Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The novel drug lubeluzole, but not its (-)-R-isomer, protects against sensorimotor deficits provoked by photochemical stroke in rats. We studied the mechanism of protection of lubeluzole against glutamate toxicity in primary hippocampal cell cultures. In a model for glutamate antagonism, i.e., treatment of the cultures with compound during the glutamate trigger, lubeluzole was not protective. In contrast, after prolonged pretreatment, i.e., administration of compound to the culture for 7 days before glutamate, lubeluzole was neuroprotective. It had an IC50 of 48 nM and its R-isomer was nine times less active. Under these conditions, lubeluzole inhibited glutamate-stimulated guanosine 3',5'-cyclic monophosphate production (IC50 37 nM). Again the R-isomer was seven times less active. The compounds did not affect nitric oxide synthase activity, guanylate cyclase activity or arginine uptake. After prolonged pretreatment, lubeluzole attenuated citrulline production in the culture, which could not be compensated for by excess arginine. Because prolonged lubeluzole treatment does not inhibit glutamate-activated [Ca+2]i rise in these cultures, the findings may indicate that expression of nitric oxide synthase or levels of its cofactors were reduced. Treatment of C6 glioma cells with lubeluzole did not affect lipopolysaccharide/gamma interferon induced guanosine 3',5'-cyclic monophosphate levels, suggesting that lubeluzole does not inhibit the glial nitric oxide synthase pathway. In conclusion, the long-term neuroprotective property of lubeluzole against glutamate toxicity in hippocampal cultures is reflected by the fact of interference with the glutamateactivated nitric oxide synthase pathway. Prolonged treatment may reduce expression of nitric oxide synthase or levels of its cofactors.
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PMID:Lubeluzole, a novel long-term neuroprotectant, inhibits the glutamate-activated nitric oxide synthase pathway. 893 Jan 81

Poly(ADP-ribose) synthetase (PARS) activation, a downstream event of nitric oxide (NO) neurotoxicity has been implicated in cerebral reperfusion injury. The aim of our study was to identify the trigger of PARS activation during stroke. Formation of poly(ADP-ribose) profoundly increased in the early phase of reperfusion. Poly(ADP-ribose) formation was attenuated in mice deficient for neuronal NO synthase (nNOS). We next tested in glioma cells whether NO, or peroxynitrite (a cytotoxic oxidant formed from NO and superoxide) is the actual trigger of PARS activation. Peroxynitrite, but not various NO donors, activated PARS and suppressed cellular viability in a PARS-dependent fashion. Thus, nNOS is responsible for PARS activation in stroke. PARS activation, however, is not a direct result of NO production, but it occurs via peroxynitrite formation.
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PMID:Role of peroxynitrite and neuronal nitric oxide synthase in the activation of poly(ADP-ribose) synthetase in a murine model of cerebral ischemia-reperfusion. 966 59

Peroxynitrite triggers DNA single-strand breakage, which activates the nuclear enzyme poly(ADP-ribose) synthetase (PARS). Activation of PARS depletes its substrate, NAD+, slowing the rate of glycolysis, electron transport, and ATP formation, resulting in cell necrosis. Here, we demonstrate that inhibition of PARS with the novel, potent PARS inhibitor 5-iodo-6-amino-1,2-benzopyrone (INH2BP) protects against peroxynitrite-induced cell death (as measured by measurement of mitochondrial respiration and release of lactate dehydrogenase) in C6 glioma cells in vitro, and in a murine stroke model in vivo. Inhibition of PARS with INH2BP may represent a novel approach for the experimental therapy of stroke.
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PMID:Protective effects of 5-iodo-6-amino-1,2-benzopyrone, an inhibitor of poly(ADP-ribose) synthetase against peroxynitrite-induced glial damage and stroke development. 972 Oct 31

Primary lymphoma of the central nervous system, until recently representing about 1% of all brain tumours, shows a dramatically increased incidence in the general population as well as in high-risk groups (immunocompromised, AIDS), and may rise up to 6% in a population of AIDS patients. The clinical presentation is variable and cannot reliably be distinguished from other intracerebral tumours. At present, CT and MRI are the methods of choice for diagnosing cerebral lymphomas. However, their characteristics are not specific. The radiological picture may suggest glioma, meningioma, metastatic carcinoma or even a cerebrovascular accident. A labelled somatostatin analogue (pentetreotide) has been proposed as a new tracer for the imaging of somatostatin receptors, which have been identified by immunocytochemical or radioimmunoassay techniques in several organ systems. Somatostatin receptors were also identified in surgical biopsy samples from patients with Hodgkin and non-Hodgkin lymphoma and extracerebral lymphoma has already been visualised in vivo by means of In-111-labelled pentetreotide. While CT images of the brain showed a regression of the tumour after radiotherapeutic treatment, the scintigraphic images showed persistence of the tumoural tissue, corresponding with the clinical evolution and outcome. Furthermore, the absence of extra-cerebral lymphoma tissue, seen on the whole body images, was confirmed by post-mortem examination. To our knowledge, this is the first report of a primary intracerebral lymphoma visualised by means In-111-pentetreotide.
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PMID:Primary cerebral lymphoma visualised by means of In-111-pentetreotide scintigraphy. 992 25

