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Biomedical subjects

Y Sakurai

Publications and source records attributed to Y Sakurai.

At least 379 records · Page 21Linked to original sources
PubMed1991

Novel cerebroprotective agents with central nervous system stimulating activity. 2. Synthesis and pharmacology of the 1-(acylamino)-7-hydroxyindan derivatives.

In a continuous search for a novel cerebroprotective drug with a central nervous system (CNS) stimulating activity, a series of 1-(acylamino)-7-hydroxyindan derivatives has been synthesized and tested for its dual activities. The cerebroprotective activities of the compounds in this series were evaluated in terms of their effect on the survival of mice in hypoxic conditions (210 mmHg), and their CNS stimulating activities were examined by evaluating their promotional effects on the recovery from coma induced by cerebral concussion in mice. Several compounds prolonged the survival of mice in the hypoxic conditions at a dose of 30 mg/kg po. Four compounds in this series showed the CNS-stimulating effect at the same dose. Among them, 7-hydroxy-1-[4-(3-methoxyphenyl)-1-piperazinyl]acetyl]amino]-2,2,4, 6-tetramethylindan (18, OPC-14117), which was active in the two tests with no side effect up to 500 mg/kg po daily for 2 weeks of administration to rats, was selected for preclinical investigations.

Animals↗
PubMed1991

Nucleotide sequence and characterization of a carbenicillin-hydrolyzing penicillinase gene from Proteus mirabilis.

The structural gene of a carbenicillinase was cloned from the chromosomal DNA of Proteus mirabilis GN79. This gene codes for a protein of 270 amino acids. Alignment of the amino acid sequence with those of known beta-lactamases revealed that the enzyme is a novel class A beta-lactamase with a unique conserved triad, RTG. By using a DNA fragment of the structural gene, a lack of cross hybridization was confirmed between the DNA probe and total DNAs from natural isolates of P. mirabilis, suggesting that the carbenicillinase may not be a species-specific beta-lactamase of P. mirabilis.

Amino Acid Sequence↗
PubMed1991

Surface-modulated skin layers of thermal responsive hydrogels as on-off switches: I. Drug release.

Thermosensitive co-polymers of isopropyl acrylamide (IPAAm) with butyl methacrylate (BMA) are capable of 'on-off' regulation of drug release in response to external temperature changes due to skin formation with increasing temperature. To clarify the role of the surface-modulated skin and controlled pulsatile drug release patterns, the surface shrinking process was regulated by changing the length of the methacrylate alkyl side-chain. Release of indomethacin in response to stepwise temperature changes between 20 and 30 degrees C from co-polymers of IPAAm with BMA, hexyl methacrylate (HMA), and lauryl methacrylate (LMA) was studied. The drug release rate during the 'on' state (20 degrees C) remained constant before and after the 'off' state (30 degrees C) when the period of the 'off' state was increased. These results suggest that the drug in the polymeric matrices diffused from the inside to the surface during the 'off' state even when no drug release was seen. The length of alkyl side-chain was found to be an important parameter in controlling the thickness and density of the surface skin layer.

Cross-Linking Reagents↗
PubMed1991

Effects of amiloride and an analogue on ventricular arrhythmias, contracture and cellular injury during reperfusion in isolated and perfused guinea pig heart.

The present study was designed to examine whether activation of Na+/H+ exchange and subsequent massive Ca2+ influx via Na+/Ca2+ exchange are involved in the pathogenesis of myocardial reperfusion injury. We tested the effects of 1 mM amiloride, which is known to inhibit both Na+/H+ and Na+/Ca2+ exchange, and 3 microM 5-(N-ethyl-N-isopropyl) amiloride (EIPA), which is known to act as a specific inhibitor against Na+/H+ exchange, on the incidence of ventricular arrhythmias, isovolumic left ventricular function and creatine kinase (CK) release during reperfusion after 15 or 30 min of global ischemia in the isolated and perfused guinea pig heart. Treatment of a normally perfused heart with amiloride decreased heart rate significantly and tended to increase coronary flow and left ventricular developed pressure (LVDP), whereas treatment with EIPA decreased all of these 3 measurements significantly. Treatment with amiloride or EIPA for 15 min before ischemia, and during reperfusion after 15 min of ischemia, under electrical pacing at 240 rpm to eliminate a negative chronotropic effect abolished ventricular tachycardia (VT) and ventricular fibrillation (VF) during reperfusion associated with highly significant inhibition of increases in left ventricular end-diastolic pressure (LVEDP) and CK release. Amiloride or EIPA pretreatment also inhibited the incidence of VF and increases in LVEDP and CK release significantly during reperfusion after 30 min of ischemia. However, amiloride was more effective in preventing these events than EIPA. The treatment with amiloride or EIPA only during reperfusion after 15 or 30 min of ischemia also decreased the incidence of VF and inhibited the increases in LVEDP and CK release significantly, though less effectively than the pretreatment modality. These results suggest that EIPA prevents ventricular arrhythmias, contracture and myocardial cellular injury during reperfusion after 15 min of ischemia by inhibiting Na+/H+ exchange, while amiloride exerts more powerful protection against these events than EIPA during reperfusion after 30 min of ischemia by inhibiting both Na+/H+ and Na+/Ca2+ exchange.

