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T Ohmoto

Publications and source records attributed to T Ohmoto.

At least 37 records · Page 2Linked to original sources
PubMed2000

Indispensable role of the transcription factor PEBP2/CBF in angiogenic activity of a murine endothelial cell MSS31.

Mice lacking the AML1/PEBP2alphaB/CBFa2 gene or PEBP2beta/CBFb gene exhibit a defect in definitive hematopoiesis and die in utero because of hemorrhage in the central nervous system. Hematopoiesis in the embryo is considered to be tightly associated with vascular development. Here we examined whether PEBP2/CBF plays any role in angiogenesis besides that in definitive hematopoiesis. We found that AML1/PEBP2alphaB/CBFa2, PEBP2alphaA/CBFa1, and PEBP2beta/CBFb were expressed in a murine endothelial cell line MSS31. The expression of these molecules as well as the DNA binding activity of PEBP2/CBF were augmented by angiogenic growth factors such as bFGF and VEGF. Moreover, the expression of PEBP2 alpha/CBFa protein in endothelial cells was confirmed at the site of angiogenesis in vivo. To further clarify the role of PEBP2/CBF in angiogenesis, we established permanent transfectants of PEBP2 beta-MYH11 gene, one that interacts with the runt domain of the alpha subunit and deregulates PEBP2/CBF in a dominant interfering manner. Proliferation, migration, and tube formation of the PEBP2 beta-MYH11 transfectants were significantly reduced in comparison with those activities of the mock transfectants. These results suggest that transcription factor PEBP2/CBF plays an important role in angiogenesis.

Animals↗
PubMed2000

Experimental gene therapy for brain tumors using adenovirus-mediated transfer of cytosine deaminase gene and uracil phosphoribosyltransferase gene with 5-fluorocytosine.

Transduction of the cytosine deaminase (CD) gene into tumor cells followed by administration of 5-fluorocytosine (5-FC), called 5-FC/CD gene therapy, was created as suicide gene therapy for various cancers. The uracil phosphoribosyltransferase (UPRT) gene, which is absent from mammalian cells, directly converts 5-fluorouracil (5-FU) to 5-fluorouridine 5'-monophosphate. We evaluated whether the coexpression of CD and UPRT genes could generate a synergistic antitumor effect on experimental brain tumors. In vitro study showed that 9L cells, transduced with the UPRT gene by an adenovirus, were 16 times more sensitive to 5-FU, and CD + UPRT-transduced cells were 6,000 times more sensitive to 5-FC than parent cells, indicating that the acquisition of CD and UPRT further increased the 5-FC sensitivity of 9L cells compared with cells transduced with CD alone. In a rat brain tumor model, decreased amounts of CD and UPRT vectors were inoculated into the tumors to detect any additional effect of UPRT. CD and UPRT coexpression followed by 5-FC administration showed an antitumor effect as detected by sequential magnetic resonance imaging. This therapy significantly prolonged animal survival. These results suggest that 5-FC/CD + UPRT gene therapy can enhance the antitumor effect of 5-FC/CD gene therapy. Consequently, this approach might be a more feasible modality for the treatment of malignant brain tumors.

Adenoviridae↗
PubMed2000

Proton magnetic resonance spectroscopy reflects cellular proliferative activity in astrocytomas.

We examined whether proton magnetic resonance spectroscopy (MRS) could provide accurate information on histological grade and cell proliferation in astrocytomas. We studied 23 patients with astrocytomas: five grade II, 10 grade III and eight with grade IV (glioblastoma multiforme). We performed proton MRS and determined the Ki-67 labeling index (LI), a tumour proliferation marker, in the same areas of the astrocytomas, and examined the statistical relationship between proton MRS and Ki-67 LI. The N-acetylaspartate (NAA)/creatine-phosphocreatine (Cr) and NAA/choline (Cho)-containing compound ratios were always significantly lower and the Cho/Cr ratios significantly higher than those for normal brain. The Cho/Cr ratio correlated positively and the NAA/Cho ratio inversely with Ki-67 LI. These findings suggest that the Cho signal in proton MRS reflects cellular proliferation. In Kaplan-Meier survival analysis, there was no significant difference between high (> 2.0, 14 cases) and low (< 2.0, 9 cases) Cho/cr ratio groups.

