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Biomedical subjects

Takeshi Kawase

Publications and source records attributed to Takeshi Kawase.

At least 19 recordsLinked to original sources
PubMed2007

Preferential expression and frequent IgG responses of a tumor antigen, SOX5, in glioma patients.

We previously reported to identify SOX5 as a glioma antigen by serological screening using a testis cDNA library. The present study was designed to analyze SOX5 expression, its immunoreactivity, and the correlation between SOX5 IgG responses and clinical features in glioma patients to evaluate the possibility of its use as a diagnostic marker. Quantitative RT-PCR and Western blot analysis revealed that SOX5 was expressed in glioma tissues, but not in normal adult tissues, except in the testis. An immunohistochemical analysis showed that SOX5 was expressed in glioma cells, but only a few SOX5-positive cells were detected in non-neoplastic tissues from the cerebral cortex. IgG antibodies against SOX5 were detected in sera from 8 of the 27 glioma patients (27.6%), 0 of the 14 patients with other brain diseases (0%), 1 of the 54 other cancer patients (1.9%) and 1 of the 37 healthy individuals (2.7%). Patients with glioblastoma (GBM) who showed IgG responses against SOX5 exhibited significantly better survival periods than GBM patients without SOX5 antibodies. In summary, SOX5 is aberrantly expressed in glioma and can be recognized as a glioma antigen using IgGs from the sera of glioma patients. Furthermore, there is a statistically significant correlation between the presence of SOX5 IgGs and survival in GBM patients, suggesting that the glioma antigen SOX5 may be useful not only as a diagnostic marker, but also as a prognostic marker in glioma patients.

Adolescent↗
PubMed2006

Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum.

Recent studies have revealed that the adult mammalian brain has the capacity to regenerate some neurons after various insults. However, the precise mechanism of insult-induced neurogenesis has not been demonstrated. In the normal brain, GFAP-expressing cells in the subventricular zone (SVZ) of the lateral ventricles include a neurogenic cell population that gives rise to olfactory bulb neurons only. Herein, we report evidence that, after a stroke, these cells are capable of producing new neurons outside the olfactory bulbs. SVZ GFAP-expressing cells labeled by a cell-type-specific viral infection method were found to generate neuroblasts that migrated toward the injured striatum after middle cerebral artery occlusion. These neuroblasts in the striatum formed elongated chain-like cell aggregates similar to those in the normal SVZ, and these chains were observed to be closely associated with thin astrocytic processes and blood vessels. Finally, long-term tracing of the green fluorescent-labeled cells with a Cre-loxP system revealed that the SVZ-derived neuroblasts differentiated into mature neurons in the striatum, in which they expressed neuronal-specific nuclear protein and formed synapses with neighboring striatal cells. These results highlight the role of the SVZ in neuronal regeneration after a stroke and its potential as an important therapeutic target for various neurological disorders.

Animals↗
PubMed2006

Intracarotid injection of granulocyte-macrophage colony-stimulating factor induces neuroprotection in a rat transient middle cerebral artery occlusion model.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was found to promote collateral flow in patients with coronary artery disease and also to induce arteriogenesis in a rat hypoperfusion brain model. Activated macrophages have been shown to induce vascular proliferation and play an important role in ischemic stroke. In this study, we examined the therapeutic effect of GM-CSF on the ischemic brain by activating microglia/macrophages. Rats were subjected to 1-h intraluminal middle cerebral artery occlusion (MCAO) and received an intracarotid injection of GM-CSF (5 ng) or saline immediately after reperfusion. Infarct volume, neurological function and histological findings were assessed 48 h later. An intracarotid injection of GM-CSF reduced the infarct volume and improved neurological function at 48 h after reperfusion. Histological analysis revealed that the number of activated microglia/macrophages to be increased and the number of apoptotic cells to be decreased in the area of the penumbra. These results suggest that intracarotid injection of GM-CSF may have a therapeutic effect on brain ischemia via activation of microglia/macrophages.

Animals↗
PubMed2006

Identification of a glioma antigen, GARC-1, using cytotoxic T lymphocytes induced by HSV cancer vaccine.