Amiloride↗
PubMed1991

Detection of mouse hepatitis virus antibody by protein A-ELISA in 6 prevalent inbred strains or outbred stocks of mice.

Protein A was applied as a reagent for the secondary reaction in ELISA (protein A-ELISA). Mouse hepatitis virus antibody in 6 prevalent mouse strains or stocks reared in a MHV-contaminated room was effectively detected by protein A-ELISA, whereas significant strain differences in the antibody detection rate were demonstrated using the complement fixation test. C57BL/6 mice were particularly reactive in the protein A-ELISA test.

Animal Husbandry↗
PubMed1991

Clinical analysis of STA-SCA bypass for vertebrobasilar occlusive disease.

In order to clarify the effectiveness of extracranial- intracranial bypass in cases of vertebro-basilar occlusive disease, we investigated the operative complication, clinical course and follow-up study of 30 cases undergoing superficial temporal artery-superior cerebellar artery (STA-SCA) bypass surgery. Postoperative angiogram showed the patency of the anastomoses in all cases. No serious surgical complications were observed. The outcome on discharge was excellent, with no morbidity and one mortality which was due to cardiac infarction. In the follow-up study, there were four cases with ischemic symptoms, two with transient ischemic attack and two with completed stroke, one of which was a supratentorial infarction due to internal carotid artery occlusion and the other was a small infarction of pons. There were also two deaths due to cardiac infarction and diabetes mellitus. Favorable outcomes were obtained for the remaining cases. The present study suggests that, STA-SCA bypass, can be performed without surgical and systemic complications and used as an effective therapy for vertebrobasilar ischemia.

Adult↗
PubMed1991

Intratumoral oxygen pressure in malignant brain tumor.

Oxygen pressure (pO2) in brain tumors, pO2 in brain cortex surrounding the tumors, and PaO2 were measured simultaneously during total resection in 16 patients with previously untreated brain tumors in order to detect hypoxic regions within the tumors. When the inhaled O2:N2O ratio was 1:3 under enflurane anesthesia, mean PaO2 was 109.2 +/- 5.8 mm Hg, a rather high value when compared with that obtained when air is inhaled under atmospheric pressure. The simultaneously measured intratumoral pO2 and pO2 in brain cortex surrounding the tumor were 15.3 +/- 2.3 and 59.8 +/- 6.5 mm Hg, respectively. Each intratumoral pO2 value was significantly lower than that of pO2 in brain cortex surrounding the tumor (mean less than 30 mm Hg, Wilcoxon signed rank test, p less than 0.005) and influenced the oxygen effects on radiation. These results appear to confirm that there are hypoxic regions within human brain tumors. A comparison between intratumoral pO2 and either the angiographic or contrast-enhanced computerized tomography scans of the tumor vasculature disclosed no correlation.

Adolescent↗
PubMed1991

[Dissecting aneurysm of distal posterior inferior cerebellar artery--case report and review of the literature].

A rare case of dissecting aneurysm of distal posterior inferior cerebellar artery (PICA) is reported. A 51-year-old woman was admitted to our hospital complaining of severe headache and nausea. CT scan revealed subarachnoid hemorrhage which was thicker in the posterior fossa. The vertebral angiography demonstrated an aneurysm on the telovelotonsillar segment (Lister's classification) of the left PICA. On the third day, the left suboccipital craniotomy was performed and the fusiform aneurysm was resected. The postoperative course was uneventful. Histological examination of the resected aneurysm showed a dissection between the ruptured elastic lamina and the tunica media. Dissecting aneurysm of distal PICA is still belong to a rare entity. In all three cases found in the literature, the dissecting aneurysms are sited in the anterior medullary segment of PICA. Probably, this is the first report described a dissecting aneurysm on the more distal part-telovelotonsillar segment of PICA. The clinical features, pathogenesis and treatment of intracranial dissecting aneurysms are briefly discussed with reviewing the literature.

