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Biomedical subjects

I Sano

Publications and source records attributed to I Sano.

At least 37 records · Page 2Linked to original sources
PubMed1994

Inhibition of phase III activity by acid in canine stomach.

Very few phase III activity of the interdigestive migrating contractions (phase III) occurs in the stomach of fasted duodenal ulcer patients. But the mechanism is not well understood. In this study, we studied the effect of gastric and duodenal acidification on the spontaneous phase III activity in the upper gastrointestinal tract of conscious dogs. Gastric and duodenal motor activity in 5 conscious dogs was monitored by means of chronically implanted force transducers. Intragastric pH changes were measured by placing a pH glass electrode in the gastric antrum. Intragastric and intraduodenal acidification was achieved by i.v. infusion of histamine, and by intragastric and intraduodenal instillation of acidic solutions of different pHs. The plasma motilin concentrations were measured by radioimmunoassay. Histamine (40 micrograms/kg/h) inhibited spontaneous phase III activity, but the histamine-induced inhibition was completely prevented by pretreatment with famotidine, a potent histamine H2 receptor antagonist (0.3 mg/kg, i.v.). Intragastric acidification at pH 1.0 strongly inhibited spontaneous phase III activity, but an acidic solution at pH 2.0 had no effect in inhibiting phase III activity. Intraduodenal acidification at pH 1.0 also inhibited spontaneous phase III activity. Histamine injection and gastric and duodenal acidification at pH 1.0 strongly suppressed motilin release. It is concluded that gastric and duodenal acidification at pH 1.0 inhibits the occurrence of the spontaneous phase III activity, and the suppression of endogenous release of motilin due to gastric and duodenal acidification at pH 1.0 is involved in this inhibitory mechanism.

Animals↗
PubMed1994

Biotinyl C-terminal-extended motilin as a biologically active receptor probe.

The synthesis, purification, and characterization of biotinylated analogues of motilin are reported. The C-terminal of canine motilin was extended by the addition of a cysteine residue, and then biotinylated. Biotinyl motilin was purified by following HPLC and characterized by amino acid analysis. Biotinylation of the ligand was confirmed by ELISA assay with the avidin-biotin system. Biotinyl motilin showed similar affinity for binding to rabbit gastric membrane fraction compared to unlabeled canine motilin, and also retained functional activity in its ability to cause contraction of rabbit duodenal segments. To determine the binding of biotinyl motilin in isolated rabbit antral smooth muscle, cells were incubated with the biotinyl motilin with and without excess of unlabeled motilin. Subsequent addition of avidin-biotinylated peroxidase complex showed the distribution of reaction products over the cell surface. Bioactive biotinyl motilin provides a useful probe for the demonstration of cell surface motilin receptors and will facilitate receptor purification and characterization.

Amino Acid Sequence↗
PubMed1994

Cortical control of saccade in normal and schizophrenic subjects: a PET study using a task-evoked rCBF paradigm.

In this study, positron emission tomography (PET) was used to evaluate cortical control of saccades. Regional cerebral blood flow (rCBF) patterns demonstrated by 15O water PET during saccadic task performance were tested in 13 normal volunteers and 20 ICD-9 schizo phrenics (10 unmedicated and 10 medicated). The following 3 saccadic tasks, which were controlled for sensory input and oculomotor output, were applied: (1) reflexive saccade = visually guided saccade, (2) volitional saccade = visually guided saccade with distracting stimuli, and (3) memory guided saccade. Schizophrenics lacked the frontal eye field (FEF) activation during every saccadic task. The left dorsolateral prefrontal cortex (DLPFC) was activated during volitional saccade only in normal controls. The rCBF of posterior parietal cortex increased in parallel with that in the DLPFC. These findings suggest functional hypofrontality in schizophrenia and the left DLPFC-PPC's crucial role in saccade against distracting stimuli and its dysfunction in the disease.

Adolescent↗
PubMed1994

EM574, an erythromycin derivative, is a potent motilin receptor agonist in human gastric antrum.

