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Biomedical subjects

S Satoh

Publications and source records attributed to S Satoh.

At least 667 records · Page 37Linked to original sources
PubMed1989

Effects of N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate on the ventriculo-atrial conductivity of accessory pathways.

The purpose of this study was to examine the effects of N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate (SUN 1165), a newly developed antiarrhythmic agent belonging to class Ic, on the ventriculoatrial (VA) conductivity of accessory pathways and paroxysmal supra-ventricular tachycardia (PSVT). Twelve patients with accessory pathways were examined by standard electrophysiologic technique before and after a single oral dose of SUN 1165 (100 mg). 1 h after administration, SUN 1165 blocked VA conduction of the accessory pathway in six of twelve patients and prevented the induction of PSVT in six of seven cases. In the cases in which VA block did not occur, the VA interval prolonged (from 178 +/- 7 to 190 +/- 11 ms, p less than 0.05), and the effective refractory period of VA conduction was also increased (from 273 +/- 10 to 318 +/- 15 ms. p less than 0.05). SUN 1165 also prolonged the conduction time in normal conduction systems (AH and HV intervals and QRS duration), but the degree of the prolongation was moderate and not dangerous. There was no adverse effect. These results indicate that SUN 1165 is a potent and safe antiarrhythmic agent, and useful for preventing or stopping PSVT by blocking or depressing VA conduction through accessory pathways.

Administration, Oral↗
PubMed1989

Kinetic studies of inhibition of estradiol 2- and 16 alpha-hydroxylases with 17 alpha-ethynyl and 17 beta-cyano steroids: preferential inhibition of the 16 alpha-hydroxylase.

Substrate preference of estrogen 2- and 16 alpha-hydroxylases in male rat liver microsomes were determined by using estrone (E1) and estradiol (E2). Kinetic parameters of the hydroxylations showed that E2 is a better substrate for the hydroxylations than E1 and the preferences principally depend on the differences in Vmax values of the hydroxylations between the two substrates. Kinetic studies of inhibition of E2 2- and 16 alpha-hydroxylase activities in the male liver microsomes with ethynylestradiol (EE) and norethisterone (NET), the active ingredients in oral contraceptives, and 17 beta-cyano-16 alpha, 17 alpha-epoxy-1,3,5(10)-estratrien-3-ol were extensively carried out. All of the steroids competitively blocked the two activities and the 16 alpha-hydroxylation was preferentially inhibited by them. Kinetic data, the apparent Ki's for the inhibitors and the apparent Km's for the substrate E2 in the assay, demonstrated that EE and NET are very potent inhibitors for the 16 alpha-hydroxylase. On the other hand, when female rat liver microsomes were used as an enzyme source in the inhibition experiments, the two hydroxylase activities were not so affected by EE and NET and the preferential inhibition was not observed with the ethynyl steroids.

Animals↗
PubMed1988

Effects of neuropeptide Y on canine cerebral circulation.

The effects of neuropeptide Y (NPY) on the vascular tone of isolated cerebral arteries and vertebral blood flow (VBF) were studied in dogs. NPY elicited a dose-dependent contraction of arteries derived from the brain with ED50 values of 2 nM for the middle cerebral and basilar arteries. Arteries from the neck did not respond to NPY. Intra-arterial administration of NPY as a bolus reduced the VBF dose dependently, with no significant alteration of mean arterial blood pressure and heart rate. The decrease in VBF developed slowly and had a long duration, which was consistent with the observations made in vitro. NPY suppressed the contractile effect of noradrenaline (NA) on isolated cerebral arteries and pretreatment with NPY suppressed the effect of NA on VBF, indicating that NPY contributes to the inhibitory modulation of postsynaptic adrenergic mechanisms. These findings suggest that NPY could have a role in the regulation of cerebral circulation.

Animals↗
PubMed1988

Properties and localization of the anterior semicircular canal-activated vestibulocollic neurons in the cat.

