Biomedical subjects

Yukitaka Ushio

Publications and source records attributed to Yukitaka Ushio.

At least 37 records · Page 2Linked to original sources

PubMed2004

The influence of sex and the presence of giant cells on postoperative long-term survival in adult patients with supratentorial glioblastoma multiforme.

OBJECT: Glioblastoma multiforme (GBM) remains incurable by conventional treatments, although some patients experience long-term survival. A younger age, a higher Karnofsky Performance Scale (KPS) score, more aggressive treatment, and long progression-free intervals have been reported to be positively associated with long-term postoperative patient survival. The aim of this retrospective study was the identification of additional favorable prognostic factors affecting long-term survival in surgically treated adult patients with supratentorial GBM. METHODS: Of 113 adult patients newly diagnosed with histologically verified supratentorial GBM who were enrolled in Phase III trials during the period between 1987 and 1998, six (5.3%) who survived for longer than 5 years were defined as long-term survivors, whereas the remaining 107 patients served as controls. All six were women and were compared with the controls; they were younger (mean age 44.2 years, range 31-60 years), and their preoperative KPS scores were higher (mean 85, range 60-100). Four of the six patients underwent gross-total resection. In five patients (83.3%) the progression-free interval was longer than 5 years and in three a histopathological diagnosis of giant cell GBM was made. This diagnosis was not made in the other 107 patients. CONCLUSIONS: Among adult patients with supratentorial GBM, female sex and histopathological characteristics consistent with giant cell GBM may be predictive of a better survival rate, as may traditional factors (that is, younger age, good KPS score, more aggressive resection, and a long progression-free interval).

Adolescent↗

PubMed2004

MR imaging features of a scalp plexiform schwannoma.

Radiologic findings of a case with scalp plexiform schwannoma-an unusual variant of the benign, solitary schwannoma in the skin-are reported. T2-weighted MR imaging exhibited the most specific features: a multinodular pattern and hypointense capsule that separated the tumor from surrounding soft tissue. A surgical specimen was histologically confirmed as schwannoma. The MR imaging findings reported herein may aid in the preoperative diagnosis of this relatively rare scalp tumor.

Adult↗

PubMed2004

MR imaging findings of spinal posterior column involvement in a case of Miller Fisher syndrome.

SUMMARY: The site of lesions causing ataxia in Miller Fisher syndrome (MFS) remains in dispute. A 43-year-old man manifested rapidly progressive left-sided ptosis, bilateral abducens palsy, areflexia, and severe ataxia. Initial MR imaging showed confined lesions of the cauda equina with gadolinium enhancement. A diagnosis of MFS was made, and the patient underwent immunotherapy. His ophthalmoplegia disappeared, but other symptoms remained. Five months after onset, MR imaging disclosed lesions confined to the spinal posterior column, which were considered to result from involvement of posterior nerve roots of the cauda equina and to be responsible for his remaining severe ataxia.

Adult↗

PubMed2003

Effect on cerebral vasospasm of coil embolization followed by microcatheter intrathecal urokinase infusion into the cisterna magna: a prospective randomized study.

BACKGROUND AND PURPOSE: Vasospasm remains the leading cause of death and permanent neurological disability in patients with aneurysmal subarachnoid hemorrhage (SAH). The objective of our prospective randomized trial of coil embolization followed by intrathecal urokinase infusion into the cisterna magna (ITUKI therapy) was to test its effectiveness in preventing or alleviating the severity of ischemic neurological deficits caused by vasospasm. METHODS: We enrolled 110 patients with ruptured intracranial aneurysms eligible for coil embolization and randomly assigned them to embolization with (n=57) or without (n=53) ITUKI therapy performed within 24 hours of aneurysmal SAH. The incidence of symptomatic vasospasms and the clinical outcomes, based on the Glasgow Outcome Scale, 6 months after SAH onset were assessed. RESULTS: There were no side effects or adverse reactions attributable to ITUKI therapy. Symptomatic vasospasm occurred in 5 patients (8.8%) with and 16 (30.2%) without ITUKI therapy; the difference was significant (P=0.012). Although the mortality rate did not differ between the groups, patients with ITUKI therapy had significantly better outcomes than those without (P=0.036). CONCLUSIONS: Our results demonstrate that ITUKI therapy significantly reduced the occurrence of symptomatic vasospasm. Although it did not completely prevent vasospasms, ITUKI therapy resulted in a lower rate of permanent neurological deficits.

