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T Yoshimine

Publications and source records attributed to T Yoshimine.

At least 19 recordsLinked to original sources
PubMed2002

Double suicide gene therapy using a replication defective herpes simplex virus vector reveals reciprocal interference in a malignant glioma model.

Herpes simplex virus thymidine kinase (HSV-TK) and Escherichia coli cytosine deaminase (CD) are non-mammalian enzymes capable of converting innocuous prodrugs into cytotoxic metabolites. Both enzymes have been utilized independently, as well as together in 'suicide' gene therapy protocols to eliminate tumor cells in vitro and in vivo. We have used a set of replication defective HSV vectors expressing either or both enzymes to compare the efficacies of single and double suicide gene therapies in the 9L gliosarcoma model in vitro and in vivo. In cell culture experiments at high and low multiplicities of infection, combined expression of the two genes by vector TOCD/TK along with exposure to the matching prodrugs (ganciclovir and 5-fluorocytosine) showed increased cytotoxicity compared with exposure to either prodrug alone. However, the two gene combination was inferior to single gene treatments, suggesting that HSVtk and CD are mutually counteractive in the prodrug-dependent killing of glioma cells. In animal experiments, survival was not significantly prolonged by administration of both prodrugs to TOCD/TK-treated animals, while each single gene/prodrug pair resulted in increased survival. These results indicate that single suicide gene systems employing HSVtk or CD may be preferable over combinations of the two.

Animals↗
PubMed2001

Structural characterization and chromosomal localization of the MAGE-E1 gene.

Genes of the melanoma-associated antigen (MAGE) family are characterized by the expression of tumor antigens on a malignant melanoma recognized by autologous cytolytic T lymphocytes. We have previously identified novel members of the MAGE gene family expressed in human glioma and named them MAGE-E1a-c. In the present study, we have revealed the genomic structure of MAGE-E1 by sequence analysis of a human chromosome bacterial artificial chromosome clone containing the MAGE-E1 gene. The MAGE-E1 gene is composed of 13 exons, and three of these (exon 2, exon 3 and exon 12) are alternatively spliced in each variant (E1a-c). The open reading frame encoding the MAGE-E1 peptides initiates in exon 2 and ends in exon 13. We have also demonstrated that the MAGE-E1 gene is located in Xp11 through the analysis of radiation hybrid panels. The genomic structure of MAGE-E1 is markedly similar to that of MAGE-D and its chromosomal locus is also identical to that of MAGE-D, but these features contrast with those of other MAGEs. These results suggest that MAGE-D and -E1 may be evolutionarily distant from other members of the MAGE family, and the two may be ancestral genes for the others.

Alternative Splicing↗
PubMed2001

MAGE-E1, a new member of the melanoma-associated antigen gene family and its expression in human glioma.

To unearth glioma-specific genes in human glioblastoma, the serial analysis of gene expression technique was applied to a primary glioblastoma, using cultured human astrocytes as a normal control. Among the top 147 most-expressed tags in glioblastoma, we found a tag, TTTTGGGTAT, that originated from an unidentified gene and which was not detected in human astrocyte cultures. Real-time quantitative reverse transcription-PCR showed that MAGE-E1 expression was 2.6-15-fold enriched in glioblastoma relative to human astrocytes. Expressed sequence tags containing this tag were homologous to the melanoma-associated antigen gene (MAGE) family, and this new cDNA, named MAGE-E1, was cloned by the 5'-rapid amplification of cDNA ends technique. Three alternatively spliced variants (MAGE-E1a-c) were found, and deduced amino acid sequence showed that MAGE-E1a and -E1b shared the MAGE-conserved region, whereas -E1c did not. This suggests that although MAGE-E1c is expressed from one of the MAGE family, it has distinct functions from other members. Tissue distribution analysis showed that MAGE-E1 was distinct from other MAGEs. MAGE-E1 expression was detected only in brain and ovary among normal tissues. Interestingly, MAGE-E1a and/or -E1b were specifically expressed in glioma cells among cancer cells. These results indicate that MAGE-E1 is a novel and glioma-specific member of MAGE family.

Antigens, Neoplasm↗
PubMed2001

Central neurocytoma presenting with intratumoral hemorrhage.

