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Biomedical subjects

S Kuroda

Publications and source records attributed to S Kuroda.

At least 253 records · Page 14Linked to original sources

Activator protein-1 binding activities in discrete regions of rat brain after acute and chronic administration of methamphetamine.

The activator protein-1 (AP-1) binding activities increased in three brain regions (striatum, nucleus accumbens, and cingulate cortex) after a single methamphetamine (METH) injection to rats. Pretreatment with SCH 23390, but not (-)-eticlopride, significantly inhibited the enhanced AP-1 binding activities induced by acute METH administration. The magnitude of enhancement of AP-1 binding activities 3 h after the last dose of chronic METH administration (4 mg/kg once daily for 14 days) was significantly attenuated as compared with those 3 h after a single METH administration. The AP-1 binding activities after a 1-, but not 4-, week abstinence from chronic administration of METH were still significantly higher than those of the saline-treated controls. A METH challenge after a 4-week abstinence period induced significantly lower AP-1 binding activities in rats chronically injected with METH than in rats chronically injected with saline. The supershift assay revealed that the levels of Jun family protein, but not Fos-related antigen, increased significantly in the striatum and nucleus accumbens of chronically METH-treated rats after a 1-week abstinence. These results suggest that chronic METH administration leads to delayed decay of the induced AP-1 binding activities and Jun component levels after abstinence for up to 1 week but results in no change in or decreases these activities and attenuates METH challenge-induced AP-1 binding activities after abstinence for 4 weeks.

Animals↗

Effect of chronic ipsapirone treatment on the density of 5-HT1A receptors and 5-HT1A receptor mRNA in discrete regions of the rat brain.

There is increasing evidence that the 5-hydroxytryptamine (HT)1A partial agonist ipsapirone is an effective anxiolytic/antidepressant agent, although its mechanism of action is not clear. In this study, we investigated the effects of chronic ipsapirone treatment (5 or 10 mg/kg; twice daily, 3 weeks) on 5-HT1A receptor density 8-hydroxy-2-(di-n-propyl amino) tetralin (8O H-DPAT) binding and the level of its mRNA (in situ hybridization) in various regions of the rat (male Wistar 250 g) brain. Receptor density was reduced in the frontal cortex, but did not change significantly in the hippocampus and dorsal raphe nucleus. The level of receptor mRNA was unchanged in each of these brain regions. The present results suggest that the clinical anxiolytic effects of ipsapirone may be mediated partly by postsynaptic action on serotonergic transmission in the frontal cortex, but not in the hippocampus or dorsal raphe nuclei.

Animals↗

Dissociation of vasoreactivity to acetazolamide and hypercapnia. Comparative study in patients with chronic occlusive major cerebral artery disease.

BACKGROUND AND PURPOSE: The aim of this study was to compare the effect of vasodilative stimuli for the measurement of cerebrovascular reactivity obtained by acetazolamide and hypercapnia in patients with chronic occlusive major cerebral artery disease. METHODS: We examined 24 patients with unilateral occlusive lesions of a major cerebral artery using the 133Xe inhalation technique and single-photon emission CT. Regional cerebral blood flow (CBF) was measured during a resting state, during inhalation of 5% CO2, and 15 minutes after the administration of acetazolamide consecutively in the same patients. Normative values of resting CBF and acetazolamide reactivity were obtained in 21 normal subjects. RESULTS: All patients with the exception of 1 showed an increase in CBF during hypercapnia ipsilateral to the occlusive lesion. Ipsilateral acetazolamide reactivity was preserved in 13 patients. Conversely, 11 patients showed an absent response or paradoxical CBF reduction. Ipsilateral CO2 reactivity did not correlate with acetazolamide reactivity when all 24 patients were considered. However, there was a significant correlation between acetazolamide and CO2 in the 13 patients who showed preserved acetazolamide reactivity (r = .60, P < .05). No significant correlation was present in the remaining 11 patients with reduced acetazolamide reactivity. Although significant blood pressure augmentation was observed in hypercapnia, we could not find a correlation between change of blood pressure and CO2 reactivity. CONCLUSIONS: Acetazolamide identified patients with reduced vasomotor reactivity who appeared to have preserved CO2 reactivity. Acetazolamide testing may be useful in the assessment of cerebral hemodynamics. However, further investigations are necessary to assess the clinical utility of these tests.

