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Biomedical subjects

Isao Date

Publications and source records attributed to Isao Date.

At least 55 records · Page 3Linked to original sources
PubMed2004

The NH2 terminus of influenza virus hemagglutinin-2 subunit peptides enhances the antitumor potency of polyarginine-mediated p53 protein transduction.

Protein transduction therapy is a newly developing method that allows proteins, peptides, and biologically active compounds to penetrate across the plasma membrane by being fused with cell-penetrating peptides such as polyarginine. Polyarginine-fused p53 protein penetrates across the plasma membrane of cancer cells and inhibits the growth of the cells. However, the protein is often entrapped inside macropinosomes in the cytoplasm. Therefore, high dose concentrations of the protein are needed for it to function effectively. To overcome this problem, in the present study, polyarginine-fused p53 was linked with the NH(2)-terminal domain of influenza virus hemagglutinin-2 subunit (HA2), which is a pH-dependent fusogenic peptide that induces the lysis of membranes at low pH levels. The protein was capable of efficiently translocating into the nucleus of glioma cells and induced p21(WAF1) transcriptional activity more effectively than did polyarginine-fused p53 protein. Moreover, low concentrations of the protein significantly inhibited the growth of cancer cells. These results suggest that protein transduction therapy using polyarginine and HA2 may be useful as a method for cancer therapy.

Animals↗
PubMed2004

Isolation and transplantation of dopaminergic neurons generated from mouse embryonic stem cells.

Embryonic stem (ES) cells differentiate into dopamine (DA)-producing neurons when co-cultured with PA6 stromal cells, but the resulting cultures contain a variety of unidentified cells. In order to label live DA neurons in mixed populations, we introduced a GFP reporter under the control of the tyrosine hydroxylase (TH) gene promoter into ES cells. GFP expression was observed in TH-immunoreactive cells that differentiated from the ES cells that carried the TH-GFP reporter gene. DA neurons expressing GFP were sorted from the mixed cell population by fluorescence-activated cell sorting of cells exhibiting GFP fluorescence, and the sorted GFP(+) cells obtained were transplanted into a rat model of Parkinson's disease. Some of these cells survived and innervated the host striatum, resulting in a partial recovery from parkinsonian behavioral defects. This strategy of isolation and transplantation of ES-cell-derived DA neurons should be useful for cellular and molecular studies of DA neurons and for clinical application in the treatment of Parkinson's disease.

Animals↗
PubMed2004

The relationship between peritumoral brain edema and the expression of vascular endothelial growth factor and its receptors in intracranial meningiomas.

We examined the radiological and histological features of, and the influences of the expression of VEGF and its two major receptors, Flt-1 and Flk-1, on the development of peritumoral brain edema (PTBE) in patients with intracranial meningiomas. The expressions of VEGF and VEGF receptors in the immunohistochemical study were analyzed in relation to several factors, including tumor size, location, vascularity, and blood supply, as seen on digital subtraction angiographic studies. The edema volume (P = 0.0003) and edema index (P < 0.0001) had a significantly positive relation to VEGF expression. The positivity of Flt-1 and Flk-1 was mainly observed in tumor vessels; 44 cases (37.2%) were positive for the Flt-1 antibody and 37 cases (31.4%) for the Flk-1 antibody. The mean value of the edema index of the positive-Flt-1 group (5.220 +/- 11.586) was significantly higher than that of the negative-Flt-1 group (1.782 +/- 2.559) (P < 0.0001). The mean value of the edema index of the positive-Flk-1 group (3.925 +/- 5.870) was slightly higher than that of the negative-Flk-1 group (2.671 +/- 8.136) (P < 0.0001). Our data suggest that the expressions of VEGF and VEGF receptors positively relate to each other and to the formation of PTBE in patients with meningiomas.

Adult↗
PubMed2004

Pseudoxanthoma elasticum with carotid rete mirabile.

We describe a case of Pseudoxanthoma elasticum (PXE) in a 14-year-old girl. This case is especially rare because of its association with carotid rete mirabile (CRM). Only three cases have been reported previously in the literature. Although the relation between P. elasticum and carotid rete mirabile is unclear, both disorders are believed to be major risk factors for cerebrovascular disease.

Adolescent↗
PubMed2004

BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model.

Examination of the clinical therapeutic efficacy of using bone marrow stromal cells, including mesenchymal stem cells (MSC), has recently been the focus of much investigation. 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 transfected telomerized human MSC with the BDNF gene using a fiber-mutant F/RGD adenovirus vector and investigated whether these cells contributed to improved functional recovery in a rat transient middle cerebral artery occlusion (MCAO) model. BDNF production by MSC-BDNF cells was 23-fold greater than that seen in uninfected MSC. Rats that received MSC-BDNF showed significantly more functional recovery than did control rats following MCAO. Specifically, MRI analysis revealed that the rats in the MSC-BDNF group exhibited more significant recovery from ischemia after 7 and 14 days. The number of TUNEL-positive cells in the ischemic boundary zone was significantly smaller in animals treated with MSC-BDNF compared to animals in the control group. These data suggest that MSC transfected with the BDNF gene may be useful in the treatment of cerebral ischemia and may represent a new strategy for the treatment of stroke.

