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Y Yajima

Publications and source records attributed to Y Yajima.

At least 55 records · Page 3Linked to original sources
PubMed1998

Synaptology of the direct projections from the nucleus of the solitary tract to pharyngeal motoneurons in the nucleus ambiguus of the rat.

During the pharyngeal phase of the swallowing reflex, the nucleus of the solitary tract (NTS) receives peripheral inputs from the pharynx by means of the glossopharyngeal ganglion and is the location of premotor neurons for the pharyngeal (PH) motoneurons. The semicompact formation of the nucleus ambiguus (AmS) is composed of small and medium-sized neurons that do not project to the pharynx, and large PH motoneurons. We investigated whether the neurons in the NTS projected directly to the PH motoneurons or to the other kinds of neurons in the AmS by using the electron microscope. When wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was injected into the NTS after cholera toxin subunit B-conjugated HRP (CT-HRP) injections into the pharyngeal muscles of male Sprague-Dawley rats, many nerve terminals anterogradely labeled with WGA-HRP were found to contact PH motoneurons retrogradely labeled with CT-HRP. Most of the labeled axodendritic terminals (63%) contained pleomorphic vesicles with symmetric synaptic contacts (Gray's type II), and the remaining ones contained round vesicles with asymmetric synaptic contacts (Gray's type I). About 14% of the axosomatic terminals on PH motoneuron in a sectional plane were anterogradely labeled, and about 70% of the labeled axosomatic terminals were Gray's type II. Observations of serial ultrathin sections revealed that both the small and the medium-sized neurons received only a few labeled axosomatic terminals that were exclusively Gray's type I. These results indicate that the NTS neurons may send mainly inhibitory as well as a few excitatory inputs directly to the PH motoneurons in the AmS.

Animals↗
PubMed1998

Role of nitric oxide in the hypersusceptibility to pentylenetetrazole-induced seizure in diazepam-withdrawn mice.

The decrease in the seizure threshold for pentylenetetrazole in diazepam-withdrawn mice was not significantly affected by L-arginine (50 and 100 microg/mouse, i.c.v.), which did have an antiseizure effect in chronically vehicle-treated mice. Sodium nitroprusside (25 and 50 microg/mouse, i.c.v.) increased the seizure threshold for pentylenetetrazole in both diazepam-withdrawn mice and chronically vehicle-treated mice. In addition, the antiseizure effect of L-arginine was blocked by the nitric oxide (NO) synthase inhibitor, N-nitro-L-arginine (NOARG) and the NO scavenger, hemoglobin, while the effect of sodium nitroprusside was inhibited by hemoglobin, but not by NOARG, indicating that the antiseizure effect of L-arginine, but not that of sodium nitroprusside, is mediated by NO production resulting from the activation of NO synthase. Therefore, a decrease in the NO production via NO synthase may be involved in the hypersusceptibility to pentylenetetrazole during diazepam withdrawal.

Animals↗
PubMed1998

Hypersusceptibility to DMCM-induced seizures during diazepam withdrawal in mice: evidence for upregulation of NMDA receptors.

The present study investigated the role of NMDA (N-methyl-D-aspartate) receptors in the hypersusceptibility to seizures induced by the benzodiazepine inverse agonist DMCM (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate) during diazepam withdrawal in mice, using behavioral and biochemical approaches. The seizure threshold of DMCM was markedly decreased during diazepam withdrawal, reflecting withdrawal hyperexcitability in response to physical dependence. The decrease in the seizure threshold of DMCM in diazepam-withdrawn mice was inhibited by the non-competitive NMDA receptor antagonists MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cycloheptan-5,10-imine maleate; 50 microg/kg, s.c.) and ifenprodil (20 mg/kg, i.p.). The effective doses of these compounds were lower than those required to prevent DMCM-induced seizures in chronically vehicle-treated mice. Since MK-801 and ifenprodil do not only bind to NMDA receptors but also to sigma receptors, the present study also investigated the effects of sigma receptor ligands. The decrease in the seizure threshold of DMCM in diazepam-withdrawn mice was not modified by the sigma receptor agonist, (+)-pentazocine (5 mg/kg, s.c.), or the sigma receptor antagonist, NE-100 (N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride; 5 mg/kg, i.p.). Furthermore, the latency to the expression of wild running induced by intracerebroventricular administration of NMDA (60 ng/mouse) was also significantly lower in diazepam-withdrawn mice than in vehicle-treated control mice. On the other hand, there was no difference in the spermidine concentration between vehicle-treated control and diazepam-withdrawn mice. In a receptor binding experiment, the Bmax value for [3H]-MK-801 binding was significantly increased in cerebrocortical tissues from diazepam-withdrawn mice, while the Kd value did not change in either group. However, the acute addition of a high concentration of diazepam (10 and 100 microM) in vitro did not alter [3H]-MK-801 binding in cerebrocortical membrane preparations. The behavioral experiments suggest that NMDA receptor antagonists may suppress benzodiazepine withdrawal responses, while the biochemical study reveals upregulation of the NMDA receptor, which may play an important role in the hypersusceptibility to DMCM-induced seizure in diazepam-withdrawn mice.