Aortic Dissection↗
PubMed1991

[Slowly progressive fluent aphasia--clinical features and an imaging study including MRI, SPECT and PET].

Three cases of slowly progressive fluent aphasia were presented. In all it began with word amnesia or stuttering, and in one to five years impairment of auditory comprehension, and reading and writing difficulties with kanji (Japanese morphograms) appeared. The neuropsychological and radiological findings were as follows: Case 1: a right-handed 65-year-old man showed severe fluent aphasia (the Western Aphasia Battery profile was rated as corresponding to Wernicke's aphasia but his score on the Token test was too high for Wernicke's aphasia) and memory disturbance. Cortical atrophy was prominent in the left temporal and parietal lobes. Hypoperfusion was evident in the bilateral anterior temporal region, suggesting the diagnosis of Pick's disease. Case 2: a right-handed 42-year-old man presented amnesic aphasia with buccofacial and ideomotor apraxia. The left frontal, temporal and parietal lobes were all atrophic. Hypoperfusion was marked in the left perisylvian and temporo-parietal regions, being similar to the pattern of Mesulam's slowly progressive aphasia. Case 3: a right-handed 55-year-old man with amnesic aphasia. Left-side dominant cortical atrophy involved the frontal, temporal and parietal lobes. The metabolic rate was lower in the left anterior temporal lobe, compatible with the finding in Pick's disease. The common clinical features of these patients were selective deficits in vocabulary, resulting in impairment of confrontation naming, and auditory comprehension. They sometimes could not recognize things even when they were told their names; case 1 could not even point to objects on command, while their syntactic comprehension was well preserved.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Aneurysms of the distal posterior inferior cerebellar artery; the report of 10 cases].

Non mycotic and non traumatic distal posterior inferior cerebellar artery (PICA) aneurysms are rare, but eleven aneurysms in ten cases were reported. They all originated from subarachnoid hemorrhage due to rupture of these aneurysms. The patients in these cases were all admitted within 5 days after the onset. The neurological state of four cases on admission was grade 4 or 5 in Hunt and Kosnik's grading system. Two patients of grade 5 died within 24 hours after the onset. The CT scan on admission revealed heavy subarachnoid hemorrhage mainly in the posterior fossa. In severe cases, ventricle hematoma, cerebellar hematoma and/or subdural hematoma were evident in the posterior fossa. The locations of these eleven aneurysms were as follows: On the bifurcation of the Telovelotonsillar segment in six cases. In the cortical segment in three cases. In the anterior medullary and tonsillomedullary segment in one case. Six saccular aneurysms were situated on bifurcations of parent arteries but three saccular aneurysms did not arise from bifurcations. Two of them were not from turning points of the arteries. One fusiform aneurysm situated on the bifurcation of telovelotonsillar segment was excised, and histologically shown to be a dissecting aneurysm with hypoplasia of elastic lamina and tunica media in the parent artery. Three cases were associated with small AVM located on the superior surface of the cerebellar vermis and fed mainly by the superior cerebellar artery (SCA) in two cases, and by SCA and PICA in one case. In these cases the hemodynamic stress on PICA did not seem to increase so remarkably.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

[Superior petrosal sinus dural arteriovenous malformation with varix indenting brain stem--report of a case and review of the literature].

A rare case of the dural AVM mainly around the left petrosal sinus was reported. A 64 years old man was admitted just after the sudden onset of severe headache and nausea. The CT scan revealed subarachnoid hemorrhage in the left ambient cisterns. A small hematoma was also found in the left cerebellar peduncle. External carotid angiogram showed a dural AVM which nidus was located adjacent to the left superior petrosal sinus. Its feeding arteries were as follows; the middle meningeal artery, the artery of foramen rotundum, the accessory meningeal artery, the dural branch of occipital artery and the ascending pharyngeal artery. The voluminous petrosal vein and the dilated cortical veins were identified as drainers and, the portion of the latter appeared as "varix" embedded in the pons, which was clearly delineated by MRI. In the venous phase, stenotic straight sinus and residual Falcine sinus were illustrated. Superselective embolization of the feeding arteries was employed followed by the direct clippings of draining vein. Postoperative course was uneventful. The present case should be classified into the tentorial dural AVM. Only 26 cases of this rarely encountered entity was reported in the literature. Based on both the present and the previously reported cases, the clinical features, treatment and pathogenesis of this disease were briefly discussed.

Brain Stem↗
PubMed1990

The interaction of acetylcholinergic and serotonergic neural systems on performance in a continuous non-matching to sample task.