Acetazolamide↗

Surgical therapy for adult moyamoya disease. Can surgical revascularization prevent the recurrence of intracerebral hemorrhage?

BACKGROUND AND PURPOSE: It is well recognized that revascularization surgery using direct and/or indirect bypass provides effective surgical management for pediatric moyamoya disease. However, surgical treatment of the adult hemorrhagic type remains controversial. In this study, the effect of surgery for adult moyamoya disease was investigated. METHODS: We analyzed 35 patients with adult moyamoya disease (patient age, over 20 years), 24 patients with initial onset of intracerebral hemorrhage, and 11 patients with initial onset of cerebral ischemia who underwent both direct bypass surgery of the superficial temporal artery to the middle cerebral artery anastomosis and indirect revascularization of encephalo-duro-arteriomyo-synangiosis. RESULTS: Of 24 patients with hemorrhagic-type disease, 3 showed rebleeding: of 11 patients with the ischemic type, 2 showed intracerebral hemorrhage after surgery. Overall, 5 of 35 patients (14.3%) had hemorrhage after revascularization surgery (mean follow-up period, 6.4 years). Postoperative angiography revealed that direct anastomosis is effective whereas indirect revascularization is not always effective for adult moyamoya disease. Moyamoya vessels, which are supposed to be responsible for hemorrhage, decreased in 25% of patients. CONCLUSIONS: Revascularization surgery cannot always prevent rebleeding. However, a decrease in moyamoya vessels was induced by surgery, which may reduce the risk of hemorrhage more effectively than conservative treatment. In cases of adult moyamoya disease, direct bypass is particularly important, since the indirect revascularization is not as useful in adult cases as in pediatric cases.

Adult↗

Cerebral hemodynamic changes during carotid artery balloon occlusion monitored by near-infrared spectroscopy.

The cerebral oxygenation state of five patients was continuously and non-invasively monitored using near-infrared spectroscopy (NIRS) during carotid artery balloon occlusion for comparison with somatosensory evoked potential (SEP) monitoring and regional cerebral blood flow (rCBF) measurements. In patients with marked reduction of rCBF and deteriorated SEP, NIRS demonstrated a continuous decrease in oxy-hemoglobin and total hemoglobin and an increase in deoxy-hemoglobin, indicating the occurrence of severe hypoxia in the ipsilateral hemisphere because of inadequate collateral circulation. In contrast, NIRS showed only a transient (<2 min) change in these parameters in the patients who showed no remarkable changes in SEP or rCBF, suggesting that well-developed collateral circulation immediately improved cerebral hemodynamics in the ipsilateral hemisphere. These results suggest that NIRS can provide direct and valuable information on cerebral hemodynamic changes during carotid artery balloon occlusion.

Aged↗

Angiographic analysis of moyamoya disease--how does moyamoya disease progress?

Differences in the clinical presentation and angiographic stages of moyamoya disease were studied in 69 patients, 35 children (6.3 +/- 2.9 years old) and 34 adults (44.6 +/- 10.5 years old). The angiographic stage (Suzuki's stage) was compared between childhood and adulthood, ischemic onset and hemorrhagic onset, and female and male. The distribution of the angiographic stage was not very different, but was significantly shifted from stage III to stage IV in adult cases. The angiographic stage in patients with hemorrhagic onset was not significantly different from those with ischemic onset. There was no significant difference between females and males. Angiographic change is not very remarkable between pediatric and adult moyamoya disease. The angiographic stage does not directly correlate with the distinct clinical presentations between pediatric and adult moyamoya disease. Other factors such as cerebral blood flow demand and arteriosclerotic change seem to cause these differences.