Animals↗
PubMed1998

Profiles of cytokines produced by CD4-positive T lymphocytes stimulated by anti-CD3 antibody in patients with chronic hepatitis C.

Helper T cells (Th) are classified as type 1 (Th1) and type 2 (Th2) according to the cytokines they produce; interferon-gamma is produced by Th1, and interleukin-4 by Th2. We counted the circulating CD4-positive Th cells that produce interferon-gamma or interleukin-4 with an enzyme-linked immunospot assay. CD4-positive T cells isolated from patients with chronic hepatitis B (n = 10), chronic hepatitis C (n = 16), and healthy subjects (n = 10) were stimulated with anti-CD3 antibody in vitro. The number of interferon-gamma-producing Th cells was significantly lower in patients with chronic hepatitis C than in healthy subjects (P = 0.0024), whereas in patients with chronic hepatitis B, the number was similar to that in healthy subjects (P = 0.8530). The number of interleukin-4-producing Th cells was significantly higher in patients with chronic hepatitis C (P = 0.0010) and chronic hepatitis B (P = 0.0089) than in healthy subjects. In chronic hepatitis C, the number of interferon-gamma-producing Th cells was increased after incubation of the cells with interferon-alpha (P = 0.008) or with recombinant interferon-gammala (P = 0.024), but not with interferon-beta (P = 0.051). The number of interleukin-4-producing Th cells was decreased after incubation with interferon-alpha (P = 0.0004), with interferon-beta (P = 0.003), and with recombinant interferon-gammala (P = 0.0004). Changes in the numbers of interferon-gamma- or interleukin-4-producing Th cells in vitro were more evident in sustained responders to interferon therapy than in non-responders. These results suggest that Th2 cells are the predominant cell type in chronic hepatitis C, and that their activity may be suppressed by the administration of interferon.

Adult↗
PubMed1998

Beta3-adrenergic receptor gene polymorphism is not associated with hypertension in NIDDM patients without nephropathy.

OBJECTIVE: We studied the relationship between a Trp64Arg mutation of beta3-adrenergic receptor gene and hypertension in Japanese NIDDM patients without nephropathy. RESEARCH DESIGN AND METHODS: Eighty-three Japanese NIDDM patients (46 men, 37 women, known duration of 12 [5-31], age of 55 [40-69] years, median and [range]) with normoalbuminuria and microalbuminuria were studied. The Trp64Arg mutation in the beta3-adrenergic receptor gene was determined by the PCR-RFLP method. RESULTS: The frequency of the mutated allele was not greater in the hypertensive patients (18.2%, n=37) than in the normotensive (20.2%, n=46) patients. Genotypes with a mutate allele (i.e. Trp64/Arg64 + Arg64/Arg64) were observed in 23.5% in the hypertensive patients and in 35.7% in the normotensive patients, respectively. A similar finding in the allele frequency was observed when the analysis was made separately in the normoalbuminuric and microalbuminuric patients, respectively. CONCLUSION: These results suggest that a Trp64Arg mutation in the beta3-adrenergic receptor gene is not associated with hypertension in Japanese NIDDM patients without nephropathy.

Adult↗
PubMed1998

VIP induces the translocation and degradation of the alpha subunit of Gs protein in rat pituitary GH4C1 cells.