A 22-year-old woman presented with acute onset of headache and vomiting. Computed tomography (CT) demonstrated hydrocephalus and a huge midline mass with heterogeneous density involving both lateral ventricles. A small amount of hematoma was detected at the bottom of the left trigone. On magnetic resonance imaging (MRI), the mass appeared grossly isointense on T1-weighted images and slightly hyperintense on T2-weighted images with a clearly demarcated low intensity area at its center. These CT and MRI findings were suggestive of an acute hemorrhagic event within the tumor. The presence of hemorrhage was confirmed at surgery. Sudden hemorrhages within the tumor were considered to cause the acute onset of symptoms. Although central neurocytoma is not commonly known as a tumor-producing intracranial hemorrhage or to cause abrupt clinical deterioration, we found five similar cases in the literature. After reviewing these cases, we concluded that the information on the possible hemorrhagic complication of central neurocytoma is important for correct diagnosis and thus for proper management of this tumor.

Adult↗
PubMed2001

PTEN mutations in malignant gliomas and their relation with meningeal gliomatosis.

A putative tumor suppressor, the PTEN gene at chromosome 10q23. was identified and found to be mutated in many different human tumors. PTEN was recently found to be also involved in focal cell adhesion and cell migration. To identify the role of PTEN gene in malignant gliomas. we used PCR-SSCP and direct sequencing methods to examine 44 malignant gliomas comprising 29 cases without and 15 cases with meningeal gliomatosis. In malignant gliomas without meningeal gliomatosis, 2/29 (7%) of the cases showed alteration of the PTEN gene. In contrast, 5/15 (33%) of malignant gliomas with meningeal gliomatosis cases showed this alteration. These findings indicate that PTEN gene mutation contributes not only to the neoplastic evolution in gliomas but also to the meningeal dissemination of glioma cells.

Adolescent↗
PubMed2001

Nuclear factor-kappa B decoy attenuates neuronal damage after global brain ischemia: a future strategy for brain protection during circulatory arrest.

OBJECTIVES: Recent studies have reported that cis element decoy oligodeoxynucleotides against nuclear factor-kappa B block the activation of genes that mediate ischemic injury. To improve brain protection during circulatory arrest in cardiac surgery, we evaluated the efficacy of nuclear factor-kappa B decoy oligodeoxynucleotides in preventing neuronal damage after global brain ischemia. METHODS: Hemagglutinating virus of Japan-liposome complex with fluorescein isothiocyanate-labeled nuclear factor-kappa B decoy oligodeoxynucleotides was injected through the carotid artery during 20 minutes of global brain ischemia in rats to evaluate the efficacy of transfecting the decoy oligodeoxynucleotides. The messenger RNA levels of several factors related to ischemia-reperfusion injury in the hippocampus were estimated by a real-time polymerase chain reaction method 1 hour after reperfusion. Neuronal damage was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining and by using immunohistochemical study of microtubule-associated protein 2 in the hippocampus CA-1 region 7 days after ischemia. RESULTS: Introduction of the nuclear factor-kappa B decoy oligodeoxynucleotides into rat brain neurons through the carotid artery during global brain ischemia was markedly successful. The polymerase chain reaction study showed that the transfected nuclear factor-kappa B decoy oligodeoxynucleotides effectively inhibited the expression of tumor necrosis factor alpha interleukin 1 beta and intracellular adhesion molecule 1 messenger RNA 1 hour after global brain ischemia. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining and microtubule-associated protein 2 immunohistochemistry showed that the transfected nuclear factor-kappa B decoy oligodeoxynucleotides significantly attenuated the neuronal damage 7 days after global brain ischemia. CONCLUSIONS: Therapeutic transfection of nuclear factor-kappa B decoy oligodeoxynucleotides during brain ischemia may be useful for attenuating neuronal damage, suggesting a strategy for cerebral protection against global ischemia.

Animals↗
PubMed2001

Implantation of a reservoir for refractory chronic subdural hematoma.

OBJECTIVE: Recurrence of chronic subdural hematoma is not rare. Among patients who experience recurrence, severe background disease may adversely influence the prognosis of chronic subdural hematoma. We treated patients with these refractory hematomas with an Ommaya cerebrospinal fluid (CSF) reservoir and analyzed the effectiveness of the treatment. METHODS: Sixteen patients with refractory chronic subdural hematoma were studied. These patients had severe diseases that adversely influenced the clinical course of chronic subdural hematoma, including cerebral infarction, liver cirrhosis, thrombocytopenia, severe Parkinsonism, severe heart disease, psychiatric disease, and spinocerebellar degeneration. All patients were treated initially in the standard fashion: evacuation of the hematoma followed by irrigation and drainage of the hematoma cavity. In each patient, an Ommaya CSF reservoir was implanted after the hematoma recurred. Whenever the volume of the hematoma either decreased very slowly or increased, the reservoir was punctured. RESULTS: The hematoma size decreased to less than 3 mm a median of 60 days after introduction of the reservoir. Postoperatively, 13 patients returned to their condition before the onset of hematoma. One patient died of myocardial infarction, and two patients with Parkinson's disease could not maintain their previous functional level; both remained in a partially dependent state. Complications consisted of minor bleeding in two patients and occlusion of the reservoir in two other patients. CONCLUSION: By use of this method, reoperation was avoided and the patients were mobile early in the postoperative period. This method was suitable for refractory chronic subdural hematoma accompanied by severe disease that adversely influenced the clinical course.