Adult↗

PubMed2003

Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme.

Glioblastoma multiforme (GBM) frequently involves amplification and alteration of the epidermal growth factor receptor (EGFR) gene, resulting in overexpression of varied mutations, including the most common mutation, EGFRvIII, as well as wild-type EGFR (EGFRwt). To test the prognostic value of EGFR, we retrospectively analyzed the relationship between treatment outcomes and the EGFR gene in 87 newly diagnosed adult patients with supratentorial GBM enrolled in clinical trials. The EGFR gene status was assessed by Southern blots and EGFR expression by immunohistochemistry using three monoclonal antibodies (EGFR.25 for EGFR, EGFR.113 for EGFRwt, and DH8.3 for EGFRvIII). EGFR amplification was detected in 40 (46%) of the 87 GBM patients; in 39 (97.5%) of these, EGFR was overexpressed. On the other hand, in 46 of 47 patients without EGFR amplification (97.9%), no EGFR overexpression was present. There was a close correlation between EGFR amplification and EGFR overexpression (P < 0.0001). EGFRwt was overexpressed in 27 of the 40 (67.5%) patients with, and in none without, EGFR amplification (P < 0.0001). Similarly, EGFRvIII was overexpressed in 18 (45.0%) of 40 patients with and in 4 (8.5%) of 47 patients without EGFR amplification (P < 0.0001). The finding that 8 (20%) of the patients with EGFR amplification/EGFR overexpression manifested overexpression of neither EGFRwt nor EGFRvIII indicates that they overexpressed other types of EGFR. Multivariate analysis demonstrated that EGFR amplification was an independent, significant, unfavorable predictor for overall survival (OS) in all patients (P = 0.038, HR = 1.67). With respect to the relationship of age to EGFR prognostication, the EGFR gene status was a more significant prognosticator in younger patients, particularly in those <60 years (P = 0.0003, HR = 3.15), whereas not so in older patients. EGFRvIII overexpression, on the other hand, was not predictive for OS. However, in patients with EGFR amplification, multivariate analysis revealed that EGFRvIII overexpression was an independent, significant, poor prognostic factor for OS (P = 0.0044, HR = 2.71). This finding indicates that EGFRvIII overexpression in the presence of EGFR amplification is the strongest indicator of a poor survival prognosis. In GBM patients, EGFR is of significant prognostic value for predicting survival, and the overexpression of EGFRvIII with amplification plays an important role in enhanced tumorigenicity.

Adolescent↗

PubMed2003

Analysis of mean transit time of contrast medium in ruptured and unruptured arteriovenous malformations: a digital subtraction angiographic study.

BACKGROUND AND PURPOSE: To clarify hemodynamic risk factors for hemorrhage in arteriovenous malformations (AVMs), the mean transit time (MTT) of feeding arteries and draining veins in AVMs with and without hemorrhage was measured and analyzed. METHODS: Morphological features such as the number and diameter of draining and feeding vessels and the AVM nidus volume were evaluated in 30 patients with supratentorial AVMs. The MTT of feeding arteries and draining veins was measured with the use of time-density curves obtained by digital subtraction angiography. The correlation between hemorrhage and morphology and hemorrhage and MTT was analyzed statistically. RESULTS: The nidus volume was not significantly different between hemorrhagic and nonhemorrhagic AVMs. However, between ruptured and unruptured AVMs there was a significant difference in the mean number of draining veins (1.5+/-0.69 versus 2.3+/-0.50; P=0.006), the MTT of the feeding artery (1.10+/-0.24 versus 1.62+/-0.55; P=0.03), and the ratio of the MTT of the draining to the feeding vessels (1.71+/-0.43 versus 1.05+/-0.07; P<0.001). CONCLUSIONS: A high ratio of the MTT of draining veins to feeding arteries suggests disequilibrium between nidal inflow and outflow. The consequent increased pressure in the draining vein may contribute to the development of AVM hemorrhage.