It has been shown that G proteins are potential regulatory molecules in the transmembrane signaling cascade. The aim of this study was to examine the possibility of equivalent G-protein redistribution and/or down-regulation in a target cell upon agonist stimulation. Short-term (0-80 min) incubation of rat pituitary GH4C1 cells with vasoactive intestinal peptide (VIP, 0.1 microM) induced a decrease in the levels of Gsalpha in the membrane fraction, whereas immunoblot analysis and reconstitution assay of adenylyl cyclase clearly showed an increase in the amount of Gsalpha in the supernatant (cytosolic) fraction. The VIP-induced release of G proteins alpha subunits from membranes was specific for Gsalpha. The VIP-dependent release of Gsalpha from membranes was blocked by a VIP-receptor antagonist, (N-Ac-Tyr,D-Phe)-GRF(1-29)-NH2 (10 microM). Pituitary adenylate cyclase-activating polypeptide (PACAP) also stimulated the release of Gsalpha from membranes of GH4C1 cells. Furthermore, prolonged exposure of cells to VIP (0.1 microM) for 2-24 h caused a 21-40% decrease in Gsalpha from membranes and a 6% increase in total Gsalpha in the cytosolic fraction. The effect of VIP was dose-dependent with ED50 values of 81.6+/-20.0 nM for down-regulation and 2.5+/-0.3 nM for translocation of Gsalpha. Concurrent treatment of GH4C1 cells with VIP and cycloheximide indicated that suppression of protein synthesis de novo did not mimic the effect of VIP. Moreover, the chase experiment of 35S-labeled Gsalpha clearly demonstrated a more rapid rate of decay in the cells maintained in the presence of the agonist. These data indicate that VIP-receptor activates Gsalpha protein and induces the release of Gsalpha from membranes along with its down-regulation in cellular levels.

Animals↗
PubMed1998

Effects of a neutral endopeptidase inhibitor, BP102, on the development of deoxycorticosterone acetate-salt hypertension in kininogen-deficient Brown Norway Katholiek rats.

The nature of all of the peptides critical to the mechanism(s) of the antihypertensive action of neutral endopeptidase (NEP) inhibitors is still unclear, but bradykinin is thought to be one such peptide. This study was designed to assess the effectiveness of an NEP inhibitor in deoxycorticosterone acetate (DOCA)-salt treated kininogen-deficient Brown Norway Katholiek (BN-Ka) rats. Oral administration of BP102 (10-100 mg/kg), an NEP inhibitor, increased urine volume and urinary sodium excretion in a dose-dependent manner in anesthetized Sprague-Dawley rats. DOCA-salt hypertension was induced in both BN-Ka and Brown Norway Kitasato (BN-Ki) rats after left nephrectomy. The development of DOCA-salt hypertension in normal BN-Ki rats was prevented, and that in BN-Ka rats was also significantly reduced, by an 8-day administration of BP102. When BP102 was administered for 5 weeks, the high blood pressure of DOCA-salt treated BN-Ka rats was markedly lowered, and their heart weights were reduced. These results suggest that kinins play no role in the antihypertensive effect of this inhibitor and that other factors may be involved in this effect.

Administration, Oral↗
PubMed1997

Molecular interactions between dynamin and G-protein betagamma-subunits in neuroendocrine cells.

Dynamin and G-proteins both are guanosine triphosphate (GTP) binding proteins, with dynamin active in cellular membrane trafficking and G-proteins in intracellular signal transduction. Here we demonstrate that dynamin physically and functionally interacts with G-protein betagamma-subunits in neuroendocrine GH4C1 cells, on stimulation with thyrotropin-releasing hormone and somatostatin. The interaction appears to be of high affinity and inhibitory on dynamin GTPase activity, mediated by the pleckstrin homology domain and regulated both by the G-protein alpha-subunit and by guanosine nucleotides. Thus, dynamin may target particular sites for receptor-mediated endocytosis by sharing betagamma-subunits with the alpha subunit of G-proteins in neuroendocrine cells.

Animals↗
PubMed1997

Direct synaptic projections to esophageal motoneurons in the nucleus ambiguus from the nucleus of the solitary tract of the rat.

