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Biomedical subjects

Isao Date

Publications and source records attributed to Isao Date.

At least 37 records · Page 2Linked to original sources
PubMed2005

Grafting of glial cell line-derived neurotrophic factor secreting cells for hypoxic-ischemic encephalopathy in neonatal rats.

OBJECTIVE: It has been reported that an infarcted area is reduced by the injection of glial cell line-derived neurotrophic factor into brain parenchyma after hypoxic/ischemic insult in neonatal rats. For use of glial cell line-derived neurotrophic factor in humans, we have developed a system for the delivery of a constant supply of glial cell line-derived neurotrophic factor to the brain. The aim of this study was to examine the neuroprotective effect of glial cell line-derived neurotrophic factor with the use of this delivery system. STUDY DESIGN: Baby hamster kidney cells were transfected with human glial cell line-derived neurotrophic factor complementary DNA, encapsulated in semipermeable hollow fibers, and implanted into the left cerebrum of 12-day-old Wistar rats (glial cell line-derived neurotrophic factor group, 11 rats). Nontransfected baby hamster kidney cells served as controls (control group, 9 rats). Two days after implantation, the rats received a hypoxic/ischemic stress, with a modification of Levine's method. Seven days later the rats were killed, and coronal brain slices were cut 2, 4, 6, 8, and 10 mm from the anterior pole. The cortex, hippocampus, striatum, and thalamus were evaluated for damage severity. The serum concentrations of glial cell line-derived neurotrophic factor were also determined. RESULTS: The left brain hemispheric area was significantly larger; the neuronal damage to each brain region was significantly less, and the serum glial cell line-derived neurotrophic factor concentrations were significantly higher in the glial cell line-derived neurotrophic factor group, compared with the control group. CONCLUSION: Grafting of encapsulated glial cell line-derived neurotrophic factor-secreting cells is a promising way to protect the neonatal brain from hypoxic/ischemic insult.

Animals↗
PubMed2005

Implantation of encapsulated glial cell line-derived neurotrophic factor-secreting cells prevents long-lasting learning impairment following neonatal hypoxic-ischemic brain insult in rats.

OBJECTIVE: Implantation of encapsulated glial cell line-derived neurotrophic factor-secreting cells into brain parenchyma reduces histological brain damage following hypoxic-ischemic stress in neonatal rats. We examined the effect of glial cell line-derived neurotrophic factors on long-term learning and memory impairment and morphological changes up to 18 weeks after hypoxic-ischemic stress in neonatal rats. STUDY DESIGN: Baby hamster kidney cells were transfected with expression vector either including (glial cell line-derived neurotrophic factor-hypoxic-ischemic group; n = 10) or not including (control-hypoxic-ischemic group; n = 8) human glial cell line-derived neurotrophic factor cDNA, encapsulated in semipermeable hollow fibers, and implanted into the left brain parenchyma of 7-day-old Wistar rats. Two days after implantation the rats received hypoxic-ischemic stress, and their behavior was then examined in several learning tasks: the 8-arm radial maze, choice reaction time, and water maze tasks, which examine short-term working memory, attention process, and long-term reference memory, respectively. The rats were killed 18 weeks after the hypoxic-ischemic insult for evaluation of brain damage. Two additional control groups were used: the control group (n = 15), which underwent no treatment, and the glial cell line-derived neurotrophic factor group (n = 6), which underwent implantation of the glial cell line-derived neurotrophic factor capsule but did not undergo hypoxic-ischemic stress. RESULTS: The decrease in the size of the cerebral hemisphere was significantly less in the glial cell line-derived neurotrophic factor-hypoxic-ischemic group, compared with the control-hypoxic-ischemic group, and improved performance was observed in all three tasks for the glial cell line-derived neurotrophic factor-hypoxic-ischemic group: for the control-hypoxic-ischemic group versus the glial cell line-derived neurotrophic factor-hypoxic-ischemic group, respectively, in the 8-arm radial maze test, average number of correct choices was 6.2 +/- 0.1 versus 6.9 +/- 0.1 ( P < .01); in the choice reaction time test, average reaction time for a correct response was 2.35 +/- 0.1 seconds versus 1.97 +/- 0.09 seconds ( P < .01); in the water maze test, average swimming length was 1120.0 +/- 95.2 cm versus 841.6 +/- 92.1 cm ( P < .01). All results for the glial cell line-derived neurotrophic factor group were similar to those for the control group. CONCLUSION: Glial cell line-derived neurotrophic factor treatment is effective in not only reducing brain damage but also inhibiting learning and memory impairment, following hypoxic-ischemic insult in neonatal rats. No adverse effects in learning and memory tests were observed in the glial cell line-derived neurotrophic factor group.

