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Biomedical subjects

Seigo Nagao

Publications and source records attributed to Seigo Nagao.

At least 19 recordsLinked to original sources

Magnetic resonance imaging and positron emission tomography findings in status epilepticus following severe hypoglycemia.

We recently experienced a case with asymmetrical cortical abnormality on MRI with focal status epilepticus following severe hypoglycemia. The cerebral blood flow and metabolisms for oxygen and glucose were determined using positron emission tomography (PET) during focal status epilepticus following severe hypoglycemia and at the follow-up period. Prolonged seizure activity produced profound glucose hypermetabolism and mild hyperemia in the region of the presumed cortical focus of epilepsy and in structures anatomically remote from the focus, corresponding to the areas of abnormal signal intensity on the MRI. The patient remained comatose and exhibited a diffuse hypoperfusion/hypometabolism and symmetrical brain atrophy on the follow-up PET and MRI, respectively. Cytotoxic brain edema due to profound glucose metabolism without compensatory increase of the blood flow during status epilepticus may account for the brain abnormality observed on the early MRI. Simultaneous examination of the cerebral blood flow and metabolism using PET can provide useful information about the pathology in patients with status epilepticus.

Aged↗

Chiari I malformation accompanied by assimilation of the atlas, Klippel-Feil syndrome, and syringomyelia: case report.

BACKGROUND: Chiari I malformation, accompanied by superposed bony anomaly of the craniovertebral junction, is comparatively rare. We report a case of Chiari I malformation accompanied by assimilation of the atlas, Klippel-Feil syndrome, and syringomyelia. CASE DESCRIPTION: The patient was a 61-year-old woman demonstrating numbness of the extremities, sensory impairment, muscular weakness, and tendon hyper-reflexia. X-ray images and CT scans demonstrated assimilation of the atlas to the occipital bone, C2 and C3 fusion, abnormal passage of the vertebral arteries, and an anomalous bony mass on the right lateral mass of the atlas protruding into the spinal column. The odontoid process was also deviated to the left. Magnetic resonance images demonstrated bilateral descent of the cerebellar tonsils and syringomyelia extending from C6 to T8. Computed tomographic scans with the head rotated to the right demonstrated increased narrowing of the vertebral column caused by the right lateral mass of the atlas, and MR images confirmed exaggerated deformation of the spinal cord at the same region. This deformation manifested no neurologic symptoms, and we therefore performed foramen magnum decompression and duraplasty using Gore-Tex (W.L. Gore & Associates, Inc., Flagstaff, AZ). In the early postoperative period, neurologic symptoms improved. CONCLUSION: We believe it is important that a treatment plan for Chiari I malformation accompanied by bony anomaly of the craniovertebral junction be determined based on morphologic investigation of the region supplemented by dynamic imaging-based evaluation of instability, or a careful inspection for atypical passage of the vertebral arteries, a frequent site of complication.

Arnold-Chiari Malformation↗

Technetium-99m sestamibi single photon emission computed tomography findings correlated with P-glycoprotein expression in pituitary adenoma.

The aim of this study is to evaluate whether the technetium-99m sestamibi ((99m)Tc-MIBI) single photon emission computed tomography (SPECT) characteristics of pituitary adenomas might be correlated with cavernous sinus invasion, proliferative potential or the multidrug-resistance (MDR-1) gene product P-glycoprotein (Pgp) expression in pituitary adenomas. Fifteen patients with pituitary adenomas, including 10 nonfunctioning adenomas, two prolactinomas, two GH producing adenomas, and one ACTH producing adenomas was investigated for this study. SPECT images with (99m)Tc-MIBI were acquired 15 minutes (early) and 3 hours (delayed) after injection. The tumor-to-normal brain ratio was calculated both early (ER) and delayed (DR) images. Retention index (RI) was calculated using the following formula: (DR-ER)/ERx100%. The pituitary adenomas specimens were examined by immunohistochemistry using anti-Pgp and MIB-1 monoclonal antibodies.(99m)Tc-MIBI SPECT findings were not related to MIB-1 labeling index or cavernous sinus invasion. (99m)Tc-MIBI SPECT RI (-38.55+/-20.77) of the Pgp-positive group was significantly lower than that (-15.78+/-19.40) of Pgp-negative group (p=0.0494). No significant difference was observed in the ER and DR of (99m)Tc-MIBI SPECT between Pgp-positive and negative groups. Our study suggests that although (99m)Tc-MIBI SPECT is not useful to evaluate the proliferative potential or cavernous sinus invasion of pituitary adenomas. (99m)Tc-MIBI SPECT could predict anti-cancer drug resistance related to the expression of Pgp in pituitary adenomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Differences in the neuronal stem cells survival, neuronal differentiation and neurological improvement after transplantation of neural stem cells between mild and severe experimental traumatic brain injury.

