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Biomedical subjects

T Itakura

Publications and source records attributed to T Itakura.

At least 19 recordsLinked to original sources

Indirect carotid cavernous fistula appeared after balloon embolization of direct CCF.

The authors describe a case of indirect carotid cavernous fistula (CCF) appearing five months after embolization for traumatic direct CCF, which was treated six months after the trauma. Long-term (six months) venous hypertension to the affected cavernous sinus due to direct CCF and cavernous sinus thrombosis following a balloon embolization were considered as an etiology of the de novo dural arteriovenous fistula. The recurrent symptoms of CCF are usually related to detached balloon disorder, but delayed recurrence may be caused by the de novo dural AVF, if the direct CCF was treated in the chronic state.

Arteriovenous Fistula↗

Generation of dopaminergic neurons in the adult brain from mesencephalic precursor cells labeled with a nestin-GFP transgene.

Mesencephalic precursor cells may one day provide dopaminergic neurons for the treatment of Parkinson's disease. However, the generation of dopaminergic neurons from mesencephalic precursors has been difficult to follow, partly because an appropriate means for recognizing mesencephalic ventricular zone precursors has not been available. To visualize and isolate mesencephalic precursor cells from a mixed population, we used transgenic mice and rats carrying green fluorescent protein (GFP) cDNA under the control of the nestin enhancer. nestin-driven GFP was detected in the mesencephalic ventricular zone, and it colocalized with specific markers for neural precursor cells. In addition, data from flow-cytometry indicated that Prominin/CD133, a cell-surface marker for ventricular zone cells, was expressed specifically in these GFP-positive (GFP(+)) cells. After sorting by fluorescence-activated cell sorting, the GFP(+) cells proliferated in vitro and expressed precursor cell markers but not neuronal markers. Using clonogenic sphere formation assays, we showed that this sorted population was enriched in multipotent precursor cells that could differentiate into both neurons and glia. Importantly, many neurons generated from nestin-GFP-sorted mesencephalic precursors developed a dopaminergic phenotype in vitro. Finally, nestin-GFP(+) cells were transplanted into the striatum of a rat model of Parkinson's disease. Bromodeoxyuridine-tyrosine hydroxylase double-labeling revealed that the transplanted cells generated new dopaminergic neurons within the host striatum. The implanted cells were able to restore dopaminergic function in the host striatum, as assessed by a behavioral measure: recovery from amphetamine-induced rotation. Together, these findings indicate that precursor cells harvested from the embryonic ventral mesencephalon can generate dopaminergic neurons able to restore function to the chemically denervated adult striatum.

AC133 Antigen↗

Visualization, direct isolation, and transplantation of midbrain dopaminergic neurons.

To visualize and isolate live dopamine (DA)-producing neurons in the embryonic ventral mesencephalon, we generated transgenic mice expressing green fluorescent protein (GFP) under the control of the rat tyrosine hydroxylase gene promoter. In the transgenic mice, GFP expression was observed in the developing DA neurons containing tyrosine hydroxylase. The outgrowth and cue-dependent guidance of GFP-labeled axons was monitored in vitro with brain culture systems. To isolate DA neurons expressing GFP from brain tissue, cells with GFP fluorescence were sorted by fluorescence-activated cell sorting. More than 60% of the sorted GFP(+) cells were positive for tyrosine hydroxylase, confirming that the population had been successfully enriched with DA neurons. The sorted GFP(+) cells were transplanted into a rat model of Parkinson's disease. Some of these cells survived and innervated the host striatum, resulting in a recovery from Parkinsonian behavioral defects. This strategy for isolating an enriched population of DA neurons should be useful for cellular and molecular studies of these neurons and for clinical applications in the treatment of Parkinson's disease.

Animals↗

Combined surgery and endovascular stenting for basilar artery stenosis refractory to balloon angioplasty: technical case report.

