggest that mutations of the APC gene, similarly to those in colorectal tumorigenesis, occur during the early stages of gastric adenoma development.

Adenoma↗

In situ hybridization study of mu- and kappa-opioid receptor mRNAs in the rat spinal cord and dorsal root ganglia.

Distributions of mu- and kappa-opioid receptor mRNAs in the lumbar spinal cord and dorsal root ganglia of the adult rat were examined using the in situ hybridization technique. In the lumbar spinal cord, mu-opioid receptor mRNA was expressed intensely in laminae I, II and VIII. On the other hand, kappa-opioid receptor mRNA was expressed intensely in laminae I and II, and moderately throughout laminae III-VIII. In the dorsal root ganglia, mu-opioid receptor mRNA was intensely expressed and kappa-opioid receptor mRNA was expressed in a smaller number of cells than mu-opioid receptor mRNA.

Animals↗

Characterization of the Su antigen, a macromolecular complex of 100/102 and 200-kDa proteins recognized by autoantibodies in systemic rheumatic diseases.

The Su autoantigen was characterized biochemically using human and murine autoimmune sera and the clinical significance of anti-Su antibodies was studied in 236 Japanese and 160 American patients with systemic rheumatic diseases. Anti-Su in immunodiffusion (ID) was strongly associated with immunoprecipitation of one or more 100- to 102-kDa proteins by MRL/lpr mouse sera (27/32 of ID positive vs 4/20 of ID negative, P = 0.000016), and all four human anti-Su reference sera immunoprecipitated the 100/102-kDa protein(s). In addition, all sera immunoprecipitated a less efficiently labeled approximately 200-kDa protein that comigrated on sucrose density gradients with the 100/102-kDa proteins. Based on these data, a complex of the 100/102-kDa and 200-kDa proteins is likely to be the main target of anti-Su antibodies. Three of four anti-Su monospecific sera were negative for immunofluorescent antinuclear antibodies (ANA), suggesting anti-Su antibodies may be associated with a negative ANA in some cases. Autoantibodies to Su were detected frequently by immunoprecipitation in systemic lupus erythematosus (17-21%), scleroderma (13-20%), and overlap syndrome (22-40%) and were associated with autoantibodies to Ku.

Animals↗

Activation of tumor-infiltrating macrophages by a synthetic lipid A analog (ONO-4007) and its implication in antitumor effects.

ONO-4007 is a novel synthetic analog of lipid A subunit and has been shown to exert antitumor activities on various experimental tumors with less toxicity than lipopolysaccharide. It remains unclear, however, what biological activities of this compound are relevant to its antitumor effects. We therefore investigated the activation of macrophages by ONO-4007 in vitro and in vivo and its implication in antitumor effects, using mouse MM46 mammary tumor as an experimental model. Intravenous injection of ONO-4007 produced significant therapeutic effects on this solid tumor. ONO-4007 could stimulate glycogen-elicited peritoneal macrophages in vitro, not only to produce tumor necrosis factor (TNF), but also to exert cytocidal activities against MM46 cells in vitro. Substantial TNF production was induced in tumor tissue by i. v. injection of ONO-4007, and its successive administration to tumor-bearing mice gave tumor-infiltrating macrophages a prominent in vitro tumoricidal activity and primed them for in vitro TNF secretion. These results suggest that activation of tumor-infiltrating macrophages to a direct tumoricidal state as well as to TNF secretion in tumor tissues may be at least some of the antitumor effects of this novel lipid A analog.

Animals↗

Delayed gastric emptying in patients with liver cirrhosis.

Using a scintigraphic technique, we investigated gastric emptying of a semisolid meal in 20 patients with liver cirrhosis and in 10 control subjects and correlated gastric emptying with gastrointestinal symptoms and with autonomic nervous function as determined by R-R interval variation on the electrocardiogram. All subjects lacked endoscopic abnormalities that might explain their gastrointestinal symptoms. None had alcoholic liver disease, diabetes, or other diseases known to affect gastric emptying. The half-time for gastric emptying was significantly prolonged in the cirrhotic patients (51.3 +/- 16.6 minutes) as compared with control subjects (29.9 +/- 8.4) (P < 0.01). There was a significant correlation between the gastrointestinal symptom score and the half-time for gastric emptying (r = 0.46, P < 0.05) in the cirrhotic patients. However, the decreases in R-R interval variation and gastric emptying were not significantly correlated. These observations indicate that delayed gastric emptying is frequently present in patients with liver cirrhosis and may produce their gastrointestinal symptoms.

