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T Itakura

Publications and source records attributed to T Itakura.

At least 145 records · Page 8Linked to original sources

[Dynamics of extracellular acetylcholine of the gerbil striatum during cerebral ischemia monitored by intracerebral microdialysis].

Neurons in the hippocampus and striatum are vulnerable to the ischemic insult. In the present study we focused on the vulnerability of acetylcholine (ACh)-containing neurons in the striatum. To determine the change of ACh content in the striatum, we employed a simple sensitive brain microdialysis method with high performance liquid chromatography electrochemical detection. Morphological change of cholinergic neurons was studied by ACh-esterase staining during ischemic insult. After bilateral carotid artery occlusion, local cerebral flow decreased less than 5 ml/min/100 g in the striatum. Ach content in dialysate for 20 min after the occlusion was elevated to 135% of the control. ACh content decreased to 15% of the control 2hs after the ischemia. Density of Cholinergic fibers and cell bodies was reduced 10 min after the ischemia and further decreased 20 min after the occlusion. Our study suggests that the transient elevation of ACh content was probably due to diffusion of ACh from destruction cholinergic terminals after the ischemic insult. The increase of ACh immediately after arterial occlusion may affect severity of ischemic damage in the brain by its excitatory effect.

Acetylcholine↗

Effect of atrial natriuretic peptide on ischaemic brain oedema.

We investigated the effect of intraventricularly administered atrial natriuretic peptide (ANP) on the brain water, sodium and potassium contents in ischaemic brain oedema. Global ischaemia (15 min) followed by recirculation (30 min) produced by a three vessel occlusion in the rat served as a model for induction of ischaemic cerebral oedema. Water content was measured by a drying-weighing method. Sodium and potassium contents were measured by means of flame photometry. The effect of ANP was evaluated by comparing these parameters of the ANP-treated group (5 micrograms/kg and 10 micrograms/kg atriopeptin) with those of the control group (administration of 0.9% NaCL). ANP did not significantly change the content of water, sodium and potassium in the preischaemic or ischaemic brain. Intraventricularly administered ANP (5 micrograms/kg and 10 micrograms/kg) caused significant decrease in the brain water (p less than 0.02) and sodium (p less than 0.01) contents after 15 min of ischaemia and 30 min of recirculation, while the brain potassium content remained unaltered. Serum osmolality, and sodium and potassium concentrations were not influenced by administration of ANP. Accordingly, ANP acts directly on the central nervous system to inhibit brain water and sodium accumulation in ischaemic brain oedema.

Animals↗

Effect of atrial natriuretic peptide on ischemic brain edema: changes in brain water and electrolytes.

The effects of intraventricularly administered atrial natriuretic peptide (ANP) on the brain water, sodium, and potassium contents in ischemic brain edema were investigated. By use of a three-vessel occlusion model, ischemic brain edema was produced in the rat brain by 15 minutes of global ischemia followed by recirculation. Water content was measured by means of a drying/weighing method; sodium and potassium contents were measured by means of flame photometry. The effects of intraventricular administration of ANP were evaluated by a comparison between the groups given 2 and 5 micrograms of atriopeptin II (treated) and those given 0.9% NaCl (sham-treated). The treated groups showed significant decreases in brain water (P less than 0.02) and sodium (P less than 0.01) contents at 15 and 30 minutes after recirculation, whereas the brain potassium contents remained unaltered. Before ischemia and immediately after 15 minutes of ischemia, intraventricularly administered ANP did not significantly change the brain water, sodium, or potassium contents. There was no significant difference in the effect on the amount of brain water and sodium between the two doses (2 and 5 micrograms). These effects of ANP were thought not to be mediated by primary changes in serum osmolality and sodium and potassium concentrations, because intraventricular administration of ANP did not change them significantly. The present results reveal that, in ischemic brain edema, ANP may act directly on the central nervous system to inhibit brain water and sodium accumulation.

Animals↗

Characterization and regulation of sex-specific mouse steroid hydroxylase genes.

We characterized the genes of the male-specific mouse steroid 16 alpha-hydroxylase (C-P-45016 alpha) and the female-specific mouse steroid 15 alpha-hydroxylase (P-45015 alpha) within two distinct gene families. In spite of the high structural identities within each family, the expression of the hydroxylase genes is uniquely regulated. Moreover, the other family members encode the P-450s which are structurally very similar to the hydroxylases but are not able to catalyze steroid hydroxylase activities. For example, only a single amino acid substitution creates steroid 15 alpha-hydroxylase activity in another family-member P-450coh, which catalyzes coumarin 7-hydroxylase but little steroid hydroxylase activity. It appears, therefore, that the mouse P-450 gene families evolved through gene duplication and selective mutation to create new P-450s structurally as well as to establish novel regulatory elements for the gene expressions.