Aged↗
PubMed2001

Conflict of intentions due to callosal disconnection.

OBJECTIVES: Three patients with callosal syndrome manifested a peculiar symptom in that they were unable to perform intended whole body actions because another intention emerged in competition with the original one. Attempts were made to clarify the symptomatology of this manifestation and its possible mechanism is discussed. METHODS: The three patients are described and previous reports on patients with callosal damage were reviewed. Four additional patients with similar symptoms were found and the clinical features common to all seven patients were examined. RESULTS: This symptom could not be attributed to unilateral movement disorders such as unilateral apraxia, intermanual conflict, or compulsive manipulation of tools. The manifestations included marked hesitation in initiating actions, interruption of actions, repetitive actions, and performance of unintended actions with difficulty in correcting them. All patients, except one, had a lesion in the posterior half of the body of the corpus callosum, and there was no significant involvement of the cerebral cortex. The symptom became manifest later than 4 weeks after callosal damage. It occurred during spontaneous actions, but not during well automated actions nor when following instructions. CONCLUSION: This symptom, tentatively named "conflict of intentions", can be regarded as a fragment of diagonistic dyspraxia originally described by Akelaitis, although it can occur independently of intermanual conflict. Normally, the right and left cerebral hemispheres may be complementarily modifying automated whole body actions in order to adapt behaviour to changes of the environment as well as to the intention. Partial callosal disconnection without significant cortical involvement would exaggerate the disparity between the role of each hemisphere through the reorganisation of neural systems after callosal damage. Such double, often contrary, behavioural tendencies may sometimes simultaneously enter the patient's awareness.

Adult↗
PubMed2001

Surgeon's position for transsphenoidal surgery--technical note.

Transsphenoidal resection of pituitary tumors is usually performed with the surgeon standing on the patient's right side. However, this configuration is awkward when the tumor extends to the right and access may be hindered if the patient has poor nuchal flexibility or a large chest due to giantism or acromegaly. The surgeon stood on the left side of the patient during transsphenoidal surgery in five selected cases. The position on the left provided good access to the tumors with minimal changes in technique.

Cardiac Surgical Procedures↗
PubMed2001

Peritoneal shunt tube placement performed using an endoscopic threaded imaging port. Technical note.

The authors used an endoscopic threaded imaging port that originally was developed for laparoscopy to access the peritoneal cavity, and applied this device to the placement of a peritoneal shunt tube in patients suffering from hydrocephalus. Using this system, the peritoneum can be opened quickly under direct vision by using an endoscope through a small skin incision. The peritoneal cavity is secured by replacing the cannula with a polyvinyl chloride (PVC) tube. At the end of surgery, the terminal end of the shunt tube is inserted through the PVC tube, which serves as a guiding catheter. Only one or two skin stitches are needed for closure. This method has proved to be safe, quick, and less invasive than conventional minilaparotomy.

Catheterization↗
PubMed2001

Treatment of glioblastoma by direct inoculation of concentrated high titer-recombinant retrovirus carrying the herpes simplex virus thymidine kinase gene.