Erythromycin and its derivatives are known to induce phase III-like contractions, which are similar to those induced by motilin, in the human gastrointestinal tract during the interdigestive state, but few detailed in vitro studies have been reported. We evaluated EM574, an erythromycin derivative, as a motilin receptor agonist in the human gastric antrum in vitro, using contraction studies of muscle strips and isolated myocytes, receptor binding assay and tissue section autoradiography. EM574 stimulated contractions of muscle strips in a concentration-dependent manner (10(-7)-10(-5) M), and this contractile effect was unaffected by pretreatment with atropine or tetrodotoxin. Isolated myocytes contracted in response to EM574 with a peak shortening at 10(-7) M, which was comparable to the response to motilin. EM574 displaced specifically 125I-motilin bound to smooth muscle homogenates with a Kd value of 7.8 x 10(-9) M, compared with 4.5 x 10(-9) M for motilin. Film autoradiograms showed that 125I-motilin-binding sites were localized in the muscle layers, and that the labeling disappeared in the presence of a 1000 times molar concentration of EM574. We conclude that EM574 directly stimulates smooth muscle cell contraction by acting on motilin receptors in the human gastric antrum in vitro.

Autoradiography↗
PubMed1994

Inhibition of motilin-induced phase III contractions by pentagastrin in Heidenhain pouch dogs.

We compared the inhibitory effects of histamine and pentagastrin (PG) on motilin-induced upper gastrointestinal phase III activity in conscious dogs that had surgically prepared Heidenhain pouchs (HP). Contractile activity was measured by means of chronically implanted force transducers, and changes in pH of the perfusate through the HP were monitored simultaneously. Intravenous infusion of PG (4 micrograms/kg-hr) inhibited motilin-induced phase III activity both in the main stomach and in the HP, whereas histamine (40 micrograms/kg-hr) inhibited activity only in the main stomach. Famotidine (0.3 mg/kg, i.v., the dose that completely inhibited gastric acid secretion by PG or histamine) blocked the inhibition of phase III activity induced by histamine but did not affect PG-induced inhibition. L-364,718 (1 mg/kg, i.v.), which had no effect on the PG-induced decrease in the pH of the perfusate lowered by PG, reversed the inhibition of phase III activity by PG in the HP but not in the main stomach. However, L-364,718, when combined with famotidine, potently reversed the PG-induced inhibition of phase III activity both in the main stomach and in the HP. These results show that the inhibitory effect of PG on motilin-induced phase III activity is brought about by two distinctive mechanisms, gastric acid and the cholecystokinin receptors-dependent mechanism, whereas the histamine-induced inhibition is mediated only by gastric acid. In the vagally denervated HP, however, gastric acid is not involved in an inhibitory effect of PG.

Animals↗
PubMed1993

Mechanism of motilin-induced contractions in isolated perfused canine stomach.

BACKGROUND: Motilin is known to induce gastric phase III contractions via neural pathways in vivo, but the local mechanism of action is not clearly determined. METHODS: An isolated perfused canine stomach was used to demonstrate the mechanism of motilin. Synthetic canine motilin at doses of 0.1, 0.3, 1.0, and 3.0 micrograms/h was infused intra-arterially, and effects of several receptor antagonists on motilin-induced contractions were examined. RESULTS: The immunoreactive motilin concentration of venous effluent showed that motilin at doses of 0.1 and 0.3 microgram/h was within the physiological range. Each dose of motilin induced phasic contractions in the isolated stomach, and a dose-related increase in frequency was observed, but not their mean amplitude. Atropine, hexamethonium, ICS205-930, BRL43694, phentolamine, yohimbine, and propranolol significantly inhibited motilin-induced contractions. Naloxone, methysergide, and timolol did not affect the response of motilin. Prazosin significantly increased the mean amplitude of motilin-induced contractions. CONCLUSIONS: Physiological dose of motilin can initiate phasic contractions in the stomach independently of the presence of the extrinsic nerves. The results suggest that cholinergic pathway, 5-hydroxytryptamine (HT)3 receptors, and alpha receptors are involved in the motilin-induced contractions.