The authors report a case of symptomatic basilar artery stenosis treated by stenting via the surgically exposed C1 vertebral artery. This case was initially treated by percutaneous transluminal angioplasty via a transfemoral route but resulted in unsatisfactory dilatation. Stenting via a transfemoral route also resulted in failure because of the coiling of the proximal vertebral artery. Direct puncture of the vertebral artery beyond the coiling portion was tried but a stent could not be delivered beyond the C2 vertebrae. Finally, the vertebral artery was surgically exposed between C1 and the occipital bone and a stent was introduced into the lesion from this portion under fluoroscopic control. The basilar artery was fully opened by stenting without new neurological deficits. Stenting of the basilar artery via a transfemoral route is not always possible even with newer generation stents if the vertebral artery has elongated tortuous curves. Combined surgery and endovascular stenting is one of the alternatives in such cases including our case.

Aged↗

Gamma knife radiosurgery for neuroepithelial tumors: radiological and histological changes.

Gamma knife radiosurgery (RS) has been introduced as a modern therapy for brain tumors. However, the effects of RS for neuroepithelial tumors are still obscure. The present study investigates the radiological and histological changes after RS to elucidate the biological effect. There were seven cases (two males and five females), ranging from 4 to 71 years with a mean age of 33 years. Two cases were located in the brainstem, another two in the cerebellum, and one each in the thalamus, the hypothalamus, and the frontal lobe. Histologically, two cases had gangliogliomas, four astrocytomas (1 pilocytic, 1 fibrillary, 2 anaplastic), and one glioblastoma. RS was performed after surgery with a central dose of 30-36 Gy. All cases were evaluated radiologically on MRI before and after RS. Four cases (3 astrocytomas and 1 glioblastoma) which neurologically deteriorated after RS were reoperated. These cases were examined using HE and immunohistochemical studies with antibodies of CD34, alpha-smooth muscle actin (SMA), p53, p21 and MIB-1 on the sections before and after RS. MRI demonstrated perifocal edema and intratumoral hypointensity on T2 weighted imaging (T2WI), suggesting radionecrosis in most of the cases within 6 months after RS. In the central part of the RS, destructive changes were observed in the tumor cells and endothelial cells: decrease in the tumor cell population, coagulation necrosis, and fibrinoid degeneration of vascular walls were revealed. In the peripheral part, however, some tumors contained viable tumor cells intermingled with blood vessels showing endothelial and pericytic proliferations. The increase of MIB-1 staining index was found in only one case. The p21 immunoreactivity was increased in endothelial cells, although the p53 immunoreactivity was unchanged. These results suggested that radionecrosis occurred earlier and more frequently in neuroepithelial tumors after RS than after conventional radiation.

Adolescent↗

Jargonagraphia with severe aphasia due to a right hemisphere lesion: case report.

The authors report a case of a patient who developed jargonagraphia, severe aphasia, unilateral spatial neglect and apraxia due to a right hemisphere lesion. Jargonagraphia with severe aphasia, unilateral spatial neglect and apraxia is quite rare. The mechanisms of jargonagraphia remain unknown. A possible mechanism underlying this case of jargonagraphia is discussed.

Agraphia↗

Unilateral spatial neglect associated with chronic subdural haematoma: a case report.

A 69-year-old right-handed man who exhibited unilateral spatial neglect in association with a chronic subdural haematoma, presented with mild left arm and leg weakness first noted 4 weeks prior to admission. Neurologic examination on admission revealed a mild left hemiparesis, including the face. Neuropsychologic examination revealed left unilateral spatial neglect, but no language disturbance. Minimal support was necessary to maintain activities of daily living. Computed tomography revealed a large right temporoparietal, extraaxial hypodense fluid collection containing scattered hypodense foci. The haematoma was evacuated via a right parietal burr hole. Following surgery, the patient dramatically improved neurologically and neuropsychologically, as well as in independent performance of daily activities. It is suggested that the improvement in ADL provides a behavioural correlate of improvement in the latter, represented a behavioural correlate of improved cerebral function, and that either direct compression by the chronic subdural haematoma or an interhemispheric pressure difference had caused unilateral spatial neglect. Such neglect is an unusual consequence of chronic subdural haematoma.

Activities of Daily Living↗

Factor analysis of the components of 12 standard test batteries, for unilateral spatial neglect, reveals that they contain a number of discrete and important clinical variables.