We developed a novel protocol for generation and selective amplification of neural progenitor cells regionally specified to the rostral brain but not the spinal cord from mouse embryonic stem cells (ESCs). The neural progenitors could differentiate in vitro and in vivo into many cholinergic and a few GABAergic neurons but rarely into astrocytes. The transplanted neurospheres could survive in the hippocampus (CA3) of animals with mild traumatic brain injury (TBI). Twelve weeks after transplantation (a week after the behavioral test), we found significant cholinergic differentiation recognized as ChAT immunoreactivity in the eGFP+transplanted cells. Moreover, the grafts contained a few GAD67+cells. However, we barely found GFAP+astrocytes within the grafts. Furthermore, presynaptic formations of graft-derived neurons were recognized by immunohistochemistry of near the grafts around CA3. However, these findings were not observed in severe TBI group. So, we examined NGF, BDNF, and FGF-2 mRNA by RT-PCR in 12 mice including normal, mild TBI and severe TBI group. Increases in the neurotrophic factors' mRNA were evident in the hippocampus on the ipsilateral side in the mild TBI group. Statistical analysis revealed significant differences between the mild and severe TBI groups. The data also revealed significant differences between the mild TBI and normal groups. The transplanted neurospheres could survive in the mild TBI animals, but not in the severe TBI group.

Animals↗

Neural stem cells transplantation in cortex in a mouse model of Alzheimer's disease.

OBJECTIVE: The goal of this study was to elucidate the effect of neurospheres (NS) on dementia in the mouse model of nucleus basalis of Meynert (NBM) lesion. METHODS: Mouse embryonic stem cell (ES) derived neurospheres were transplanted into the frontal association cortex and barrel field of S1 cortex of C57BL/6 mice 4 weeks after including a lesion of NBM by ibotenic acid, while other healthy mice that received ES cells served as control. Behavioral tests by 8-arm radial maze were conducted 8 weeks after transplantation, and double staining of choline acetyltransferase (ChAT), serotonin, amyloid-beta protein (AP) and green fluorescent protein (GFP) 12 weeks after transplantation. We found that the neurospheres transplanted into the mouse cortex survived and produced many ChAT-positive neurons and a few serotonin-positive neurons in and around the grafts. The working memory error decreased significantly in the mice grafted with neurospheres. In contrast, the ES cells developed into teratomas in all of the control mice and expressed no neurons, and the working memory deteriorated remarkably. CONCLUSIONS: Transplantation of neurospheres, but not ES cells, into the prefrontal and parietal cortices, dramatically alleviated the cholinergic deficits and recent memory disruption in the NBM lesioned mice.

Alzheimer Disease↗

Crossed cerebellar glucose hypermetabolism demonstrated using PET in symptomatic epilepsy--case report.

A 65-year-old male with an old cerebral contusion in the frontal lobes had suffered from status complex partial seizures. Ictal positron emission tomography with an F-18 fluorodeoxyglucose ([18F]FDG-PET) scan revealed hypermetabolism in the frontal, temporal and parietal lobes and the contralateral cerebellar hemisphere. The patient underwent a next-day PET scan with the 15O-labeled gas inhalation technique, which showed mild hyperperfusion and oxygen hypermetabolism in these areas. An interictal [18F]FDG-PET scan 17 days after the initial epilepsy demonstrated glucose hypometabolism of the frontal, temporal and parietal lobes and the contralateral cerebellar hemisphere. Increased glucose metabolism on the interictal PET scan and decreased glucose metabolism on an interictal PET scan in the epileptogenic supratentorial zones and the contralateral cerebellar hemisphere are interesting observations for understanding the pathophysiology in long-standing partial seizures.

Aged↗

Evaluation of tumor FDG transport and metabolism in primary central nervous system lymphoma using [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) kinetic analysis.