Animals↗
PubMed1992

Temporal lobe CO2 vasoreactivity in patients with complex partial seizures.

The topography of CO2 vasoreactivity during hyperventilation in 8 patients with complex partial seizure (CPS) was visualized using the regional cerebral blood flow (rCBF) as measured by H(2)15O-PET (positron emission tomography) and compared with that of 10 normal volunteers. In the normal volunteers, the vascular response to CO2 (VrCO2 = delta CBF%/delta PaCO2) in the temporal lobe was 2.46 +/- 0.56 (%/mmHg). In the patients with CPS, VrCO2 in the temporal lobe of the affected side was 2.08 +/- 0.40 (%/mmHg), while VrCO2 on the contralateral side was 2.30 +/- 0.46 (%/mmHg). There was a significant difference in VrCO2 between the affected side of the temporal lobes and the temporal lobes of the normal volunteers. Furthermore, there was a tendency for VrCO2 to be lower in the affected than in the contralateral side of the temporal lobe in patients with CPS. As CO2 is the main regulator of CBF, this impaired vasoreactivity may reflect the brain dysfunction in the seizure focus and adjacent areas.

Adolescent↗
PubMed1991

Dual effect of trimebutine on contractility of the guinea pig ileum via the opioid receptors.

Preparations of longitudinal muscle attached to myenteric plexus from guinea pig ileum were used to observe the effect of trimebutine on intestinal motility. Electrical stimulation at 0.2 Hz and 5 Hz produced contraction mediated by the release of acetylcholine in the preparations. The response to low-frequency stimulation (0.2 Hz) was inhibited by trimebutine (10(-8)-10(-5) mol/L), and the response to high-frequency stimulation (5 Hz) was enhanced by the drug at low concentrations (10(-8)-10(-7) mol/L) and inhibited by high concentrations (10(-6)-10(-5) mol/L). This enhancement was mimicked by [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin, and was antagonized by naloxone but not by MR2266. Enhancement by trimebutine was inhibited by yohimbine. Trimebutine (greater than or equal to 10(-8) mol/L) inhibited stimulation (5 Hz)-evoked release of norepinephrine, and the trimebutine effect was antagonized by naloxone but not by MR2266. Low concentrations of trimebutine inhibit norepinephrine release via the mu-opioid receptor and enhance intestinal motility by preventing the adrenergic inhibition of acetylcholine release. Inhibition by trimebutine was antagonized either by naloxone or MR2266. High concentrations of trimebutine may inhibit acetylcholine release via the mu- and kappa-opioid receptors, after which the intestinal motility is inhibited. Trimebutine at further high concentrations (greater than 10(-5) mol/L) contracted single smooth muscle cells from the circular muscle layers but not from the longitudinal muscle layers. The usual dose of trimebutine may exert dual effect on the intestinal motility indirectly through cholinergic and adrenergic neurons without direct effect on the smooth muscle.

Acetylcholine↗
PubMed1991

Clebopride enhances contractility of the guinea pig stomach by blocking peripheral D2 dopamine receptor and alpha-2 adrenoceptor.

The mechanism of action of clebopride on the motility of guinea pig stomach was examined by the receptor binding assay for bovine brain membrane and by measuring gastric contractility and the release of acetylcholine from the stomach. The receptor binding assay revealed that clebopride bound to the D2 dopamine receptor with a high affinity and to the alpha-2 adrenoceptor and 5-HT2 serotonin receptor with relatively lower affinity, and not to D1 dopamine, alpha-1 adrenergic, muscarinic acetylcholine, H1 histamine, or opioid receptor. In strips of the stomach, clebopride at 10(-8) M to 10(-5) M enhanced the electrical transmural stimulation-evoked contraction and the release of acetylcholine. This enhancement was attributed to the blockade of the D2 dopamine receptor and alpha-2 adrenoceptor because: 1) Maximum responses obtained with specific D2 dopamine receptor antagonist, domperidone, and with specific alpha-2 adrenoceptor antagonist, yohimbine, were smaller than that with clebopride, and the sum of the effects of these two specific receptor antagonists is approximately equal to the effect of clebopride. 2) The facilitatory effect of clebopride was partially eliminated by pretreatment of the sample with domperidone or yohimbine, and the facilitatory effect of clebopride was not observed in preparations treated with the combination of domperidone and yohimbine. Clebopride also antagonized the inhibitory effects of dopamine and clonidine on the electrical transmural stimulation-evoked responses. These results indicate that clebopride acts on post ganglionic cholinergic neurons at D2 and alpha-2 receptors in this preparation to enhance enteric nervous system stimulated motility.

