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Biomedical subjects

S Shibata

Publications and source records attributed to S Shibata.

At least 703 records · Page 39Linked to original sources

Freeze-fracture replica study of capillary endothelium after embolization in the dog.

The underlying mechanisms that lead to brain edema following ischemic insult have been subject to much debate. In this study, experimental cerebral infarction was produced in 25 dogs by injecting 1 or 2 silicone rubber cylinders through the cervical internal carotid artery. The animals were sacrificed 24 hours after embolization. Freeze-fracture studies were conducted on the plasma membrane of the capillary endothelium from 15 control and 25 ischemic dogs. No definite findings of tight junction opening were made in the ischemic preparations. Pinocytotic vesicles were seen as concave areas on the protoplasmic face (PF) of the plasma membrane and as protrusions on the extracellular face (EF). The average pinocytotic vesicle count per square micron was increased in ischemic animals. On the luminal side, it reached 22.0 +/- 1.2/sq mu in the 50 PF samples and 29.5 +/- 1.3/sq mu in the 50 EF samples in the experimental preparations, as compared to 7.2 +/- 0.5 sq mu in the 50 PF samples and 9.0 +/- 0.6 sq mu in the 50 EF samples in normal cortex. The average area of the vesicles was also enlarged in experimental animals: 4990.7 +/- 798 sq nm in the 50 PF samples and 4762.8 +/- 878 sq nm in the 50 EF samples, as compared to 3567.7 +/- 570 sq nm in the 50 PF samples and 3404.5 +/- 573 sq nm in the 50 EF samples in normal cortex (p greater than 0.01). These results indicate that transcellular transportation by pinocytotic vesicles plays an important role in the increase of capillary permeability observed in an ischemic model.

Animals↗

A new 5'-nucleotidase inhibitor, nucleoticidin. II. Physico-chemical properties and structure elucidation.

A novel 5'-nucleotidase inhibitor, named nucleoticidin, was isolated from a fermentation broth of Pseudomonas sp. The molecular weight was estimated by gel filtration to be over 1,000,000. Nucleoticidin is composed of D-glucose and D-mannose at a molar ratio of 1.7 to 1.0. Combined analyses using chemical and physico-chemical methods, such as gas liquid chromatography and mass fragmentography, revealed that nucleoticidin has a structural unit with mannosyl residues at the terminal of a (1----4) linked D-glucosyl main chain with beta-configuration.

Anti-Bacterial Agents↗

Effects of dimethylpropranolol (UM-272) on the electrophysiological properties of guinea-pig ventricular muscles.

The effects of dimethylpropranolol (UM-272) on transmembrane action potentials were examined in isolated right ventricular papillary muscles of the guinea pig. UM-272 (10(-5) to 3 X 10(-4) M) caused a dose-dependent decrease in the Vmax of the action potential. At 3 X 10(-4) M, a slight decrease in the amplitude of action potential was also observed. The resting potential and the action potential duration were not affected by the drug. In the presence of UM-272, trains of stimuli at rates higher than 0.1 Hz led to an exponential decline in Vmax (onset rate, 0.13-0.28 per action potential) to a new plateau level. This use-dependent block was augmented at the higher stimulation frequency. The time constant for the recovery of Vmax from the use-dependent block (offset) was 7.1 to 7.3 sec. In depolarized papillary muscles with 8 or 10 Mm [K+]0, the inhibitory action of UM-272 on Vmax of the first action potential after a long quiescent period (tonic block) was augmented markedly, but the rates of onset and offset of the use-dependent block were similar to those in normally polarized preparations under 5 mM [K+]0. The curves relating membrane potential and Vmax in preparations stimulated infrequently were shifted by 7.2 mV with UM-272 at 10(-4) M in the direction of more negative potentials. These findings suggest that UM-272 has kinetically similar use-dependent inhibitory action of the fast sodium channels of cardiac muscles as other Class Ia antiarrhythmic drugs like quinidine or procainamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Dual effect of ouabain on the palytoxin-induced contraction and norepinephrine release in the guinea-pig vas deferens.