Analysis of Variance↗
PubMed2005

Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model.

Mesenchymal stem cells (MSC) were reported to ameliorate functional deficits after stroke in rats, with some of this improvement possibly resulting from the action of cytokines secreted by these cells. To enhance such cytokine effects, we previously transfected the telomerized human MSC with the BDNF gene using a fiber-mutant adenovirus vector and reported that such treatment contributed to improved ischemic recovery in a rat transient middle cerebral artery occlusion (MCAO) model. In the present study, we investigated whether other cytokines in addition to BDNF, i.e., GDNF, CNTF, or NT3, might have a similar or greater effect in this model. Rats that received MSC-BDNF (P < 0.05) or MSC-GDNF (P < 0.05) showed significantly more functional recovery as demonstrated by improved behavioral test results and reduced ischemic damage on MRI than did control rats 7 and 14 days following MCAO. On the other hand, rats that received MSC-CNTF or MSC-NT3 showed neither functional recovery nor ischemic damage reduction compared to control rats. Thus, MSC transfected with the BDNF or GDNF gene resulted in improved function and reduced ischemic damage in a rat model of MCAO. These data suggest that gene-modified cell therapy may be a useful approach for the treatment of stroke.

Animals↗
PubMed2005

A case of solitary subependymal giant cell astrocytoma: two somatic hits of TSC2 in the tumor, without evidence of somatic mosaicism.

Subependymal giant cell astrocytoma (SEGA) is a unique brain tumor arising in tuberous sclerosis complex (TSC), an autosomal dominant inherited phacomatosis. There are several case reports of solitary SEGA without any other manifestations of TSC. Usually these cases are thought to be forme fruste of TSC due to somatic mosaicism. However, no previous reports have used molecular methodology to fully investigate mutations in TSC genes or the possibility of somatic mosaicism. Here, we report a 20-year-old woman with a brain tumor. Pathological diagnosis was consistent with SEGA, but comprehensive clinical screening found no other lesions indicative of TSC. Molecular analysis of the tumor revealed loss of heterozygosity and allelic mutation (5228G>A, R1743Q) of TSC2. To detect the small fraction of mosaic mutation in somatic cells, we developed a highly sensitive new method: triple-nested polymerase chain reaction-restriction fragment length polymorphism. The identical TSC2 missense mutation was not detected in any other tissues from the same patient, including peripheral blood, buccal mucosa, urinary sediment, nail, and hair. According to these results, this patient should be considered as having SEGA that developed from two somatic hit mutations in TSC2, rather than being a TSC2 patient with a very small fraction of somatic mosaicism.

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↗
PubMed2005

Periodic secretion of adrenocorticotropin in a patient with Cushing's disease manifested during pregnancy.

We report the case of 19-year-old woman with cyclical Cushing's disease, in whom plasma adrenocorticotropin (ACTH) was secreted periodically after her first pregnancy. Since the 33rd week of pregnancy, hypertension and proteinuria became clinically remarkable. She gave normal birth at 36th week of pregnancy; however she continued to gain body weight even after delivery and developed typical Cushingoid features. Her ACTH secretion lacked normal daily fluctuation but exhibited periodic change during 1-year observation, showing 119 pg/ml, 34.6 pg/ml and 115 pg/ml at the 4th, 7th and 13th months after delivery. Plasma ACTH levels were increased by corticotropin releasing hormone and metyrapone, while low-dose dexamethasone suppressed cortisol secretion. Gel filtration analysis of the patient's plasma detected big ACTH molecules being eluted with a peak of authentic 1-39 ACTH. Cranial magnetic resonance imaging revealed a 1-cm pituitary mass in right cavernous sinus. The pituitary tumor was removed by transsphenoidal surgery at 13th month after delivery and was pathologically compatible with ACTH-producing pituitary adenoma by immunohistochemistry. This case includes clinically rare subsets of Cushing's syndrome showing periodic ACTH secretion and aberrant ACTH molecules.

