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Biomedical subjects

Y Ushio

Publications and source records attributed to Y Ushio.

At least 109 records · Page 6Linked to original sources

Intraspinal osteogenic meningioma: report of a case.

Dense calcification and psammomatous bodies are common in spinal meningioma, but are rarely reported in osteogenic meningioma. We present a 73-year-old woman with an extramedullary, intradural tumor located at the T5 vertebra. The tumor showed mixed intensity and heterogeneous enhancement on the T1-weighted image and hypointensity on the T2-weighted image, and was situated near the spinal nerve root. The tumor's initial symptom was myelopathy, as is usual with spinal meningioma. We successfully removed the tumor under microscopy and found it to be separated from the vertebral column by the epidural space. The symptoms and signs improved gradually after the operation. Because the pathologic examination revealed areas of lamellar bone with bone marrow in the transitional meningioma, and because these were not related to the psammomatous bodies, osteogenic meningioma was diagnosed. Metaplasia of arachnoid cells is considered to be the putative etiology of osteogenic meningioma.

Aged↗

[Treatment of children with malignant brain tumors].

The current treatment of children with malignant brain tumors is reviewed. Multidisciplinary treatment is essential for malignant gliomas or glioblastoma. The prognosis of children with glioblastoma remains dismal and a new treatment approach needs to be established. Recent aggressive multi-drug chemotherapy in combination with radiotherapy and surgery have markedly improved the treatment of children with medulloblastoma and primary intracranial malignant germ cell tumors. The number of long-term survivors and even cure rates have been increasing.

Antineoplastic Combined Chemotherapy Protocols↗

Prognostic significance of the MIB-1 labeling index for patient with craniopharyngioma.

Proliferative activity of 17 craniopharyngiomas were determined using an immunohistochemical method with monoclonal antibody MIB-1. A considerable variation of the MIB-1 labeling indices was found between the different tumors with a minimum of 0.4% and a maximum of 32.5% (median, 10.84%). The mean MIB-1 labeling index (LI) for 4 craniopharyngiomas that showed no evidence of recurrence (n=4) was 3.4 +/- 2.3%. This was significantly lower than that for craniopharyngiomas that showed recurrence and regrowth (13.2 +/- 7.7%) (n=13), based on the initial resected tumors. Statistical analysis reveal that craniopharyngiomas with an MIB-1 LI of 7% or more have a significantly high tendency for recurrence and regrowth during clinical course. Our data suggest that a MIB-1 LI greater than 7% may be a useful predictor of regrowth/recurrence of craniopharyngiomas and may be useful for planning of adjuvant therapy.

Adolescent↗

Serine/threonine phosphatase activity of calcineurin is inhibited by sodium orthovanadate and dithiothreitol reverses the inhibitory effect.

Orthovanadate is known to be an inhibitor of protein tyrosine phosphatases. However, we found that it inhibited calcineurin which has the activity of a serine/threonine protein phosphatase, using casein phosphorylated by cyclic AMP-dependent protein kinase as a substrate. Orthovanadate inhibits the Mn2+-activated activity of purified calcineurin to 20%; this is not the case without Mn2+. Furthermore, 10 mM dithiothreitol (DTT) reversed the inhibitory effects of orthovanadate. Orthovanadate showed the same inhibitory effect for calcineurin activity in homogenates as for the purified enzyme; the inhibitory effect was reversed by DTT. These results indicate that orthovanadate inhibits not only protein tyrosine phosphatases as reported, but also serine/threonine phosphatase activity of calcineurin.

Animals↗

Identification of a novel human homolog of the Drosophila dlg, P-dlg, specifically expressed in the gland tissues and interacting with p55.

We have identified a novel human homolog of the Drosophila dlg tumor suppressor gene, termed P-dlg, which has been mapped at chromosome 10q23. Unlike other human dlg homologs, P-dlg is expressed in placenta and various gland tissues but not in brain. The P-dlg protein is localized at the plasma membrane and cytoplasm, and it is expressed in the gland epithelial cells in normal prostate tissue but not in prostate cancer cell lines. Furthermore, we identified interaction between P-dlg and p55 palmitoylated membrane protein by yeast two-hybrid screening. These findings suggest that P-dlg forms a complex with p55 at the plasma membrane and plays roles in maintaining the structure of epithelial cells and transmitting extracellular signals to the membrane and cytoskeleton, which may negatively regulate cell proliferation.