Amino Acid Sequence↗

Transplantation of autologous superior cervical ganglion into the brain of parkinsonian monkeys.

Autologous transplantation of the superior cervical ganglion (SCG) into the caudate nuclei of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian monkey was studied in regard to animal behavior and catecholamine (CA) metabolites in cerebrospinal fluid. Monkeys which had undergone autotransplantation of the SCG revealed an apparent improvement in motor activity. The homovanillic acid content in cerebrospinal fluid increased following the SCG transplantation and was correlated with an increase in motor activity. CA histofluorescence studies confirmed the long-term survival of the SCG graft in which many CA fibers and cells were observed. The present experiment indicates that dopamine released from the graft improved the symptoms of parkinsonism in the monkey.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Transplantation of peripheral cholinergic neurons into Alzheimer model rat brain.

The effect of transplantation of peripheral cholinergic neurons was examined in rats with a lesion of the nucleus basalis Meynert (NBM). The rats with an NBM lesion showed abnormal increase of spontaneous activity, disturbance of memory retention, and disturbance of learning acquisition. In contrast, the rats which had received transplantation of cholinergic neurons into the cerebral cortex displayed amelioration of abnormal behavior produced by the destruction of the NBM. Morphological study (acetylcholinesterase) clearly showed survival of many transplanted cholinergic cells. The present study suggests that autotransplantation of peripheral cholinergic cells may be a possible therapy for Alzheimer's disease.

Acetylcholinesterase↗

Stereotactic hyperthermia for brain tumors.

We have developed a localized hyperthermia system using computed tomography-stereotactic surgery as malignant brain tumor therapy. In an experimental study, the temperature in the area of the cat brain within 20 mm from a radiofrequency electrode reached more than 43.7 degrees C. Intravenous administration of MCNU during hyperthermia caused a significant increase of MCNU content in the heated brain as compared with a control brain. In the clinical study, localized radiofrequent hyperthermia using stereotactic surgery was performed on 7 malignant deep-seated gliomas and 21 metastatic brain tumors. Especially, combination therapy of stereotactic hyperthermia and chemotherapy was effective treatment for gliomas less than 30 mm deep in the brain.

Adolescent↗

Autologous transplantation of the superior cervical ganglion into the brain of parkinsonian monkeys.

The effect of autologous transplantation of the superior cervical ganglion (SCG) into the brain of parkinsonian monkeys was studied through quantitative measurement of animal behavior. The motor activity of the monkey was measured with a telemetry system during the experiment. After experimental parkinsonism was induced by repeated intravenous injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), three monkeys were treated with autologous transplantation of the SCG into both caudate nuclei. One monkey served as a control without SCG transplantation after MPTP treatment. Three SCG-transplanted monkeys showed biphasic (acute and chronic) behavioral amelioration of parkinsonism after transplantation. In the acute stage, the animals showed transient hyperkinesia with aggressive behavior and loss of circadian rhythm. In the chronic stage following acute hyperkinesia, the animals regained normal behavior and circadian rhythm without aggressiveness. In contrast with the transplanted monkeys, the control monkey failed to show recovery of the bradykinesia and muscle rigidity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Functional characterization of two cytochrome P-450s within the mouse, male-specific steroid 16 alpha-hydroxylase gene family: expression in mammalian cells and chimeric proteins.

Two cDNAs, pc16 alpha-2 and pc16 alpha-25, which encode P-450s from within the mouse, male-specific steroid 16 alpha-hydroxylase (C-P-450(16 alpha)) gene family, were transfected into COS-1 cells in order to study catalytic activities of the expressed P-450s. pc16 alpha-2 was shown previously to encode the growth hormone dependent and androgen-dependent C-P-450(16 alpha) in adult male mice (Wong et al., 1987). The sequence of pc16 alpha-25-encoded P-450 (P-450cb) was identical with gene cb within the C-P-450(16 alpha) family. There was 94% and 87% nucleotide and amino acid sequence identity, respectively, between P-450cb and C-P-450(16 alpha). We expressed both P-450s by transfecting their cDNAs into COS-1 cells and found that steroid 16 alpha-hydroxylase activity was catalyzed by C-P-450(16 alpha) but not by P-450cb. In addition to testosterone, progesterone and estradiol were hydroxylated specifically at the 16 alpha-position by the expressed C-P-450(16 alpha). The results indicated that a broad steroid substrate specificity with high regio- and stereoselectivity at that position was a characteristic of C-P-450(16 alpha). We constructed and expressed chimeras between the two P-450s and found that the presence of about two-thirds of the C-P-450(16 alpha) molecule from its C-terminus was necessary for the chimeric cytochrome to maintain steroid 16 alpha-hydroxylase activity.