Adenoma↗
PubMed2005

Early transplantation of an encapsulated glial cell line-derived neurotrophic factor-producing cell demonstrating strong neuroprotective effects in a rat model of Parkinson disease.

OBJECT: Glial cell line-derived neurotrophic factor (GDNF) has been shown to confer neuroprotective effects on dopaminergic neurons. The authors investigated the effects of GDNF on 6-hydroxydopamine (6-OHDA)-treated dopaminergic neurons in vitro and in vivo. METHODS: First, the authors examined how 1, 10, or 100 ng/ml of GDNF, administered to cells 24 hours before, simultaneously with, or 2 or 4 hours after 6-OHDA was added, affected dopaminergic neurons. In a primary culture of E14 murine ventral mesencephalic neurons, earlier treatment with the higher dosage of GDNF suppressed 6-OHDA-induced loss of dopaminergic neurons better than later treatment. Next, the authors examined whether continuous infusion of GDNF at earlier time points would demonstrate a greater neuroprotective effect in a rat model of Parkinson disease (PD). They established a human GDNF-secreting cell line, called BHK-GDNF, and encapsulated the cells into hollow fibers. The encapsulated cells were unilaterally implanted into the striatum of adult rats 1 week before; simultaneously with; or 1, 2, or 4 weeks after 6-OHDA was given to induce lesions of the same striatum. With the earlier transplantation of a BHK-GDNF capsule, there was a significant reduction in the number of amphetamine-induced rotations displayed by the animals. Rats that had received earlier implantation of BHK-GDNF capsules displayed more tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta and a tendency for glial proliferation in the striatum. CONCLUSIONS: These neuroprotective effects may be related to glial proliferation and signaling via the GDNF receptor alpha1. The results of this study support a role for this grafting technique in the treatment of PD.

Adrenergic Agents↗
PubMed2005

Encapsulated vascular endothelial growth factor-secreting cell grafts have neuroprotective and angiogenic effects on focal cerebral ischemia.

OBJECT: The authors evaluated the neuroprotective and angiogenic effects of a continuous and low-dose infusion of vascular endothelial growth factor (VEGF)-165 on cerebral ischemia in rats. METHODS: The authors introduced VEGF complementary (c)DNA into baby hamster kidney (BHK) cells and established a cell line that produces human VEGF165 (BHK-VEGF). The BHK-VEGF cells and BHK cells that had been transfected with an expression vector that did not contain human VEGF165 cDNA (BHK-control) were encapsulated. Both capsules were implanted into rat striata. Six days after capsule implantation, the right middle cerebral artery (MCA) was occluded. Some animals were killed 24 hours after occlusion to measure the volume of the resulting infarct and to perform immunohistochemical studies. Other animals were used for subsequent behavioral studies 1, 7, and 14 days after MCA occlusion. The encapsulated BHK-VEGF cell grafts significantly reduced the volume of the infarct and the number of apoptotic cells in the penumbral area when compared with the effect of the BHK-control cell capsule. In addition, angiogenesis and gliogenesis significantly increased in the region around the capsule in animals that received BHK-VEGF cell capsules without an increase in focal cerebral blood flow; this did not occur in animals that received the BHK-control cell capsule. In behavioral studies rats that received the BHK-VEGF cell capsule displayed significant recovery while participating in the accelerating rotarod test after stroke. CONCLUSIONS: Continuous intracerebral administration of low-dose VEGF165 through encapsulated grafts of VEGF-producing cells produces neuroprotective and angiogenic effects. These effects improve subsequent motor function.

Animals↗
PubMed2005

Enhanced brain angiogenesis in chronic cerebral hypoperfusion after administration of plasmid human vascular endothelial growth factor in combination with indirect vasoreconstructive surgery.