Adolescent↗

PubMed2003

Lack of Reelin causes malpositioning of nigral dopaminergic neurons: evidence from comparison of normal and Reln(rl) mutant mice.

The reeler gene (Reln(rl), formerly rl) product Reelin controls neuronal migration and positioning and thereby plays a key role in brain development. Mutation of Reln leads to widespread disruption of laminar cortical regions and ectopia in some brainstem nuclei. In the embryonic striatum of normal mice, a substantial expression of reelin mRNA has been documented; however, the anomalous positioning of neurons in the basal ganglia of reeler mice remains to be studied. We provide first evidence for a potential role of Reelin in the developmental formation of the substantia nigra. In reeler mutant mice lacking Reelin, dopaminergic neurons destined for the substantia nigra fail to migrate laterally and become anomalously clustered just lateral to the ventral tegmental area. Their axons appear to project to striatal patches forming "dopamine islands." Results from the normal mice show that, at the midembryonic stage, Reelin identified with CR-50 is highly concentrated in the ventral mesencephalon, where nigral dopaminergic neurons are in progress to migrate laterally to their eventual position of the adult brain. A combination of CR-50 labeling and anterograde axonal tracing provided evidence that embryonic striatal neurons may supply the ventral portion of the mesencephalon with Reelin through their axonal projections. We hypothesize that Reelin plays a role in the positioning of nigral dopaminergic neurons and that it can act as an environmental cue at a remote site far from its birthplace via a transaxonal delivery system.

Animals↗

PubMed2003

Correlation of molecular genetic analysis of p53, MDM2, p16, PTEN, and EGFR and survival of patients with anaplastic astrocytoma and glioblastoma.

This article reviews studies on the correlation between genetic abnormalities in malignant astrocytic tumors and patient survival. It is almost certain that alterations of PTEN on chromosome 10 represent a significant unfavorable prognostic factor in glioblastoma patients. The association of alterations in p53, MDM2, p16 or EGFR with the survival of patients with anaplastic astrocytoma or glioblastoma remains controversial. It is possible that the p16 alteration and EGFR amplification are associated with poor survival in certain groups of patients and that there might be a relationship with age. Malignant transformation of astrocytic cells are driven by the sequential acquisition of genetic alteration. Therefore, it is reasonable to subgroup gliomas by their patterns of genetic alterations. However the studies that correlated the multiple genetic alterations with survival are still limited. Further studies on large cohorts are necessary to elucidate the genetic factors that affect the prognosis and response to therapy of patients with malignant gliomas and to develop effective management strategies.

Astrocytoma↗

PubMed2003

Full-length dystrophin cDNA transfer into skeletal muscle of adult mdx mice by electroporation.

We showed that a LacZ expression plasmid (pCAG-lacZ) injection followed by electroporation increased the expression of the LacZ gene in the skeletal muscles of adult mdx mice up to ninefold higher as compared with simple intramuscular DNA injection. When full-length mouse dystrophin plasmid (pCAG-dys) and pCAG-lacZ were co-transfected by electroporation, 56% of dystrophin-positive fibers were stained for beta-galactosidase activity suggesting most of these myofibers are not revertants but transfected ones. Our data indicate that electroporation in vivo could introduce large full-length dystrophin cDNA into skeletal muscle of adult mdx mice.

Age Factors↗

PubMed2003

Usefulness of multiple-site venous sampling in the treatment of adrenocorticotropic hormone-producing pituitary adenomas.