Amino Acid Sequence↗

Gene family of male-specific testosterone 16 alpha-hydroxylase (C-P-450(16 alpha)) in mice. Organization, differential regulation, and chromosome localization.

Three genes in the testosterone 16 alpha-hydroxylase (C-P-450(16 alpha)) family, ca, cb, and cc, are characterized. The sizes of the genes are approximately 4.5 to 5.2 kilobase pairs, and all three consist of nine exons with junctions at identical sites. Gene ca is identified as the male-specific, androgen-dependent C-P-450(16 alpha) gene in adult mice, since the exonic sequence matched 100% to the cDNA, pc16 alpha-2 (Wong, G., Kawajiri, K., and Negishi, M. (1987) Biochemistry 26, 8683-8690). Gene cb and cc are organized in tandem within 18-kilobase pair DNA. Their encoded P-450s contain an approximate 94% nucleotide sequence similarity to the C-P-450(16 alpha). The high similarity in gene nucleotide sequences, including the introns and flanking regions, suggests a combination of an ancestral gene duplication and gene conversion as a mechanism for evolution of the C-P-450(16 alpha) family. Gene ca shows male-specific expression in mouse kidney as well as in liver; gene cb, neither sex-specific nor androgen-dependent, is seen only in liver; gene cc is not expressed in either adult mouse liver or kidney. Expression of these three genes is not detected in adult mouse lung. It appears, therefore, that the C-P-450(16 alpha) gene family includes a large number of genes whose expressions are differentially regulated. Southern hybridization of C-P-450(16 alpha) cDNA to genomic DNAs from mouse-hamster somatic hybrid cells localizes tentatively this gene family on mouse chromosome 15. The recombination frequency in BXD recombinant inbred mice suggests that the C-P-450(16 alpha) gene family is approximately 16M from the 55-kDa locus.

Animals↗

Adriamycin-lipiodol suspension for i.a. chemotherapy of hepatocellular carcinoma.

Physicochemical properties of two types of adriamycin preparation, suspensions and emulsions prepared for i.a. chemotherapy of hepatocellular carcinoma, were investigated. A suspension was prepared by dispersing adriamycin directly into the lipid contrast medium, Lipiodol, whereas an emulsion was obtained by emulsifying an aqueous solution of adriamycin into Lipiodol. The dispersibility of the drug in each preparation was examined microscopically. The chemical stability of and drug release from the preparation were determined by high-performance liquid chromatography and spectrophotometry, respectively. The suspension was then given to ten patients with primary hepatocellular carcinoma. The suspension maintained good dispersibility without coagulation of drug particles, whereas coalescence of aqueous droplets and the resultant phase separation occurred 4 h after preparation of the emulsion. Both preparations maintained the initial drug content for at least 1 week at room temperature. The release of adriamycin was more prolonged in the suspension than in the emulsion. After i.a. administration of the suspension, a selective accumulation of Lipiodol in the tumor and decrease in serum alpha-fetoprotein (AFP) levels were found in most patients. A significant amount of adriamycin was still detected in hepatic specimens resected from two patients 1 and 2 months after treatment. These findings suggest that the adriamycin-Lipiodol suspension may be a useful preparation for targeting chemotherapy to hepatocellular carcinoma.

Adult↗

Non-Hodgkin's lymphoma involving the brain. Diagnostic usefulness of stereotactic needle biopsy in combination with paraffin-section immunohistochemistry.