Unit activities of secondary vestibular neurons that selectively responded to stimulation of the anterior semicircular canal nerve (ACN) were recorded extracellularly in the anesthetized cat. Axonal pathways and projections in the spinal cord of the ACN-activated neurons were examined by recording their antidromic responses to stimulation of the lateral and medial vestibulospinal tracts (LVST and MVST), and the bilateral neck extensor motoneuron pools in the C1 segment (C1 dorsal rami [DR] motoneuron pools). In order to determine whether the neurons had ascending axon collaterals to the extraocular motoneurons, the contralateral (c-) inferior oblique (IO) motoneuron pool was also stimulated. Twenty-seven neurons sent their axons to the ipsilateral (i-) C1DR motoneuron pool via the LVST without any projection to the extraocular motoneuron pool. All the cells except one were located in the ventral part of the lateral vestibular nucleus. This pathway produced monosynaptic EPSPs with short time-to-peak and short half-width in C1DR motoneurons (16/16 motoneurons). Eight neurons sent axons to the i-C1DR motoneuron pool via the MVST without any to the extraocular motoneuron pool. Cell somata were located in the descending nucleus or in the ventral part of the lateral nucleus. These neurons did not produce postsynaptic potentials (PSPs) in any C1DR motoneurons. All thirty-five neurons sending axons to the c-C1DR motoneuron pool have ascending axon collaterals to the c-IO motoneuron pool.

Action Potentials↗
PubMed1988

Axonal trajectories of posterior canal-activated secondary vestibular neurons and their coactivation of extraocular and neck flexor motoneurons in the cat.

Unit activities of 148 secondary vestibular neurons related to the posterior semicircular canal were recorded extracellularly in anesthetized cats. Axonal projections of these neurons were examined by their antidromic responses to stimulation of the excitatory target motoneurons of the contralateral (c-) inferior rectus muscle (IR) and bilateral (bi-) motoneuron pools of longus capitis muscles, neck flexors, in the C1 segment (C1LC). The neurons were classified into 4 groups according to their axonal projections. The first group of neurons, termed vestibulo-oculo-collic (VOC) neurons, sent axon collaterals both to the c-IR motoneuron pool and to the c-C1LC motoneuron pool. The majority of them (72%) were located in the descending nucleus. The second group of neurons were termed vestibuloocular (VO) neurons and sent their axons to the c-IR motoneuron pool but not to the cervical cord. Most of them (86%) were located in the medial nucleus. The third group of neurons, termed vestibulo-collic (contralateral) (VCc) neurons, sent axons to the c-C1LC motoneuron pool via the contralateral ventral funiculus but not to the oculomotor nuclei. They were mostly (75%) found in the descending nucleus. The last group of neurons were vestibulo-collic (ipsilateral) (VCi) neurons, which gave off axons to the ipsilateral (i-) C1LC motoneuron pool via the ipsilateral ventral funiculus but not to the oculomotor nuclei. One of them also sent an axon collateral to the c-C1LC motoneuron pool. The majority of them (74%) were located in the ventral part of the lateral nucleus. It was also observed in some of the VOC and VCi neurons that they produced unitary EPSPs in the c-C1LC and i-C1LC motoneurons, respectively. Their synaptic sites were estimated to be on the cell somata and/or proximal dendrites of the motoneurons.

Animals↗
PubMed1988

Analysis of the angiographic findings in cases of childhood moyamoya disease.

Cerebral angiograms of 34 patients with childhood moyamoya disease have been analysed, this analysis having revealed the following findings. The blood flow to abnormal net-like vessels (ANV) in the base of the brain is mainly supplied from the internal carotid artery (ICA) in the early stage of this disease. In a later stage, however, the blood supply is mainly from the posterior cerebral artery (PCA). Though, no remarkable change was found in the volumes of ANV from the early to later stages of the disease, the leptomeningeal collaterals, the most prominent anastomoses in moyamoya disease, had a tendency to decrease during the later stage with the development of PCA stenosis. Eighteen occlusive PCA lesions were found in the proximal portion of the PCA in eight cases (44%), and in the distal in nine cases (50%). The incidence of aneurysm (1.5%) and intracranial bleeding was low as compared to cases of adult moyamoya disease.