The aim of this study was to investigate a conventional battery of tests capable of assessing the presence of the component and extent of the lesions in patients with unilateral spatial neglect. Ninety-four patients who had unilateral spatial neglect with a stroke in right hemisphere were assessed on 12 traditional neglect batteries 4 weeks after the onset. Computerized tomography was also performed to investigate the possible anatomical relationships with each neglect battery. Factor analysis showed that the tests loaded significantly on five factors. There are not only visual scanning factors but also factors of imaging, visual judgement, visual cognition and effectiveness from left hemisphere in the unilateral spatial neglect. There are high correlations between each neuropsychological test and neglect batteries. Furthermore, lesions in the paraventricular white matter were associated with clock and person drawing tasks. Lesions in the occipital lobe were associated with reading, explaining and visual counting tasks. Lesions in the temporal lobe and the posterior limb of the internal capsule were associated with line bisection tasks. It is suggested that it is possible that there are some different components in unilateral spatial neglect. Failure in some tasks may predict different lesions in terms which include localization.

Adolescent↗

Expression of c-fos, heat shock protein 70, neurotrophins, and cyclooxygenase-2 mRNA in response to focal cerebral ischemia/reperfusion in rats and their modification by magnesium sulfate.

The marginal area surrounding a region of ischemic brain tissue, designated as the penumbra, is of interest as a potential area for the rescue of neurons from cell death. Despite its clinical importance, relatively little is known about the molecular events leading to changes in brain cells in the penumbra following ischemia. In the first part of this study, we used in situ hybridization to investigate the temporal and spatial expression of c-fos, heat shock protein 70 (HSP70), neurotrophins and inducible cyclooxygenase-2 (COX-2) in the rat brain following a 2-h occlusion of the middle cerebral artery (MCA) with reperfusion. In the penumbra and surrounding cortex, upregulation of c-fos, brain-derived neurotrophic factor (BDNF), and COX-2 mRNAs was observed, while expression of HSP70 mRNA was restricted to the penumbra. This spatial discrepancy of mRNA expression suggests that different mechanisms are involved in the regulation of c-fos/BDNF/COX-2 and HSP70 expression. Intravenous infusion of magnesium sulfate (25 mg/kg) decreased both the infarct volume and upregulation of these mRNAs, suggesting its therapeutic potential.

Animals↗

Enhancement of the response to levodopa therapy after intrastriatal transplantation of autologous sympathetic neurons in patients with Parkinson disease.

OBJECT: There is growing evidence to indicate that tissue transplantation can potentially be a restorative neurosurgical treatment for patients with Parkinson disease (PD). In this study the authors investigated the clinical effect of unilateral intrastriatal grafting of autologous sympathetic neurons in patients with PD. METHODS: Four patients with PD who had been observed for 1 year after graft placement of autologous sympathetic neurons were selected for an analysis of the effect of that procedure. Sympathetic ganglion tissue was endoscopically excised from the thoracic sympathetic trunk and grafted into the unilateral caudate head and putamen of the PD patients. No changes were made in the patients' preoperative regimens of antiparkinsonian medications, and clinical evaluations were made principally according to those established by the Core Assessment Program for Intracerebral Transplantation Committee. Whereas the sympathetic neuron grafts failed to affect clinical scores reflecting the patients' motor performance, which was evaluated during either the "on" or "off' phases, the grafts significantly increased the duration of the levodopa-induced on period with consequent reduction in the percentage of time spent in the off phase. This beneficial effect may be explained by the results of the present in vitro experiment, which show that human sympathetic neurons have the ability to convert exogenous levodopa to dopamine and to store this synthesized dopamine. CONCLUSIONS: Sympathetic neuron autografts were found to improve performance status in patients with PD by reducing the time spent in the off phase. This clearly indicates that sympathetic ganglion tissue, the use of which involves few ethical issues, can be an efficacious donor source in cell transplantation therapy for PD. Further studies are needed to determine whether the grafts may provide long-lasting clinical benefits.

Antiparkinson Agents↗

Dephosphorylation-induced decrease of anti-apoptotic function of Bcl-2 in neuronally differentiated P19 cells following ischemic insults.