Amino Acid Sequence↗

Combined chemotherapy and radiation therapy for central nervous system germ cell tumors: preliminary results of a Phase II study of the Japanese Pediatric Brain Tumor Study Group.

The authors conducted a multiinstitutional phase II study to establish a postsurgical combined chemotherapy and radiation therapy regimen for patients with primary germ cell tumors of the brain. After surgical debulking of the tumor and histological verification, patients were divided into three therapeutic groups: good prognosis, intermediate prognosis, and poor prognosis. Patients received two kinds of chemotherapy (three courses) prior to receiving radiation therapy: carboplatin-etoposide combination ([CARB-VP]: carboplatin 450 mg/m(2) on Day 1, etoposide 150 mg/m(2) on Days 1-3) or ifosphamide-cisplatin-etoposide combination ([ICE]: ifosphamide 900 mg/m(2), cisplatin 20 mg/m(2), and etoposide 60 mg/m(2) on Days 1-5). Patients in the good prognosis group (those with germinomas) were treated with CARB-VP followed by local radiation therapy (24 Gy). Patients in the intermediate prognosis group received CARB-VP followed by local radiation therapy (50 Gy); they received five additional chemotherapy treatments. Patients in the poor prognosis group received ICE followed by whole craniospinal radiation therapy; they also received five additional chemotherapy treatments. Eighty-two patients were evaluated. For the 56 patients with germinomas, a 93% rate of complete remission after treatment was achieved. The remission rate was 76% for 21 patients in the intermediate prognosis group, and no recurrence was detected during a median follow-up period of 2.6 years. In the group of five patients with poor prognosis, the disease in three patients progressed during chemotherapy or radiation therapy and they died within 6 months. There were no serious complications in the surviving patients. The authors found their treatment protocols to be currently effective for patients with germinomas and those with an intermediate prognosis.

Journal Article↗

Expression of CD44 adhesion molecules in intracranial germinomas.

Adhesion molecules play a role in tumor growth, invasiveness, and the metastatic process. The expression of CD44 adhesion molecules in 11 intracranial germinoma specimens was investigated using anti-CD44 monoclonal antibody and immunohistochemical methods. In six of 11 specimens studied, CD44 antibodies were bound to the membrane of tumor cells; in five of six specimens, CD44 antigen was also present in the cytoplasm of tumor cells. The only three patients who showed CD44-positive expression in tumor cells, lymphocytes, and extracellular matrix (ECM) exhibited either cerebrospinal fluid dissemination or multiple tumors at different locations. In all 11 specimens, no expression of CD44 in normal glial cells or capillary endothelium was detected. According to the authors' findings, the expression of CD44 in intracranial germinomas is similar to that of gonadal seminomas. Analysis of the results further suggests the possibility that the expression of CD44 in intracranial germinoma tumor cells, lymphocytes, and ECM may contribute to tumor cell migration, adhesion to cerebrospinal fluid dissemination, and/or multiple tumor locations.

Journal Article↗

Pineal germinomas with granulomatous inflammation. Report of two cases and review of the literature.

The authors report on two cases of pineal germinomas with granulomatous inflammation (granulomatous germinomas). Macroscopically, both tumors were relatively hard and grayish in color. Histological examination revealed a germinoma with multinucleated giant cells and Schaumann bodies in one case, and a germinoma with the background of acellular fibrillated matrix in the other. On immunohistochemical analysis, the granulomatous germinomas were shown to contain many macrophages, T- and B-lymphocytes, and glial fibrillary acid protein-positive cells infiltrating the specimens, compared to nongranulomatous germinomas. Analysis of Masson's trichrome staining tests showed that large areas of the granulomatous germinomas were occupied by a collagenous component; this was not the case in cases of nongranulomatous germinomas. Analysis of monoclonal anti-human Ki-67 results showed that the granulomatous germinomas had a lower score than nongranulomatous germinomas (p < 0.05, unpaired t-test), indicating that germinomas with granulomatous inflammation may have a better prognosis.