Adolescent↗
PubMed1988

Magnetic resonance imaging of subarachnoid hemorrhage.

Magnetic resonance (MR) imaging of subarachnoid hemorrhage (SAH) due to a ruptured aneurysm has been evaluated in relation to CT findings on 30 patients. In the acute stage, particularly less than 24 hours after the bleeding episode (25 patients), SAH appeared of high intensity relative to the surrounding brain on a T-2 weighted SE image but isointense where the corresponding CT scan showed blood clot of attenuation value over 60 H. A T-2 weighted SE image was able to reveal subtle evidence of SAH not visible on the CT scan. The T-1 weighted IR image was not as sensitive. Blood clot (HU greater than 60) appeared isointense, but mild and moderate SAH (HU less than 60) was indistinguishable from normal CSF. MR imaging was also sensitive to subacute and chronic SAH (5 patients). Three out of four SAH appearing normal on CT showed high intensity on T-2 weighted images. Thirteen out of 24 aneurysms (54%) larger than 5 mm in diameter on angiography were detected on T-2 weighted images. Smaller aneurysms less than 4 mm were not visualized. MR imaging was able to indicate the ruptured one in cases of multiple aneurysms by showing hemorrhagic lesions more clearly than CT. We conclude that MR imaging is very helpful for diagnosing SAH, particularly when CT is normal, and in indicating aneurysm location as well as rupture site.

Acute Disease↗
PubMed1988

The effects of an intracellular calcium antagonist HA 1077 on delayed cerebral vasospasm in dogs.

The effectiveness of calcium antagonists on a chronic cerebral vasospasm after an SAH is still under debate. Calcium channel blockers such as nimodipine, nifedipine etc. can dilate spastic arteries by intrathecal administration, but not by systemic (iv or po) use. HA 1077 is a novel and potent calcium antagonist vasodilator which is considered to act by employing different mechanisms from the usual calcium channel blockers since it inhibits 1. calcium ionophore A 23187 induced contraction in arterial strips and 2. phenylephrine induced contraction in calcium free media, suggesting that its site of action is in the intracellular space. HA 1077 is water soluble and relatively stable in light. In the present study, the efficacy of HA 1077 was evaluated on dogs by using the spiral arterial strips in vitro and by angiography in vivo. In the arterial strips from the control dogs, a 50% relaxation of KCl (15 mM) induced contraction was obtained by a 10(-6) M HA 1077 for the "intracranial" basilar and middle cerebral arteries, while a 10(-5) M was needed to obtain the same effect for the "extracranial" common carotid and vertebral arteries, indicating that HA 1077 is more effective for the intracranial arteries. A vasospasm was produced by the "two haemorrhage" model of Varsos et al. The average angiographic diameter of the basilar artery was reduced to 60% of the control on SAH day 7. Intravenous infusion of HA 1077 (0.5-3 mg/kg/30 min) significantly dilated the spastic basilar artery (up to 20-30%), for over 2 hours. A fall in the systemic BP remained less than 20% during this time.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

Kinetic studies of inhibition of estradiol 2- and 16 alpha-hydroxylases in rat liver microsomes with various cytochrome P-450 inhibitors.

Kinetic studies of inhibition of estradiol 2- and 16 alpha-hydroxylase activities in male rat liver microsomes with cytochrome P-450 inhibitors, alpha-naphthoflavone, DL-aminoglutethimide, SKF-525A and metyrapone, were extensively carried out. All of the inhibitors competitively blocked the two enzyme activities. The former three inhibitors preferentially inhibited the 16 alpha-hydroxylase activity while the reverse result was obtained in the case of metyrapone, and SKF-525A was the most potent inhibitors for the two enzyme among the four inhibitors. The kinetic data, the apparent Ki's for the four inhibitors and Km's for the substrate estradiol in the assays, along with the inhibition results with carbon monooxide suggest that different forms of cytochrome P-450 may be involved in the two hydroxylations. Kinetic parameters of the two hydroxylase activities in female rat liver microsomes were then determined to be an apparent Km of 23.0 and 158 microM and Vmax of 99.0 and 5.65 pmol/min/mg protein for the 2-hydroxylation and the 16 alpha-hydroxylation, respectively. The kinetic data show that the 2-hydroxylation may be quantitatively an exclusive hydroxylative pathway in estrogen metabolism in female.