Despite several ongoing clinical trials of immunotherapies against glioma, few glioma-specific antigens recognized by cytotoxic T lymphocytes (CTLs) have been identified. We recently demonstrated that intratumoral inoculation with herpes simplex virus (HSV) as a cancer vaccine activates tumor-specific CTLs. To identify glioma antigens recognized by CTLs, we used the HSV cancer vaccine to vaccinate mice harboring a syngeneic mouse glioma cell line, GL261. From the splenocytes of the immunized mice, we generated an H-2Db-restricted CTL line, GCL-1, that was specific for GL261. Then, a cDNA expression library generated from GL261 was screened with GCL-1, and a new gene encoding glioma antigen, GARC-1, was isolated. Sequence analysis revealed that the GARC-1 gene isolated from GL261 had a point mutation causing an amino acid change (Asp to Asn at position 81). T-cell epitope analysis revealed that the mutated peptide GARC-1(77-85) (AALLNKLYA) but not the wild-type peptide (AALLDKLYA), was recognized by GCL-1. These results suggest that HSV cancer vaccination may be a useful method for inducing tumor-specific CTLs and identifying tumor antigens. Furthermore, this GL261/GARC-1 murine glioma model may be useful for the development of immunotherapy for brain tumors.

Animals↗
PubMed2006

Enhanced therapeutic efficacy of oncolytic herpes vector G207 against human non-small cell lung cancer--expression of an RNA-binding protein, Musashi1, as a marker for the tailored gene therapy.

BACKGROUND: Oncolytic herpes vectors like G207 have shown considerable promise in the treatment of solid tumors, but their potency must be enhanced for the full achievement of therapeutic efficacy. Deletion of the innate gamma34.5 gene made these vectors extremely safe, but their efficacy was also severely attenuated. Use of tumor-specific promoters is one method to direct toxicity and enhance efficacy against tumors. Recently, Musashi1 has been shown expressed in some tumor tissues. METHODS: Eleven human cancer cell lines including five non-small cell lung cancers (NSCLCs) were investigated. Musashi1 mRNA expression was examined by RT-PCR analysis. Western blotting was also performed. Transcriptional activity of P/musashi1 in NSCLCs was assayed by GFP reporter plasmids. Then we constructed a defective amplicon vector containing musashi1 promoter/ICP34.5 with G207 as helper virus (dvM345). In vitro cytotoxicity against NSCLCs and growth characteristics of helper virus were examined. A Lu-99 subcutaneous tumor model was used in an animal study. The tumor volume treated with G207 alone or dvM345 was measured. RESULTS: Musashi1 mRNA was detected in four cell lines. Two in five NSCLCs were positive, and P/musashi1 was proved functional within them. Against these cell lines, dvM345 showed enhanced cytotoxicity, and helper viral growth was augmented. A subcutaneous tumor study confirmed the enhanced therapeutic efficacy of G207 by dvM345 without compromising safety. CONCLUSIONS: These results suggest that Musashi1 might be involved in the development of several carcinomas including NSCLC. In the context of oncolytic herpes vector strategy, the P/musashi1-ICP34.5 method could be used for the treatment of cancers expressing Musashi1.

Animals↗
PubMed2006

TMS orientation for NIRS-functional motor mapping.

Functional near-infrared spectroscopic imaging (NIRS imaging) has the potential to elucidate the relationship between neuronal activity and oxygenation responses. However, its signal specificity to the functional cortex is sometimes spoiled by its rough spatial resolution. In this study we incorporated transcranial magnetic stimulation (TMS) motor mapping into an NIRS imaging study to enhance spatial specificity to the functional cortex. Distinctive biphasic responses in the cortical oxygenation status were observed in the center of the primary motor cortex during a motor task. The early response phase, occurring within 1 to 3 seconds after task initiation, represents a cortical deoxygenation which consists of a significant increase in deoxygenated hemoglobin concentration (HbR) and a nonsignificant decreasing tendency in oxygenated hemoglobin concentration (HbO(2)). The delayed response phase represents an excess of incoming blood flow, which appears as an increase in HbO(2)/total Hb (tHb) and a decrease in HbR following the early response. In the surrounding area, cortical oxygenation change showed a monophasic response consisting of an increase in HbO(2)/tHb and a decrease in HbR. Combining TMS mapping with NIRS imaging enabled us to specify the cortex with the strongest functional activity.