Adolescent↗
PubMed2000

GDNF induces recovery of the nigrostriatal dopaminergic system in the rat brain following intracerebroventricular or intraparenchymal administration.

BACKGROUND: Glial cell line-derived neurotrophic factor (GDNF) has been shown to be a survival and neuroprotective factor for nigrostriatal dopaminergic neurons in vivo. The present study was designed to investigate the possible neuroprotective and restorative role by GDNF for dopaminergic neurons which were exposed to the neurotoxin 6-hydroxydopamine (6-OHDA). METHOD: We compared neurochemical, morphological and behavioural changes following striatal infusion of GDNF to those following intracerebroventricular (i.c.v.) infusion. FINDINGS: Apomorphine-induced rotation showed significant recovery after both types of infusion. Significant recovery of tyrosine hydroxylase (TH)-immunoreactive (IR) neurons and fibers were found in the substantia nigra and striatum following both striatum and i.c.v. infusion except for the number of TH-IR neurons in the i.c.v. infusion group. INTERPRETATION: These results suggest that GDNF induces recovery of the nigrostriatal dopaminergic system, and this indicates a potential usefulness of GDNF for the treatment of Parkinson's disease.

Adrenergic Agents↗
PubMed2000

The effect of intrastriatal single injection of GDNF on the nigrostriatal dopaminergic system in hemiparkinsonian rats: behavioral and histological studies using two different dosages.

Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor-beta superfamily and acts as a neurotrophic factor for the nigrostriatal dopamine (DA) system. Although previous studies have shown that pretreatment with GDNF could prevent degenerative changes of nigrostriatal DA system by DA neurotoxin 6-hydroxydopamine (6-OHDA), it is not really known whether GDNF can induce recovery of nigrostriatal DA system after partial lesioning by 6-OHDA. Substantia nigra has been commonly chosen as injection site for GDNF but a limited number of studies have used striatum as injection site where neural transplantation is commonly performed. Unilateral intrastriatal administration of 6-OHDA was performed in Sprague-Dawley rats to create partial lesion of the nigrostriatal DA system. These hemiparkinsonian model rats received a 10- or 100-microg single injection of human recombinant GDNF into the same portion of the striatum 4 weeks after 6-OHDA treatment. Both animals that received a 10- or 100-microg single injection of GDNF showed decreased apomorphine-induced rotation at 2 weeks after injection. More potent and prolonged functional recovery was observed in animals receiving 100 microg of GDNF than in those receiving 10 microg of GDNF. Tyrosine hydroxylase (TH) immunocytochemistry revealed that TH positive DA fiber density in the striatum and the number of DA cell bodies in the substantia nigra were greater in animals receiving 10 or 100 microg of GDNF than those receiving saline. These immunocytochemical results have also shown that 100 microg of GDNF was more potent than 10 microg of GDNF. These morphological and functional results indicate that GDNF treatment 4 weeks after 6-OHDA lesioning could induce recovery of nigrostriatal DA system. Striatum was a good site for GDNF administration for hemiparkinsonian rats and a single injection of 100 microg of GDNF was more potent than 10 microg of GDNF.

Animals↗
PubMed2000

Intrathecal chemotherapy with MX2 for treating glioma dissemination in vivo.

