PubMed HealthSearch

Biomedical subjects

Y Ushio

Publications and source records attributed to Y Ushio.

At least 19 recordsLinked to original sources

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

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

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

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

[NF2].

Explore the source record for details and available documents.

Brain Neoplasms

MR evaluation of radiation otomastoiditis.

PURPOSE: The purpose of this study was to evaluate the incidence of radiation otomastoiditis, on using T2-weighted magnetic resonance (MR) imaging, in relation to radiation fields, doses, intervals, and clinical symptoms after radiotherapy that included the temporal bone in the fields. METHODS AND MATERIALS: We performed follow-up MR examinations at various intervals after radiotherapy including the temporal bones for 270 ears of 114 patients with various diseases of the head and neck and intracranial regions. The middle ear and mastoid air cells on T2-weighted images were scored as follows; showing no high signal intensity, a local high signal intensity area, or a high signal intensity area occupying the entire middle ear and all mastoid air cells. The radiation fields as depicted on the lateral simulator films classed as anterior to the clival line, posterior to the clival line, or both. RESULTS: The incidence of radiation otomastoiditis depicted on T2-weighted MR images increased in the patients who had received irradiation doses of 50 Gy or more. In the patients with doses of less than 50 Gy, the incidence was 18% within 6 months following radiotherapy, 13% at between 6 and 12 months, and 8% after 12 months, whereas it was more than 50% at any period after radiotherapy in the patients with 50 Gy or more. The incidence of radiation otomastoiditis was quite high in the patients whose radiation fields included region both anterior and posterior to the clival line. CONCLUSION: The incidence of radiation otomastoiditis as demonstrated on T2-weighted MR images is increased at irradiation doses of 50 Gy or more. To reduce the incidence of severe radiation otomastoiditis, the irradiation fields of the temporal bone when the dose is 50 Gy or more should be limited to as small as possible. The clival line is considered to be a good landmark in reducing the irradiation field when doses of 60-70 Gy are delivered in curative radiotherapy.

Adolescent

Cloning and characterization of NE-dlg: a novel human homolog of the Drosophila discs large (dlg) tumor suppressor protein interacts with the APC protein.

We have cloned a cDNA for a novel human homolog of the Drosophila discs large (dig) tumor suppressor protein, termed NE-dlg (neuronal and endocrine dig). Northern blot analysis revealed that the gene is highly expressed in neuronal and endocrine tissues. Fluorescence in situ hybridization (FISH) and radiation hybrid mapping studies localized the NE-dlg gene to chromosome Xq13. We also found that the NE-dlg gene encoded a 100 kDa protein. Immunolocalization studies using an NE-dlg antibody showed that the protein tended to be expressed in non-proliferating cells, such as neurons, cells in Langerhans islets of the pancreas, myocytes of the heart muscles, and the prickle and functional layer cells of the esophageal epithelium. Proliferative cells, including various cultured cancer cell lines and basal cells in the esophageal epithelium, showed little expression of the NE-dlg protein. In addition, yeast two-hybrid screening and in vitro binding assays revealed that the NE-dlg interacted with the carboxyl-terminal region of the APC tumor suppressor protein. These data suggest that NE-dlg negatively regulates cell proliferation through its interaction with the APC protein.

Adaptor Proteins, Signal Transducing

Postnatal ontogeny of striatal-enriched protein tyrosine phosphatase (STEP) in rat striatum.

The present study was undertaken to examine developmental change in expression of striatal-enriched protein tyrosine phosphatase (STEP) in the postnatal striatum of rats. For this purpose, immunohistochemical staining and transimmunoblotting analyses were carried out using a cDNA-generated polyclonal antibody to the STEP with a molecular weight of 46 kDa. Immunostaining showed that in neonatal striatum STEP-immunoreactivity was found in discrete patches composed of many immature cells, which corresponded to the tyrosine hydroxylase-immunopositive "dopamine islands." With development there was an increase in staining intensity and in the number of positively reacting cells. By 4 weeks postnatally, STEP-immunoreactivity was almost homogeneously distributed throughout the striatum, as was seen at the adult stage. Immunoblotting analysis showed that STEP protein expression abruptly increased from 2 to 4 weeks postnatally when it reached the adult level. These findings suggest that STEP is involved in development and maturation of the striatal neurons.