Adult↗
PubMed2006

Trochlear nerve schwannoma with intratumoral hemorrhage: case report.

OBJECTIVE AND IMPORTANCE: Schwannomas originating from the trochlear nerve without neurofibromatosis are extremely rare. Thirty-four cases have previously been reported in the literature, and only 25 cases were pathologically diagnosed. In addition, intratumoral hemorrhage in intracranial schwannomas is also rare. Approximately 30 cases of intracranial schwannomas with intratumoral hemorrhage have been reported. CLINICAL PRESENTATION: A 42-year-old man presented with left hemiparesis and right trochlear nerve palsy. Magnetic resonance imaging revealed an abnormal cystic lesion beside the brainstem. His symptoms rapidly worsened after enlargement of the mass because of intratumoral hemorrhage. INTERVENTION: Gross total removal of the tumor was performed via the anterior transpetrosal approach. The tip of the trochlear nerve was fanned out and unified with the tumor. The tumor was diagnosed as a schwannoma. CONCLUSION: The patient's hemiparesis improved postoperatively, and he was discharged 1 week after the operation. Magnetic resonance imaging performed 4 months later revealed no regrowth of the tumor. Only right trochlear nerve palsy has persisted. This report is the second case of intratumoral hemorrhage from a trochlear nerve schwannoma.

Adult↗
PubMed2006

Intradural C-1 ventral root schwannomas treated by surgical resection via the lateral suboccipital transcondylar approach--three case reports.

Three female patients aged 50-79 years (mean 61.0 years) presented with extremely rare intradural C-1 root schwannoma manifesting as foramen magnum syndrome. Magnetic resonance imaging revealed the intradural extra-axial tumors extending from the anterior aspect of the medullospinal junction, with a mean major diameter of 2.7 cm. Total resection of the tumors was performed via the lateral suboccipital transcondylar approach after a mean period of 11.7 months from the symptom onset. The final diagnosis of schwannoma of the C-1 ventral root was based on the intraoperative and histological findings. All three patients were successfully rehabilitated, with symptomatic improvement and no evidence of tumor recurrence. All three patients were successfully treated by surgical resection via the lateral suboccipital transcondylar approach. This approach is effective and safe provided individual anatomy, drilling of the occipital condyle, and patient position are considered carefully.

Aged↗
PubMed2006

Spinal arachnoid cyst causing paraplegia following skull base surgery.

A 40-year-old woman presented with a right petroclival meningioma compressing the brainstem and manifesting as a 6-month history of headache and gait difficulty. The patient underwent subtotal removal of the tumor via an anterior transpetrosal approach. The postoperative course was complicated by cerebrospinal fluid rhinorrhea, bacterial meningitis, and acute hemorrhagic rectal ulcer. The patient was discharged home in good condition after prolonged medical treatment. Four months after the surgery, the patient noted recurrence of gait difficulty. Magnetic resonance (MR) imaging of the brain showed enlargement of the ventricles and no residual brainstem compression. A ventriculoperitoneal shunt was placed, but the symptoms were unchanged. The shunt was removed 2 months later because of infection. The patient's gait gradually deteriorated, although repeat brain MR imaging showed no significant increase in ventricular size. Ten months after the initial surgery she became paraplegic. MR imaging of the thoracic spine revealed a large arachnoid cyst extending from C-6 to T-6. The patient underwent T2-4 laminectomy, partial removal of the cyst wall, and duraplasty, but no clinical improvement was observed. Preexisting long-tract signs and coincidental hydrocephalus confused the neurological findings and delayed detection of the spinal lesion in this case. Neurosurgeons should be alert to the possibilities of insidious spinal lesion if the patient has progressive neurological disorder which does not match the known cranial lesion.

Adult↗
PubMed2006

Adenoid cystic carcinoma of the cavernous region. Case report.

