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Takuo Hashimoto

Publications and source records attributed to Takuo Hashimoto.

12 recordsLinked to original sources
PubMed2006

High-performance liquid chromatographic assay for carboplatin in ultrafiltered plasma combined with hyperbaric oxygenation.

A specific, sensitive and reproducible high-performance liquid chromatographic procedure was developed for the quantitative analysis of carboplatin in human plasma. Plasma was ultrafiltered with an Amicon Centrifree system and then injected onto an analytical NH2 column. Carboplatin was monitored at 230 nm and eluted by 10 min using acetonitrile/methanol/5 mM sodium perchlorate buffer (pH 2.4) (75:15:10, v/v) as a mobile phase. The method yielded intra-day and inter-day precision and accuracy of <6% with a linearly from 0.1 to 80 microg/mL and a recovery of >98%. Plasma concentrations of intravenously administered carboplatin in three patients could be determined by this system. Slightly higher plasma concentrations of carboplatin were detected even 30 min after hyperbaric oxygenation therapy for 60 min than expected. The results suggest that this method could be applicable for measurement of carboplatin in plasma samples to evaluate carboplatin therapy together with hyperbaric oxygenation.

Aged↗
PubMed2005

Noggin and basic FGF were implicated in forebrain fate and caudal fate, respectively, of the neural tube-like structures emerging in mouse ES cell culture.

We developed neural tube-like structures accompanying neural crest-like cells by treating embryonic stem (ES) cells with retinoic acid. The structures contained pseudostratified Nestin+Vimentin+ neuroepithelial cells surrounded by Masson staining+ basement membrane. betaIIItubulin+Synaptophysin+ mature neurons and glial fibrillary acidic protein (GFAP)+ glial cells dispersed outside of the membrane. Addition of Noggin to the culture induced prominent proliferation of the neuroepithelial cells, leading to epithelial hyperstratification of the structures. mRNAs of transcription factors essential for forebrain development such as Emx1/2 and Pax6 were specifically expressed and Islet1+Lim1/2- motoneurons appeared by the addition of Noggin. In contrast, basic fibroblast growth factor (bFGF) promoted enlargement of central lumen and elongation of the structures. mRNAs of caudal markers, Gbx2, Cdx2 and Hoxb4/9 were expressed and Lim1/2+ spinal motoneurons appeared by the addition of bFGF. Addition of BMP-4 similarly brought about mild enlargement of central lumen of the structures. Interestingly, the addition of BMP-4 induced Slug+ neural crest-like cells surrounding the tube-like structures. mRNAs of Snail and dHand, other markers for neural crest cells, were also expressed by the addition of BMP-4. These results suggest that Noggin lead the neural-tube like structures to forebrain fate, whereas bFGF was involved in the caudalization. BMP-4 was implicated in emergence of the neural crest-like cells. Differentiation of ES cells by the present methods may mimic neurulation and subsequent neural development of early embryos, and elucidates the opposite effects of Noggin and bFGF for the neural tube development.

Animals↗
PubMed2005

Transplantation of neural cells derived from retinoic acid-treated cynomolgus monkey embryonic stem cells successfully improved motor function of hemiplegic mice with experimental brain injury.

We induced neural cells by treating cynomolgus monkey embryonic stem (ES) cells with retinoic acid. The treated cells mainly expressed betaIIItubulin. They further differentiated into neurons expressing neurofilament middle chain (NFM) in elongated axons. Half of the cells differentiated into Islet1+ motoneurons in vitro. The monkey ES-derived neural cells were transplanted to hemiplegic mice with experimental brain injury mimicking stroke. The neural cells that had grafted into periventricular area of the mice distributed extensively over the injured cortex. Some of the transplanted cells expressed the neural stem/progenitor marker nestin 2 days after transplantation. The cells expressed markers characteristic of mature motoneurons 28 days after transplantation. Mice with the neural cell graft gradually recovered motor function, whereas control animals remained hemiplegic. This is the first demonstration that neural cells derived from nonhuman primate ES cells have the ability to restore motor function in an animal model of brain injury.

Animals↗
PubMed2004

Anatomical and functional recovery by embryonic stem cell-derived neural tissue of a mouse model of brain damage.

We have treated undifferentiated mouse embryonic stem (ES) cells with all-trans retinoic acid (RA) to induce differentiation in vitro into neuron-like cells with good cell viability for use as a graft. Furthermore, we asked whether the RA-induced neuron-like cells restored neurological dysfunction. To this end, the cells were transplanted into right hemiplegia model of mice, developed by a cryogenic injury of motor cortex. Motor function of the recipients was gradually improved, whereas little improvement was observed in control mice. The lesion showed clustering of mature and almost mature neuron-like cells in mice transplanted with the RA-treated cells. The grafted cells had synaptic vesicles. This finding may suggest their maturation and synaptic connection in the recipient brain. Even though further study is necessary to elucidate molecular and cellular mechanisms responsible for the functional recovery, we consider that the ES cells may have advantage for use as a donor source in various neurological disorders including motor dysfunction.