The interactions of cholinergic and serotonergic neural systems were investigated in a working memory, continuous non-matching-to-sample task in an operant chamber. Each rat was injected (i.p.) with scopolamine and/or methysergide. The serotonergic system was destroyed by p-chloroamphetamine (PCA) injection. Scopolamine, but not PCA, impaired response accuracy. The effects of methysergide and scopolamine together were not different from scopolamine alone. Scopolamine had a significantly smaller effect on choice accuracy in PCA-treated than in untreated rats.

Acetylcholine↗
PubMed1990

Characterization and anticancer activity of the micelle-forming polymeric anticancer drug adriamycin-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer.

Adriamycin (ADR), an anthracycline anticancer drug, was bound to the poly(aspartic acid) chain of poly(ethylene glycol)-poly(aspartic acid) block copolymer by amide bond formation between an amino group of Adriamycin and the carboxyl groups of the poly(aspartic acid) chain. The polymeric drug thus obtained was observed to form a micelle structure possessing diameter of approximately 50 nm, with a narrow distribution, in phosphate-buffered saline and to show excellent water solubility despite a large amount of ADR introduction. Further, it was able to be stored in lyophilized form without losing its water solubility in the redissolving procedure. Increased stability of the bound Adriamycin molecules in phosphate-buffered saline and elimination of binding affinity for bovine serum albumin due to the micelle formation were further advantages of this polymeric drug. In vivo high anticancer activity of this micelle-forming polymeric drug against P 388 mouse leukemia was obtained with less body weight loss than that seen with free ADR, due to low toxicity as compared with free ADR.

Animals↗
PubMed1990

Cerebral blood flow in moyamoya disease. Part 1: Correlation with age and regional distribution.

A study has been made of the cerebral blood flow (CBF) in moyamoya disease from the perspective of hemispheric cerebral blood flow and regional CBF (rCBF). The material includes 21 children between the ages of 5 and 15 years with moyamoya disease, and 19 adult moyamoya cases--all of which had virtually no neurological symptoms at the time of the study. CBF was measured using the 133Xe intravenous injection method. Comparison was made with the measurements from 16 normal children and 14 normal adults. Study was also made of the relationship between the angiographic stage of the disease and the CBF. With the exception of the more elderly patients, CBF was found to be significantly lower in the moyamoya cases than in normal subjects of the same age group. In all age groups, the distribution of rCBF showed a dominant posterior distribution, dissimilar to the dominant anterior distribution found in the normals. Among the juvenile moyamoya cases, there was a tendency toward decreasing hemispheric blood flow together with advancing disease--as determined angiographically. Moreover, with advancing stages of the disease, there was a continuing transition from the normal pattern of frontal dominance to one of occipital dominance. This dominance of posterior rCBF is thought to be a characteristic feature of moyamoya disease.

Adolescent↗
PubMed1990

Hippocampal cells have behavioral correlates during the performance of an auditory working memory task in the rat.

Single unit activity was recorded from the rat hippocampal CA1 and CA3 subfields, dentate gyrus (DG), entorhinal cortex (EC), subicular complex (SB), motor cortex (MC), prefrontal cortex (PFC), and dorsomedial thalamus (DMT) during performance of a continuous non-matching-to-sample task. The rats made go and no-go responses to indicate whether the current tone was the same as (match) or different from (nonmatch) the preceding tone. About half of the units from the MC, CA1, CA3, and DG had motor correlates, increments of activity immediately prior to a go response. This suggests that those regions are involved in making a response. The CA1 and CA3 had more units with comparison-motor correlates, increases of activity prior to a correct go response on nonmatch trials. This pattern of activity suggests that the CA1 and CA3 are involved in a mnemonic process of comparison between retained and current stimuli in a nonspatial auditory task.

Animals↗
PubMed1990

Cells in the rat auditory system have sensory-delay correlates during the performance of an auditory working memory task.

Single unit activity was recorded from rat auditory cortex (AC), medial geniculate body (MGB), and inferior colliculus (IC) during performance of a continuous nonmatching-to-sample task. The rats made go and no-go responses to indicate whether the current tone was the same as (match) or different from (nonmatch) the preceding tone. Between 31% and 55% of the units from AC, MGB, and IC showed sensory correlates (differences in activity to the two types of tones), indicating an involvement in sensory discrimination. Twenty percent of the units from AC and MGB had delay correlates (sustained differential activity during the delay immediately after the tones), indicating an involvement in retention. Most of the units with delay correlates also had sensory correlates. These results suggest that the auditory system, especially AC and MGB, discriminates and retains auditory stimuli in an auditory working memory.

Animals↗