Acetylcholine↗
PubMed1991

Cisapride stimulates motility of the intestine via the 5-hydroxytryptamine receptors.

The effects of cisapride on intestinal contractility and on release of acetylcholine (ACh) were examined using the longitudinal muscle with the myenteric plexus preparation from the guinea pig ileum, as related to the 5-hydoxytryptamine (5-HT) receptor. 5-HT exerted a dual effect, transient increase in ACh release (EC50 = 2 X 10(-6)M) via the 5-HT3 receptor, followed by inhibition (EC50 = 5 X 10(-9)M) via the 5-HT1 receptor. Cisapride at low concentrations (10(-9)M to 10(-8)M) enhanced electrical stimulation -evoked contraction and ACh release. The effect of cisapride was mimicked by methysergide and was not altered by ICS 205-930. Cisapride antagonized the 5-HT (5 X 10(-9) M)-induced inhibitory effect and the IC50 of cisapride was 1.5 X 10(-9) M. These findings indicate that enhancement by low concentrations of cisapride may be due to a block of the inhibitory 5-HT1 receptor. Cisapride at medium concentrations (10(-8) M to 3 X 10(-7) M) induced enhancement of electrical stimulation-evoked twitch contractions and ACh release evoked by electrical stimulation which were antagonized by 10(-6) M ICS 205-930, while this compound antagonized the 5-HT (2 X 10(-6) M)-and 2-methyl-5-HT-induced excitatory effects, and the IC50 of cisapride was 5.2 X 10(-8) M. Thus, cisapride acts on the putative 5-HT4 receptor as an agonist and the 5-HT3 receptor as an antagonist. Cisapride at high concentrations (10(-6) M to 10(-5) M) evoked contraction and the release of ACh, and these effects were antagonized by ICS 205-930 (10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1990

[Legionellosis].

Although increasing attention is being given to Legionella pneumonia in Japan, reports of solitary onset of this disease are scant in Japan. The patient, from whom L. dumoffii was isolated, was a 59-year-old male with no underlying disease. He visited our hospital because of fever and cough, and was admitted to our department for X-ray findings consistent with pneumonia. After admission, pulmonary lesions spread rapidly, and based on the suspicion of Legionella pneumonia, drugs such as EM, RFP and MINO were used. However, the patient died on the 26th hospital day. L. dumoffii was isolated from specimens obtained by airway aspiration before death and specimens of lung abscess and airway discharge obtained during autopsy (7 specimens in total). In addition, the L. dumoffii antibody titer in the serum became elevated. This is the first case of L. dumoffii pneumonia reported in Japan. The other case was in an 81-year-old male with underlying disease. He was admitted urgently with suspected pneumonia but died on the following day. L. pneumophila serogroup 5 was isolated from autopsied lung tissue. Fatality is high for this disease, making early diagnosis and treatment with appropriate antibiotics essential. Physicians should bear in mind the possibility of this disease and request the necessary laboratory tests in suspected cases without delay.

Aged↗
PubMed1989

[Legionella dumoffii and Legionella pneumophila serogroup 5 isolated from 2 cases of fulminant pneumonia].