Neurofibromatosis type 1 (NF1) is a genetic disease with a wide range of neurological manifestations. To examine these, and to evaluate neurological morbidity in adulthood of patients with NF1, we studied a hospital-based series of 158 patients that included 138 adult patients aged >18 years and 20 children. NF1 evaluation included a multidisciplinary clinical and a clinically oriented radiological investigation. Neurological events occurring during childhood (in both children and adults of the series) and adulthood were recorded. One or several neurological manifestations have been observed in 55% of patients (adults and children) (n = 87). These included: headache (28 patients); hydrocephalus (7); epilepsy (5); lacunar stroke (1); white matter disease (1); intraspinal neurofibroma (3); facial palsy (1); radiculopathy (5); and polyneuropathy (2). Tumours included: optic pathway tumours (20); meningioma (2); cerebral glioma (3); and malignant peripheral nerve sheath tumours (6). Life-threatening complications were observed in five adults and included four malignant peripheral nerve sheath tumours and one meningioma. Pain was the leading symptom in 11 adults and was related to malignant peripheral nerve sheath tumours, complications of intraspinal neurofibromas, subcutaneous neurofibromas and peripheral nerve neurofibromas. NF1 in adults was not associated with other disabling or life-threatening neurological complications. Symptomatic optic pathway tumours, cerebral gliomas, symptomatic aqueductal stenosis and spinal compression due to intraspinal NF were observed exclusively during childhood. In this series, the predominant neurological features of adults with NF1 were chronic pain and malignant peripheral nerve sheath tumours.
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PMID:Neurological complications of neurofibromatosis type 1 in adulthood. 1009 56

Disparities in manpower and facilities notwithstanding, neuroepidemiology might explain the observed differences in the mix of neurosurgical caseload in different parts of the world. The highest incidence rate of primary intracranial tumor was in Europe and the lowest rate in Africa. Glioma was more common in the West, teratoma in Japan and the Far East and meningioma in Africa. The lowest rates of childhood brain tumors were in South America, Africa and Asia. Stroke rates were very high in Finland and China. Blacks, Japanese and Chinese had more intracranial vascular occlusive disease while whites had more extracranial disease. Finland had a very high SAH incidence rate but the Middle East and Africa had low rates and a reversal of the aneurysm: AVM ratio. Highest incidence rates of neural tube defects occurred in countries where consanguineous marriages are common. Brain abscess, tuberculoma and other granulomas from infestations were preponderant in developing countries. Head injuries accounted for up to 40% of all neurosurgical admissions in some developing countries. Outside the USA and South Africa, civilian gunshot injuries were uncommon.
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PMID:Geographical neurosurgery. 1010 Feb 2

Elevated levels of extracellular glutamate ([Glu]o) cause uncontrolled Ca2+ increases in most neurons and are believed to mediate excitotoxic brain injury following stroke and other nervous system insults. In the normal brain, [Glu]o is tightly controlled by uptake into astrocytes. Because the vast majority of primary brain tumors (gliomas) are derived from astrocytes, we investigated glutamate uptake in glioma cells surgically isolated from glioma patients (glioblastoma multiforme) and in seven established human glioma cell lines, including STTG-1, D-54 MG, D-65 MG, U-373 MG, U-138 MG, U-251 MG, and CH-235 MG. All glioma cells studied showed impaired glutamate uptake, with a Vmax < 10% that of normal astrocytes. Moreover, rather than removing glutamate from the extracellular fluid, glioma cells release large amounts of glutamate, resulting in elevations of [Glu]o in excess of 100 microM within hours in a space that is 1000-fold larger than the cellular volume. Exposure of cultured hippocampal neurons to glioma-conditioned medium elicited sustained [Ca2+]i elevations that were followed by widespread neuronal death. Similarly, coculturing of hippocampal neurons and glioma cells, either with or without direct contact, resulted in neuronal death. Glioma-induced neuronal death could be completely prevented by treating neurons with the N-methyl-D-aspartate receptor antagonists MK-801/D(-)-2-amino-5-phosphonopentanoic acid or by depletion of glutamate from the medium. Interestingly, several phenylglycine derivatives including the metabotropic glutamate receptor agonist/antagonist (S)-4-carboxyphenylglycine (S-4CPG) potently and selectively inhibited glutamate release from glioma cells and prevented neurotoxicity. These data suggest that growing glioma tumors may actively kill surrounding neuronal cells through the release of glutamate. This glutamate release may also be responsible in part for tumor-associated seizures that occur frequently in conjunction with glioma. These data also suggest that neurotoxic release of glutamate by gliomas may be prevented by phenylglycine derivatives, which may thus be useful as an adjuvant treatment for brain tumors.
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PMID:Glioma cells release excitotoxic concentrations of glutamate. 1048 87

The neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) modulates inflammation by inhibiting production of proinflammatory cytokines. Using a plasmid vector encoding alpha-MSH, we examined whether autocrine alpha-MSH inhibits activation of the nuclear transcription factor NF-kappaB, a factor that is essential to expression of proinflammatory cytokines, in human glioma cells (A-172). Electrophoretic mobility shift assays of nuclear extracts demonstrated that NF-kappaB activation induced by lipopolysaccharide was inhibited in glioma cells transfected with alpha-MSH vector. Western blot analysis revealed that this inhibition was linked to preservation of expression of IkappaBalpha protein. Chloramphenicol acetyltransferase assay indicated that NF-kappaB-dependent reporter gene expression was suppressed in A-172 cells transfected with alpha-MSH vector. Finally, fluorescence staining confirmed that A-172 cells bear alpha-MSH receptors. The findings are consistent with the idea that, in central nervous system (CNS) inflammation, autocrine alpha-MSH exerts anti-inflammatory actions via modulation of NF-kappaB activation by preservation of IkappaBalpha protein. Based on this action of the peptide, it should be possible to treat neurodegenerative disease, stroke, encephalitis, trauma, and other CNS disorders that have an inflammatory component through gene therapy with alpha-MSH vector.
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PMID:Autocrine alpha-melanocyte-stimulating hormone inhibits NF-kappaB activation in human glioma. 1056 96

Magnetic resonance imaging (MRI) is more sensitive than computerized tomography in the detection of many intracerebral lesions; however, the significance of some MRI findings may be unclear. Over four years, nine patients, aged 40-79 years, have been encountered whose initial MRI scans were negative or had minimal abnormalities and soon thereafter had high grade glioma. Initial MRI was performed in eight patients for new-onset seizures and one patient for a focal deficit. MRI was negative in four of the patients and mildly abnormal in five of the patients (small areas of increased T2 and/or minimal enhancement). The initial diagnoses usually included inconclusive differentials of stroke and infection with neoplasm less frequently considered. Radiographic progression leading to the diagnosis of high grade glioma became evident on repeat MRI in 1-8 months with six patients showing progression within three months. All patients underwent surgery and had histologic diagnosis of glioma. Although MRI is quite sensitive, four of the initial scans were negative with reasonable quality studies. Conversely, in five of the initial scans, the tumors were detected when so small that the radiographic findings were not typically diagnostic. Glioma must be considered as a possible cause of initial seizures or new neurologic deficits in adults with normal or minimally abnormal MRI. In this group, seizures were the overwhelming hallmark of presentation. In such a clinical situation, close follow-up with short interval repeat MRI should be performed.
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PMID:Early MRI findings in high grade glioma. 1093 Jan 2

A 49-year-old woman with 6 months history of body weight loss, muscle weakness, and dysarthria, was found with respiratory arrest and resuscitated in the morning of January 1999. An MRI brain scan revealed diffuse swelling and T2/FLAIR high signal intensity with mild Gadolinium enhancement in the lower pons and medulla oblongata. Although the histological diagnosis could not be obtained, glioma (astrocytoma) was suspected. In the morning of July 3rd she presented sweating and cyanosis. Her arterial oxygen saturation was 18%. When we asked her to breathe more, she kept breathing and oxygen saturation was normalized. However, she could not breathe at all when she fell asleep without stimulation. She was kept under respiratory support for 2 months. Her symptoms improved with fluctuating course after 70 Gy of radiation therapy. Ondine curse is one type of sleep apnea syndrome, defined as the selective disturbance of autonomous breathing. Surgical operation and stroke are the reported causes of this syndrome. Brainstem tumor is relatively common cause for children's Ondine curse. On the other hand, it rarely causes adult's Ondine curse as a main symptom.
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PMID:[A case of Ondine curse associated with a medullary tumor]. 1121 2


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