OBJECT: Vascular endothelial growth factor (VEGF) is a secreted mitogen associated with angiogenesis. The conceptual basis for therapeutic angiogenesis after plasmid human VEGF gene (phVEGF) transfer has been established in patients presenting with limb ischemia and myocardial infarction. The authors hypothesized that overexpression of VEGF using a gene transfer method combined with indirect vasoreconstruction might induce effective brain angiogenesis in chronic cerebral hypoperfusion, leading to prevention of ischemic attacks. METHODS: A chronic cerebral hypoperfusion model induced by permanent ligation of both common carotid arteries in rats was used in this investigation. Seven days after induction of cerebral hypoperfusion, encephalomyosynangiosis (EMS) and phVEGF administration in the temporal muscle were performed. Fourteen days after treatment, the VEGF gene therapy group displayed numbers and areas of capillary vessels in temporal muscles that were 2.2 and 2.5 times greater, respectively, in comparison with the control group. In the brain, the number and area of capillary vessels in the group treated with the VEGF gene were 1.5 and 1.8 times greater, respectively, relative to the control group. CONCLUSIONS: In rat models of chronic cerebral hypoperfusion, administration of phVEGF combined with indirect vasoreconstructive surgery significantly increased capillary density in the brain. The authors' results indicate that administration of phVEGF may be an effective therapy in patients with chronic cerebral hypoperfusion, such as those with moyamoya disease.

Animals↗
PubMed2005

[Sequentially occurred bilateral atlantoaxial rotatory subluxation following craniotomy: a case report].

Atlanto-axial rotatory subluxation (AARS) often presents in childhood as a stiff, painful neck with associated typical cock-robin type of torticollis. It can occur spontaneously or following minor trauma or an inflammatory process in the cervical tissues or following otorhinolaryngeal surgery. We report a case of bilateral AARS which occurred sequentially following craniotomy. To the best of our knowledge, no case of AARS after craniotomy has been reported previously and only one case in which bilateral AARS was observed has been reported to date. Failure to recognize the condition may result in a fixed rotatory subluxation, which can be difficult to treat. Awareness of this condition by surgeons involved in brain surgery should lead to its early recognition and treatment, preventing a fixed deformity occurring. We discuss the clinical presentation and management of AARS. The literature on this subject is briefly reviewed.

Astrocytoma↗
PubMed2005

Visualization of aneurysmal contours and perianeurysmal environment with conventional and transparent 3D MR cisternography.

We have developed conventional and transparent 3D MR cisternography to investigate the spatial relationship between the contours of aneurysmal complex and the perianeurysmal structures including the cranial nerves, dural fold, cranial base bone, and brain parenchyma. Volume data obtained by a T2-weighted 3D fast spin-echo sequence were reconstructed by using a perspective volume-rendering algorithm with a transluminal imaging technique. 3D MR cisternograms provide useful anatomic information in the therapeutic and follow-up management of unruptured cerebral aneurysms.

Aged↗
PubMed2005

[Assessment of the signal intensity distribution pattern within the unruptured cerebral aneurysms using color-coded 3D MR angiography].

To evaluate the interaction between the MR signal intensity distribution pattern and bleb formation/ deformation of the aneurysmal dome, fifty cases of the unruptured cerebral aneurysms were investigated with the color-coded 3D MR angiography. Patterns were categorized into central-type, neck-type and peripheral-type according to the distribution of MR signals with low-, moderate- and high signal intensity areas. Imaging analysis revealed the significant relationship (P < 0.02) of the peripheral-type aneurysms to the bleb formation and deformation of the dome, compared with those of central- and neck-type. Additionally, peripheral-type signal intensity distribution pattern was shown with aneurysms harboring relatively large dome size and lateral-type growth including internal carotid aneurysms. Prospective analysis of intraaneurysmal flow pattern with the color-coded 3D MR angiography may provide patient-specific analysis of intraaneurysmal flow status in relation to the morphological change of the corresponding aneurysmal dome in the management of unruptured cerebral aneurysms.

Adolescent↗
PubMed2005

[Assessment of the perianeurysmal environment of unruptured internal carotid-posterior communicating artery aneurysms with fusion imaging of three-dimensional magnetic resonance cisternography and angiography].

The anatomical relationship of an unruptured internal carotid-posterior communicating artery aneurysm and the perianeurysmal environment was investigated by using three-dimensional (3D) magnetic resonance cisternography (MRC), angiography (MRA) and newly developed fusion images of 3D MRC and 3D MRA. Contact of an aneurysm with the adjacent intra- and pericisternal structures was observed in cases with the aneurysm developing and extending beyond the capacity of the surrounding subarachnoid space. Deformation and bleb formation of the aneurysmal dome was depicted at the dome in contact with the perianeurysmal environment, including the tentorial edge, the anterior petroclinoid dural fold, the oculomotor nerve, the posterior clinoid process, the dorsum sellae and the cranial base bone. By using the fusion imaging technique of 3D MRC and 3D MRA, assessment of the contact of an unruptured cerebral aneurysm with its perianeurysmal environment can be made. Such contact gives ride to risk of deformation and bleb formation of the aneurysmal dome; and may result in cranial nerve symptoms and accelerate rupture from an unruptured cerebral aneurysm.