It is known that Bcl-2 has a protective effect against neuronal ischemia. Some reports speculate anti-apoptotic function of Bcl-2 depends not on the expression level but on the phosphorylation state. We found induction of apoptosis and CPP32 activation by energy impairment (3-nitropropionic acid (3-NP)-treatment or glucose-deprivation) in the neuronally differentiated P19 cells. Time course study of cell viability following ischemic insults showed that the number of viable cells decreased along with the increase in the amount of dephosphorylated Bcl-2 without obvious quantitative alteration of the protein. Then, we generated differentiated P19 cells overexpressing wild-type Bcl-2 (P19/wt. Bcl-2) or phosphorylation-negative Bcl-2 mutant (P19/mut.Bcl-2), in which alanine was substituted for serine 70. When the cell viability was examined within 24 h, P19/mut.Bcl-2 was more vulnerable to energy impairment as compared with P19/wt.Bcl-2. In addition, overexpression of wild-type Bcl-2 inhibited DNA laddering and CPP32 activation induced by the insults, while that of mutant Bcl-2 did not. These findings suggest that the phosphorylation state, as well as the expression level, of Bcl-2 plays an important role to modulate its protective effect against ischemic insults.

Animals↗

Human amniotic epithelial cells produce dopamine and survive after implantation into the striatum of a rat model of Parkinson's disease: a potential source of donor for transplantation therapy.

We have recently found that human amniotic epithelial (HAE) cells synthesize catecholamines including dopamine (DA). The present study was designed to explore the possibility of HAE cells to serve as a donor for transplantation therapy of Parkinson's disease (PD). Thus, we investigated their ability to produce DA in vitro and the survival and function of HAE cells grafted into a rat model of PD. RT-PCR and Western blotting revealed that HAE cells express tyrosine hydroxylase (TH) mRNA and protein, respectively. TH-immunohistochemistry on cultured HAE cells demonstrated that around 10% of the total cells are immunopositive for this protein. The production of DA by HAE cells was increased with time in the presence of L-tyrosine and BH(4), and was abolished with a specific TH inhibitor, alpha-methyl-rho-tyrosine. Dissociated HAE cells transduced with the Escherichia coli LacZ marker gene (beta-gal) were implanted into the previously DA-depleted striatum of immunosuppressed rats. Two weeks postgrafting HAE grafts were demonstrated to survive without overgrowth, as evidenced by the presence of beta-gal-positive cells and TH-immunoreactive cells within the grafts. The grafts also provided partial amelioration of apomorphine-induced rotational asymmetry. The results clearly indicate that HAE cells capable of producing DA can survive and function in the brain of a rat model of PD. Although DA replacement therapy of PD could possibly be achieved with implantation of HAE cells, further studies are needed to develop strategies to enhance the ability of HAE cells to produce DA as well as the graft survival.

Amniotic Fluid↗

Treatment of restenosis after percutaneous transluminal angioplasty for internal carotid artery stenosis.

The efficacy of repeated percutaneous transluminal angioplasty (PTA) and carotid endarterectomy (CEA) was examined in patients with restenosis after PTA for carotid stenosis. After percutaneous transluminal angioplasty (PTA) for 63 cases of internal carotid stenoses 13 cases of restenosis appeared. They were treated by PTA or carotid endarterectomy. The treatment was chosen by the patient after explanation of each treatment. We initially treated seven patients by repeat PTA and six by carotid endarterectomy. The degree of stenosis improved from 82% to 30% on average after repeated PTA. However, one patient in the PTA group had restenosis, and carotid endarterectomy was then performed. The other cases also had restenosis and were treated by PTA. The six cases treated by carotid endarterectomy were successfully treated without difficulty. The success rate of PTA was 5/7 (71%) in the restenosis cases. Patients with a greater residual stenosis after initial PTA had significantly more frequent restenosis. Repeat PTA and CEA both appeared effective treatment for restenosis after initial PTA, although PTA had a restenosis rate similar to that of initial PTA.

Aged↗

Haemorrhagic complication following percutaneous transluminal angioplasty for carotid stenosis.

We report 2 cases with haemorrhagic complications following percutaneous transluminal angioplasty (PTA) for carotid stenosis. Computed tomography (CT) scanning of these cases demonstrated diffuse subarachnoid haemorrhage in 1 case, and intracerebral haemorrhage in the other case on the next day after PTA. In the latter case, we measured cerebral blood flow velocity and mean transit time with transcranial doppler (TCD) and dynamic CT scan, which demonstrated remarkable increases in the blood flow velocity and peak height, respectively. From these results, postoperative hyperperfusion was suggested to have caused haemorrhagic complications.