Aminoglutethimide↗
PubMed1988

S-adenosylmethionine-dependent inactivation and radiolabeling of 1-aminocyclopropane-1-carboxylate synthase isolated from tomato fruits.

1-Aminocyclopropane-1-carboxylic acid (ACC) synthase was partially purified from the homogenate of wounded tomato (Lycoperiscon esculentum Mill.) pericarp tissue by (NH(4))(2)SO(4) fractionation followed by conventional column chromatography with diethylaminoethyl-Sepharose, Sephadex G-150, Affi-Gel blue and hydroxylapatite. The partially purified ACC synthase preparation attained a specific activity of about 12,000 nmoles per hour per milligram protein. Employing this enzyme preparation, we confirmed that the ACC synthase was inactivated by its substrate, S-adenosyl-l-methionine (SAM), during its catalytic action. When the partially purified enzyme preparation was incubated with [3,4-(14)C]SAM and the resulting proteins were analyzed by sodium dodecyl sulfate-gel electrophoresis, only one radioactive protein band was observed. This protein was thought to be ACC synthase based on its molecular mass of 50 kD and on the fact that it was specifically bound to a monoclonal antibody against ACC synthase (AB Bleecker et al. 1986 Proc Natl Acad Sci USA 83, 7755-7759). These results suggest that the substrate SAM acts as an enzyme-activated inactivator of ACC synthase by covalently linking a fragment of SAM molecule to the active site of ACC synthase, resulting in the inactivation of the enzyme.

Journal Article↗
PubMed1988

Linkage of K99 production and STa activity in a plasmid of an Escherichia coli porcine isolate.

An Escherichia coli strain ZP118 of porcine origin was shown to harbor a 68-megadalton (Md) plasmid coding for a colonization factor K99 and heat-stable enterotoxin (STa), and a self-transmissible 51-Md plasmid coding for drug resistance. One of the transconjugants obtained by mating between ZP118 and E. coli C was found to harbor a 90-Md plasmid coding for K99, STa and drug resistance. Restriction endonuclease analysis suggested that the 90-Md plasmid could be a recombinant between the 68-Md plasmid and the 51-Md plasmid.

Animals↗
PubMed1988

DNA-binding activity of hepatitis B e antigen polypeptide lacking the protaminelike sequence of nucleocapsid protein of human hepatitis B virus.

The characteristics of binding of hepatitis B core antigen (HBcAg) and hepatitis B e antigen (HBeAg) polypeptides to hepatitis B virus (HBV) DNA were analyzed. HBcAg polypeptide from recombinant HBV core particles and HBeAg polypeptide from partially purified serum HBeAg were prepared and verified to have molecular weights of 21,500 (P21.5) and of 17,000 (P17) and 18,000 (P18), respectively, by immunoblot analysis. By reaction of these proteins on a nitrocellulose membrane with cloned 32P-HBV DNA, it was revealed that the HBeAg polypeptide, which lacks the C-terminal 34 amino acids of P21.5, as well as the HBcAg polypeptide, bound to the DNA. The secondary structures of nucleocapsid proteins of HBV, woodchuck hepatitis virus, and ground squirrel hepatitis virus were predicted by the Garnier algorithm. Amino acid sequences which, in addition to those of the C-terminal regions, may contribute to binding were proposed to be the 21-amino-acid residues located at amino acids 100 to 120 of the nucleocapsid proteins of these hepadnaviruses.

Algorithms↗
PubMed1988

Influences of pressure surrounding the heart and intracardiac pressure on the diastolic coronary pressure-flow relation in excised canine heart.