Palytoxin (PTX), C129H223N3O54, isolated from marine coelenterates of Palythoa tuberculosa, caused a first rapid contraction followed by the slow phasic contraction of guinea-pig vas deferens. In the presence of ouabain (10(-5) M), PTX (10(-8) M) failed to cause the first contraction; however, the second contraction was potentiated. In the presence of phentolamine (10(-6) M), the second contraction was inhibited selectively. When ouabain was applied to the muscle in the presence of phentolamine, both first and second contractile responses to PTX were abolished. When the muscle was exposed to the potassium-depleted solution, the first contractile response to PTX was rather potentiated. PTX caused the release of norepinephrine from the muscle. Exposure of the muscle to ouabain (10(-5) M) markedly increased the PTX-induced release. It is indicated that the first and second contractile responses to PTX have entirely different properties. The second response is due to a release of norepinephrine from nerves and was potentiated by ouabain through the increase in the norepinephrine release, whereas the first response was not due to the norepinephrine release but presumably to a direct action on smooth muscle cell and was inhibited by ouabain. The mechanism of the action of PTX was discussed in the relation with Na,K-ATPase.

Acrylamides↗

Inhibitory effect of ouabain on the palytoxin-induced contraction of human umbilical artery.

Palytoxin (PTX), C129H223O3N54, isolated from marine coelenterates of Palythoa tuberculosa, caused contraction of the human umbilical artery in a dose-dependent manner (10(-11)-10(-8) M). Pretreatment with ouabain (10(-5) M) abolished the PTX (10(-8) M)-induced contraction but had no effect on the serotonin- (10(-6) M) and potassium- (40 mM) induced contractions. When the muscle was exposed to a potassium-free medium, application of PTX was able to cause a contraction similar to the contraction in normal medium. In the presence of verapamil (3 X 10(-6) M) or in the calcium-free medium. PTX-induced contraction was inhibited. In the depolarized muscle with 126 mM potassium, PTX did not induce a contraction whereas serotonin did. Our results suggest that PTX causes calcium influx through the plasma membrane of the umbilical artery, causing contraction. The site of action of PTX is presumably related to the Na,K-ATPase on the plasma membrane, although the precise relation between the site of action and increase in calcium influx is not known now.

Acrylamides↗

The inhibitory actions of acebutolol and propranolol on the contractile response to 5-hydroxytryptamine in various isolated vascular smooth muscles.

Pretreatment with acebutolol or propranolol at high concentrations had an inhibitory effect on the contractile response to 5-hydroxytryptamine (5-HT) in most vascular smooth muscles such as rabbit aorta and basilar, mesenteric, renal, femoral arteries and cat coronary artery. The inhibitory actions of both agents were generally greater than on the responses to excess Ca2+ and potassium. In rabbit renal arteries, acebutolol had no effect on the response to 5-HT but inhibited the responses to excess Ca2+ and potassium. Propranolol had a marked inhibitory effect on the response to 5-HT. In all preparations used, the contractions induced by norepinephrine (NE) and histamine showed a much greater resistance to the effect of acebutolol and propranolol than the contractions induced by 5-HT, Ca2+ and potassium. Nifedipine had no inhibitory effect on the response to 5-HT in most of the preparations. Nifedipine inhibited the response to 5-HT only in the basilar arteries. The inhibitory actions of propranolol on the response to 5-HT was greater than that of acebutolol. The inhibitory action of acebutolol and propranolol on the response to 5-HT may be related to mechanisms other than the beta-adrenoceptor blocking action of the drugs. The possible mechanisms of inhibitory action of both beta-adrenoceptor antagonists on 5-HT are discussed.

Acebutolol↗

[Ultrastructure of capillary permeability in human brain tumors. Part 1: Gliomas associated with cerebral edema (low density area)].