Animals↗
PubMed2004

Transplantation of motoneurons derived from MASH1-transfected mouse ES cells reconstitutes neural networks and improves motor function in hemiplegic mice.

Mouse embryonic stem (ES) cells were transfected with a MASH1 expression vector and G418-resistant cells were selected. The MASH1-transfected cells became neuron-like appearance and expressed betaIIItubulin and panNCAM. Glial fibrillary acidic protein (GFAP) and galactocerebroside (GalC)-expressing cells were rarely detected. Half of the neural cells differentiated into the Islet1+ motoneuron lineage. Thus, we obtained motoneuron lineage-enriched neuronal cells by transfection of ES cells with MASH1. A hemiplegic model of mice was developed by cryogenic injury of the motor cortex, and motoneuron lineage-enriched neuronal cells were transplanted underneath the injured motor cortex neighboring the periventricular region. The motor function of the recipients was assessed by a beam walking and rotarod tests, whereby the results gradually improved, but little improvement was observed in vehicle injected control mice. We found that the grafted cells not only remained close to the implantation site, but also exhibited substantial migration, penetrating into the damaged lesion in a directed manner up to the cortical region. Grafted neuronal cells that had migrated into the cortex were elongated axon-positive for neurofilament middle chain (NFM). Synaptophysin immunostaining showed a positive staining pattern around the graft, suggesting that the transplanted neurons interacted with the recipient neurons to form a neural network. Our study suggests that the motoneuron lineage can be induced from ES cells, and grafted cells adapt to the host environment and can reconstitute a neural network to improve motor function of a paralyzed limb.

Animals↗
PubMed2004

[Intracranial metastasis of pituitary adenoma: a case report].

Growth hormone-secreting pituitary adenoma is usually benign, and distant metastases are extremely rare. A case of growth hormone-secreting pituitary adenoma with multiple dural metastases is reported. A 53-year-old male was initially admitted to our hospital complaining of visual loss, presenting a pituitary abnormal mass with suprasellar extension. At the initial surgery, transsphenoidal surgery was selected, and the histological finding was benign pituitary adenoma. Seven and 16 months after the initial surgery, second and third surgeries via a transcranium route were performed for recurrence of the pituitary tumor. Histological findings revealed an appearance similar to the initial tumor in both surgical specimens. After the third operation, radiation therapy (local irradiation: total; 44 Gy) was performed. Six years after the first surgery, three tumors were located in the right frontal, parietal convexity and cerebellar tentorium. The tumors were totally removed by 4th and 5th surgeries. Histological examination showed malignant transformation from the primary benign growth hormone-secreting pituitary adenoma, with dural metastasis. Immunohistochemical staining with MIB-1 antibody demonstrated a high index of 7%. The patient is still alive after more than one year since the diagnosis of distant metastasis. According to previous reviews, few patients have survived more than one year. We conclude patients with benign pituitary adenoma should be carefully followed up for fear of malignant transformation or dural metastasis.

Adenoma↗
PubMed2004

[Therapeutic effect of spinal cord stimulation for a patient suffering spasticity after hypoxia of the brain].

We reported a case of severe spasticity of the bilateral upper and lower limbs which was improved by cervical spinal cord stimulation (SCS). A 53-year-old man was suffering from sudden cardiopulmonary arrest while walking. After receiving cardiopulmonary resuscitation for 40 minutes, his cardiopulmonary function re-started, but he failed to regain consciousness. MRI revealed a hypoxic brain in his bilateral basal ganglia and occipital lobes. After 2 months, his consciousness advanced to a vegetative state and the muscle tone of his bilateral upper and lower limbs deteriorated to severe spasticity. SCS was performed in the expectation of improving his consciousness. Contrary to this anticipated result, his vegetative state continued but the severe spasticity of his upper and lower limbs improved during the SCS. Single photon emission computed tomography (SPECT) during the period of stimulation revealed a high blood flow, especially in the area of the basal ganglia, thalamus, brain stem and cerebellum, compared with off-stimulation blood flow. The neurophysiologic mechanisms of these abnormal fields and the underlying aberrant afferent nerve impulses from the posterior funiculus in the cervical cord to the cerebral sensory cortex, which may indeed be secondary to ischemic brain, may be regulated by SCS, also adding the effect of increased blood flow to the brain.