OBJECTIVE: Although 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been used as a promising tool to diagnose primary central nervous system lymphoma (PCNSL) because the tumor shows very high FDG accumulation, no data exist evaluating the extent of tumor FDG transport and metabolism. The aim of this study was to evaluate the feasibility of FDG-PET kinetic analysis in measurement of uptake parameters of FDG in the lymphoma tissues and in the assessment of treatment effects in patients with PCNSL. METHODS: Dynamic FDG-PET examination was performed in 7 histologically proven PCNSL patients before and after methotrexate-based chemotherapy. RESULTS: Before the chemotherapy, the highest CMRglc in the tumor for all 7 patients was 79.4 +/- 27.2 micromol/100 g/min. This value was significantly higher than that observed in the normal cortex in 14 control patients (44.3 +/- 6.0 micromol/100 g/min, p < 0.001). The phosphorylation (k3) activity was also significantly higher in the tumor (0.093 +/- 0.026 min(-1)) compared with the normal cortex (0.064 +/- 0.014 min(-1), p < 0.05). On the other hand, the transporter (K1) activity in the tumor (0.079 +/- 0.016 ml/min) was similar to that observed in the normal cortex (0.082 +/- 0.012 ml/min). The chemotherapy significantly reduced the volume of the tumor in 6 of 7 patients and the highest CMRglc in the tumor examined 18.0 +/- 5.5 days after the chemotherapy (34.0 +/- 21.8 micromol/100 g/min) was significantly lower than that observed before the chemotherapy (p < 0.01). This reduction in FDG uptake was concomitant with a significant reduction in both the K1 and k3 values (p < 0.05). The reduction in the k3 value after the chemotherapy was marked in 6 of 7 patients in whom the tumor responded to the first chemotherapy. CONCLUSIONS: Dynamic image acquisition can separate regional FDG uptake into FDG transport and phosphorylation activity in the lymphoma tissues. Tumor FDG uptake was significantly higher with accelerated phosphorylation activity compared with that observed in the normal cortex.

Aged↗

Usefulness of [18F]FDG-PET kinetic analysis in non-enhancing primary central nervous system lymphoma: case report.

A 62-year-old woman experienced headache and rapidly progressive left hemiparesis over 2 weeks. Diffusion-weighted and fluid-attenuated inversion recovery MR images of the head showed increased signal intensity in the right basal ganglia, periventricular white matter and the brain stem. Enhancement was not observed on a T1-weighted spin-echo MR image after the administration of a contrast material. An 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) study with kinetic analysis showed decreased FDG transport and increased hexokinase activity in the lesions compared with the contralateral hemisphere. The diagnosis was made by biopsy of the right caudate head and pathologic specimens were positive for malignant large-cell lymphoma, B-cell phenotype. The patient received high-dose methotrexate with CHOP chemotherapy, and an [18F]FDG-PET study with kinetic analysis showed decreased hexokinase activity after the first chemotherapy. Kinetic [18F]FDG-PET analysis may be useful to diagnose and monitor the treatment effect in non-enhancing primary central nervous system lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗

Matrix metalloproteinase-2 expression correlates with cavernous sinus invasion in pituitary adenomas.

UNLABELLED: The aim of this study was to evaluate the relationship between expression of matrix metalloproteinase-2 (MMP-2) and cavernous sinus invasion in pituitary adenoma. METHOD: Tissue samples from 54 pituitary adenomas were examined for expression of MMP-2 protein by immunohistochemistry. In sixteen tumors, the expression of MMP-2 mRNA was also examined by RT-PCR. Immunostaining was semiquantatively scored based on intensity (0-3) and distribution (0-3). RESULTS: There were 34 women and 20 men, with a mean age of 49.9 years (range 18-76). There were 12 tumors with cavernous sinus invasion, and 42 noninvasive cases. The MMP-2 score of pituitary adenomas with cavernous sinus invasion (3.9 +/- 0.5) was significantly higher than those without invasion (2.3 +/- 0.2; P < 0.01). There was no difference in MMP-2 score between macroadenomas (3.0 +/- 0.3) and microadenomas (2.1 +/- 0.4; P > 0.05), and also, no difference between the functioning adenomas (2.8 +/- 0.3) and non-functioning adenomas (2.8 +/- 0.3; P > 0.05). We found no correlation between the MMP-2 score and the Ki-67 labeling index (r2 = -0.05; P = 0.72). MMP-2 mRNA expression was also intense in invasive pituitary adenomas and was significantly higher in invasive pituitary adenomas than those without invasion (68.2 +/- 15.3; 21.8 +/- 8.2; P < 0.05). CONCLUSION: This study suggests that MMP-2 may be associated with aggressiveness and invasion in pituitary adenoma but is not related to tumor size or secretory function. MMP-2 may be a useful tool for assessing the invasive potential.

Adolescent↗

Hemodynamic and metabolic changes in a patient with cerebral venous sinus thrombosis: evaluation using O-15 positron emission tomography.