A 62-year-old Japanese male patient presented with right oculomotor, abducens, and trigeminal nerve disturbances. Neuroimaging revealed a right middle cranial fossa mass lesion with the characteristics of trigeminal schwannoma. The patient underwent a right temporal craniotomy for gross total resection. Histological examination confirmed a metastasis of adenoid cystic carcinoma (ACC). After the operation, no evidence of the primary lesion could be found. The patient was treated with radiation therapy. ACC can be difficult to identify before histological confirmation. The incidence of intracranial invasion of ACC is 4-22%, but in this case no evidence of the primary lesion was found.

Carcinoma, Adenoid Cystic↗
PubMed2005

Motor-related intracortical steal phenomenon detected by multichannel functional near-infrared spectroscopy imaging.

BACKGROUND: Patients with severe cerebral ischemia may lose autoregulation to increase cerebral blood flow following neural activity. Although the steal phenomenon under conventional cerebral blood flow study has been known as a high-risk factor for stroke, the cerebral oxygen hemodynamics in ischemic patients during functional activation has not been thoroughly investigated. In this study, we present rare cases with intracortical steal phenomenon during motor tasks detected by multichannel functional near-infrared spectroscopy before and after surgery. METHODS: The relative concentration change of oxygenated, deoxygenated and total hemoglobin in and around the primary sensorimotor cortex during contralateral hand grasping was investigated in 11 patients with severe internal carotid artery stenosis. RESULTS: In 3 patients, the concentration of total hemoglobin around the primary sensorimotor cortex significantly decreased in response to motor stimulation and returned to baseline soon after termination of the motor task. This phenomenon partially disappeared postoperatively in all patients who underwent surgery. The remaining 8 patients showed no signs of total hemoglobin decrease in and around the sensorimotor cortex. In 9 patients, lack of decrease in deoxygenated hemoglobin in the center of the primary motor cortex during the motor task was observed and 3 of them showed significant increase in deoxygenated hemoglobin. CONCLUSIONS: We have demonstrated that in some patients with severe ischemia, an abnormal motor-related steal phenomenon can be observed. This phenomenon can be modulated by surgical intervention and might imply the severity of ischemia.

Aged↗
PubMed2005

Potential functional neural repair with grafted neural stem cells of early embryonic neuroepithelial origin.

The fate of grafted neuroepithelial stem cells in the normal mature brain environment was assessed both morphologically and electrophysiologically to confirm their feasibility in the functional repair of damaged neural circuitry. The neuroepithelial stem cells were harvested from the mesencephalic neural plate of transgenic green fluorescence protein-carrying rat embryos, and implanted into the normal adult rat striatum. The short- and long-term differentiation pattern of donor-derived cells was precisely monitored immunohistochemically. The functional abilities of the donor-derived cells and communication between them and the host were investigated using host-rat brain slices incorporating the graft with whole-cell patch-clamp recording. Vigorous differentiation of the neuroepithelial stem cells into mostly neurons was noted in the short-term with positive staining for tyrosine hydroxylase, suggesting that the donor-derived cells were exclusively following their genetically programmed fate, together with gamma-aminobutyric acid (GABA) and glutamate expression. In the long-term, the large number of donor-derived neurons was sustained, but the staining pattern showed expression of dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein 32, suggesting that some neurons were following environmental cues, together with the appearance of some cholinergic neurons. Some donor-derived astrocytes were also seen in the graft. Many action potentials indicating the presence of both dopaminergic and non-dopaminergic patterns could be elicited and recorded in the donor-derived neurons in addition to spontaneous glutamatergic and GABAergic post-synaptic currents which were strongly shown to be of host origin. Neuroepithelial stem cells are therefore an attractive candidate as a source of donor material for intracerebral grafting in functional repair.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2005

Predicting the overall management outcome in patients with a subarachnoid hemorrhage accompanied by a massive intracerebral or full-packed intraventricular hemorrhage: a 15-year retrospective study.