We prepared retroviruses carrying the lacZ gene or herpes simplex virus thymidine kinase (HTK) gene with titers of 1.4-2.5 x 10(11) colony-forming units (cfu)/ml, and stereotaxically inoculated only 3 microliters of the retroviruses into a mouse glioma model. This resulted in highly efficient transduction in vivo. The transduced glioma cells migrated far from the implantation site, potentiating the induction of the remarkable bystander effect. Following repetitive ganciclovir (GCV) intraperitoneal injection, effective killing of glioma cells in the mouse brain was observed. The transduction efficiency was nearly as high as that observed for the implantation of high-titer retrovirus-producing fibroblasts. Eighty per cent of brain tumor-bearing mice were completely cured by our treatment protocol using concentrated HTK-harboring retroviruses. Our results suggest that repeated inoculations of high-titer retroviruses carrying the HTK gene followed by GCV treatment may be a promising strategy for the clinical treatment of malignant gliomas. To achieve further safety in the gene therapy of glioma, genes abundantly expressed in human glioblastoma were searched by the Serial Analysis of Gene Expression (SAGE) technique. Among the top-147 most expressed tags in glioblastoma, we found a tag, TTTTGGGTAT, originated from an unidentified gene, which was not detected in human astrocyte cultures. Real-time quantitative RT-PCR showed that MAGE-E1 expression was 2.6-15 fold enriched in glioblastoma relative to human astrocytes. Expressed Sequence Tags (ESTs) containing this tag were homologous to melanoma-associated antigen gene (MAGE) family, and this new cDNA, named MAGE-E1, was cloned by 5'-rapid amplification of cDNA ends (RACE) technique. MAGE-E1 expression was enriched in glioblastoma and low in other cancers, and MAGE-E1 expression was detected only in brain and ovary among normal tissues. These results indicate that MAGE-E1 is a novel and glioma-specific member of MAGE family, which can be applied to glioma-specific gene transduction.

Animals↗
PubMed2000

Theta rhythm increases in left superior temporal cortex during auditory hallucinations in schizophrenia: a case report.

Auditory hallucinations (AH), the perception of sounds and voices in the absence of external stimuli, remain a serious problem for a large subgroup of patients with schizophrenia. Functional imaging of brain activity associated with AH is difficult, since the target event is involuntary and its timing cannot be predicted. Prior efforts to image the patterns of cortical activity during AH have yielded conflicting results. In this study, MEG was used to directly image the brain electrophysiological events associated with AH in schizophrenia. We observed an increase in theta rhythm, as sporadic bursts, in the left superior temporal area during the AH states, whereas there was steady theta band activity in the resting state. The present finding suggests strong association of the left superior temporal cortex with the experience of AH in this patient. This is consistent with the hypothesis that AH arises from areas of auditory cortex subserving receptive language processing.

Adult↗
PubMed2000

Induction of aquaporin-4 water channel mRNA after focal cerebral ischemia in rat.

Aquaporin-4 (AQP4) is a member of a water-selective channel aquaporin-family and mainly expressed in the several structures of the brain and in the collecting duct of the kidney. Here we show its functional involvement in the water homeostasis of the ischemic brain. The expression of AQP4-mRNA is increased in the peri-infarcted cortex during the observation period ( approximately 7 days) after MCA-occlusion, maximally on day 3. The change corresponds to the generation and resolution of brain edema monitored by MRI. The signals for the mRNA are predominantly observed in glial cells in the molecular and outer granular layer of the peri-infarcted cortex. These results indicate that AQP4 plays a role in post-ischemic edema formation.

Animals↗
PubMed2000

Quantitative analysis of glioma cell invasion by confocal laser scanning microscopy in a novel brain slice model.

To quantitatively analyze the spatial extent of glioma cell migration in an organotypic brain slice culture, we developed a new invasion model with the aid of confocal laser scanning microscopy (CLSM). CLSM allowed not only for three-dimensional visualization of the invasive pattern of human T98G glioma cells in the living brain slice but also for serial analysis of the invasive process over several weeks. Twenty-four hours after the T98G glioma spheroid was initiated to coculture with a brain slice, the glioma cells detached themselves from the spheroid and spontaneously continued to migrate on the surface of the brain slice, while they diffusely invaded into the slice by migrating to a deeper site. Immunohistochemical analysis revealed that these migrating glioma cells much more strongly immunostained for matrix metalloproteinase (MMP)-2 and -9 than the tumor spheroid which remained at the implanted site. Treatment of the T98G glioma spheroid with 1,10-phenanthroline, a specific inhibitor of MMPs, significantly inhibited not only the cell migration on the surface of the brain slice but also the invasion of the glioma cells into the slice. The present version of the glioma invasion model using CLSM makes it possible to spatially and serially analyze the extent of glioma cell invasion in the living brain slice for several weeks, making it a very useful tool for investigating the cellular and molecular mechanisms of glioma invasion under conditions most analogous to those of normal brains in vivo.

Animals↗
PubMed2000

Movement-related desynchronization of the cerebral cortex studied with spatially filtered magnetoencephalography.