Brain↗
PubMed2004

[Spontaneous regression of primary central nervous system lymphoma: a case report].

A rare case of primary central nervous system lymphoma that regressed spontaneously as shown on serial cranial magnetic resonance imagings (MRI) is described. A 60-year-old woman was admitted to our hospital with a well-enhanced mass lesion in the cerebellum although MRI had demonstrated no abnormal findings 4 months before admission. On admission, She complained of headache, but no neurological deficits were observed. The patient underwent exploratory craniotomy and the tumor was partially removed on February 14. Pathologic examination suspected B-cell type of malignant lymphoma. Postoperative MRI performed on February 23, 2001 showed disappearance of the mass lesion without further treatment. Different polymerase chain reaction (PCR) assays detected clonal immunoglobulin heavy chain gene rearrangements in paraffin-embedded tissues diagnosed as B-cell lymphoma. The patient was discharged without any neurological deficits for two weeks and was followed up on MRI. One year after operation, MRI revealed an abnormal finding in the cerebellum without apparent neurological deterioration. Radiation therapy of the whole brain and the local site was carried out with a total dose of 50Gy. MRI demonstrated complete remission of the tumor following radiation therapy. She was admitted again to our hospital with right hemiparesis on May, 2003. Subsequently, systemic chemotherapy was carried out. The patient died 2 years and 10 months after her initial presentation.

Cerebellar Neoplasms↗
PubMed2003

[Solitary fibrous tumor of the fourth ventricle: case report].

A rare case of solitary fibrous tumor, located wholly within the fourth ventricle, is reported. A 57-year-old male presented with headache and nausea. The preoperative magnetic resonance images revealed a well circumscribed mass in the fourth ventricle that exhibited a low intensity on T1-weighted images and homogeneously enhanced with gadolinium. Vertebral angiogram revealed a tumor stain supplied from the choroidal branches of the posterior inferior cerebellar artery. The tumor was totally resected through a midline suboccipital approach. Histologically, the tumor was composed of spindle-shaped cells growing in fascicles within a collagenous matrix. Immunohistochemical staining demonstrated vimentin and the CD34 positivity of tumor cells. Solitary fibrous tumor is a newly described entity, which should be considered in the differential diagnosis for dural-based lesions.

Cerebral Ventricle Neoplasms↗
PubMed2003

[Progressive brain injury].

The aim of this study was to evaluate the clinical manifestations and prognostic factors of progressive brain injury following trauma. We reviewed the records of 779 patients with head injury who had an admission Glasgow Coma Scale of 9 or more; 70 (7.0%) developed progressive brain injury as evidenced on serial CT scans. Of these 70 patients, 19 (27.1%) had a subdural hematoma, 19 (27.1%) an epidural hematoma, 16 (22.9%) a cerebral contusion, 13 (18.6%) an intracerebral hematoma, and 3 (4.3%) a diffuse brain swelling. Three months after injury, 36 (51.4%) patients died, 2 (2.9%) were left in a vegetative state and 23 (32.9%) had a favorable outcome. The appearance of progressive brain injury was associated with patient age, admission Glasgow Coma Scale, injury mechanisms, skull fracture and hemorrhagic lesions on the initial CT scan. Patients with the extracerebral lesions deteriorated 4 hours after injury, whereas those with intracerebral lesions deteriorated 8 hours after injury. The outcome based on Glasgow Outcome Scale was significantly associated with age, type of intracranial lesion, Glasgow Coma Scale following deterioration, the mechanism of injury and surgical treatment. It is concluded that early repeated CT scan is indicated in patients with risk factors of developing progressive brain injury.

Adult↗
PubMed2003

[Two cases of lymphocytic infundibuloneurohypophysitis].

We report two cases of lymphocytic infundibuloneurohypophysitis (LIH). A 32-year-old male and a 13-year-old male were admitted to our hospital because of a sudden occurrence of the diabetes insipidus (DI). MRI of both patients showed the disappearance of hyperintensity of the posterior pituitary in T1WI, pituitary stalk swelling and enlargement of the pituitary gland, with homogeneous enhancement by gadolinium. We thereby diagnosed LIH, so neither patient was operated on, but both were followed-up conservatively. We reviewed 51 cases of LIH. The patient's ages ranged from 4 to 74 years (mean 45.4 years). Based on the initial symptoms, DI was found in all cases. Almost all these cases revealed characteristic MRI findings similar to those in our cases. The mean follow-up period was 3.1 years. The rate of disappearance of radiological abnormalities was 56.2%, but only 13.7% of DI improved. If we encounter a patient presenting with idiopathic DI whose MRI is strongly suggestive of LIH, and barring the necessity of an urgent operation, careful conservative treatment is advised.

Adolescent↗