BACKGROUND: While venous sampling for adrenocorticotropic hormone (ACTH) may be the most accurate way to establish a diagnosis of Cushing's disease, its usefulness for lateralization of adenomas is limited even in combination with simultaneous bilateral sampling methods. Therefore, to increase accuracy in predicting the lateralization of adenomas, we performed a trial in which we carried out simultaneous venous sampling from multiple sites of the cavernous sinus (CS) and inferior petrosal sinus (IPS). Here we report on the usefulness of our method in the correct tumor lateralization in patients with Cushing's disease. METHODS: Eighteen patients with Cushing's disease underwent simultaneous bilateral ACTH sampling. The samples were obtained from the anterior, middle, and posterior CS and the IPS. CS sampling after stimulation with corticotropin-releasing hormone (CRH) was also performed. The central-to-peripheral ACTH ratio (c/p ratio) was calculated using sampling data from each site; the lateralizing gradients (right versus left) were calculated using the c/p ratio. Instead of the conventional method where the lateralization gradient is based on sampling data from a single site, we used the distribution of the c/p ratio determined from multiple-site data. RESULTS: There was no significant difference in the mean lateralization gradient obtained from each set of sampling data (p > 0.05). With the conventional method, correct tumor lateralization was obtained in 50% of tumors in the IPS; 72.2 to 77.8% of tumors in the CS; and 77.8% of tumors in the middle CS after CRH. Our method using ACTH contour analysis based on multiple sites produced correct results in all 18 of the patients examined. The difference in correct calls between the conventional method and our method was significant (p < 0.05). CONCLUSIONS: Multiple-site sampling of ACTH is valuable for lateralizing the adenoma in patients with Cushing's disease; it produces more correct results than does single venous sampling.

Adenoma↗

PubMed2003

Neuronal cell migration for the developmental formation of the mammalian striatum.

The mammalian striatum is the largest receptive component of the basal ganglia circuit. It is involved in the control of various aspects of motor, cognitive, and emotional functions. In the telencephalon, the striatum has a unique histological property totally different from the cortical area and its ontogenesis remains largely unknown. In this review, we introduce recent advances in the understanding of neuronal cell migration, one of the most critical processes in the early phase of histogenesis that occurs in the embryonic striatum. It appears that there are three major modes of neuronal cell migration in the developmental formation of the striatum. They are (radial) outward, tangential, and inward migration, supplying the striatum with projection neurons, interneurons, and early-generated transient neurons that originate in the preplate, respectively. We challenge the classical concept that the striatum is solely derived from the restricted germinal area located in the basal telencephalon by providing evidence that striatal development requires the intermixture of different types of neurons originating from distinct regions of the telencephalon.

Animals↗

PubMed2003

GPi pallidotomy for Parkinson's disease with drug-induced psychosis.

Levodopa-induced psychosis may seriously threaten the ability of patients with Parkinson's disease (PD) to continue leading an independent life. A retrospective assessment of the therapeutic effects of the globus pallidus internus (GPi) pallidotomy on the activities of daily living (ADL) of seven PD patients presenting with mild or moderate degrees of psychosis was carried out. Their scores according to the Unified Parkinson's Disease Rating Scale (UPDRS) Part I-2 (maximum=4) were 2 or 3 (mean +/- SD=2.4 +/- 0.5). Bilateral procedure was needed in 5 out of 7 patients to obtain sufficient improvement of motor symptoms. At 3 months after surgery, UPDRS part III motor scores in the 'off' state were significantly decreased and motor fluctuations were abolished. Nevertheless, their score of Schwab and England (S-E) ADL scale scores responded poorly to the surgery, while the scores in other 12 patients without psychosis was significantly improved after pallidotomy. The data indicate that GPi pallidotomy ameliorates the motor symptoms in patients with drug-induced psychosis (DIP), but has no significant impact on their consequent daily activities. A regression model for all 19 patients who underwent pallidotomy revealed that postoperative S-E scale was affected by the preoperative UPDRS Part I-2 rather than by Part III motor score. The present study suggested that DIP, even if its degree is not severe, may be a limiting factor of the therapeutic potential of pallidotomy in patients with PD.

Adult↗

PubMed2003

CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function.

The Aurora (Ipl1)-related kinases are universal regulators of mitosis. We now show that Aurora-A, in addition to Aurora-B, regulates kinetochore function in human cells. A two-hybrid screen identified the kinetochore component CENP-A as a protein that interacts with Aurora-A. Aurora-A phosphorylated CENP-A in vitro on Ser-7, a residue also known to be targeted by Aurora-B. Depletion of Aurora-A or Aurora-B by RNA interference revealed that CENP-A is initially phosphorylated in prophase in a manner dependent on Aurora-A, and that this reaction appears to be required for the subsequent Aurora-B-dependent phosphorylation of CENP-A as well as for the restriction of Aurora-B to the inner centromere in prometaphase. Prevention of CENP-A phosphorylation also led to chromosome misalignment during mitosis as a result of a defect in kinetochore attachment to microtubules. Our observations suggest that phosphorylation of CENP-A on Ser-7 by Aurora-A in prophase is essential for kinetochore function.