Event-related desynchronization (ERD) within the alpha and beta bands on unilateral index finger extension and hand grasping was investigated on six normal volunteers with magnetoencephalography (MEG). A novel spatial filtering technique for imaging cortical source power, synthetic aperture magnetometry (SAM), was employed for the tomographic demonstration of ERD. SAM source image results were transformed into statistical parametric images. On the same hand grasping task, a functional MRI (fMRI) study was conducted on two subjects and compared with the ERD result. When the MEG data were analyzed with the fast Fourier transformation, power attenuation within the alpha and beta bands was evident on the contralateral sensorimotor area just prior to movement onset. The tomographic distribution of ERD was clearly obtained with SAM statistical imaging analysis. The equivalent current dipole (ECD) for the signal-averaged motor field was localized to the hemisphere contralateral to the hand movement, roughly at the center of the region displaying beta-band ERD. The signal increase on fMRI roughly colocalized with the ERD on the contralateral sensorimotor area. In conclusion, with the novel spatial filtering technique for the brain magnetic field, SAM, cortical regions contributing to ERD on finger movement were successfully demonstrated in a tomographic manner. The relative colocalization of the contralateral SAM ERD with ECD as well as the fMRI activation suggests that SAM is a practically useful technique to extract event-related signals from brain noise.

Adult↗
PubMed2000

Whole-genome analysis of human astrocytic tumors by comparative genomic hybridization.

Frozen sections of 35 astrocytic tumors of various histologic malignancies were analyzed by comparative genomic hybridization in an attempt to characterize the profile of genetic aberrations. Over 94% of the samples revealed DNA copy number aberrations, which increased with higher histological malignancy grades, and also involvement of more than one chromosome was seen in 85% of instances. The aberrations observed were mainly deletions and most frequently incorporated chromosomes 1p, 10, 19q, and 22q. On the other hand, gains or amplifications were detected only in glioblastomas. Additionally, such gains or amplifications were present in all tumor samples where the initial histopathological diagnosis was glioblastoma and immunohistochemical study disclosed p53 tumor suppressor protein negative and epidermal growth factor receptor positive immunoreactivity; such glioblastomas possessing p53 tumor suppressor protein positive and epidermal growth factor receptor negative immunoreactivity seldom displayed any gain. Thus, glioblastomas exhibiting two different profiles of genetic aberrations were recognized--one with and the other without any gains/ amplifications. We speculate that the former variety is de novo glioblastoma.

Adult↗
PubMed2000

Intracavernous sinus ectopic adrenocorticotropin-secreting tumours causing therapeutic failure in transsphenoidal surgery for Cushing's disease.

BACKGROUND: The major cause of surgical failure in the treatment of Cushing's disease lies in unsuccessful identification of adenomas. In the present study, we investigated the pathogenesis of negative exploration in transsphenoidal surgery for Cushing's disease by analyzing neuro-imaging studies, endocrinological examination and selective venous sampling. METHODS: Thirty patients with ACTH-dependent Cushing's syndrome that met the endocrinological criteria for Cushing's disease were treated by transsphenoidal microsurgery. Depending on positive or negative identification of adenomas during the surgery, selective adenomectomy, partial hypophysectomy or subtotal hypophysectomy was performed. FINDINGS: All nine patients who underwent selective adenomectomy showed endocrinological remission and did not need any hormone replacement therapy. Of the 12 patients who underwent partial hypophysectomy, 11 showed normalization of hypercortisolism but seven needed permanent replacement of hydrocortisone. Four patients underwent subtotal hypophysectomy because no adenoma could be identified in spite of detailed exploration, and three of them showed remission but with permanent requirements of hydrocortisone and other pituitary hormones. Five patients, whose hypercortisolism persisted after initial surgery, underwent total hypophysectomy as secondary transsphenoidal surgery, and only one of them showed endocrinological remission. Of the six patients with surgical failure, four were thought to be rare cases in whom the ACTH-secreting tumours may have occurred ectopically in the cavernous sinus without direct contact with the pituitary gland. Endocrinologically, these four patients showed a low or no response to corticotropin releasing hormone (CRH) stimulation, and for three of them, radiation therapy to the sellar region including the cavernous sinus was effective for persistent hypercortisolemia. INTERPRETATION: Recognition of an ectopic intracavernous sinus ACTH-secreting tumour as a pathological entity for Cushing's disease may not only enhance the diagnostic accuracy but also be important for determining the optimal surgical mode for persistent Cushing's disease.

Adenoma↗