Adolescent↗

Ruptured aneurysm of the middle meningeal artery associated with occlusion of the posterior cerebral artery. Case report.

The authors describe the case of a 69-year-old man with an intracerebral hemorrhage due to rupture of a nontraumatic aneurysm of the middle meningeal artery (MMA). The ipsilateral posterior cerebral artery (PCA) was occluded, and dural anastomoses developed as the main collateral pathway between the MMA and the cortical branch of the PCA, on which the aneurysm was located. It is considered that increased hemodynamic stress to the collateral pathway contributed to the formation of the aneurysm.

Aged↗

[Long-term surgical effects of trabeculotomy combined with sinusotomy].

We retrospectively analyzed long-term effects of trabeculotomy combined with sinusotomy. We reviewed 29 eyes with primary open angle glaucoma and 6 eyes with psuedexfoliation glaucoma. The preoperative intraocular pressure was equal to or over 21 mmHg. All cases had been subjected to initial trabeculotomy combined with sinusotomy. The had been followed up for at least 3 years after surgery. The mean age was 57.8 years and the mean follow-up period was 40.5 months. The preoperative intraocular pressure was 24.3 +/- 5.9 mmHg (Mean +/- standard deviation) and the postoperative intraocular pressure was 15.8 +/- 3.8 mmHg. There was statistically significant difference between preoperative and postoperative intraocular pressure. The Kaplan-Meier life table method indicated a success rate at 50 months after surgery of 0.63 +/- 0.15, as defined by intraocular pressure of 20 mmHg or lower, and of 0.35 +/- 0.08 as defined by intraocular pressure equal to or lower than 14 mmHg. The success rate of filtering blebs was 0.10 +/- 0.05 at 50 months. Eleven of 35 eyes (37%) were controlled at equal to or below 14 mmHg and 20 of 35 (67%) eyes were controlled at equal to or lower than 16 mmHg at final postoperative intraocular pressure. The surgical results of trabeculotomy combined with sinusotomy remain effective in controlling intraocular pressure levels for long periods.

Adult↗

[Intraocular pressure decrease after phacoemulsification-aspiration+ intraocular lens implantation in primary open angle glaucoma eyes].

Phacoemulsification-aspiration and intraocular lens implantation (PEA + IOL) were carried out in 40 primary open angle glaucoma (POAG) eyes without history of surgery and 53 control (cataract only) eyes. Postoperative change in intraocular pressure (IOP) was evaluated over a long period (at least 18 months, average follow-up period 34 months). The postoperative IOP was significantly lower than the preoperative level in every group from 6 months to 3 years. An IOP decrease of 1.5 mmHg was maintained for 3 years in the control group. A decrease of 2.5 mmHg was stable for 3 years in the good POAG group in which preoperative IOP was controlled (< or = 20 mmHg) with medication. IOP decrease in the poor POAG group in which preoperative IOP was over 21 mmHg with medication, was 5.5 mmHg, and was maintained for 3 years. Medication did not differ significantly before or after the operation. These results imply that in POAG an IOP decrease can be expected after PEA + IOL.

Aged↗

[Surgical effects of trabeculotomy combined with sinusotomy in advanced glaucoma patients controlled in normal intraocular pressure of 15 mmHg or higher].