We examined whether the intrathecal MX2 chemotherapy for treating dissemination of malignant glioma would be a feasible therapy. In the toxicity study, physiological and histological neurotoxicity was not observed in the rats treated with less than 100 microg/kg of MX2 administered intracisternally. But physiological side effects were observed in the treatment group of more than 200 microg/kg and histological brain toxicity was in the treatment group of more than 1000 microg/kg. Dissemination models were induced in rats by intracisternal inoculation of C6 glioma cells. The median survival times of the rats treated with 100 microg/kg of intrathecal MX2 on day 1, 3, or 7 after tumor inoculation were prolonged by 52.4% (p = 0.0006), 31.5% (p = 0.0007), and 7.1% (p = 0.0180), respectively, compared to that of untreated control animals. Intrathecal MX2 treatment also cured 33.6% of rats in the treatment group. These findings suggested that there was a possibility that intrathecal MX2 would be a safe and effective method for treating dissemination of malignant glioma.

Animals↗
PubMed2000

In vivo efficacy and toxicity of 5-fluorocytosine/cytosine deaminase gene therapy for malignant gliomas mediated by adenovirus.

We evaluated the therapeutic efficacy and neurotoxicity of adenovirus-mediated transduction of the cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) for experimental malignant brain tumors. The 5-FC sensitivity in 9 L cells infected by an adenovirus vector expressing CD (AdexCACD) was increased 1700-fold compared with control cells. Rats bearing 9 L brain tumors were treated with an intratumoral injection of AdexCACD followed by intraperitoneal administration of 5-FC. The rats demonstrated remarkable inhibition of tumor growth by magnetic resonance imaging, and 7 of 10 rats survived for >90 days. To evaluate the potential side-effects of the 5-FC/CD gene therapy, rats were treated with an intracerebral injection of AdexCACD into the right basal ganglia and with 5-FC. The magnetic resonance imaging showed a highly enhanced area on the gadollinium-enhanced T1-weighted image at 18 days postinjection. Pathologically, this corresponded to an area of necrosis with surrounding apoptotic cells. In addition, there was demyelination and gliosis with enlargement of the lateral ventricles. These results suggest that the 5-FC/CD gene therapy may provide an anticancer effect for malignant brain tumors in humans, but also show that there are neurotoxic effects on normal brain tissue.

Adenoviridae↗
PubMed2000

Curative treatment of cerebral arteriovenous malformations by embolisation using cellulose acetate polymer followed by surgical resection.

AIM: To investigate the usefulness of embolising cerebral arteriovenous malformations (AVMs) with a cellulose acetate polymer solution before surgical resection. METHODS: The cases of 12 patients with AVMs treated by embolisation before surgical resection were renewed. Two types of cellulose acetate polymer solutions were used to occlude 40 feeding vessels. All patients underwent surgical resection 1-51 days after embolisation. RESULTS: Reduction of the nidus volume after embolisation ranged from 20% to nearly 100%. Transient neurological deficits occurred in three patients, persistent deficits occurred in one and there were no haemorrhagic complications. All but one arteriovenous malformation were completely resected. Embolisation helped to identify feeding vessels and ease dissection. Histopathological examination of resected specimens disclosed mild inflammatory reactions in the acute stage and no unfavourable granulomatous changes in the chronic stage. CONCLUSION: Embolisation with cellulose acetate polymer solutions followed by surgical resection is safe and efficacious for treating cerebral AVMs.

Adult↗
PubMed2000

Single or continuous injection of glial cell line-derived neurotrophic factor in the striatum induces recovery of the nigrostriatal dopaminergic system.

Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor beta superfamily and acts as a neurotrophic factor for the nigrostriatal dopaminergic system. GDNF at a dose of 100 micrograms was injected stereotactically into the striatum of Sprague-Dawley rats that had been treated with intrastriatal 6-hydroxydopamine (6-OHDA) injection four weeks earlier. Immunocytochemical and behavioral analyses showed significant recovery of the nigrostriatal dopaminergic system after a single GDNF injection or continuous GDNF injection. Immunocytochemical and behavioral study showed that there was no significant difference between the results obtained from the two different injection methods. This result demonstrates the potential usefulness of GDNF for the treatment of Parkinson's disease.