We encountered two cases of legionella pneumonia which ran a dramatic course and isolated Legionella dumoffii from one patient and Legionella pneumophila serogroup 5 from the other patient. The patient from whom L. dumoffii was isolated was a 59-year-old male with no basic disease. He presented chill, fever, coughing and other symptoms, starting on July 3, 1986, his disease was diagnosed as pneumonia at the clinic of his company. The patient was then introduced and admitted to our hospital. On admission chest radiography disclosed zonal pneumonia with an unclear border in the right superior lobe of the lung; a beta-lactam preparation was administered, but no effect was obtained and the lung lesion showed a rapid advance. From this condition, we suspected legionella pneumonia and changed the therapy to treatment with erythromycin and rifampicillin. Despite this, no improvement occurred and the patient died on the 26th hospital day. Colonies like Legionella colonies were separated from a total of seven specimens of biopsy aspirated matter from the airway and autopsy collected lung abscess and tracheal secretions, and the bacterium was identified L. dumoffii based on the biochemical and serological properties. In addition, the patient's serum was found to have an increased antibody titer against L. dumoffii. Based on these findings, the patient's disease was diagnosed as pneumonia as caused by L. dumoffii, a relatively rare bacterium as a member of the genus Legionella. The patient from whom Legionella pneumophila serogroup 5 was isolated was an 81-year-old man with basic diseases such as heart failure, anemia and hypothyroidism. He presented fever, general fatigue, anorexia and other symptoms, starting around June 2, 1987; pneumonia was suspected and the patient was urgently admitted to our hospital. The patient died of pneumonia of unknown cause on the second hospital day. To clarify the cause, autopsy was conducted; a large number of colonies like Legionella colonies were noted in the lung tissue. Identification test was then conducted and the bacterium was identified as L. pneumophila; we concluded that the patient's pneumonia had been caused by the identified bacterium L. pneumophila. The isolate was further subjected to slide agglutination test and identified as L. pneumophila serogroup 5.

Aged↗
PubMed1989

Inhibitory effect of peptide YY on gastric acid output in rats.

The administration of peptide YY (PYY: 0.8, 1.6 and 3.2 nmol/kg/h, i.v.) to fasting rats inhibited not only baclofen (2 mg/kg, s.c.)-stimulated gastric acid output and gastric mucosal blood flow, but also pentagastrin (8 micrograms/kg/h, i.v.)-stimulated gastric acid output. PYY (3.2 nmol/kg/h) reduced baclofen-induced acid output more than pentagastrin-induced acid output, i.e., by 61.8 +/- 11.5% compared to 35.3 +/- 8.2%. PYY inhibited acetylcholine (ACh) release from cholinergic nerve endings of gastric body evoked by electrical transmural stimulation (ETS: 1 msec, 10 V, 3 Hz, 30 sec) by 47.2 +/- 3.5%. The mechanism of the inhibitory effect of PYY on gastric acid output seems to involve decreased gastric mucosal blood flow and reduced ACh release from cholinergic nerves.

Animals↗
PubMed1989

The mechanism of acute gastric ulcer after induced hemorrhagic shock.

Changes in gastric mucosal blood flow were investigated for their relationship to gastric mucosal prostaglandin E2 (PGE2) and noradrenaline (NA) in rats with hemorrhagic shock. The results were as follows: 1) Gastric mucosal blood flow and NA decreased after hemorrhage. Gastric mucosal PGE2 initially increased after exsanguination and then markedly decreased. 2) Administration of NA before hemorrhage resulted in an increase of PGE2. However, the PGE2 value for animals receiving NA after hemorrhage was not different from that of non-NA-treated group. 3) Pre-treatment with PGE2 suppressed the reduction in both gastric mucosal blood flow and NA and the development of ulcer. These results suggest that the increase in gastric mucosal PGE2 in the early stage of shock might represent a phenomenon of adaptation by the adrenergic activation, and the decrease in PGE2 in the late stage might result from impaired synthesis of PGE2 due to persistent hypoxia and might be one of the possible factors in ulcer formation.