Amino Acid Sequence↗

PubMed2003

CREB is required for acquisition of ischemic tolerance in gerbil hippocampal CA1 region.

Ischemic tolerance is well known as a neuroprotective effect of pre-conditioning ischemia against delayed neuronal death, however, the mechanism or mechanisms underlying this effect are not fully understood. We investigated the relationship between CREB and ischemic tolerance in gerbil hippocampal CA1 neurons using CRE decoy oligonucleotide. Sublethal ischemia led to an increase in the level of CREB phosphorylation in CA1 regions while lethal ischemia did not. Experiments with NG108-15 cells showed that adding CRE decoy oligonucleotide to culture media significantly inhibited the cell growth rate. The administration of CRE decoy oligonucleotide into gerbil cerebral ventricle decreased CREB-DNA binding activity to 38% of the control. Pre-treatment with CRE decoy oligonucleotide 24 h before the induction of ischemic tolerance decreased CA1 neuronal cell survival to 21% of the control. The present findings suggest that a CREB-mediated transcription system is necessary for the induction of ischemic tolerance.

Animals↗

PubMed2003

Neuroprotective effect of postischemic administration of sodium orthovanadate in rats with transient middle cerebral artery occlusion.

Orthovanadate is a competitive inhibitor of protein tyrosine phosphatases. Some of its reported biologic effects are its insulin mimetic property and its activation of phosphoinositide 3-kinase and extracellular-signal regulated kinase (ERK). The authors previously reported its neuroprotective effect on delayed neuronal death of gerbil hippocampal CA1 neurons via Akt and ERK activation after transient forebrain ischemia. In the present study, the neuroprotective effect of postischemic intraperitoneal administration of sodium orthovanadate (2 l/kg of 50-mmol/l sodium orthovanadate in saline) was investigated in rats with transient middle cerebral artery occlusion. Ischemic neuronal injury was evaluated 1 day and 28 days after ischemia. The neuroprotective effect of orthovanadate was significant in the cortex but not the caudate putamen (ischemic core) at both 1 and 28 days after ischemia. In orthovanadate group, the activities of Akt and ERK were maintained after reperfusion; they were decreased in saline group. Blood glucose level decreased but within normal range. Regional cerebral blood flow was lower than that of saline group only at 0 hours after reperfusion. These data suggest that orthovanadate has neuroprotective effects in rats with transient middle cerebral artery occlusion and that these effects are mediated by Akt and ERK activation. Furthermore, low blood glucose levels and gradual recovery of regional cerebral blood flow may contribute to neuroprotection.

Animals↗

PubMed2003

Angiographic dilatation and branch extension of the anterior choroidal and posterior communicating arteries are predictors of hemorrhage in adult moyamoya patients.

BACKGROUND AND PURPOSE: The cause of intracranial bleeding in moyamoya disease patients is still unknown. To identify factors that contribute to bleeding, we assessed the angiographic findings of moyamoya disease patients. METHODS: We examined angiograms obtained from 107 moyamoya patients; 70 manifested ischemic and 37 had hemorrhagic lesions. Patients with intracerebral aneurysms or both hemorrhagic and ischemic lesions in the same cerebral hemisphere were not included. Patients were divided into those <20 years of age (n=47) and those > or =20 years of age (n=60). The right and left hemispheres in each patient were individually classified as hemorrhagic, ischemic, or asymptomatic. Each hemisphere was assessed for dilatation and branch extension of the anterior choroidal artery (AChA) and posterior communicating artery (P-CoM) and for the degree of proliferation of basal moyamoya vessels. These data were then statistically analyzed for correlation with intracranial bleeding events. RESULTS: The degree of proliferation of basal moyamoya vessels was not statistically correlated with hemorrhagic events. On the other hand, there was a correlation between hemorrhage and dilatation and abnormal branching of the AChA. In 27 of 37 hemorrhagic hemispheres (73.0%), this artery was dilated, and its abnormal branches served as collateral supply vessels to other regions. This phenomenon was observed in 4 of 5 hemorrhagic hemispheres from young patients; it was noted in fewer than one third of ischemic and asymptomatic hemispheres from this age group. Similarly, 71.9% of hemorrhagic hemispheres from adult patients manifested AChA dilatation and branching, and the difference between hemorrhagic hemispheres and those that were ischemic or asymptomatic was statistically significant (P<0.01). Although the incidence of dilatation and abnormal branching of the P-CoM was relatively low in hemorrhagic hemispheres from adult patients (18.8%), it was significantly higher than in the ischemic and asymptomatic hemispheres from this age group. Using dilatation and abnormal branching of the AChA and/or P-CoM as assessment criteria, we obtained high specificity (86.4%) and sensitivity (84.4%) for hemorrhagic events in adult moyamoya patients. CONCLUSIONS: In adult moyamoya patients, dilatation and abnormal branching of the AChA and/or P-CoM are strong predictors of hemorrhagic events.

