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Biomedical subjects

T Itakura

Publications and source records attributed to T Itakura.

At least 37 records · Page 2Linked to original sources
PubMed2001

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Apraxia and cerebral haemorrhage: the relationship between haematoma volume and prognosis.

In this study, we examined twenty-five patients with left putaminal haemorrhage to investigate the relations between ideational apraxia (IA) and intracerebral haemorrhage. Apraxias were determined at 1 and 6 months after the stroke onset. Extension and volume of haematoma were examined with CT scan within 2 days of stroke onset. IA was present in 10 cases at 1 month and disappeared in 6 cases (transient IA) and persisted in 4 cases(persisted IA) at 6 months from the onset. Although the haematoma volume related to the existence of IA, there was no significant difference between transient and persistent IA. All three patients with the haematoma volume larger than 40 ml in the transient IA group were younger than 50 years old. All cases with persistent IA were older than 50 years old. Consequently, the existence of IA seems to be partially dependent on the haematoma volume which may cause the organic damage of subcortical white matter. However, patient's age is also important to determine the prognosis of IA. This maybe related to the nature of the haemorrhage and the mode of the onset. These factors remain to be determined.

Adult↗
PubMed2000

Interhemispheric neuroepithelial cyst associated with agenesis of the corpus callosum. A case report and review of the literature.

This report describes a neonatal case in whom a large interhemispheric cyst associated with agenesis of the corpus callosum was revealed by fetal ultrasonography and demonstrated by MRI to be multilobulated. Endoscopic fenestration of cysts was initially designed in view of the development of the patient's brain and surgical invasiveness. One year later, when motor paresis of the left arm and progressive enlargement of the cyst on MRI were revealed, open surgery was performed. The histological diagnosis was a neuroepithelial cyst with the feature of choroid plexus epithelia. The clinicopathological features of interhemispheric epithelial cysts associated with agenesis of the corpus callosum are reviewed in the light of differential diagnosis and therapeutic considerations.

Agenesis of Corpus Callosum↗
PubMed2000

Promotion of survival and regeneration of nigral dopamine neurons in a rat model of Parkinson's disease after implantation of embryonal carcinoma-derived neurons genetically engineered to produce glial cell line-derived neurotrophic factor.

OBJECT: The P19 embryonal carcinoma-derived cell line consists of undifferentiated multipotential cells, which irreversibly differentiate into mature neurons after exposure to retinoic acid (RA). In the present study, the authors genetically engineered P19 cells to produce glial cell line-derived neurotrophic factor (GDNF), and grafted the cells in a rat model that had been rendered parkinsonian. METHODS: Undifferentiated P19 cells were grown in vitro and transduced with GDNF complementary DNA. The level of GDNF released from the transduced cells was measured using an enzyme-linked immunosorbent assay, and its neurotrophic activities were assessed by testing the effects on rat embryonic dopamine (DA) neurons in culture. After having been exposed to RA for 48 hours and allowed to differentiate into postmitotic neurons, the GDNF gene-transduced cells were implanted into the midbrain of immunosuppressed rats. A unilateral nigrostriatal lesion was then induced by intrastriatal infusions of 6-hydroxydopamine. Immunohistochemical analyses performed 4 weeks postgrafting revealed that the GDNF-producing cells expressed several neuronal markers without evidence of overgrowth. The grafts expressed GDNF protein and prevented the death of nigral DA neurons. Furthermore, the GDNF-producing cells implanted 4 weeks after nigrostriatal lesions restored the expression of tyrosine hydroxylase in injured DA neurons and induced their dendritic sprouting. CONCLUSIONS: The results indicate that the P19 cell line transduced with the GDNF gene can stably secrete functional levels of GDNF, even after being converted to postmitotic neurons. Because it is has been established that GDNF exerts trophic effects on DA neurons, the means currently used to deliver GDNF into the brain could be a viable strategy to prevent the death of nigral DA neurons in cases of Parkinson's disease.

Analysis of Variance↗
PubMed2000

[Agenesis of the right internal carotid artery associated with complicated anastomosis of middle cerebral artery: a case report].

A 57-year-old female was admitted to our hospital because of headache, nausea, and vomiting. Head CT scan demonstrated subarachnoid hemorrhage. Cerebral angiography showed the absence of the right internal carotid artery, and skull base CT of the bone window level revealed the absence of the right carotid canal. The right middle cerebral artery (MCA) and anterior cerebral artery (ACA) were opacified from the left internal carotid artery. The right A1 portion was hypoplastic and the distal portion of the right M1 portion was replaced by several minute complicated anastomotic vessels connected to the right M2 portion. The right MCA territory was mainly supplied by collateral flow from the right ACA and the right posterior cerebral artery via the leptomeningeal anastomosis. These was neither aneurysm nor arteriovenous malformation. The second angiography, 1 week after the initial angiography, showed the same hemodynamic pattern and aneurysms were not found. We diagnosed the patient as agenesis of the right internal carotid artery and the etiology of subarachnoid hemorrhage was suspected to be a rupture of the anastomotic vessels between the right M1 and M2. She was discharged on the 21st hospital day without any neurological deficit.

Carotid Artery, Internal↗
PubMed2000

[Cell transplantation therapy for Parkinson's disease].

We found that Parkinson's disease(PD) patients receiving autotransplants of the cervical sympathetic ganglia show a significant improvement in the parkinsonian symptoms with a consequent reduction in the daily intake of levodopa. The grafting procedure have recently been modified to further enhance the efficacy of the transplantation. Thus, in order to increase the amount of donor tissue we opted for the endoscopically excised thoracic sympathetic ganglia as a donor. With the aid of CT-guided stereotaxic surgery, we unilaterally placed one transplant deposit in the caudate head and three deposits in the putamen. Four patients that had received the grafts were followed with antiparkinsonian medication being unchanged at least one year postgrafting. Although no patients exhibited a substantial improvement in motor performance rated in either "on" or "off" phase, the awake time spent in "off" phase was reduced by 30-40% in all the patients. In two patients, dyskinesia in "on" phase was also attenuated. Our new transplantation paradigm is encouraging and deserves further investigation.