The cerebral hemodynamics and oxygen metabolism before and after the recanalization of the occluded sinus were evaluated using O-15 positron emission tomography (PET) scanning in a 21-year-old woman with superior sagittal sinus thrombosis. During the initial presentation, there was increased regional cerebral blood volume (rCBV) in the left frontal and parietal lobes with moderately increased rCBV in the right parietal lobe. Recanalization of the occluded sinus resulted in a normalization of elevated rCBV in the frontal and parietal lobes and improvements of rCBF and regional cerebral metabolic rate for oxygen in the occipital lobe. Clinical improvement after recombinant tissue plasminogen activator therapy was accompanied by restoration of cerebral hemodynamics and oxygen metabolism, although magnetic resonance venography showed only partial recanalization of the occluded sinus. PET evaluation of the cerebral hemodynamics and oxygen metabolism may be of value in gaining further insight into pathophysiological characteristics of human cerebral venous sinus thrombosis.

Adult↗

Rhomboid perforator flap for a large skin defect due to lumbosacral meningocele: a simple and reliable modification.

To date, very few studies have reported the use of perforator flaps in newborn infants with an immature vascular system. Therefore, it is not clear whether perforator flaps can be used in newborns, as in adults. In this study, we applied the perforator flap procedure to a newborn infant, who had a large skin defect due to lumbosacral meningocele. We used the rhomboid perforator flap, which was a combination of using a rhomboid flap reported by Ohtsuka et al and preserving paraspinal perforator vessels according to Thomas. Although perforator vessels were so thin as to necessitate careful dissection and flap design, a good result was obtained by this procedure. We consider that the rhomboid perforator flap is a simple and reliable procedure for the treatment of lumbosacral meningocele.

Humans↗

Matrix metalloproteinase 2 and 9 expression correlated with cavernous sinus invasion of pituitary adenomas.

OBJECT: Matrix metalloproteinase (MMP) 2 and 9 are important for tissue breakdown in the process of tumor invasion. The aim of this study is to evaluate the relationship between the expression of MMP-2, MMP-9, MIB-1 LI and cavernous sinus invasion in pituitary adenomas. METHODS: Tissue samples from 54 patients with pituitary adenomas were studied. Expression of MMP-2, MMP-9, and MIB-1 labeling index (LI) were evaluated by immunohistochemical method. In sixteen cases, the expression of MMP-2 and MMP-9 mRNA was also examined by RT-PCR assay. RESULTS: Thirty-four patients were women and 20 were men, with a mean age of 49.9 years old (range 18-76 years). There were 12 cases with cavernous sinus invasion, and 42 were noninvasive cases. MMP-2 and MMP-9 score of invasive case (3.9 +/- 0.5,4.1 +/- 0.4) were significantly higher than those (2.3 +/- 0.2; p < 0.01; 2.6 +/- 0.2; p < 0.01) without invasion. The MIB-1 LI of this study presented no significantly difference between the invasive and noninvasive pituitary adenomas. The percentage of MMP-2 mRNA/beta-actin mRNA and MMP-9 mRNA/beta-actin mRNA were also observed significantly higher in invasive pituitary adenomas (68.2 +/- 15.3%; 59.7 +/- 12.5%) than noninvasive pituitary adenomas (21.8 +/- 8.2%, p < 0.05; 33.3 +/- 5.4%, p < 0.05). CONCLUSIONS: Our study suggests that the expression of MMP-2 and MMP-9 may have a value to assess the invasive pituitary adenomas, and proliferation and invasion of pituitary adenomas may present a different mechanism.

Adenoma↗

Resistance to topoisomerase II inhibitors in human glioma cell lines overexpressing multidrug resistant associated protein (MRP) 2.