We investigated the change in the instantaneous diastolic left coronary pressure-flow relation (DPFR) when the pressure surrounding the heart (SHP), right heart pressure (RHP), and left heart pressure (LHP) were systematically varied. Eight excised and maximally vasodilated canine hearts placed in an air-tight chamber were used. To obtain a capacitance-free DPFR, coronary perfusion pressure was slowly decreased (about 2 mm Hg/sec) during a prolonged diastole. The zero-flow pressure (Pf = 0) and the slope of the DPFR were analyzed. The mean values of the slope did not change significantly throughout the interventions. The mean value of Pf = 0 in the control state (SHP = RHP = LHP = 0 mm Hg) was 6.0 +/- 2.0 mm Hg (mean +/- SD, n = 8), significantly higher than the venous outflow pressure, RHP (p less than 0.001), and the other two pressures (p less than 0.001). When SHP was raised to 15 and 30 mm Hg, while the other pressures remained at 0 mm Hg, the mean values of Pf = 0 increased to 20.9 +/- 2.4 and 35.6 +/- 3.1 mm Hg (p less than 0.001 and p less than 0.0005, respectively, vs. control). The mean values of Pf = 0 when only RHP was elevated to 15 and 30 mm Hg were 16.0 +/- 1.5 and 29.3 +/- 1.5 mm Hg (p less than 0.001 and p less than 0.0005 vs. control). On elevation of LHP to 15 and 30 mm Hg, the mean values of Pf = 0 were 12.0 +/- 2.8 and 17.3 +/- 3.6 mm Hg (p less than 0.01 and p less than 0.01 vs. control). When both SHP and LHP were almost evenly elevated to about 15 and 30 mm Hg, the mean values of Pf = 0 were raised to 22.0 +/- 2.9 and 35.3 +/- 3.2 mm Hg, respectively. These mean values were not significantly different from those when only SHP was elevated to the comparable levels. The observation that Pf = 0 exceeded RHP in the control state and that RHP, which was elevated above the preceding Pf = 0, was identical with the present Pf = 0 supports the vascular waterfall mechanism when RHP is low. Furthermore, the evidence that the degree of DPFR shift was almost linearly dependent on the SHP level rather than on the LHP level indicates that the pressure on the epicardial side is one of the factors that determines the pressure at the top of the vascular waterfall.

Animals↗
PubMed1988

Protein kinase activity in canine basilar arteries after subarachnoid hemorrhage.

To investigate the intracellular physiology of cerebral arterial vasospasm after subarachnoid hemorrhage (SAH), we measured the activity of three protein kinases related to vascular smooth muscle function. Myosin light chain kinase (MLCK), cyclic adenosine monophosphate (cAMP)-dependent protein kinase and cyclic guanosine monophosphate (cGMP)-dependent protein kinase activity was determined in canine basilar arteries using the SAH model created by two intracisternal injections of autologous blood. Moderate chronic cerebral vasospasm was confirmed angiographically 7 days after the first injection of blood, with a mean decrease in the diameter of the basilar artery to 61.2 +/- 2.3% (SE) of preinjection controls. Enzymatic analysis of basilar arteries excised from control dogs and from SAH model dogs 2 to 10 days after an intracisternal injection of blood demonstrated detectable MLCK and cyclic nucleotide-dependent protein kinase activity. The MLCK activity was approximately 3 times higher than the cyclic nucleotide-dependent protein kinase activity. There was no significant difference in basilar artery protein kinase activity between control animals and SAH model animals at any time for up to 10 days after the intracisternal injection of blood. As MLCK is involved with smooth muscle contraction and cAMP- and cGMP-dependent protein kinases are involved in smooth muscle relaxation, our results suggest that the metabolic machinery of vascular smooth muscle in the cerebral arterial wall is intact after SAH and that prolonged vasospasm represents an appropriate physiological response by the vascular smooth muscle to external stimuli. If this is correct, the successful pharmacological manipulation of vasospasm after SAH is more likely than if profound disruption had occurred, and further investigative efforts in this area should be encouraged.

Animals↗
PubMed1988

The dual effects of hemodialysis on cardiac function assessed by pulsed Doppler echocardiography.