BACKGROUND: Patients with a subarachnoid hemorrhage (SAH) accompanied by a massive intracerebral hemorrhage (ICH) or a full-packed intraventricular hemorrhage (IVH) have poor outcomes. We evaluated the clinical factors to predict the overall outcome in such patients. METHODS: Data on nontraumatic SAH patients were collected and classified into 3 groups: the pure SAH group (SAH accompanied with neither ICH nor IVH), the ICH group (SAH accompanied with a massive ICH; hematoma 30 mL), and the IVH group (SAH and all ventricles were full-packed with hematoma). One hundred seventy-nine patients were in the ICH group and 109 in the IVH group. We evaluated clinical factors, such as the Hunt & Hess (H&H) score on admission, age, sex, history, rebleeding ratio, and the computerized tomography findings (SAH score). RESULTS: The result of multivariate logistic regression analysis of clinical variables in the ICH group, good and intermediate H&H grades, younger age (<70), no rebleeding, and lower SAH score were associated with a favorable outcome. In the result of the multivariate logistic regression analysis of clinical variables in the IVH group, only a higher SAH score was associated with an unfavorable outcome. CONCLUSIONS: In the ICH group, factors that could be used to predict a favorable outcome included good and intermediate H&H scores (1, 2, and 3) on admission, younger age (<70), and a lower SAH score. In the IVH group, the main factor that could be used to predict a favorable outcome was a lower SAH score.

Adult↗
PubMed2005

Surgical treatment of temporal bone chondroblastoma.

BACKGROUND: Temporal bone chondroblastoma is a rare primary bone tumor that affects the floor of the middle cranial fossa. This tumor is known to have high recurrence rate after curettage, and wide resection is therefore recommended. However, the literature provides little information regarding long-term results after wide resection of temporal bone chondroblastoma. METHODS: Four cases of surgically treated temporal bone chondroblastoma underwent long-term follow-up. RESULTS: Four patients, 3 males and 1 female, with mean age of 34, were surgically treated at the neurosurgery department of Keio University Hospital. Two patients were treated for recurrent tumor and the other two for new disease. In all cases the tumor mainly involved the mandibular fossa with variable degree of infiltration into tympanic and petrous parts. The tumor was totally removed via zygomatic approach in all patients. In 3 patients, the mandibular condyle was removed to expose the tumor. These patients had temporary malocclusion and restricted motion postoperatively, which resolved within 3 to 12 months with conservative treatment. All patients have no recurrence to date with a mean follow-up period of 9 years. CONCLUSION: Temporal bone chondroblastoma was removed totally with skull base surgical technique and no recurrence has occurred for 6 to 13 years postoperatively. We found that removal of the mandibular head does not cause permanent problems of mastication in patients with normal dentures.

Adult↗
PubMed2005

Identification of glioma-specific RFX4-E and -F isoforms and humoral immune response in patients.

For regulatory factor X4 (RFX4), two alternatively spliced variants, RFX4-A and -B, were reported in the testis. In this study, we identified transcript variants RFX4-C, -D, -E, and -F, and demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) that RFX4-A, -B and -C mRNAs were expressed only in the testis, and RFX4-D mRNA was expressed only in normal brain tissues. In tumors, RFX4-E and -F in addition to RFX4-D mRNA were expressed in gliomas by rapid amplification of cDNA ends and RT-PCR analyses. Expression of RFX4 mRNA was not observed in other tumors, such as lung, esophageal, stomach, colon or liver cancers. Quantitative real-time RT-PCR using common primer pairs detecting all of the variant transcripts showed high expression in normal testis, low expression in the brain (1% compared to the expression in testis), and overexpression in 17 of 61 gliomas (28%). Western blot analysis using DC28 monoclonal antibody (mAb) produced against recombinant RFX4-D C-terminus protein showed expression of RFX4-A and -C proteins, but not RFX4-B protein, in the testis, and expression of RFX4-D protein in the brain. Moreover, expression of RFX4-E and -F proteins, but not RFX4-D protein, was observed in gliomas. Immunohistochemistry analysis using DC28 mAb showed positive staining in the nuclei of spermatocytes in the testis and glioma cells. Antibody against RFX4 was detected in the sera of 3 of 58 (5%) glioma patients by enzyme-linked immunosorbent assay, suggesting the immunogenicity of RFX4-E and -F proteins in glioma patients.

Adolescent↗