In order to elucidate pathogenesis of perifocal edema in the human brain tumors, we observed the alteration of capillary permeability between the glioblastomas with remarkable edema (4 cases) and astrocytoma with slight edema (3 cases). Specimens were studied by conventional ultrathin section and freeze-fracture replica technique. In ultrathin sections of capillaries in glioblastomas, some of these cell junctions were tortuous, elongated, in fact, open. Other capillary abnormalities included endothelial hyperplasia with extensive vesicular formation, surface infolding of endothelial cells, irregularity of the basal lamina and the presence of a large collagen filled extracellular space. In freeze-fracture replicas of capillary endothelium, pinocytotic vesicles markedly increased and were an average fo 52 per micron. Tight junction in one area was seen as network of 6 strands composed of about 100A particles, but in the other areas as one or two strands. In ultrathin sections of astrocytoma, yet there were blood vessels appeared relatively normal. In freeze-fracture replicas, pinocytotic vesicles markedly increased and were an average of 34 per micron. Tight junction was seen as network of 7 strands. We concluded that fewer strands of the tight junction play an important role in increasing the permeability in the vessels of glioblastomas with severe perifocal edema, in addition to increasing the pinocytotic vesicles.

Adult↗

[UFT concentration in serum and tissues of patients with gynecologic malignant tumors following oral administration].

Oral UFT was given to patients with genital carcinoma prior to surgery. 5-FU, FT and uracil levels in the tumor site were then measured in the surgical specimens obtained. Simultaneous estimates of tissues and plasma 5-FU indicated that the amount of drug in the tumor site (0.227 +/- 0.117 micrograms/g wet weight) had a 6.3-fold increase in concentration compared with that in normal tissues (0.036 +/- 0.019 micrograms/g wet weight) and was approximately 13.4 times that of the peripheral circulation (0.017 +/- 0.007 micrograms/ml). The rate of increase in concentration of tissue 5-FU rose especially in carcinoma of the cervix (0.394 +/- 0.215 micrograms/g), corpus uteri (0.116 +/- 0.042 micrograms/g) and ovary (0.171 +/- 0.047 micrograms/g). In the case of carcinoma of the cervix, the concentration of 5-FU in the tumor site was found to be about 14.1 times higher in invasive carcinoma than in carcinoma in situ. 5-FU concentration in the tumor site showed a still higher level compared with normal tissue after the drug was administered, suggesting an accumulation of 5-FU within the tumor.

Antineoplastic Combined Chemotherapy Protocols↗

The effect of prophylactic heparinization on DIC arising from transitory circulatory arrest in dogs.

To evaluate the beneficial effect of heparin administration on the prevention of disseminated intravascular coagulation (DIC) which appears following circulatory arrest, experimental studies were carried out with one group of dogs during circulatory arrest (control group) and compared to a group of dogs that received heparinization (heparinized group) soon after termination of circulatory arrest. Dogs of the control group were subjected to transitory circulatory arrest with occlusion balloons in the aorta and the femoral vein for a period of 8 minutes and allowed to recover without further treatment. Dogs of the heparinized group were given continuous infusions of 20 units/kg/hour of heparin as soon as circulatory arrest was started. The control group developed DIC 5 hours after circulatory arrest; however, the heparinized group demonstrated reduced platelet counts and low levels of antithrombin III (AT-III) 2 to 3 hours subsequently to circulatory arrest, but these changes were not serious, and normal levels of platelet count and AT-III were restored rapidly thereafter. Prophylactic heparin therapy is, accordingly, recommended as a useful measure of preventing the occurrence of DIC in circulatory arrest and the subsequent detrimental consequences.

Animals↗

[Surgical management of an internal carotid lesion by contralateral pterional approach in bilateral intracranial aneurysms: report of two cases].

Two cases of bilateral carotid aneurysms are reported in which the neck of remaining aneurysm was successfully clipped by way of a contralateral pterional approach. The authors emphasized that in some cases of bilateral intracranial aneurysms (e.g. Aneurysms of the unilateral circle of Willis' and ipsilateral middle cerebral aneurysm plus contralateral internal carotid aneurysm), this is the preferred approach.

Carotid Artery Diseases↗