Neurons of the nucleus of the solitary tract (NTS) serve as interneurons in swallowing. We investigated the synaptology of the terminals of these neurons and whether they project directly to the esophageal motoneurons in the compact formation of the nucleus ambiguus (AmC). Following wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) injection into the NTS, many anterogradely labeled axodendritic terminals were found in the neuropil of the AmC. The majority of labeled axodendritic terminals (89%) contained round vesicles and made asymmetric synaptic contacts (Gray's type I), but a few (11%) contained pleomorphic vesicles and made symmetric synaptic contacts (Gray's type II). More than half of the labeled terminals contacted intermediate dendrites (1-2 microm diameter). There were no retrogradely labeled medium-sized motoneurons, but there were many retrogradely labeled small neurons having anterogradely labeled axosomatic terminals. A combined retrograde and anterograde transport technique was developed to verify the direct projection from the NTS to the esophageal motoneurons. After the esophageal motoneurons were retrogradely labeled by cholera toxin subunit B conjugated HRP, the injection of WGA-HRP into the NTS permitted ultrastructural recognition of anterogradely labeled axosomatic terminals contacting directly labeled esophageal motoneurons. Serial sections showed that less than 20% of the axosomatic terminals were labeled in the esophageal motoneurons. They were mostly Gray's type I, but a few were Gray's type II. In the small neurons, more than 30% of axosomatic terminals were labeled, which were exclusively Gray's type I. These results indicate that NTS neurons project directly not only to the esophageal motoneurons, but also to the small neurons which have bidirectional connections with the NTS.

Animals↗
PubMed1997

Idiopathic perforation of the gallbladder: report of a case and a review of the Japanese literature.

A 79-year-old man was admitted to our hospital because of severe epigastric pain. Ultrasonography and computed tomography revealed a slightly distended gallbladder with a small amount of free intraabdominal fluid. At emergency laparotomy, perforation of the gallbladder was recognized and thus a cholecystectomy was performed. Histopathologically, localized necrosis was seen at the site of perforation: however, the inflammation of the surrounding tissue was mild and no thrombus was detected within the intramural vessels. In addition, the gallbladder contained no stones and a bile culture was negative. Postoperatively, the diagnosis of idiopathic perforation of the gallbladder was established. The findings of this case help to emphasize the importance of considering this disorder in elderly patients presenting with peritonitis of unknown origin.

Aged↗
PubMed1997

Effectiveness of Tc-99m MIBI scintigraphy in diagnosing lung cancer.

The use of Tc-99m hexakis 2-methoxy isobutyl isonitrile (MIBI) scintigraphy for qualitative diagnosis was examined. A total of 37 lesions from 31 patients with respiratory disease (19 lesions from 19 primary lung cancer patients, 8 lesions from 3 metastatic lung cancer patients and 10 lesions from benign lung disease patients) were examined. Positive results were seen in 89.4% of the primary lung cancer lesions, 50.0% of the metastatic lung cancer lesions, and 20.0% of the benign lung disease lesions. The positive rate of 77.7% for malignant lung cancer was significantly higher (P < 0.01) than that for benign lung cancer. In particular, for lesions with a tumor diameter of 1.0 cm or more, the positive rate for malignant lung cancer lesions (95.2%) was significantly higher (P < 0.001) than that for benign lung disease lesions (25.0%). These results thus indicate Tc-99m MIBI scintigraphy to be useful for qualitative diagnosis of lung peripheral coin lesions with a diameter of 1.0 cm or more.

Adenocarcinoma↗
PubMed1997

GABA(A) receptor-mediated inhibition in the nucleus ambiguus motoneuron.

GABA-sensitive ambiguus motoneurons were investigated by microiontophoretic application of GABAergic drugs including bicuculline and muscimol in alpha-chloralose- and urethane-anaesthetized rats. Ambiguus motoneurons were activated by recurrent laryngeal nerve stimulation through a small cuff electrode and identified as laryngeal motoneurons when they met the conventional criteria for antidromic activation. GABA(A) antagonist, bicuculline, and its agonist, muscimol, were iontophoretized on ambiguus motoneurons through a three-multibarrel electrode glued to the recording microelectrode. One-hundred and nineteen out of 155 neurons sampled from the loose formation and its vicinity were found to be respiratory neurons, most of which were inspiratory neurons. A small proportion (32 neurons) was classified as laryngeal motoneurons according to the criteria. A majority of laryngeal motoneurons was found to be GABA sensitive. Namely, application of GABA and its antagonist and agonist affected the antidromic spikes in a dose-dependent manner; GABA and muscimol usually decreased the amplitude and slowed the slope in the spike, whereas bicuculline, reversed these inhibitory effects. The dose-dependent relationships were limited exclusively to the measurements analysed in the negative-going phase but not in the positive-going phase in the antidromic spike. GABA and muscimol decreased but bicuculline increased the ratios to control in these measurements. The effects of distributions of the histograms shifting towards the opposite direction were statistically significant. The line of evidence suggests strongly that a majority of laryngeal motoneurons located in the nucleus ambiguus presumably possesses GABA(A) receptors on their postsynaptic membrane. These GABA-sensitive laryngeal motoneurons may receive inputs either from inhibitory interneurons subserving the reciprocal inhibition in the reflexive integration or from inhibitory respiratory interneurons which control the synchronized glottic movements during vocalization and respiration.