Aged↗
PubMed2005

[Local intraarterial fibrinolysis in central retinal artery occlusion: case report].

The authors report a case of local intraarterial fibrinolysis (LIF) in central retinal artery occlusion (CRAO). A 79-year-old man with stenosis of the left internal carotid artery (ICA) suffered sudden loss of vision in his left eye. LIF was carried out using a microcatheter in the origin of the ophthalmic artery on the side of the CRAO. Treatment was performed with 120,000 IU of urokinase. After LIF, marked improvement of vision was established. No complication occurred during LIF. One month later, carotid artery stenting was performed for the left ICA stenosis. We consider LIF in CRAO is effective treatment.

Aged↗
PubMed2005

[Percutaneous vertebroplasty combined with radiofrequency ablation for a patient with a spinal metastatic tumor: case report].

Recent technological development has allowed expanding applications of radiofrequency ablation (RFA) for malignant tumor therapy. We report a case with a spinal metastatic tumor treated with combination of percutaneous vertebroplasty (PVP) that provides pain relief and spinal stabilization and RFA. A 68-year-old male who had undergone resection of left ureteric carcinoma was referred to our hospital with lower back pain due to the fifth lumbar (L5) vertebral metastatic tumor. Conventional radiation therapy was discontinued because of pneumonia. One year later, the patient was admitted again with weakness of the right knee and foot and severe pain of the back and the right lower extremity. Radiographs demonstrated a compressive fracture of the L5 vertebra predominantly on the right side. CT and MRI showed a tumor of the L5 body invading the right pedicle, the intervertebral foramen, and the retroperitoneal space. RFA was performed in the ventral part of the L5 body, and then around the right L5/the first sacral intervertebral foramen. Temperature and time for ablation ranged from 74 degrees C to 95 degrees C and from 11 min. to 30 min., respectively. Next, PVP was performed by the right transpedicular approach. Bone cement was injected into the L5 body and the pedicle by an amount of 3.0 ml in total without technical complications. Postoperatively, visual analogue scale demonstrated decreased pain degree from 10 cm to 5.4 cm. Combined treatment with RFA and PVP is a feasible and promising procedure for spinal metastatic tumors. Further evaluation is necessary to confirm its long-term efficacy.

Aged↗
PubMed2005

Influence of perianeurysmal environment on the deformation and bleb formation of the unruptured cerebral aneurysm: assessment with fusion imaging of 3D MR cisternography and 3D MR angiography.

BACKGROUND AND PURPOSE: Surface irregularity and bleb formation are anatomical factors that are associated with aneurysm rupture. The perianeurysmal environment has been proposed as one factor that may influence aneurysm morphology. We have developed a fusion imaging technique of 3D MR cisternography and angiography that allows clear visualization of an aneurysm and its environment. This technique may prove useful in further understanding of the natural history of intracranial aneurysms. METHODS: Fusion images of 3D MR cisternography and angiography were reconstructed by a perspective volume-rendering algorithm from the volume datasets of MR cisternography, obtained by a T2-weighted 3D fast spin-echo sequence, and coordinated MR angiography, by a 3D time-of-flight sequence. On the fusion images, the anatomic relationship of an aneurysm to the perianeurysmal structures was assessed, and the influence of perianeurysmal environment on the deformation and bleb formation of the aneurysm was investigated. RESULTS: Marked and minor deformation and bleb formation of the aneurysmal dome were found at the areas confronted or adjacent to a certain contact with perianeurysmal structures, including cranial nerves, brain parenchyma, cranial base bones, petroclinoidal dural folds, and dura mater. CONCLUSION: Fusion images of 3D MR cisternography and angiography can depict the contact of an aneurysm with its perianeurysmal environment; this may provide an additional parameter in consideration for the natural history of cerebral aneurysms.

Aged↗