Cell Transplantation↗
PubMed1999

Induction of Two Forms of Eel Cytochrome P450 1A Genes by 3-Methylcholanthrene.

: In eel (Anguilla japonica), exposure to polyaromatic hydrocarbons such as 3-methylcholanthrene leads to induction of two CYP1A enzymes, CYP1A1 and CYP1A6. We studied the time course and tissue specificity of induction of messenger RNAs for CYP1A1 and CYP1A6 in eel by administering 3-methylcholanthrene intraperitoneally. In both cases, the drug induced a rapid increase of mRNAs and biphasic expression. In the liver, mRNA levels of CYP1A1 and CYP1A6 increased 22-fold at 3 hours and 27-fold at 6 hours after the administration, respectively, showing initial peaks in the induction. After the initial inductions, mRNA levels decreased unexpectedly. Following these temporary decreases, the mRNA levels again increased and reached levels that were 35 and 41 times the basal levels at 24 hours after administration, respectively. CYP1A1 and CYP1A6 resembled each other also in the tissue specificity of gene expression; the expression levels were liver >> gill > intestine > kidney. The rapid induction, the biphasic expression, and the tissue-specific expression were common features of gene expression in CYP1A1 and CYP1A6 and may come from common structures of the regulatory regions of the two genes.

Journal Article↗
PubMed1999

Cloning and Sequencing of Cytochrome P450 1A Complementary DNA in Eel (Anguilla japonica).

: Cytochrome P450 1A (CYP1A) complementary DNA was isolated from eel (Anguilla japonica) liver treated with 3-methylcholanthrene. The cDNA contained a 5' untranslated region of 163 bp, an open reading flame of 1560 bp coding for 519 amino acids and a stop codon, and a 3' untranslated region of 1730 bp. The predicted molecular weight was approximately 58.4 kDa. The deduced amino acid sequence exhibited identities with reported CYP1A sequences of 80% for rainbow trout, 79% for scup, 76% for plaice and butterfly fish, and 74% for toadfish. When compared with mammalian CYP proteins, the eel CYP1A was more similar to CYP1A1 (54%-56%) than to CYP1A2 (49%-52%). Northern and Southern blot analyses showed two distinct bands, suggesting the existence of another 3-methylcholanthrene-inducible CYP1A gene in eel.

Journal Article↗
PubMed1999

Functional Analysis of Promoter Region from Eel Cytochrome P450 1A1 Gene in Transgenic Medaka.

: Transcription of the CYP1A1 genes in mammals and fish is stimulated by polyaromatic hydrocarbons. DNA sequencing analysis revealed that CYP1A1 gene in eel (Anguilla japonica) contains two kinds of putative cis-acting regulatory elements, XRE (xenobiotic-responsive element) and ERE (estrogen-responsive element). XRE is known as the enhancer that is responsible for the inducibility of the genes of CYP1A1 and some other drug-metabolizing enzymes. In the eel CYP1A1 gene, XRE motifs are distributed as follows: five times in the region from -2136 to -1125 bp, XRE(-6) to (-2); once in the proximal basal promoter region, XRE(-1); and once in the first intron, XRE(+1). The region between XRE(-2) and XRE(-1) contains three ERE motifs. To investigate the function of the cis-acting regulatory elements in the eel CYP1A1 gene, recombinant plasmids prepared with its 5' upstream sequence and the structural gene for luciferase were microinjected into fertilized eggs of medaka at the one-cell stage. Hatched fry were treated with 3-methylcholanthrene, and the transcription efficiency was assayed using competitive polymerase chain reaction analysis. Deletion of the region containing the five XREs, XRE(-6) to XRE(-2), and the point mutation of XRE(-1) reduced the inducible expressions by 75% and 56%, respectively, showing apparent dependency of the drug induction on the XREs. Constitutive expression, however, was not significantly affected by deletion or disruption of the XREs. When the region between XRE(-2) and XRE(-1) containing no XREs but three ERE motifs was internally deleted, the inducible expression and the constitutive expression were reduced by 88% and 75%, respectively. Replacement of this region with a partial fragment of eel CYP1A1 complementary DNA, with slight alteration of the distance between the five XREs and XRE(-1), reduced the inducible expression and the constitutive expression by 91% and 60%, respectively. These results strongly suggest that not only XRE but also other regulatory elements, possibly ERE, play an important role in induced and constitutive expressions of the eel CYP1A1 gene.

Journal Article↗
PubMed1999

Isolation and Sequence Analysis of the Eel Cytochrome P450 1A1 Gene.

: The putative CYP1A1 gene was isolated from a genomic library of eel (Anguilla japonica) chromosomal DNA. Sequence analysis of 8184 bp showed that the clone obtained was the structural gene of CYP1A1, which consisted of seven exons and six introns in a region approximately 5800 bp in length, as well as a 5' upstream region of about 2300 bp. The initiation codon was found not in the first exon, but in the second exon, as was reported for the CYP1A genes of mammals and fish. The GC box, CAAT box, and TATA box were located proximately to the first exon, at 110, 62, and 38 bp upstream of the transcriptional start site, respectively. We found six core sequences of xenobiotic-responsive elements (XREs) in the 5' upstream region, and also one in the first intron. All the XRE core sequences in the 5' upstream region were unique in their localization in the sense strand. The XRE core sequence in the first intron was in the antisense strand.

Journal Article↗