Animals↗
PubMed2000

Presence of two trans-o-hydroxybenzylidenepyruvate hydratase-aldolases in naphthalenesulfonate-assimilating Sphingomonas paucimobilis TA-2: comparison of some properties.

Two trans-o-hydroxybenzylidenepyruvate hydratase-aldolases named tHBP HA A and tHBP HA B were purified from a cell-free extract of naphthalenesulfonate-assimilating Sphingomonas paucimobilis (formerly Pseudomonas sp.) TA-2 to an electrophoretically homogeneous state by successive column chromatographies on DEAE-cellulose, DEAE-Toyopearl 650M, Sephacryl S-100, Hydroxyapatite, and Mono Q. These enzymes were similar to each other in molecular mass (ca. 37 kDa on SDS-PAGE, ca. 110 kDa on ultracentrifugation), thermal stability (<50 degrees C) and optimum pH (pH 9.0). However, they differed from each other in N-terminal amino acid sequences, pH stability, K(m) values for trans-o-hydroxybenzylidenepyruvate (tHBP), and inhibition by p-chloromercuribenzoic acid (PCMB). tHBP HA B had a homologous N-terminal amino acid sequence with tHBP HAs from Pseudomonas vesicularis DSM 6383 (strain BN6) and Sphingomonas aromaticivorans F119, and tHBP HA A had a homologous sequence with tHBP HAs of Pseudomonas putida strain OUS82, Pseudomonas sp. strain C18 and NAH7 plasmid. tHBP HA B was inhibited by PCMB, but tHBP HA A was not. Their K(m) values for tHBP were 9 and 3 M, respectively. tHBP HA B was stable in the range of pH 7.1 to pH 10.7, and tHBP HA A was stable in the range of pH 6.0 to 9.3.

Amino Acid Sequence↗
PubMed2000

Effect of external stenting and systemic hypertension on intimal hyperplasia in rat vein grafts.

OBJECTIVE: Overdistention of vein grafts in arterial circulation and systemic hypertension are thought to be influential risk factors contributing to vein graft failures. This study tested the effects of external stenting in preventing systemic hypertension and overdistention of the rat vein graft in the long term. METHODS: Jugular vein grafts were interposed into the carotid artery of normotensive (n = 39) and two-kidney, one-clip hypertensive (n = 30) rats. Jugular vein grafts wrapped with 1.5-mm-diameter polyester stents were used in normotensive (n = 26) and hypertensive (n = 25) rats. The vein grafts were harvested at 1, 2, 4, 8, 12, and 24 weeks after the grafting procedure. The neointimal area and wall thickness were measured by computerized planimetry, and Ki-67 immunohistochemistry was used to detect replicative smooth muscle cells in the graft wall. RESULTS: In each group, intimal hyperplasia was apparent at 1 week and increased gradually to 24 weeks. The number of Ki-67-positive cells was most increased at 2 weeks after the grafting procedure and gradually decreased thereafter. The numbers of Ki-67-positive cells and the extent of intimal hyperplasia were not significantly different between normotensive and hypertensive rats. Both neointima formation and cell proliferation in the graft wall were significantly reduced by external stenting as compared with the results with unstented grafts. CONCLUSION: Systemic hypertension by itself is not a risk factor for intimal hyperplasia and experimental vein graft failure in the long term. External stenting is effective against intimal hyperplasia, and it is possible to reduce the subsequent atherosclerotic change of the vein graft wall and improve the long-term patency of the vein graft with external stenting.

Animals↗
PubMed2000

Intermittent propofol sedation during embolization of cerebral arteriovenous malformations.

Embolization procedure was performed for a 12-year-old boy with a left parietal arteriovenous malformation. Although provocative tests for the feeders to be occluded were considered very informative, the patient had to be sedated during microcatheter insertion. We used intermittent sedation with propofol during the interventional procedure, and obtained successful embolization.

Anesthetics, Intravenous↗
PubMed2000

Spinal atypical teratoid/rhabdoid tumor in an infant.