Adenoviridae↗
PubMed2004

Neuroprotective effects of vascular endothelial growth factor (VEGF) upon dopaminergic neurons in a rat model of Parkinson's disease.

Vascular endothelial growth factor (VEGF) has previously been shown to display neuroprotective effects following ischemia, suggesting that VEGF may potentially be applied as a neuroprotective agent for the treatment of other neurological diseases. In this study, we investigated the neuroprotective capacity of VEGF in a model of Parkinson's disease. VEGF was found to be neuroprotective against cell death of primary E14 murine ventral mesencephalic neurons induced by 6-hydroxydopamine (6-OHDA) treatment in vitro. Further, rats receiving a continuous infusion of VEGF into the striatum via encapsulated hVEGF-secreting cells (baby hamster kidney-VEGF) displayed a significant decrease in amphetamine-induced rotational behavior and a significant preservation of tyrosine hydroxylase-positive neurons and fibers compared with control animals. VEGF likely functions via direct mechanisms by signaling through the neuropilin receptor expressed upon dopaminergic neurons in response to 6-OHDA treatment. Further, VEGF is likely to promote neuroprotection indirectly by activating the proliferation of glia and by promoting angiogenesis. Our results support a potential neuroprotective role for VEGF in the treatment of Parkinson's disease.

Adrenergic Agents↗
PubMed2004

The potential role of vascular endothelial growth factor in the central nervous system.

During the past decade, vascular endothelial growth factor (VEGF) has been widely investigated, and reported to have pleiotropic functions in the central nervous system (CNS) and its supporting physiological environment. VEGF is involved in not only such well-known functions as angiogenesis, accentuation of vessel permeability, and glial proliferation, but also more recently acknowledged functions such as neuroprotection and even neurogenesis itself. Most recently, the neurogenesis function has attracted much attention, and a number of research groups have taken up the challenge of elucidating this activity. In keeping with this trend, our knowledge of VEGF receptors has increased, and certain suggestions concerning the mechanisms of neuroprotection have come to light in the course of the ongoing work, though at times what the researchers had to work with was only a tiny percent of the signal transduction of VEGF. Together with flt-1 (VEGF receptor 1) and flk-1 (VEGF receptor 2), neuropilin (NP) is frequently described as being involved in the neuroprotective effects of VEGF. In this review, both the direct and indirect neuroprotective effects of VEGF, including various signaling pathways as well as the neurogenesis induced by this factor, are discussed in the context of the newly emerging insights into the biological mechanisms of VEGF and closely related, interacting molecules.

Animals↗
PubMed2004

Large supratentorial ectopic ependymoma with massive calcification and cyst formation--case report.

A 6-year-old boy presented with a large supratentorial ependymoma with massive calcification and central cyst formation manifesting as generalized convulsion and right hemiparesis. Computed tomography and magnetic resonance imaging showed a large, poorly enhanced, left frontal mass with massive calcification and a central cyst. Angiography revealed no extracranial blood supply to the tumor, which was supplied by branches of the left middle cerebral artery. The patient underwent total resection of the tumor, which was located in the parenchyma with no dural attachment. The tumor was clearly demarcated and dissected subpially from the surrounding brain parenchyma. The surgical findings suggested no relationship with the lateral ventricular system. Histological examination of the tumor demonstrated perivascular pseudorosette formation and mitosis with massive calcification, and immunocytochemical reactivity for glial fibrillary acidic protein and epithelial membrane antigen, but not synaptophysin. These findings were compatible with ependymoma, World Health Organization grade 2. Postoperative magnetic resonance imaging clearly showed that the tumor was located in the intradural, intraaxial space with no relationship to the ventricles.

Calcinosis↗
PubMed2004

Persistent primitive trigeminal artery-cavernous sinus fistula with intracerebral hemorrhage: endovascular treatment using detachable coils in a transarterial double-catheter technique. Case report and review of the literature.

Intracerebral hemorrhage occurred in this 61-year-old woman with preexisting diplopia and proptosis. Results of angiography demonstrated a persistent primitive trigeminal artery (PPTA)-cavernous sinus fistula with cortical venous reflux. Two microcatheters were introduced transarterially through the PPTA into the two draining pathways in the cavernous sinus. Coils were delivered in both pathways simultaneously to prevent further venous overload on either path. The fistula was successfully occluded without complication while the PPTA was preserved. The authors describe this double-catheter technique for coil embolization of a fistula and review the literature concerning PPTA-cavernous sinus fistulas.

Catheterization↗
PubMed2004

[Evaluation of the contours and perianeurysmal environment of unruptured cerebral aneurysms, using three-dimensional magnetic resonance cisternogram].

