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Biomedical subjects

Y Ushio

Publications and source records attributed to Y Ushio.

At least 235 records · Page 13Linked to original sources

N-methyl-D-aspartate receptor antagonist MK-801 induced circling behavior in rats with unilateral striatal ischemic lesions or nigral 6-hydroxydopamine lesions.

The present study shows that systemic administration of the selective, non-competitive N-methyl-D-aspartate antagonist MK-801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo (a,d)-cyclohepten-5,10-imine] dose-dependently induces ipsiversive rotational behavior in the rats with a unilateral striatal lesion produced by transient middle cerebral artery occlusion or in those with a unilateral nigrostriatal lesion produced by 6-hydroxydopamaine. In relation to a functional model of the basal ganglia-thalamocortical 'motor' circuit, the present data suggest that the striatum may be one of the most important sites where MK-801 acts in the basal ganglia, with its being responsible for the circling behavior of the animal models.

Animals↗

Striatonigral involvement following transient focal cerebral ischemia in the rats: an immunohistochemical study on a reversible ischemia model.

A topographical and cellular immunohistochemical analysis was performed on the striatonigral system of rats with unilateral, reversible middle cerebral artery (MCA) occlusion. Antibodies to calcineurin (CaN), parvalbumin (PV), choline acetyltransferase (ChAT) and glial fibrillary acidic protein (GFAP) were used in this study. Sixty days after the operation, the ipsilateral striatum showed a characteristic cell type-specific injury in the dorsolateral part of the nucleus (i.e., non-limbic striatum): a marked reduction in the number of medium-sized spinous neurons expressing CaN immunoreactivity and a selective sparing of PV- and ChAT-positive interneurons. There was also a marked depletion of striatonigral afferents visualized by CaN immunostaining in the lateral portion of the substantia nigra pars reticulata, which is considered to be implicated with motor function. In addition, it was noted that such striatonigral involvement was accompanied by marked gliosis showing strong GFAP immunolabeling. The present data suggest that rats with reversible MCA occlusion can be a useful animal model for studying cell type-specific ischemic injury and subdivisional involvement of the striatonigral pathway as a part of the cortico-subcortical loop subserving motor function.

Animals↗

Distinct neuronal subset reveals perikaryal immunostaining for synaptophysin (protein p38) in the striatum of rats.

An immunoperoxidase technique was used to locate synaptophysin (protein p38), a major integral membrane glycoprotein of synaptic vesicles, in the rat brain. In addition to a diffuse distribution of nerve terminal stainings for synaptophysin appearing as numerous small puncta, the large-sized cells with spindled or polygonal shapes revealed perikaryal staining for synaptophysin in the striatum. The double labeling with immunofluorescence technique disclosed that the cell bodies, immunoreactive for synaptophysin, appeared to be those of the striatal giant cholinergic neurons. In addition, in rats that underwent the transient middle cerebral artery occlusion, the striatal ischemic lesions with cell type-specific injury revealed a survival of synaptophysin-positive large cells, presumably identical with the cholinergic neurons. The present study suggests that the metabolism and/or axonal transportation of synaptophysin of the giant cholinergic cells may be different from those of other neuronal populations in the striatum. Also, synaptophysin can act as a neurochemical marker for identification of the giant cholinergic neurons in the striatum of rats.

Animals↗

Immunocytochemical detection of calcineurin and microtubule-associated protein 2 in central neurocytoma.

An immunohistochemical study was carried out on four cases of central neurocytoma, which had characteristic clinicopathological features including ultrastructural findings. Specific antibodies to calcineurin (CaN), microtubule-associated protein 2 (MAP2) and synaptophysin (SYP) were used. All tumor tissues examined showed specific immunoreactivity for CaN and MAP2. Immunolabelling of both molecules revealed that they were mainly localized in the perikarya and proximal processes of the tumor cells. SYP immunoreactivity was found in three of the four cases. SYP immunoreaction products were predominantly seen in the tumor cell processes, while the perikarya were weakly or moderately positive for SYP. The data suggest that CaN and MAP2, together with SYP, can be useful tools for identifying and characterizing of the central neurocytoma.

Calcineurin↗

Correlation of sequential magnetic resonance imaging of experimental brain ischemia with histologic changes in gerbils.