Journal Article↗

Identification of a human homolog of the Drosophila neuralized gene within the 10q25.1 malignant astrocytoma deletion region.

The loss of chromosome 10 is the most frequent genetic alteration found in malignant astrocytomas. In particular, the long arm of chromosome 10 was previously reported to have two or more common deletion regions where tumor suppressor genes may be located. In this study, we performed deletion mapping of 44 malignant astrocytomas using 12 microsatellite markers on chromosome 10q and demonstrated that the minimal common region of loss of heterozygosity (LOH) was present between D10S192 and D10S566 localized at 10q25.1. Subsequently, we have identified a novel gene, termed h-neu, within the region frequently deleted and found that h-neu encodes a protein with strong homology to the Drosophila neuralized (D-neu) protein. Northern blot and RT-PCR analyses revealed that h-neu mRNA was expressed at very low levels in human malignant astrocytoma tissues and the majority of glioma cell lines examined, while normal brains expressed h-neu transcript. Furthermore, DNA sequencing analysis of the h-neu transcript revealed one of the glioma cell lines, U251MG, had a single nucleotide substitution which resulted in an amino acid change from glycine (GGC) to serine (AGC) at codon 253. The D-neu gene is known to serve a critical function in neurogenesis in Drosophila, and loss-of-function mutations produce hyperplasia of primitive neuronal cells. These observations led us to hypothesize that h-neu gene plays a role in determination of cell fate in the human central nervous system and may act as a tumor suppressor whose inactivation could be associated with malignant progression of astrocytic tumors.

Amino Acid Sequence↗

Heterogeneity of cadherin-8 expression in the neonatal rat striatum: comparison with striatal compartments.

Mechanisms of organization of the striatal compartments are poorly understood, although involvement of cell adhesion molecules in the compartmentalization has been suggested. Cadherin-8 distribution in the neonatal rat striatum was immunohistochemically studied using a rabbit anti-cadherin-8 antiserum. Intensity of cadherin-8 immunolabeling in the striatum was heterogeneous from postnatal day 0 to postnatal day 7. At postnatal day 9, cadherin-8 immunoreactivity was so weak that heterogeneity was no longer clearly seen. Cadherin-8 immunoreactivity was not detectable at postnatal day 14. Cadherin-8-rich and cadherin-8-poor areas were identical to calbindin-rich areas and tyrosine hydroxylase-rich patches, respectively, in allocation, indicating that cadherin-8 was predominantly expressed in the striatal matrix. These results suggest that cadherin-8 is involved in formation of the striatal compartmentalized structures during brain development.

Animals↗

Neurotoxicity evoked by N-methyl-D-aspartate in the organotypic static slice cultures of rat cerebral cortices: effect of GABA(A) receptor activation.

We investigated the neurotoxicity evoked by N-methyl-D-aspartate (NMDA) receptor stimulation in the organotypic static slice cultures of rat cerebral cortices. We also examined whether the gamma-aminobutyric acid (GABA)A receptor agonist muscimol has a protective effect on the NMDA-mediated neurotoxicity in this culture system. NMDA-mediated cytotoxicity was evaluated histologically and quantified by the measurement of lactate dehydrogenase (LDH) release into the culture medium. There was an NMDA-induced, dose-dependent leakage of LDH release and neuronal cell death, which were not attenuated by muscimol treatment. The results suggested that NMDA neurotoxicity is reproduced in the organotypic culture, and that GABA(A) receptor activation exerted no protective action against the NMDA cytotoxicity.

Animals↗

Clinical features of moyamoya disease in sibling relations under 15 years of age.