Animals

GABA receptor agonist promotes reformation of the striatonigral pathway by transplant derived from fetal striatal primordia in the lesioned striatum.

Striatal lesions are known to cause the anterograde transneuronal degeneration of the substantia nigra pars reticulata (SNr) neurons in consequence to loss of GABAergic inhibitory striatonigral efferents. The present study was undertaken to examine whether long-term intraventricular administration of the GABA agonist muscimol could promote reformation of the striatonigral pathway arising from transplants by rescuing host SNr neurons from transneuronal death in rats with striatal ischemic lesions. Compared to nongrafted rats with striatal lesions, (i) a prominent axonal projection from the transplants to the ipsilateral substantia nigra, (ii) a significant increase in number of survived neurons in the ipsilateral SNr, and (iii) a significant reduction in number of apomorphine-induced turning behaviors were found in grafted animals with muscimol infusion, but not in those without muscimol administration. These findings suggest that preservation of the host target neurons for grafted cells may increase an efficacy of cerebral implants in establishment of the host-graft fiber connections, possibly, leading to functional restoration.

Animals

Initial and postoperative hyponatremia associated with pituitary adenoma: a case report.

This 67 year-old man experienced 3 episodes of symptomatic hyponatraemia. Radiological examination revealed a sellar lesion and the tumour was removed via the transsphenoidal route. Thereafter, he simultaneously developed intractable diabetes insipidus and serious hyponatraemia with persistent natriuresis. His level of atrial natriuretic peptide was not significantly elevated, however, his plasma aldosterone concentration was low. The oral administration of salt gradually improved his hyponatraemia as well as the coincident symptoms. By the administration of a mineralocorticoid, fludrocortisone acetate, we succeeded in maintaining his serum sodium level without salt replacement. We discuss the mechanism(s) and treatment of hyponatraemia associated with pituitary tumour.

Adenoma

Intracranial intraparenchymal schwannoma: report of three cases.

Intracranial intraparenchymal schwannomas are rare. We report three patients with an intracranial intraparenchymal schwannoma and discuss the clinical and neuroradiological aspects of this particular tumour. The patients were a 21-year-old male, a 64-year-old female and a 17-year-old male. The tumours were located in cerebrum in two patients and the cerebellum in one patient. Computerized tomography (CT) scans demonstrated a slightly high density area with homogeneous enhancement by contrast medium. Magnetic resonance imaging (MRI) showed slightly low signal intensity on the T1-weighted image, high or mixed signal intensity on the T2-weighted image and homogeneous enhancement by gadolinium diethylene triamine penta-acetic acid (Gd-DTPA). Radiological studies revealed cystic components in 2 of the 3 patients. All tumours were firm, well-demarcated, and completely removed. The diagnosis of schwannoma was derived from histological and immunohistochemical studies in all 3 cases; 2 cases were also examined by electron microscopy.

Adolescent

Dynamic MRI of meningiomas and schwannomas: is differential diagnosis possible?

We studied 23 patients with meningiomas and 14 with schwannomas using dynamic spin-echo (TR/TE 200/15 ms) MRI. Histologically the meningiomas were classified according to the 1993 WHO classification. Serial images were obtained every 30s for 210s after rapid injection of gadopentetate dimeglumine (0.1 mmol/kg). The contrast-enhancement ratio (CER) was divided into three patterns; a sharp rise with a peak within 60 s (A), a relatively rapid increase with a peak between 60 and 210s (B), a slow increase without a peak (C). The patterns were correlated with the histology of the tumors. The signal intensities of the tumours on T2-weighted images were also analyzed and correlated with the dynamic patterns. Meningiomas had more varied dynamic patterns than schwannomas. Almost half of the meningiomas showed pattern A, and one third pattern C. Of six meningiothelial meningiomas showed pattern A; all schwannomas and fibrous meningiomas showed pattern C. Various patterns were observed in transitional meningiomas. Of the 8 meningiomas showing pattern C, only one gave high signal on T2-weighted images, and could not be differentiated from the schwannomas. Thus, one third of meningiomas could not be differentiated from schwannomas by the dynamic contrast enhancement alone. However, when this was combined with the signal intensity on T2-weighted images, most meningiomas could be differentiated from schwannomas.

Brain