RATIONAL AND OBJECTIVES: To characterize Gd-DTPA-enhanced T1-weighted images (Gd-T1WI) in the acute phase of cerebral ischemia, sequential magnetic resonance images of 84 Mongolian gerbils with occlusion of the left common carotid artery were evaluated. METHODS: Twelve gerbils were used for each group, among which the occlusion time (5-180 minutes, permanent) varied. Histopathologic changes developing within the first 2 weeks were compared with patterns on T2-weighted images and Gd-T1WI on a 7.05-Tesla system. RESULTS: Although T2-weighted images and Gd-T1WI both demonstrated abnormal findings as early as 3 hours after occlusion, Gd-T1WI demonstrated more definite abnormalities with shorter occlusion than T2-weighted images (especially when there were only mild histologic changes). The earliest changes were an abnormal enhancement around and within the lateral ventricles in temporary occlusions; this was not demonstrated in permanent occlusions. CONCLUSIONS: Magnetic resonance images using Gd-DTPA demonstrated abnormal permeability within 3 hours after occlusion, and the pattern is correlated with intensity of ischemia.

Animals↗

Histochemical study of alkaline phosphatase in primary human brain tumors: diagnostic implications for meningiomas and neurinomas.

Histochemical analysis of frozen, thin sections revealed the distribution of alkaline phosphatase (ALPase) in 47 primary intracranial neoplasms in humans. The cytoplasm of meningioma cells exhibited the strongest ALPase reactivity. Pretreatment of these materials by levamisol indicated that the isozymes of ALPase had the characteristic liver-bone-kidney form. In meningiomas and astrocytomas, there was no particular relationship between ALPase activity and malignancy. In neurinomas, there was weak ALPase reactivity in a few neoplastic cells. These findings are suggestive of diagnostic implications for fibroblastic meningiomas and neurinomas at the light microscopic level.

Alkaline Phosphatase↗

Clinical investigation of lumbar epidural pressure.

To evaluate the usefulness of measuring lumbar intraspinal epidural pressure (ISEDP) measurements for the estimation of intracranial pressure, we studied the relationship between ISEDP and intracranial epidural pressure (ICEDP) in 12 patients with high intracranial pressure after neurosurgical procedures. ISEDP was measured with a Gaeltec catheter-tip pressure transducer placed percutaneously in the lumbar epidural space with a Touhy needle. ICEDP was determined by the conventional method. During the measurement, some manipulations were carried out. ISEDP and ICEDP measurements exhibited a linear correlation. In all but one patient with normal cerebrospinal fluid, ISEDP was 84 to 100% of ICEDP. In patients with mild subarachnoid hemorrhage, ISEDP was 82 to 86% of ICEDP. In patients with severe subarachnoid hemorrhage, ISEDP was 45 to 57% of ICEDP and always fluctuated in parallel with ICEDP. ISEDP accurately reflected ICEDP in response to manipulations such as breath holding, neck compression, compression at the cranial defect, mannitol administration, and coughing. These data suggest that ISEDP measurement is useful in monitoring intracranial pressure in patients with intracranial hypertension. In addition, the measurements can be obtained easily and safely.

Adult↗

Experimental investigation of lumbar epidural pressure measurement.

To evaluate the usefulness of lumbar intraspinal epidural pressure (ISEDP) measurements for the estimation of intracranial pressure, we studied the relationship between ISEDP and intracranial epidural pressure (ICEDP) in 25 adult mongrel dogs. ICEDP and ISEDP were measured simultaneously with Gaeltec catheter-tip pressure transducers placed in the parietal epidural space and in the lumbar epidural space. Groups 1 and 2 dogs served as normal cerebrospinal fluid condition models. Group 1 received sequential steady-state normal saline infusions (0.5, 1.0, and 1.5 ml/min) into the cisterna magna. ISEDP and ICEDP measurements exhibited a linear correlation, and ISEDP was 80 to 90% of ICEDP at any pressure level. There was no significant difference in the pressure curves obtained at the different infusion rates. Group 2 dogs were subjected to rapid pressure changes by a cisternal bolus injection. Although compliance calculated from the change in ISEDP was slightly greater than that from ICEDP at resting pressure, the compliance calculated from both ISEDP and ICEDP decreased at 20 and 30 mm Hg of ICEDP and the values became almost equivalent. Groups 3 and 4 dogs were mild and severe experimental subarachnoid models, respectively. The ISEDP and ICEDP measurements also showed a linear correlation; however, ISEDP was about 70% of ICEDP in Group 3 and about 50% of ICEDP in Group 4. Although there are varying degrees of discrepancy between ISEDP and ICEDP in the normal or subnormal pressure range and in the presence of severe spinal block, our findings suggest that ISEDP measurements can be used to estimate intracranial pressure in a clinical practice.