This study was undertaken to define the clinical features of moyamoya disease in sibling relations less than 15 years of age. We analysed five pairs of siblings (6 boys, 4 girls) with moyamoya disease from among 56 moyamoya patients less than 15 years of age. Of 56 paediatric patients with moyamoya disease, 5 were sibling pairs. At onset of the disease, all patients were under 10 years of age. Clinical manifestations in the proband and the affected sibling tended to present as transient ischaemic attacks; none of the 10 patients presented with intracranical haemorrhage. The probands were not always the older sibling, however, the time lapse between disease onset in the proband and his/her sibling was less than one year. Among the sibling pairs, there was no striking difference in disease staging based on angiographic findings. The incidence of sibling occurrence of moyamoya disease appears to be higher than previously assumed and the family of children with moyamoya disease should be cautioned that their other children have an increased risk of developing the illness.

Adolescent↗

Cadherin-8 protein expression in gray matter structures and nerve fibers of the neonatal and adult mouse brain.

The topological distribution of mouse cadherin-8 protein in the neonatal and adult mouse brain was studied immunohistochemically using a rabbit antiserum. Cadherin-8 expression was restricted to several areas in neonatal brains constituting particular neural circuits, i.e. the limbic system, the basal ganglia-thalamocortical circuit, and the cerebellum and related nuclei. In addition, the nerve fibers linking some of the cadherin-8-positive areas, i.e. the habenulo-interpeduncular tract, decussation of the dorsal tegmentum, the medial longitudinal fasciculus, transverse pontine fibers, the brachium conjunctivum and the inferior cerebellar peduncle were cadherin-8 positive, as were the spinal tract of the trigeminal nerve, oculomotor nerve, facial nerve and trigeminal nerve. Cadherin-8 expression also showed a patch-like distribution in the intermediate gray layer of the superior colliculus, resembling acetylcholinesterase-rich patches in allocation. Segmentally organized cadherin-8-positive areas were found in the neonatal cerebellar Purkinje cell layer. Some nuclei and fibers in the brainstem and cerebellum, expressing cadherin-8 at neonatal stages, were also stained in the adult mouse brain. These findings suggest that cadherin-8 is involved in the formation of particular neural circuits by connecting areas expressing this molecule with positive nerve fibers, and indicate its possible implication in subdivisional organization in the superior colliculus and cerebellum.

Animals↗

Delayed posttraumatic middle cerebral artery vasospasm demonstrated by magnetic resonance angiography: case report.

OBJECTIVE AND IMPORTANCE: Magnetic resonance (MR) angiographic diagnosis is a noninvasive method having high sensitivity and specificity in the detection of various cerebrovascular disorders. This is the first report of MR angiographic detection of delayed posttraumatic middle cerebral artery vasospasm, the occurrence of which has been rarely described. CLINICAL PRESENTATION: A 42-year-old man sustained head trauma in a traffic accident, which caused a right subdural hematoma. Even though the hematoma was irrigated through one burr hole on Day 10, the patient subsequently developed left hemiparesis in association with dysarthria 4 days after surgery. MR angiography demonstrated decreased flow signal in the right M1 and M2 portions, suggestive of vasospasm. INTERVENTION: The patient underwent intravascular volume expansion/ hemodilution therapy for 3 days. CONCLUSION: After the therapy, the ischemic symptoms completely disappeared. Follow-up study confirmed resolution of the flow signal in the right middle cerebral artery. It is suggested that MR angiography is a useful noninvasive method in the evaluation of posttraumatic cerebrovascular disorders, which constitute important secondary insults in head trauma.