To evaluate the anatomical relationship between cerebral aneurysm and the perianeurysmal environment within a cisternal space, the contours of an unruptured cerebral aneurysm and pericisternal structures were depicted on a three-dimensional (3D) MR cisternogram. By using perspective volume-rendering algorithm, the 3D MR cisternograms were reconstructed from the source axial volume data set obtained by the T2-weighted 3D fast spin-echo sequence. Those images were shown together with the coordinated 3D MR angiograms through similar visual projections, and then compared with the intraoperative findings. The outer wall configurations of cerebral aneurysms within the cisternal space were shown in conjunction with the accompanying surface veins, adjacent cranial nerves, dura mater and tentorial edge, cranial base bone, and surrounding pericisternal brain surfaces. With application of 3D MR cisternograms in the management of unruptured cerebral aneurysm, the anatomical relationship between the aneurysmal contours and the perianeurysmal environment could be evaluated the within the cisternal space. This might provide another clinical factor when considering the potential risk of growth, rupture, and symptomatic cranial nerve signs of an unruptured cerebral aneurysm.

Adolescent↗
PubMed2004

[A case of convulsion during selective intra-arterial infusion of fasudil hydrochloride for treatment of vasospasm following subarachnoid hemorrhage].

The authors report a case of convulsion during intra-arterial selective infusion of fasudil hydrochloride (FSD) for treatment of vasospasm following subarachnoid hemorrhage (SAH). A 47-year-old man (Hunt and Kosnik grade I) presented with sudden onset of headache and was diagnosed with SAH on CT, and admitted to our hospital. Digital subtraction angiography (DSA) performed on admission revealed an anterior communicating artery aneurysm. Neck clipping of the aneurysm was performed on the same day and no neurological deficits were noted postoperatively. Motor aphasia appeared on day 11 after the operation, and emergency DSA revealed vasospasm of the left middle cerebral artery and its branches. Emergency percutaneous transluminal angioplasty was performed with successful dilation of the left M1 artery, and 25 milligrams of FSD was injected into the left M1 artery selectively. During this injection, right hemifacial convulsion appeared, and three minutes later disappeared. No treatment was needed for the seizure. Additional injection of 30 milligrams of FSD into the left internal carotid artery resulted in vasodilatation of the left M1 artery and its branches, improvement of their blood flow on angiography, and recovery from motor aphasia. The patient was discharged 1 month later with no neurological deficits. Intra-arterial selective infusion of FSD plays an important role in treatment for vasospasm following SAH, however, we must be aware of risks of complications such as convulsion.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2004

Loss of heterozygosity on chromosome 10q associated with malignancy and prognosis in astrocytic tumors, and discovery of novel loss regions.

Certain tumor suppressor genes (TSG) residing on human chromosome 10q are implicated in astrocytic tumors. We thoroughly examined loss of heterozygosity (LOH) on chromosome 10q in astrocytic tumors to determine the extent of deletion and their relation to prognostic variables of patients. We analyzed 63 astrocytic tumors, including 9 diffuse astrocytomas, 36 anaplastic astrocytomas, and 18 glioblastomas. DNAs from tumors and leukocytes were analyzed for LOH at 18 microsatellite loci by polymerase chain reaction using fluorescence-labeled primers. Then correlation between LOH and clinicopathological variables was examined statistically. Twenty-four (66.7%) anaplastic astrocytomas and 15 (83.3%) glioblastomas had at least one LOH on chromosome 10q. However, diffuse astrocytomas exhibited no LOH. Nineteen tumors (10 anaplastic astrocytomas and 9 glioblastomas) were believed to have a total loss of one chromosome 10. Analyses on 20 tumors with interstitial LOH revealed that most of the high LOH regions matched the location of known TSGs, while some novel LOH regions were found preferentially in anaplastic astrocytoma. The median survivals of the total, partial, and no loss groups were 10.1, 14.8, and 46.8 months, respectively, indicating a significant difference in the survivals of these groups (P=0.0289). Thus, analyzing chromosome 10q loss is helpful for diagnosing malignancy in astrocytic tumors and for predicting patients' survival. Our data also suggested that there are novel TSGs for anaplastic astrocytoma at 10q24 and 10q26.

Adolescent↗
PubMed2004

[A case of lipomatous meningioma].

We present a case of a 55-year-old woman with intracranial lipomatous meningioma attached to the left sphenoid ridge. A CT showed a mass lesion partially with a hypodensity area in the left fronto-temporal lobe. On MRI, the mass lesion contained a hyperintensity portion on T1 weighted images, which changed to hypointensity on fat-suppressed-T1 images. Histological examinations demonstrated a transitional meningioma containing lipomatous portions. Immunohistochemical studies showed negative reactivity for epithelial membrane antigen (EMA) and positive reactivity for vimentin and S-100 in the areas with lipomaous foci. This pattern of reactivity was different from that of lipomatous meningiomas reported previously. Further examinations are needed concerning the origin of tumor cells in lipomatous meningiomas.

Female↗