Animals↗

Dissecting aneurysm of the posterior inferior cerebellar artery: case report.

A patient with a dissecting aneurysm of a posterior inferior cerebellar artery who presented with Wallenberg's syndrome is reported. A 31-year-old man suddenly experienced an occipital headache, vertigo, and vomiting, followed by dysphagia. A neurological examination revealed partial Wallenberg's syndrome. Vertebral angiography revealed aneurysmal dilatation at the origin of the left posterior inferior cerebellar artery, with distal luminal narrowing. T1-weighted magnetic resonance imaging demonstrated an area of high-signal intensity, indicating an intramural hemorrhage in the arterial wall of the narrowed lumen. The dissecting aneurysm with a typical intramural hematoma of the posterior inferior cerebellar artery was entrapped with clips after an anastomosis of the left occipital artery to the distal posterior inferior cerebellar artery. The diagnosis and the treatment of dissecting aneurysms of the posterior inferior cerebellar artery are discussed.

Adult↗

Ventriculolumbar perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosou rea hydrochloride.

We report on the toxicity, intrathecal pharmacokinetics, and therapeutic effect of the ventriculolumbar perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitros our ea hydrochloride (ACNU) against the subarachnoid dissemination of primary central nervous system tumors. Fifteen patients received ventriculolumbar perfusion of ACNU. One was treated with ventriculolumbar perfusion of ACNU alone, and the others underwent concomitant systemic chemotherapy; three of these patients received irradiation as well. ACNU was administered at an initial dose of 0.5 and was increased to 1.5 to 10.0 mg in six patients. Because of a lack of Level 2 or greater toxicity, the subsequent seven patients received 8.7 to 10.0 mg of ACNU dissolved in artificial cerebrospinal fluid (CSF) at a concentration of 0.1 mg/ml, from the start of the treatment. During ACNU administration, the lumbar CSF was drained at approximately the same rate as that of the infusion. Twelve patients received from 3 to 42 courses (average, 14 courses). The cumulative dose of ACNU ranged from 5 to 330.4 mg (average, 82.9 mg). One patient had a convulsion; two patients experienced transient headache, nausea, and vomiting; two others reported transient headache, nausea, vomiting, and fecal incontinence; and one experienced transient nausea, vomiting, and fecal incontinence. No side effects were noted in the other nine patients. When 9.0 to 9.5 mg of ACNU, dissolved in 90 to 95 ml of artificial CSF, was administered for 37 to 52 min, the maximum concentration of ACNU in the lumbar CSF was 9.86 to 12.79 micrograms/ml and the area under the drug concentration-time curve was 260.8 to 502.5 micrograms.min/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Carotid and vertebral rete mirabile in man--case report.

Rete mirabile is a normal vascular network in the carotid artery distribution of some vertebrates, but is an abnormal and extremely rare finding in humans. We describe a 40-year-old male with a carotid and vertebral rete mirabile manifesting as cerebrovascular disorder. This was the second case of carotid and vertebral rete mirabile in man.

Adult↗

Anaplastic astrocytoma with extracranial extension--case report.

A 44-year-old female presented with anaplastic astrocytoma of the right temporal lobe which had destroyed the skull base and extended extracranially. Histologically, the extracranial portion of the tumor was astrocytoma with desmoplastic reaction. She was treated by subtotal tumor removal, radiation therapy, and chemotherapy, but died of meningeal dissemination. Spontaneous extradural extension of malignant glioma is rare and always fatal.

Adult↗

Huge subdural empyema with unusual presentation in infant--case report.

An 11-month-old boy presented with a huge subdural empyema in the left hemisphere associated with a subsequent contralateral chronic subdural hematoma. Burr-hole drainage and antibiotic therapy achieved a successful outcome. Subdural empyema may result from hematogenous seeding of infection into a pre-existing chronic subdural hematoma.

Brain↗

[Sinus thrombosis during CDDP and VP-16 (PE) therapy for suprasellar germ-cell tumor: case report].