Autonomic Nervous System↗

HMT regulates histamine-induced Cl- secretion across the canine tracheal epithelium.

Although histamine N-methyltransferase (HMT), the primary enzyme responsible for the inactivation of histamine, has been shown to exist in the airway epithelium, it is still unknown whether this enzyme regulates ion transport across the airway epithelium. Using an Ussing chamber, we examined the effect of a HMT inhibitor, SKF 91488, on potential difference (PD) and short circuit current (SCC) in epithelial membranes from the posterior portion of canine trachea. SKF 91488 itself did not significantly alter PD or SCC values. Pretreatment with SKF 91488 significantly augmented PD and SCC induced by histamine. Amiloride did not significantly alter the augmentation by SKF 91488 in histamine-induced PD and SCC rises. These findings indicate that HMT regulates Cl- secretion across airway epithelium.

Amiloride↗

CGRP induces [Ca2+]i rise and glycoconjugate secretion in feline tracheal submucosal gland.

Submucosal glands were isolated from feline trachea. The intracellular Ca2+ concentration ([Ca2+]i) of the acinar cells of isolated glands was measured using the fluorescent dye Fura-2. Calcitonin gene-related peptide (CGRP) at 10(-8) to 10(-5) M produced a significant and sustained rise in the [Ca2+]i of isolated glands, reaching a maximal response of 127% of the prior baseline level but did not alter the intracellular adenosine 3', 5'-cyclic monophosphate ([cAMP]i). In a Ca(2+)-free solution, CGRP produced no significant alteration in [Ca++]i. Glycoconjugate secretion from isolated glands was stimulated by CGRP in a dose dependent fashion, reaching a maximal response of 167% of control at 10(-6) M but was without effect in tracheal explants. Further, CGRP did not produce any significant increase in glycoconjugate secretion in the Ca(2+)-free medium. These findings indicate that CGRP stimulates glycoconjugate secretion from airway submucosal glands by inducing Ca2+ influx from the extracellular solution.

Animals↗

Magnesium regulates ion transport across canine tracheal epithelium.

We examined the effect of Mg2+ on potential difference (PD) and short circuit current (SCC) of the posterior epithelial membrane of canine trachea using an Ussing chamber. After the exchange to a Mg(2+)-free solution, PD and SCC rapidly increased, reaching maximal values within 3 min, followed by a gradual return towards the baseline over 60 min. In a Ca(2+)-free solution, Mg2+ removal did not alter PD and SCC values. Increased Mg2+ in the solution produced significant gradual decreases in PD and SCC. The decreases in PD and SCC were reversed by the addition of excessive Ca2+ to the solution. Mg2+ removal did not alter significantly isoproterenol-induced increases in PD and SCC values, while increased Mg2+ significantly reduced the increases. These findings indicate that extracellular Mg2+ is an important determinant in ion transport across the airway epithelium, probably through antagonistic actions of Mg2+ and Ca2+.

Amiloride↗

Roles of endogenous cholinergic neurons in the induction of long-term potentiation at hippocampal mossy fiber synapses.