Adult↗

PubMed2003

Preliminary observations on genetic alterations in pilocytic astrocytomas associated with neurofibromatosis 1.

Neurofibromatosis 1 (NF1) is an autosomal dominant disorder that predisposes sufferers to various forms of neoplasia. Among affected individuals, 15%-20% develop astrocytomas, especially pilocytic astrocytomas (PA), which are benign and classified as grade I by the World Health Organization. They are generally well circumscribed, and their progression is slow. NF1-associated PAs (NF1-PAs) occasionally behave as aggressive tumors. To elucidate underlying genetic events in clinically progressive NF1-PAs, we performed molecular genetic analysis on 12 PAs, including 3 NF1-PAs, for pS3, p16, and epidermal growth factor receptor genes, as well as loss of heterozygosity (LOH) on chromosome 1p, 10, 17, and 19q. None of the obvious genetic alterations typically seen in higher grade astrocytomas were found in 9 sporadic PAs. However, in 2 of 3 NF1-PAs, microsatellite analysis showed LOH10, including the PTEN (phosphatase and tensin homolog deleted on chromosome 10) gene locus, despite the diagnosis of pilocytic astrocytoma;one of these also manifested homozygous deletion of the p16 gene. The other NF1-PA harbored only LOH of the NF1 gene locus (17q). Our preliminary results support the hypothesis that some NF1-PAs differ genetically from sporadic PAs.

Adolescent↗

PubMed2003

Postoperative hyperperfusion in a patient with a dural arteriovenous fistula with retrograde leptomeningeal venous drainage: case report.

OBJECTIVE AND IMPORTANCE: Hyperperfusion has been reported after carotid endarterectomy or stenting for stenosis of the internal carotid artery. Because few reports have examined postoperative hyperperfusion after treatment for dural arteriovenous fistulae (DAVFs), we present a case describing a patient who manifested this clinical entity. CLINICAL PRESENTATION: The patient was a 63-year-old man with a DAVF in the left transverse sigmoid sinus with retrograde leptomeningeal venous drainage. He experienced slowly progressive disorientation lasting for several months. Preoperative single-photon emission computed tomography with (123)I-labeled N-isopropyl-p-iodoamphetamine revealed an area of hyperintensity on T2-weighted magnetic resonance imaging (MRI) scans that coincided with the hypoperfusion area; it was not increased after acetazolamide challenge. Complete DAVF obliteration was achieved by embolization, then sinus isolation. After treatment, he experienced frequent generalized convulsions that were terminated by 2-day barbiturate therapy. INTERVENTION: On T2-weighted MRI scans obtained 3 days after surgery, the hyperintense area not only persisted but had expanded to the left parietal lobe. Moreover, a subcortical hyperintense lesion was recognized on T1-weighted MRI scans; this was considered to reflect cortical laminar necrosis. Single-photon emission computed tomography revealed hyperperfusion in the left parietal lobe; it changed to hypoperfusion a month after treatment. CONCLUSION: In patients with DAVFs with preoperative findings of marked low perfusion and a poor perfusion reserve, postoperative study may reveal hyperperfusion on single-photon emission computed tomography or cortical laminar necrosis on MRI. This may be evidence of severe perfusion disturbance as a result of venous infarction. In these patients, careful blood pressure control and early treatment of seizures are important after DAVF treatment.

Central Nervous System Vascular Malformations↗