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Biomedical subjects

I Sano

Publications and source records attributed to I Sano.

18 recordsLinked to original sources

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

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

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

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

[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

[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

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

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

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

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

Metabolism of putrescine in the central nervous system.

The metabolism of putrescine in rat brain was studied systematically by the intraventricular injection of radioactive diamine. Putrescine injected into the brain was metabolized mainly to polyamines, spermidine, and spermine. A small portion of the radioactivity of putrescine was incorporated into gamma-glutamylputrescine, putreanine, gamma-aminobutyric acid, and homocarnosine. Comparison of the specific radioactivities of gamma-aminobutyric acid and homocarnosine after the injection of radioactive putrescine with those after the injection of radioactive glutamic acid indicated that there may be a metabolic pool of gamma-aminobutyric acid (putrescine-gamma-aminobutyric acid system) which is different from the glutamic acid-gamma-aminobutyric acid system and which is effectively used for synthesis of the dipeptide.

Animals

Putrescine, spermidine, N-acetylspermidine and spermine in the urine of patients with leukaemias and tumors.

1. N-Monoacetylspermidine A and B were isolated from human urine. Structures of the isolated compounds were assigned to monoacetylspermidines by analyses of the products of acid hydrolysis and elementary analyses. The identification was confirmed by comparison of the chromatographic and electrophoretic properties and infrared spectra of the isolated compounds with those of the authentic compounds. 2. The concentrations of urinary polyamines were determined by the combination of ion-exchange chromatography and high-voltage paper electrophoresis. The amount of putrescine fell in the range of 1--6;spermidine, 1--3;spermine, 3--15 and N-acetylspermidines, 2--10 nmoles/mg creatinine for both sexes and different ages. 3. The amounts of urinary polyamines were measured in patients with cancers. The remarkable increase of urinary spermine was observed in blood cancer, while in the other solid cancers the increase of urinary polyamines was not observed.

Age Factors

Functional brain studies with H2(15)O-PET: strategies and problems for approaching higher brain functions with H2(15)O-PET.

Activation study using H2(15)O and PET is promising as a noninvasive approach to higher brain functions in humans. However before reaching a more complex paradigm, many fundamental problems need to be solved. In this study, we investigated the following issues: (1) reproducibility of regional cerebral blood flow in the resting state as measured by this method, (2) effect of physiological stimulation on cerebral blood flow, and (3) identification of activated areas on anatomical structures. Our data suggest that relative CBF images and their paired subtraction are more suitable for tapping functional localization. Changes in rCBF in the association cortex for more complicated tasks are, in general, smaller than those in the primary cortex. Combined display of PET images with three-dimensional reconstructed brain surface MR images was the most reliable technique for anatomical identification of the activated site.

Acoustic Stimulation