To evaluate the functional role of endogenous acetylcholine (ACh) in the induction of long-term potentiation (LTP) at mossy fiber-CA3 synapses, the influence of cholinergic hypofunction on it was investigated. Administration of a cholinergic neurotoxin, ethylcholine mustard aziridinium ion (AF64A; 5 nmol, i.c.v.), to guinea pigs one week prior to preparing slices resulted in a significant decrease in the magnitude of LTP, associated with a significant decrease in cholineacetyltransferase (ChAT) activity and the number of ChAT immunoreactive cells in the hippocampal slices. Bath-application of a cholinesterase inhibitor, physostigmine at 0.1 microM and 10 microM, attenuated and augmented, respectively, the magnitude of LTP in slices prepared from vehicle-treated animals (naive slices), whereas that in slices prepared from AF64A-treated animals (lesioned slices) was not significantly affected by physostigmine at any concentration tested. The induction of LTP in naive slices was inhibited or facilitated by a muscarinic M1 antagonist pirenzepine (1 microM) and by an M2 antagonist AF-DX 116 (1 microM) alone, respectively, whereas that in lesioned slices was not significantly changed by either of them. Furthermore, bath-applied carbachol (CCh) at 0.01-10 microM augmented the magnitude of LTP in lesioned slices, whereas the induction of LTP in naive slices was inhibited and facilitated by CCh at 0.01-0.1 microM and 1-10 microM, respectively, as reported previously. Such an augmentation of LTP by CCh was reversed by pirenzepine, but not by AF-DX 116. These observations suggest that AF64A induces the defect in ACh release and the hypofunction of M2 receptors, but not of M1, at least during the induction of LTP at mossy fiber-CA3 synapses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evidence that glutamate is released from capsaicin-sensitive primary afferent fibers in rats: study with on-line continuous monitoring of glutamate.

The aim of this study is to elucidate whether the excitatory amino acid glutamate is released from capsaicin-sensitive primary afferent fibers, and to compare the releasing effect of capsaicin on glutamate with that on substance P. The release of glutamate was measured using a fluorometric on-line continuous monitoring system, in which the immobilized glutamate dehydrogenase column was connected to an in vitro superfusion system. In the presence of 0.3 microM tetrodotoxin, 2-min application of capsaicin produced an increased outflow of glutamate, as well as an increase in the release of immunoreactive substance P from dorsal horn slices of the rat. The release of glutamate was concentration-dependently increased by capsaicin at concentrations in the range of 0.1-3 microM, and the release evoked by 10 microM capsaicin was not higher than that evoked by 3 microM. On the other hand, capsaicin at concentrations of 1-10 microM produced a concentration-dependent increase in the release of immunoreactive substance P, without effect at 0.1 microM. The amount of glutamate release evoked by 3 microM capsaicin was about 42.8 pmol.mg-1 protein, and 290 times that of immunoreactive substance P. The release of glutamate by 3 microM capsaicin was suppressed by the depletion of calcium from the superfusate. Capsaicin at 3 microM failed to increase the release of glutamate from the dorsal horn slices of the rats made an L4-L6 dorsal rhizotomy. These results suggest that capsaicin evoked the release of glutamate from primary afferent fibers in the dorsal horn and that glutamate may play an important role in pain transmission between primary afferent fibers and dorsal horn neurons.

Animals↗

Involvement of substance P and excitatory amino acids in aversive behavior elicited by intrathecal capsaicin.

The rat given an intrathecal injection of capsaicin (0.3-10 nmol/rat) through a lumbar puncture showed biting or licking the tail and hind paws. The substance P antagonist, CP-96,345 (3 nmol/rat), co-administered intrathecally with capsaicin (10 nmol/rat), caused a significant inhibition of the behavioral responses to capsaicin (10 nmol/rat). When co-administered intrathecally with the NMDA antagonist, 2-amino-5-phosphonovaleric acid (APV, 10 nmol/rat), the capsaicin (10 nmol/rat) -induced behavioral responses were significantly inhibited. A co-administration of the non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 nmol/rat), resulted in a significant reduction of the behavioral responses produced by capsaicin (10 nmol/rat). Administration of the combination of two antagonists (CP-96,345 and either APV or CNQX, or APV and CNQX) more markedly inhibited the behavioral responses to capsaicin (10 nmol/rat) than when either antagonist was co-administered with capsaicin. The results suggest that aversive behaviors induced by intrathecal capsaicin are mediated not only by the activation of NK-1 receptors but also by that of NMDA and non-NMDA receptors.

2-Amino-5-phosphonovalerate↗

Inhibitory influence via 5-HT3 receptors on the induction of LTP in mossy fiber-CA3 system of guinea-pig hippocampal slices.