Aged↗

An Eel Cytochrome P450 1A Gene Having No XRE Sequences in Its 5' Upstream Region of 1600 bp.

The gene family cytochrome P450 (CYP) 1A is ubiquitous among animals, and CYP1A1 genes have been identified in teleost and mammals. We isolated another CYP1A gene, which is inducibly expressed by exposure to 3-methylcholanthrene, from the genomic library of the eel (Anguilla japonica). The genomic clone obtained, approximately 17,500 bp in length, contained the structural gene of the CYP1A and a 5' upstream region of about 1600 bp. Sequence analysis of the 5' upstream region and the first and second exons revealed that the initiation codon was in the second exon, as in the CYP1A genes reported for mammals and teleosts. CAAT and TATA boxes were found 51 and 29 bp upstream from the transcriptional start site, respectively. Unlike the CYP1A1 genes of eel and other animals, we found no xenobiotic responsive element (XRE) core sequences in the 5' upstream region studied (1631 bp) or in the first intron, whereas three peculiar regions, each composed of multiple repeats of the trinucleotide TAA, were found between 824 and 1356 bp upstream from the transcriptional start site. Absence of XRE core sequences and presence of the multiple repeats in the 5' upstream region sequenced may suggest that the expression mechanism of the eel CYP1A gene is somewhat different from the mechanisms of other reported CYP1A genes.

Journal Article↗

Fetal tissue transplants in animal models of Huntington's disease: the effects on damaged neuronal circuitry and behavioral deficits.

Accumulating evidence indicates that grafts of embryonic neurons achieve the anatomical and functional reconstruction of damaged neuronal circuitry. The restorative capacity of grafted embryonic neural tissue is most illustrated by studies with striatal tissue transplantation in animals with striatal lesions. Striatal neurons implanted into the lesioned striatum receive some of the major striatal afferents such as the nigrostriatal dopaminergic inputs and the gluatmatergic afferents from the neocortex and thalamus. The grafted neurons also send efferents to the primary striatal targets, including the globus pallidus (GP, the rodent homologue of the external segment of the globus pallidus) and the entopeduncular nucleus (EP, the rodent homologue of the internal segment of the globus pallidus). These anatomical connections provide the reversal of the lesion-induced alterations in neuronal activities of primary and secondary striatal targets. Furthermore, intrastriatal striatal grafts improve motor and cognitive deficits seen in animals with striatal lesions. Since the grafts affect motor and cognitive behaviors that are critically dependent on the integrity of neuronal circuits of the basal ganglia, the graft-mediated recovery in these behavioral deficits is most likely attributable to the functional reconstruction of the damaged neuronal circuits. The fact that the extent of the behavioral recovery is positively correlated to the amount of grafted neurons surviving in the striatum encourages this view. Based on the animal studies, embryonic striatal tissue grafting could be a viable strategy to alleviate motor and cognitive disorders seen in patients with Huntington's disease where massive degeneration of striatal neurons occurs.

Animals↗

Fetal striatal transplants reinstate the electrophysiological response of pallidal neurons to systemic apomorphine challenge in rats with excitotoxic striatal lesions.

Previous studies with single-unit recording and 2-[14C]deoxyglucose quantitative autoradiography have shown that systemic administration of apomorphine increases the functional activity of pallidal neurons, and that the enhancement in the globus pallidus (GP) activity is abolished by striatal lesions. The present study employing electrophysiological techniques tested whether embryonic striatal tissue implanted in the excitotoxically damaged striatum of rats may affect the lesion-induced alteration in the neuronal response of GP to apomorphine. Systemically administered apomorphine significantly increased spontaneously firing rates of GP cells. The blockade of dopamine receptors with haloperidol reversed the increased rate to baseline levels. Quinolinate-induced striatal lesions attenuated the rate-increasing effect of apomorphine. Embryonic striatal grafts placed in the lesioned striatum restored the response of GP cells to systemic apomorphine. The graft-mediated restoration of the GP neuron response to apomorphine were accompanied by an improvement in the motor asymmetry induced by this drug. Considering previous anatomical data to demonstrate extensive innervation of the GP by embryonic striatal grafts, the present results suggest that the grafts reconstruct the functional striatopallidal pathway which is capable of transmitting apomorphine-induced changes in the neuronal activity.

Action Potentials↗