Trabeculotomy combined with sinusotomy was performed in 30 eyes with advanced open angle glaucoma, whose intraocular pressure (IOP) had been controlled in their high teens with only topical medications. The mean pre- and postoperative IOP levels were 18.2 +/- 1.2 mmHg (mean +/- standard deviation) and 13.2 +/- 1.2 mmHg and the pressure reduction was 4.6 +/- 2.4 mmHg. Average pressure reduction was 28.8 +/- 9.3% and pressure reduction of 30% or more was obtained in 45% of the treated eyes. The pre- and postoperative medication scores were 4.47 +/- 1.50 and 3.07 +/- 1.17, respectively. There was statistically significant difference between the pre- and postoperative medication score. We had no cases in which the IOP reduction was greater than 9 mmHg and postoperative IOP was 9 mmHg or less. A 3-line drop in visual acuity was seen in only one eye. Twenty two of 30 eyes (73%) were controlled at 14 mmHg or less with medications at the last examination. These results show that trabeculotomy combined with sinusotomy in effective, and this procedure can be considered as an alternative choice for surgical treatment in advanced glaucoma.

Aged↗

A new method to selectively injure the optic nerve using argon-laser photocoagulation.

To create a model by noninvasive means for the study of Wallerian and transneuronal degeneration of the central nervous system, we devised a two-step argon laser photocoagulation (ALP) procedure with which we could selectively injure the optic nerve in rats. Changes in the optic nerve distal to the site of injury were studied histologically to evaluate this method; we succeeded in selectively and completely injuring the optic nerve. We found this ALP technique to be superior to either the panretinal or one-step photocoagulation method. Changes within astrocytes of the intracerebral optic tract and the lateral geniculate body in animals were also studied immunohistochemically following ALP and compared with those which follow enucleation. Reactive astrocytes with enhanced immunoreactivity for glial fibrillary acidic protein (GFAP) increased in number in the intracerebral optic tract and in the lateral geniculate body on the contralateral side of the optic injury in both groups of animals. The increased GFAP immunoreactivity was sustained for 6 weeks following injury; the proliferative tendency of the glial cells, shown by the bromodeoxyuridine method, peaked 3 days after injury and then decreased gradually. These glial responses in the optic tract and lateral geniculate body of animals subjected to ALP are similar to those of animals following enucleation. Our results indicate that this new technique for selectively and noninvasively injuring the optic nerve with ALP is applicable to the study of Wallerian and transneuronal degeneration.

Animals↗

Plasma homovanillic acid levels and therapeutic outcome in schizophrenics: comparisons of neuroleptic-naive first-episode patients and patients with disease exacerbation due to neuroleptic discontinuance.

Plasma homovanillic acid (pHVA) levels were measured and the Brief Psychiatric Rating Scale (BPRS) scores were evaluated in 26 schizophrenic patients who had either never been medicated (neuroleptic-naive, first-episode subjects) or whose condition had become exacerbated following neuroleptic discontinuance (exacerbated subjects). All the subjects received medication with a fixed dose of a neuroleptic (haloperidol or fluphenazine, both 9 mg/day) for the first week and variable doses for the subsequent 4 weeks. In the neuroleptic-naive subjects, pHVA levels increased significantly 1 week after starting the protocol; this increase correlated significantly with clinical improvement of the BPRS positive symptom scores at week 5. In the neuroleptic-naive subjects, pHVA levels had declined to the baseline level by week 5. In the exacerbated subjects, there were no significant correlations between pHVA level changes at week 1 and later improvements of the BPRS positive symptom scores. These results suggest that the rise in pHVA levels occurring within 1 week after starting a fixed neuroleptic dose may predict a favorable clinical response in neuroleptic-naive schizophrenic patients.

Adult↗

Molecular cloning and characterization of a new member of the RAC protein kinase family: association of the pleckstrin homology domain of three types of RAC protein kinase with protein kinase C subspecies and beta gamma subunits of G proteins.

cDNA clones encoding the third member of the RAC protein kinase family, termed RAC-PK gamma, were isolated from a rat brain cDNA library. The deduced amino acid sequence of RAC-PK gamma was highly related to those of previously identified family members, RAC-PK alpha and beta, that have a pleckstrin homology domain and a protein-serine/threonine kinase catalytic domain at the amino- and carboxyl-terminal regions, respectively. Northern blot analysis indicated that RAC-PK gamma was expressed abundantly in brain and testis. Specific activities of RAC-PK alpha, beta, and gamma purified from transfected COS-7 cells were similar when measured by using myelin basic protein as a phosphate acceptor. Analysis using fusion proteins of glutathione S-transferase revealed that the pleckstrin homology domain of the three subtypes of RAC-PK associate with both protein kinase C subspecies and beta gamma subunits of G proteins. These results suggest that the pleckstrin homology domains of RAC protein kinase family could associate more than one protein to regulate the activity and/or intracellular distribution of this enzyme family by different ways.