For understanding of the resistance to topoisomerase II inhibitors, 50 sublines were isolated as single clones from parental glioma cell lines by exposure to VP-16 or m-AMSA. The quantitative aspects of topoisomerase II alpha,multi drug resistant gene (MDR)-1, breast cancer resistance protein (BCRP), and multidrug resistant associated protein (MRP) 1-5 were studied by Northern blotting in 50 resistant cell lines. By understanding the function of MRP2, we picked up three drug resistant sublines (T98G-ml, T98G-m2, and gli36-VP1) that overexpressed MRP2, but did not overexpress MDR-1 or MRP1-5 except 2. Moreover, in the results of northern blot analysis of mRNA for topoisomerase II alpha identical results are observed in parental cell lines and their resistant cell lines, suggesting that alterations in topoisomerase II do not account for the resistance in these cells. To determine whether the cellular sensitivity to anticancer agents was closely associated with the cellular levels of MRP2, we established cell lines with the same levels of MRP2 as their parental cells by introducing the MRP2 antisense expression plasmid into resistant cells. Etoposide (VP-16) accumulation and efflux studies were carried out in the parental cell lines and their drug resistant cell lines. Decreases in the HS-VP-16 accumulation and increases in the efflux were observed in these drug resistant cell lines. In the cytotoxicity assay, these drug resistant cell lines were resistant to multiple topoisomerase II inhibitors with little cross resistance to vincristine, and display efflux of VP-16. We found that the resistant cells transfected with MRP2 antisense cDNA displayed increased cellular levels of VP-16 and enhanced sensitivities to topoisomerase II inhibitors. In this study on the T98G-ml, T98G-m2, and gli36-VP1 cell lines, we showed a high correlation between MRP2 mRNA and VP-16 efflux, suggesting that MRP2 could be a new transporter for topoisomerase II inhibitors.

Antineoplastic Agents, Phytogenic↗

Disappearance of hemifacial spasm after ventriculoperitoneal shunting in a patient with achondroplasia--case report.

A 15-year-old boy with achondroplasia developed right hemifacial spasm associated with headache, vomiting, and hearing disturbance. Computed tomography showed hydrocephalus. A ventriculoperitoneal shunt was placed. His hydrocephalus subsequently resolved, the hemifacial spasm and headache disappeared, and his hearing disturbance improved. The episodes of hemifacial spasm were probably related to a small posterior cranial fossa volume, the so-called crowding of the posterior fossa. Increased intracranial pressure due to hydrocephalus apparently contributed to further reduction in the posterior cranial fossa volume and led to the hemifacial spasms. In addition, his hearing disturbance may have been the result of dysfunction of the cochlear nerve due to the increase in intracranial pressure caused by hydrocephalus.

Achondroplasia↗

Parietal lipomeningocele--case report.

A 2-month-old female infant had had a parietal mass since birth. Neuroimaging revealed a lipoma under the splenium of the corpus callosum that was connected to the subcutaneous lipoma via a bone defect in the cranium bifidum of the parietal region. At the age of 5 months, partial resection of only the extracranial mass was carried out. The histological diagnosis was lipoma. She grew up normally without neurological disorders during follow up for 12 years after the surgery. In the present case, the intracranial lipoma was associated with the cranium bifidum, and dysraphism was possibly involved in the pathogenesis. Resection of only the extracranial subcutaneous tumor can be performed for cosmetic reasons.

Brain Neoplasms↗

Improvement of cerebral arterial stenosis associated with Basedow's disease. Case report.

A 29-year-old female presented with Basedow's disease manifesting as sudden vomiting, diarrhea, fever over 38 degrees C, transient aphasia, and numbness in her extremities. These symptoms were considered due to cerebral ischemia at a local clinic. Magnetic resonance angiography indicated stenosis of the bilateral distal internal carotid arteries and the bilateral proximal anterior cerebral and middle cerebral arteries. Thyroid swelling and exophthalmos were observed. She was transferred to our hospital. Endocrine function tests showed hyperthyroidism. The diagnosis was Basedow's disease. Her symptoms disappeared after receiving intravenous drip infusion of fluid replacement, and antithyroid and antiplatelet medication. After she became euthyroid, cerebral angiography and magnetic resonance angiography revealed improvement of the stenosis of the cerebral arteries. Stenosis of the terminal portion of the internal carotid artery associated with Basedow's disease is extremely rare. Conservative treatment mainly including antithyroid medications for Basedow's disease, and antiplatelet drugs and intravenous replacement fluid for the ischemic manifestations should be the first choice of treatment unless immediate vascular reconstruction is necessary.

Adult↗

Mechanical thrombolysis for treatment of acute sinus thrombosis--case report.

A 55-year-old woman presented with consciousness disorders. Computed tomography revealed hemorrhage in the left temporoparietal region. The angiographic diagnosis was progressive sinus thrombosis from the superior sagittal sinus to the bilateral transverse sinuses. Her condition deteriorated despite heparin administration. Therefore, mechanical thrombolysis was performed for sinus thrombosis using a balloon catheter, in addition to supportive thrombolytic therapy with urokinase, resulting in sinus patency. Mechanical thrombolysis is an effective therapeutic modality for sinus thrombosis refractory to heparin administration.

Catheterization↗