Adult↗

Intradermal injection of monocyte chemoattractant protein-1 induces emigration and differentiation of blood monocytes in rat skin.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant for blood monocytes in vitro. Recent studies in MCP-1-transgenic mice revealed that the local production of MCP-1 caused monocyte infiltration. However, the kinetics of monocyte infiltration after the production of MCP-1 or the amount of MCP-1 necessary for monocyte recruitment are not known. METHODS: We purified recombinant rat MCP-1 expressed in COS-7 cells, and injected it into rat skin. The infiltrating cells were examined by immunohistochemistry and ultrastructural peroxidase cytochemistry. RESULTS: Rat recombinant MCP-1 had a molecular mass of approximately 30 kD and exhibited the peak monocyte chemotactic activity at 10(-9) M. One microgram of MCP-1 caused intra- and extravascular accumulation of mononuclear cells 3 h after injection. The cells were ED1+, indicating they were blood monocytes. The infiltration of mononuclear cells peaked at 12-24 h, and most of them were TRPM-3+ and ED3+, characteristic to exudate macrophages. None of the cells expressed ED2 or Ki-M2R antigens, markers for resident macrophages, until 3 days after injection. There was no uptake of [3H]thymidine by the infiltrating cells. Ultrastructural peroxidase cytochemistry confirmed that the infiltrating cells were monocytes and exudate macrophages. The number of OX8+ lymphocytes also peaked at 12 h, consisting of approximately 9% of the total infiltrating cells. CONCLUSION: These results indicate that MCP-1 attracts blood monocytes as early as 3 h and the infiltrating monocytes differentiate into exudate macrophages in loco. However, this effect was transient and the infiltration of monocytes did not result in tissue damage.

Animals↗

Primary malignant lymphoma of the brain in childhood.

A 5-year-old boy presented with a 1-year history of frontal headache and nausea. Neurological examination showed left abducens nerve palsy, left facial nerve palsy, Bruns' nystagmus, and wide-based gait. Neuroimaging demonstrated a lesion with moderate linear enhancement in the left cerebellar hemisphere. He underwent stereotactic needle biopsy. The histological diagnosis was well-differentiated small lymphocytic type of malignant lymphoma. Following the biopsy, the patient underwent radiotherapy (whole brain 30 Gy, local 20 Gy). He has been in good condition for more than 5 years. The long-term survival is attributable to the absence of aggressiveness and the good response to radiation of this subtype of malignant lymphoma.

Brain Neoplasms↗

Correlation of MR imaging-determined cerebral blood volume maps with histologic and angiographic determination of vascularity of gliomas.

OBJECTIVE: Our purpose was to evaluate the relationships between the ratio of maximum relative cerebral blood volume (rCBV) (rCBV ratio = rCBV[tumor]/rCBV[contralateral white matter]) and histologic and angiographic vascularities of gliomas using the gradient-echo echoplanar MR imaging technique. We also evaluated the usefulness of rCBV maps for grading gliomas. SUBJECTS AND METHODS: We examined 30 patients with histologically verified gliomas. Gliomas were classified as glioblastoma, anaplastic glioma with enhancement, anaplastic glioma without enhancement, and low-grade glioma. The maximum rCBV ratio of each glioma was compared with both histologic and angiographic vascularities, and the relationship between the maximum rCBV ratios and each type of glioma was established. RESULTS: The maximum rCBV ratios of the gliomas significantly correlated with both histologic and angiographic vascularities (p < .001). Mean values and SDs of maximum rCBV ratios of each type of tumor were 7.32+/-4.39 for glioblastomas, 5.84+/-1.82 for anaplastic gliomas with enhancement, 1.53+/-0.75 for anaplastic gliomas without enhancement, and 1.26+/-0.55 for low-grade gliomas. The maximum rCBV ratios of the glioblastomas were significantly higher than those of the anaplastic gliomas without enhancement (p = .002) and the low-grade gliomas (p < .001). The maximum rCBV ratios of the anaplastic gliomas with enhancement were higher than those of the anaplastic gliomas without enhancement and the low-grade gliomas, but the differences were not statistically significant (p = .08 and p = .03, respectively). CONCLUSION: The results of perfusion-sensitive MR imaging with gradient-echo echoplanar technique correlated with both histologic and angiographic vascularities.

Adolescent↗

Loss of merlin-p85 protein complex in NF2-related tumors.

The NF2 tumor suppressor gene product, designated merlin, belongs to the family of molecules that links membranous protein with the cytoskeleton. We have previously shown that merlin was co-immunoprecipitated with a cellular protein, p85, in cultured cell. To analyze the alteration of merlin and associated proteins in surgical specimens, we developed a new method for biotin-labeling of whole cellular proteins. Screening of tumor tissues using our method showed that none of malignant gliomas and half of the NF2-related tumors had altered p85 and merlin. Our detection method seems useful for the screening of merlin alterations in NF2-related tumors.

Avian Proteins↗