The effects of 5-HT3-receptor-related agents on long-term potentiation (LTP) in the mossy fiber-CA3 system were studied in guinea pig hippocampal slices. 5-HT3 receptor agonists, 1-(m-chlorophenyl)-biguanide (mCPBG) and 2-methyl serotonin (2-Me-5-HT) significantly attenuated the magnitude of LTP of the population spike at 0.3-1 microM and at 10 microM respectively. At these doses neither of these drugs did affect the amplitude of the population spike (PSA) evoked by test stimuli in the absence of tetanic stimulation. The attenuating effect of mCPBG on LTP was reversed by the GABAA receptor antagonist bicuculline. On the other hand, 5-HT3 receptor antagonists ondansetron and granisetron significantly augmented the magnitude of LTP at 1-3 microM and at 0.1-0.3 microM, respectively, without changes in PSA before tetanus. The augmenting effect of granisetron on LTP was partially but significantly reversed by the muscarinic receptor antagonist atropine. These findings suggest that the induction of the LTP in the mossy fiber-CA3 system is inhibited by an activation of 5-HT3 receptors through the facilitation of GABAergic neurons (GABAA receptors) and the inhibition of cholinergic neurons (muscarinic receptors).

Animals↗

Molecular cloning and in situ hybridization histochemistry for rat mu-opioid receptor.

We cloned a cDNA for the rat mu-opioid receptor from a rat thalamus cDNA library. The deduced amino-acid sequence of rat mu-opioid receptor consists of 398 residues with the features shared by the members of the G-protein coupled receptor family, and is 59% and 60% identical with those of rat kappa-opioid and mouse delta-opioid receptors, respectively. Northern blot analysis showed that expression of mu-opioid receptor mRNA was intensive in the thalamus, striatum, hypothalamus and pons-medulla, moderate in the hippocampus and midbrain, and slight in the cerebral cortex and cerebellum. More detailed distribution of the mRNA in the rat brain was examined using the in situ hybridization technique. Intense expression of mu-opioid receptor mRNA was observed in the internal granular and glomerular layers of the olfactory bulb, caudate putamen, nucleus accumbens, medial septum, diagonal band, medial preoptic area, several nuclei of thalamus, amygdala, interpeduncular nucleus, medial raphe nucleus, inferior colliculus, parabrachial nucleus, locus coeruleus, nucleus solitary tract and ambiguus nucleus. Furthermore, mu-opioid receptor mRNA was moderately expressed in the hippocampus, globus pallidus, ventral pallidus, arcuate hypothalamic nucleus, supramammillary nucleus, superior colliculus, periacqueductal gray, and several nuclei of lower brain stem, including raphe magnus nucleus, reticular gigantocellular nucleus and lateral paragigantocellular nucleus.

Animals↗

Mobilization of intracellular Ca2+ and stimulation of cyclic AMP production by kappa opioid receptors expressed in Xenopus oocytes.

The intracellular metabotropic pathway, following kappa opioid receptor activation, was investigated in the Xenopus oocyte translation system. When oocytes were injected with cRNA for kappa opioid receptor cDNA, U50488H rarely evoked phospholipase C-mediated, oscillatory Cl- current responses. However, after the oocytes were incubated with staurosporine, both the occurrence and the amplitude of U50488H-evoked responses were increased. The U50488H-evoked response was antagonized by naloxone and inhibited by pretreatment of the oocytes with pertussis toxin. When oocytes were coinjected with RNAs encoding kappa opioid receptor and cystic fibrosis transmembrane conductance regulator (CFTR), treatment of the oocytes with forskolin and 3-isobutyl-1-methylxanthine (IBMX) evoked a smooth-shaped Cl- current flowing through the CFTR channels. The forskolin/IBMX-evoked response was never inhibited but was greatly potentiated in the presence of U50488H, indicating stimulation of adenylyl cyclase by U50488H. This U50488H-induced potentiation of CFTR channel opening was antagonized by naloxone and inhibited by pretreatment with pertussis toxin. These results suggest that kappa opioid receptors mobilize intracellular Ca2+ and stimulate cyclic AMP production by coupling positively to both phospholipase C and adenylyl cyclase via pertussis toxin-sensitive GTP-binding proteins in the oocytes.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Functional expression of Ca(2+)-mobilizing opioid receptors in Xenopus oocytes injected with rat brain mRNA.