A stereotactic needle biopsy was examined for applicability in diagnosing brain non-Hodgkin's lymphoma (NHL), because the procedure is far less aggressive than biopsy by open surgery. Formalin-fixed materials including four stereotactic specimens were available from nine patients with brain NHL. In addition to routine histopathology and histochemistry, paraffin-section immunohistochemistry was performed using a panel of monoclonal antibodies suited to such sections. Although several histopathological features characteristic of brain NHL could not be evaluated in three of the four stereotactic specimens owing to the small size of the specimens and partial invasion by lymphoma cells, the lesions in all cases could be characterised by immunohistochemistry. Examination for cytoplasmic immunoglobulin (cIg) was also performed, but specific identification of cIg was difficult in five cases because of diffuse background staining and passive diffusion of plasma protein into the cells during tissue processing. A review of the literature indicates the technical difficulty in cIg staining, since the incidence of cIg-positive cases in an individual study varied considerably, and lymphoma cells in 15 of 128 cIg-positive brain NHL cases have been reported to possess both light chains. From these findings, together with the relative difficulty in obtaining fresh tissues for study, it is concluded that, when the specimens are to be examined by paraffin-section immunohistochemistry using the above monoclonal antibodies, stereotactic needle biopsy is a useful, less aggressive method for diagnosing brain NHL.

Adult↗

Cystic arteriovenous malformation. A case report.

The authors report on a rare case of arteriovenous malformation (AVM) associated with cyst formation. Only five similar cases have been reported. CT findings of the cyst are divided into two types: 1) slit-like low density and 2) round one. Three patients showing slit-like cysts had experienced sudden severe headaches, probably due to haemorrhage. In contrast, two patients showing round cystic lesions had not experienced such sudden headaches and they revealed a nodule in the cyst at surgery. These facts suggest that there may be two different mechanisms for cyst formation in AVM's: haemorrhage and exudation. Slit-like cysts may result from old haemorrhage from the AVM nidus. Round cystic lesions may be due to exudation from the AVM nidus.

Adult↗

[Arteriovenous malformation associated with cyst. Case report].

The authors present the fifth reported case of arteriovenous malformation (AVM) associated with cyst formation. Among these five cases, computed tomography has demonstrated two types of cyst: round, and slit-like with low density. The three patients with slit-like cysts experienced sudden, severe headache, probably due to hemorrhage. The two patients with round cystic lesions did not have sudden headache, and at surgery the cysts were found to contain a mural nodule. These facts suggest that there may be two different mechanisms of cyst formation in the vicinity of an AVM: hemorrhage (slit-like cysts) and exudation (round cysts).

Adult↗

[Osteoblastic skull metastasis of lung cancer].

A case of osteoblastic skull metastasis of lung cancer is reported. A 56-year-old female patient was admitted to our hospital with complaints of headache and tumor of the right parietal bone. A plain skull X-ray showed hyperostotic feature of the right parietal bone. CT scan displayed that right parietal bone became thick and osteoblastic. Soft tissue was shown in the hyperostotic bone under MRI. An external carotid angiogram showed that the skull tumor was fed by the middle meningeal artery. The skull tumor and 2 solid intracerebral tumors were extirpated. Histological examination revealed adenocarcinoma in the skull and intracerebral lesions. The present case indicates that osteoblastic stimulating factor may be secreted by lung cancer.

Adenocarcinoma↗

Immunohistochemical demonstration of vasopressin nerve fibers in the cerebral artery.

Vasopressin-immunoreactive nerve fibers were demonstrated in the cerebral pial arteries by peroxidase immunohistochemistry. In the large pial artery (proximal part of the middle cerebral artery), they ran longitudinally to the long axis of the vessel. They ran in a spiral pattern in the distal part of the middle cerebral artery. Even in small arteries, vasopressin nerve fibers were found arranged in a longitudinal fashion. The present morphological data suggest that vasopressin nerve fibers in the cerebral artery may play a role in cerebral circulation.

Animals↗

Enhanced bioavailability of morphine after rectal administration in rats.

Plasma morphine levels and the area under the plasma concentration-time curve (AUC) after i.v. (10 mg kg-1), p.o. (100 mg kg-1) and rectal (unrestricted or restricted to 1.5 cm from the anus, 10 mg kg-1) administration of morphine hydrochloride were determined in 10 or 11-week-old male Wistar rats to compare bioavailability of morphine after the rectal dosage with that after oral administration. The AUC value after oral administration (15 micrograms min mL-1), which was normalized by the dose, was only one-tenth of that after i.v. dosing (151 micrograms min mL-1). In contrast, the AUC after rectal administration (unrestricted, 133 micrograms min mL-1; restricted, 142 micrograms min mL-1) was almost comparable with that after i.v. administration. From the comparison of these AUC values, the extent of systemic availability of morphine after rectal (unrestricted or restricted) and p.o. administration was estimated to be approximately 90 and 10%, respectively.

Administration, Oral↗