Atypical teratoid/rhabdoid tumor of the central nervous system in infancy and childhood was established as an entity based on histological, immunohistochemical, and cytogenetic studies. We report the case of a 7-month-old girl who presented with progressive paraplegia and hypesthesia of her legs. Imaging studies revealed a spinal cord mass occupying the entire spinal canal below the T(7) level. Through a T(12)-L(3) laminectomy, the intramedullary tumor was partially debulked. Histologically, the tumor specimen had rhabdoid cells, and immunostaining showed vimentin and cytokeratin positivity. No abnormality of chromosome 22q was detected with the fluorescence in situ hybridization method.

Biomarkers, Tumor↗
PubMed2000

Ascorbic acid stimulation of production of a highly branched ,beta-1,3-glucan by Aureobasidium pullulans K-1--oxalic acid, a metabolite of ascorbic acid as the stimulating substance.

The production of a highly branched beta-1,3-glucan by Aureobasidium pullulans K-1 in Czapek's medium has been found to be stimulated by ascorbic acid. When the culture supernatant, after removal of polysaccharide from the culture filtrate by ethanol precipitation, was concentrated, then added to a new medium and this strain was cultured in the medium, the polysaccharide production was stimulated the same as when L-ascorbic acid was added to the medium. The stimulating substance was partially purified from the supernatant, and was found to be oxalic acid; 0.03% oxalic acid was the most effective concentration for the stimulation of polysaccharide production. The stimulating substance, oxalic acid, was proved to be derived from ascorbic acid added to a medium in an experiment using L-[1-14C]ascorbic acid. We suggest that oxalic acid generated from the metabolism of ascorbic acid in cells of Aureobasidium pullulans K-1 participated in the stimulation of the polysaccharide production by ascorbic acid.

Ascorbic Acid↗
PubMed2000

Combined use of cellulose acetate polymer and retrievable platinum coils for the thrombosis of cervical carotid aneurysms.

Cellulose acetate polymer (CAP) solution is a new liquid embolic material, and it has been used clinically for the thrombosis of cerebral aneurysms. The purpose of the study was to test a method of aneurysm treatment. In an experimental model, retrievable interlocking detachable coils (IDCs) were used to create an intraaneurysmal frame or prop and then CAP was injected into 20 experimentally induced canine cervical aneurysms. Intraaneurysmal thrombosis was induced 1 week after aneurysm creation. Complete thrombosis was attempted in 12 aneurysms, and partial thrombosis was attempted in 4. Four other aneurysms served as controls. Follow-up angiography was performed for up to 8 weeks, and with the exception of 4 aneurysms, which were kept for a 2-year long-term follow-up study, the aneurysms were then harvested for histological examination. Thrombosis was successfully achieved in all cases except for 2 enlarged aneurysms that were initially partially thrombosed. No thromboembolism to distal vessels was observed. No compaction or shift of the CAP-IDC complex occurred even after 2 years. Histologically, CAP and IDCs conformed to the massive thrombotic complex without any fragmentation. By creating a frame or prop with retrievable microcoils, we were able to inject the CAP implies a comparison safely and precisely than has been previously reported. Our findings suggest that this method will be useful for the treatment of cerebral aneurysms.

Aneurysm↗
PubMed2000

Ganglioglioma in a patient with Turcot syndrome. Case report.

A 33-year-old woman with Turcot syndrome harbored a brain tumor and colon cancer and had a familial history of this syndrome. On histological examination, the brain tumor was found to have large and diffusely scattered ganglion cells within a diffuse background of astrocytic cells in a fibrillary matrix. The tumor was diagnosed as a ganglioglioma. No germline mutation in the adenomatous polyposis coli gene was detected using a protein truncation assay. These findings indicate that this patient had brain tumor-polyposis syndrome Type 1 of Turcot syndrome. This is the first report of a ganglioglioma related to Turcot syndrome.

Adenomatous Polyposis Coli↗