Amino Acid Sequence↗

The farnesyl group of H-Ras facilitates the activation of a soluble upstream activator of mitogen-activated protein kinase.

To study the function of the farnesyl modification of Ras, the farnesyl group and a variety of its structural analogs, which lack one or more double bonds and/or the methyl groups, were enzymatically incorporated into recombinant H-Ras in vitro. These proteins were used in a cell- and membrane-free, Ras-dependent mitogen-activated protein kinase (MAP kinase) activation system derived from Xenopus laevis eggs to examine the contribution of the farnesyl group toward the activation of the kinase. Whereas non-farnesylated H-Ras is unable to activate MAP kinase, farnesylation of H-Ras alone, in the absence of further processing, is sufficient to cause the activation of MAP kinase in this system. All of the analogs of the farnesyl group, when incorporated into H-Ras, support the activation of the kinase to variable extents. These results suggest a direct but fairly nonspecific interaction of the farnesyl moiety of H-Ras with a soluble upstream activator of MAP kinase.

Animals↗

NBQX, a selective antagonist of the AMPA receptor, affects neither field potentials nor long-term potentiation in vivo.

NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline), a selective antagonist of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptors, at an anticonvulsant dose of 40 mg/kg (i.p.), was shown in vivo to have no effects on either the field potentials in the piriform cortex or those in the dentate gyrus of the hippocampus. The same dose of NBQX also exerted no significant effects on long-term potentiation in the hippocampus. These results suggest that the mechanism underlying the anticonvulsant action of NBQX in vivo does not involve a suppressive action on physiological synaptic transmission. The possible clinical usefulness of AMPA receptor antagonists as antiepileptic drugs is suggested.

Animals↗

Purification of a Ras-dependent mitogen-activated protein kinase kinase kinase from bovine brain cytosol and its identification as a complex of B-Raf and 14-3-3 proteins.

We previously purified a protein factor, named REKS (Ras-dependent Extracellular Signal-regulated Kinase (ERK)/mitogen-activated protein kinase Kinase (MEK) Stimulator), from Xenopus eggs by use of a cell-free assay system in which recombinant GTP gamma S (guanosine 5'-(3-O-thio)triphosphate)-Ki-Ras activates recombinant MEK. By use of this assay system, we purified here bovine REKS to near homogeneity from the cytosol fraction of bovine brain by successive chromatographies of Mono S, Mono Q, GTP gamma S-glutathione S-transferase-Ha-Ras-coupled glutathione-agarose, and Mono Q columns. It was composed of three proteins with masses of about 95, 32, and 30 kDa as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The 95-, 32-, and 30-kDa proteins were identified by immunoblot analysis to be B-Raf protein kinase, 14-3-3 protein, and 14-3-3 protein, respectively. Moreover, the REKS activity was specifically immunoprecipitated by an anti-B-Raf antibody. Bovine REKS was activated by lipid-modified GTP gamma S-Ki-Ras far more effectively than by a lipid-unmodified one. Lipid-modified GDP-Ki-Ras was inactive. Exogenous addition of 14-3-3 proteins stimulated further the REKS activity both in the presence and absence of GTP gamma S-Ki-Ras. These results indicate that at least one of the direct targets of Ras is B-Raf complexed with 14-3-3 proteins in bovine brain.

14-3-3 Proteins↗