Functional expression of opioid receptors was detected in the Xenopus oocyte translation system by a voltage-clamp recording. After injection of poly(A)+ RNA isolated from 3-week-old rat striatum or whole brain, the oocytes often demonstrated intracellular Ca(2+)-mediated oscillatory responsiveness to [D-Ala2, N-methyl-Phe4, Gly5-ol]enkephalin (DAMGO), [D-Pen2, D-Pen5]enkephalin (DPDPE) and U50488H at a concentration of 1 microM. These responses were very transiently expressed after injection of the mRNA, however, water-injected oocytes never responded to any of these opioid agonists. After fractionation by a sucrose-density gradient, an RNA size of about 3-4 kb encoded these opioid receptors. In the oocytes injected with size-selected striatal mRNA, DPDPE evoked the fluctuating current with higher probability and larger amplitude than other agonists, whereas oocytes injected with size-selected whole brain mRNA produced DAMGO and U50488H responses predominantly. The DPDPE response of striatal mRNA-injected oocytes was antagonized by naloxone as well as the delta-specific antagonist ICI 174864. The DAMGO and U50488H responses have not been characterized yet because of a strong desensitizing property making repeated recordings impossible. These observations suggest that putative mu, delta and kappa subtypes of opioid receptors mobilizing intracellular Ca2+ are expressed in Xenopus oocytes by rat brain mRNA.

Animals↗

An in situ hybridization study on interleukin-1 beta mRNA induced by transient forebrain ischemia in the rat brain.

Expression of interleukin-1 beta (IL-1 beta) mRNA in the rat brain after transient forebrain ischemia was investigated by in situ hybridization histochemistry. Thirty min after the start of recirculation, IL-1 beta mRNA was induced in the several brain regions, including the olfactory bulb, cerebral cortex, hippocampus, striatum and thalamus where neuronal degeneration was reported to be observed after transient forebrain ischemia. The hybridization signals were observed both on the glial cells and around the vascular walls.

Animals↗

Localization of type I interleukin-1 receptor mRNA in the rat brain.

The distribution of type I interleukin-1 receptor (IL-1R1) mRNA in the rat brain was examined by in situ hybridization technique. IL-1R1 mRNA was expressed in several brain regions including the anterior olfactory nucleus, medial thalamic nucleus, posterior thalamic nucleus, basolateral amygdaloid nucleus, ventromedial hypothalamic nucleus, arcuate nucleus, median eminence, mesencephalic trigeminal nucleus, motor trigeminal nucleus, facial nucleus and Purkinje cells of the cerebellum. Furthermore, we identified neuronal expression of IL-1R1 mRNA using simultaneous detection (double in situ hybridization) of IL-1R1 mRNA with neuron specific enolase mRNA. In addition to the expression in neuronal cells, IL-1R1 mRNA was also expressed on the vascular walls and the epithelial cells of the choroid plexus and the ventricles. These findings suggest the possibility that IL-1 produces its multiple effects on the central nervous system through the actions not only on neuronal cells but also on endothelial and epithelial cells.

Animals↗

Rat FGF receptor-4 mRNA in the brain is expressed preferentially in the medial habenular nucleus.

The fibroblast growth factor (FGF) receptor family consists of four members, FGFR-1, FGFR-2, FGFR-3 and FGFR-4, that are closely related receptor tyrosine kinases. We examined the expression of rat FGFR-4 mRNA in the brain by in situ hybridization and compared it with that of the mRNAs for other FGF receptors. In contrast with FGFR-1, FGFR-2 and FGFR-3 mRNAs which are expressed widely in the brain, the FGFR-4 mRNA in the brain is expressed preferentially in the medial habenular nucleus neurons. The present finding indicates that FGFR-4 has a function specific to the medial habenular nucleus.

Animals↗