Animals↗
PubMed1997

Lung carcinogenesis and formation of 8-hydroxy-deoxyguanosine in mice by diesel exhaust particles.

In order to clarify the involvement of oxygen radicals in lung carcinogenesis induced by diesel exhaust particles (DEP), the relationship between lung tumour response and formation of 8-hydroxydeoxyguanosine (8-OHdG) in lung DNA was examined. The role of high dietary fat and beta-carotene on these responses was also studied. Mice were intratracheally injected with 0.05, 0.1 and 0.2 mg of DEP per animal once weekly for 10 weeks. After 12 months, the lung tumour incidence in mice treated with 0.05 mg and 0.1 mg showed similar increases (30% and 31%), but was decreased to 24% at 0.2 mg. High dietary fat enhanced the incidence of both benign and malignant tumours. beta-carotene partially prevented the tumour development. After the 10 weekly treatments of DEP, inflammatory reaction was observed in the respiratory tract and alveoli. The formation of 8-OHdG in lung DNA from mice treated with DEP showed a dose dependent increase. 8-OHdG formation was enhanced by high dietary fat and partially reduced by beta-carotene. Formation of 8-OHdG was significantly correlated with the lung tumour incidence except at 0.2 mg. These results suggest that the induction of oxidative DNA damage may be an important factor in the initiation of DEP-induced lung carcinogenesis, and that beta-carotene and high dietary fat may play a role in the regulation of tumour development via modulation of the formation of 8-OHdG.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1997

Mastoparan-stimulated prolactin secretion in rat pituitary GH3 cells involves activation of Gq/11 proteins.

Mastoparan has been reported to induce a wide variety of cellular actions by activating GTP-binding proteins (G proteins) in various cells. Here, we demonstrate that mastoparan is able to stimulate the secretion of PRL from rat anterior pituitary tumor GH3 cells in dose- and time-dependent manners. Mastoparan had no effect on the accumulation of intracellular cAMP; however, it induced a rapid increase in the intracellular Ca2+ concentration in GH3 cells. Extracellular Ca2+ was required for mastoparan-induced PRL secretion, which was inhibited by nifedipine, an L-type Ca2+ channel blocker. Incubation of mastoparan with myo-[3H]inositol-labeled GH3 cells also resulted in the increased formation of inositol phosphates (InsPs) compared with control cells. Neomycin sulfate and U73122, both phospholipase C inhibitors, suppressed mastoparan-induced PRL secretion. Guanosine 5'-1beta-thioldiphosphate (GDPbetaS) encapsulated in GH3 cells by reversible electropermeabilization suppressed the response to mastoparan. However, pretreatment with pertussis toxin had no effect on the stimulation of PRL secretion by mastoparan, and both Mas7 (a highly active analogue of mastoparan) and Mas17 (an inactive analogue) enhanced the secretion of PRL to a similar level to that of mastoparan-induced GH3 cells. In contrast, the substance P-related peptide GPant-2A, a Gq antagonist, inhibited mastoparan-induced PRL release, whereas GPant-2, a G(i/o) antagonist, did not in electropermeabilized GH3 cells. Moreover, a specific G(q/11) antibody against the carboxyl terminus of the G(q/11) alpha-subunit blocked the stimulatory effect of mastoparan on secretion and mastoparan-stimulated InsPs production in digitonin-permeabilized GH3 cells. These results indicate that mastoparan induces the Ca2+-regulated secretion of PRL from GH3 cells by activating G(q/11) and the phospholipase C pathway.

Animals↗