To assess the effect of hemodialysis on cardiac function, a change of preload due to water removal was considered. In order to keep the preload constant during hemodialysis, extracorporeal ultrafiltration was induced before hemodialysis (step 1), and then hemodialysis without water removal was achieved (step 2). Cardiac performance in 8 patients was evaluated before and at the end of each step using pulsed doppler echocardiography. Step 1: Ultrafiltration was 1350 +/- 410 ml and hematocrit increased significantly. Left ventricular end-diastolic dimension (LVDd) decreased from 40.3 +/- 4.2 (mean +/- standard deviation) mm to 36.1 +/- 4.6 mm (p less than 0.005) and aortic peak flow velocity (PFV) also decreased from 59.9 +/- 16.0 cm/s to 49.0 +/- 11.0 cm/s (p less than 0.005). Step 2: In contrast, after hemodialysis without water removal, the mean velocity of circumferential fiber shortening (mVcf) increased from 1.36 +/- 0.26 circ/s to 1.86 +/- 0.36 circ/s (p less than 0.005). PFV and average acceleration (Aa) increased from 49.0 +/- 11.0 cm/s to 63.8 +/- 11.4 cm/s (p +/- 0.001) and from 750 +/- 220 cm/s/s to 1270 +/- 280 cm/s/s (p less than 0.001), respectively. During this step, serum potassium and osmolality decreased significantly. In conclusion, hemodialysis improves cardiac function under constant preload condition and this is due to the direct effects of hemodialysis by the correction of electrolytes and osmolar components such as uremic toxin.

Adult↗
PubMed1988

2S,3R 3-amino-2-hydroxy-4-phenylbutanoic acid derivatives, enkephalinase inhibitors, augment met5-enkephalin-induced antinociception.

It has been accepted that the periaqueductal gray matter of the mid brain (PAG) and the reticular formation of the medulla oblongata in the brain stem have antinociceptive roles in the pain control pathways of mammals, and met5-enkephalin may act as one of the pain control substances in those regions. In the present study, the effects of 2S,3R 3-amino-2-hydroxy-4-phenylbutanoic acid (AHPA) derivatives on met5-enkephalin-induced antinociception were examined by a hot plate method in mice. The elevation of pain threshold induced by an intracisternal administration of met5-enkephalin was enhanced by AHPA derivatives. The rank order of potency for these agents was as follows: bestatin greater than D-Phe-AHPA greater than AHPA-D-Ala greater than p-OH-AHPA-D-Phe greater than AHPA. This order was roughly correlated to that of the enkephalinase inhibitory activity of the AHPA derivatives. These results indicate that the inhibition of enkephalinase may produce the augmentation of the exogenous met5-enkephalin-induced antinociception. It is also suggested that AHPA derivatives may cause the enhancement of the endogenous met5-enkephalin-mediated antinociception.

Analgesics↗
PubMed1988

Vitamin K-reversible hypoprothrombinemia in rats. I. Sex differences in the development of hypoprothrombinemia and the effects of beta-lactam antibiotics.

Male and female rats were fed an ordinary diet which contained about 500 ng vitamin K/g or a vitamin K-deficient diet containing less than 5 ng vitamin K/g. Hypoprothrombinemic changes such as prolongation of the prothrombin time (PT) and activated partial thromboplastin time (APTT) were detected in male rats within 4-6 days after feeding of the vitamin K deficient diet. Blood clotting factor VII and descarboxy prothrombin (PIVKA) levels changed rapidly, with maximum alteration at 2-4 days. Similar changes in factor VII and PIVKA levels were observed in female rats, but they appeared only after feeding of the K deficient diet for a long period. PT and APTT in female rats showed slight or no alteration even after 10 day feeding of the K-deficient diet. These results indicate that male rats are more susceptible to vitamin K deficiency than female rats. Administration of latamoxef led to a dose-dependent development of hypoprothrombinemia in vitamin K-deficient female rats. The hypoprothrombinemia in vitamin K-deficient female rats was caused by beta-lactam antibiotics with N-methyltetrazolethiol, thiadiazolethiol and methyl-thiadiazolethiol as the 3'-position substituent of the cephem nucleus.

Animals↗