Acute Disease↗
PubMed1989

Cholecystokinin, but not gastrin, induces gamma-aminobutyric acid release from myenteric neurons of the guinea pig ileum.

Effects of cholecystokinin (CCK) and gastrin on the release of acetylcholine (ACh) and gamma-aminobutyric acid (GABA) were examined in the longitudinal muscle with myenteric plexus (LM-MP) preparations of the guinea pig small intestine. CCK and gastrin induced the Ca++-dependent and tetrodotoxin-sensitive release of [3H]ACh from the LM-MP preparations preloaded with [3H]choline. Proglumide, but not scopolamine, hexamethonium and [D-Pro2,D-Trp7,9]substance P inhibited the release of [3H]ACh induced by CCK and gastrin. The desensitization to CCK and gastrin was observed with a 30-min exposure of the preparation to CCK and gastrin, respectively, and the cross-desensitization to peptides was not observed, thereby indicating that these peptides induce the release of ACh mainly via respective receptors. Bicuculline which inhibited completely the release of [3H]ACh induced by GABA inhibited the release of [3H]ACh induced by CCK but not by gastrin by 42.3 +/- 4.22%. CCK, but not gastrin, produced the Ca++-dependent and tetrodotoxin-sensitive release of endogenous GABA and [3H]GABA from LM-MP preparations preloaded with [3H]GABA. The release of [3H]GABA induced by CCK was antagonized by proglumide, but not by scopolamine, hexamethonium and [D-Pro2,D-Trp7,9]substance P. These results provide evidence that the GABAergic neuron is stimulated by CCK, but not by gastrin and stimulates the cholinergic neuron.

Acetylcholine↗
PubMed1988

Experimental study of vagotomy for prevention of stress ulcer after hepatectomy of cirrhotic livers. Its influence on hepatic regeneration.

We experimentally studied the influence of vagotomy on hepatic regeneration in rats after hepatectomy of cirrhotic livers. In animals that underwent hepatectomy plus vagotomy the reduction in gastric pH was suppressed, but gastric mucosal blood flow was less than that in control animals that received hepatectomy alone. The suppression of 3H-thymidine uptake percentage and thymidine kinase activity after hepatectomy was more marked in animals treated with hepatectomy plus vagotomy than in controls treated with hepatectomy alone. Hepatic DNA level tended to be lower in animals treated with hepatectomy plus vagotomy than in controls. In animals treated with hepatectomy plus vagotomy, the peak level of the mitotic index was lower and the hepatic regeneration rate was evidently suppressed. These results suggest that it is not appropriate to apply vagotomy, during hepatectomy of cirrhotic livers, for the prevention of postoperative stress ulcer because it causes a marked reduction in gastric mucosal blood flow and suppresses hepatic regeneration.

Animals↗
PubMed1987

[Experimental study on mechanism of onset of acute ulcer viewed from blood coagulation and activities of fibrinolysis after hepatectomy in liver cirrhosis].

Using liver cirrhosis rats induced by intraperitoneal administration of 4% thioacetamide (TAA) consecutively for 10 weeks, the authors made a study on the activities of blood coagulation and fibrinolysis in the onset of acute ulcer after hepatectomy. The results were as follows: 1. On the 3rd day after hepatectomy increase in the portal blood pressure, approximate 30% decrease in gastric wall blood flow and increase in fibrinolysis in blood and gastric mucosa were observed. While no bleeding was recognized, edema and hyperemia were noticeable. 2. On the 3rd postoperative day when the maximum increase of fibrinolysis in blood and gastric mucosa was observed water immersion restraint stress was loade. Two hours after loading, fibrinolysis in blood and tissue increased further, and in accordance with it, bleeding and erosion were seen to a high degree in gastric mucosa. On the other hand, in the EACA group, in which anti-fibrinolytic agent, epsilon-amino carpic acid was administered, the increase was moderate in the fibrinolysis in blood and mucosa after loading the stress. Though bleeding and development of erosion were not completely controlled, values of fibriolytic activity of the tissue in the EACA group were lower than those of control group.

Acute Disease↗