A case of sinus thrombosis occurring during combination chemotherapy with CDDP and VP-16 (PE) for a suprasellar germ-cell tumor is presented. A 5-year-old girl developed polyuria, polydipsia and headache in April, 1991 and became unconscious on May 10, 1991, when MRI and CT demonstrated a suprasellar tumor and marked hydrocephalus. After a ventriculo-peritoneal shunt operation, radiotherapy and two courses of PE therapy were carried out. During the second course of PE therapy, diabetes insipidus became quite difficult to control and severe hypovolemic hypernatremia developed. While it was being treated, the patient developed a clonic convulsion of her left extremities and visual disturbance. CT scan demonstrated a right parietal hemorrhagic infarction and IV-DSA suggested thrombosis of the superior sagittal sinus. Laboratory data disclosed DIC. The main cause of sinus thrombosis in this patient was considered severe dehydration. It is also possible that cisplatin and steroid played a role. In addition to these, dysfunction of hypothalamus, which is one of the regulatory centers of the plasma concentration of factor VIII, may have contributed to the acceleration of blood coagulation. This case re-emphasized the importance of preventing dehydration and monitoring the blood coagulation fibrinolytic system during PE therapy in patients with a suprasellar germ-cell tumor accompanied with diabetes insipidus.

Antineoplastic Combined Chemotherapy Protocols↗

Novel 5-HT3 antagonists. Isoquinolinones and 3-aryl-2-pyridones.

Synthesis and pharmacological evaluation of a series of 1,2-dihydro-1-[(5-methyl-1-imidazol-4-yl)methyl]-2-oxopyridine 5-HT3 antagonists are described. The key pharmacophoric elements were defined as a basic nitrogen, a linking group capable of hydrogen bonding interactions, and an aromatic moiety. 1,2-Dihydro-2-oxopyridine moiety could be a good linking group because of its nicely planar structure. The steric limitations of the aromatic moiety were investigated by X-ray analysis and computer analysis and shown to be optimal when the aromatic moiety was constrained within an arched planar system, which could be successfully replaced by 3-(2-thienyl)-2-oxopyridine function or 6-amino-7-chloro-1-isoquinolinone function without any loss of the activity. Among the synthesized compounds, 42 showed the most potent activity in the inhibition of Bezold-Jarisch reflex in rats. Compounds 44a and 64 were orally active in the protection against cisplatin-induced emesis in dogs or ferrets. Structure-activity relationships are discussed.

Animals↗

Calcineurin, a calcium/calmodulin-regulated protein phosphatase, in mammalian neuroendocrine cells and neoplasms.

Calcineurin is a calcium/calmodulin-regulated protein phosphatase. By using enzyme-immunoassay and immunocytochemistry with an affinity-purified specific antibody to this protein, we have found that calcineurin is expressed in the central and peripheral neuroendocrine cells, also termed amine precursor uptake and decarboxylation cells. In addition, calcineurin immunoreactivity was found in the central neuroendocrine neoplasms such as pineocytoma, olfactory neuroblastoma and paraganglioma. The present findings indicate that the activity of phosphatase regulated by calcium and calmodulin is involved in neuroendocrine functions, and that the enzyme can be useful for the identification and characterization of neuroendocrine cell tumors.

Animals↗

Characterization of the phosphatase activity of a baculovirus-expressed calcineurin A isoform.

Calcineurin A was purified by calmodulin-Sepharose affinity chromatography from Sf9 cells infected with recombinant baculovirus containing the cDNA of a rat calcineurin A isoform. The Sf9-expressed calcineurin A has a low basal phosphatase activity in the presence of EDTA (0.9 nmol/min/mg) which is stimulated 3-5-fold by Mn2+. Calmodulin increased the Mn2+ stimulated activity 3-5-fold. Bovine brain calcineurin B increased the A subunit activity 10-15-fold, and calmodulin further stimulated the activity of reconstituted A and B subunits 10-15-fold (644 nmol/min/mg). The Km of calcineurin A for 32P-RII pep (a peptide substrate (DLDVPIPGRFDRRVSVAAE) for CaN), was 111 microM with or without calmodulin, and calmodulin increased the Vmax about 4-fold. The Km of reconstituted calcineurin A plus B for 32P-RII pep was 20 microM, and calmodulin increased the Vmax 18-fold without affecting the Km. CaN A467-492, a synthetic autoinhibitory peptide (ITSFEEAKGLDRINERMPPRRDAMP) from calcineurin, inhibited the Mn2+/calmodulin-stimulated activities of the reconstituted enzyme and the A subunit with IC50's of 25 microM and 90 microM, respectively. The reconstitution of the phosphatase activity of an expressed isoform of calcineurin A by purified B subunit and calmodulin may facilitate comparative studies of the regulation of calcineurin A activity by the B subunit and calmodulin.

Amino Acid Sequence↗