Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two additional patients with alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency are described. An 11-month-old girl with nonconsanguineous parents had generalized seizures and no angiokeratoma. Biochemical investigation showed persistent slight oligosacchariduria; enzymatic analysis of plasma, leukocytes, and fibroblasts revealed profound alpha-NAGA deficiency. Heterozygote enzyme levels were found in both parents. The mother has epilepsy, and epilepsy is present in the father's family. A younger, clinically healthy brother also had the enzyme deficiency. Electron microscopy of lymphocytes from the index patient showed no vacuolization. Incubation of cultured fibroblasts with Helix pomatia lectin showed the presence of intracellular N-acetylgalactosamine-containing storage material, not present in a series of 12 normal fibroblast lines. Our cases cannot be classified definitely as infantile cases. Biochemically the diagnosis could easily have been missed. Urinary oligosaccharide pattern after resorcinol staining was identical to those previously described, but excretion was significantly lower than in the reported infantile cases and the bands disappeared after the urine was desalted. The enzyme defect in leukocytes would have been missed with one of the commercial substrates used. For this mild variant of alpha-NAGA deficiency, the clinical pattern is not yet clear; a longer follow-up period is needed.
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PMID:alpha-N-acetylgalactosaminidase deficiency with mild clinical manifestations and difficult biochemical diagnosis. 807 45

The issue of whether neuronal degeneration is a primary factor in activation of astrocytes during epileptogenesis was addressed using the kindling model of epilepsy. No degenerative changes specific to the kindling process were observed in brain sections from kindled animals, sampled from the olfactory bulbs through to cerebellum and processed with the degeneration-sensitive cupric silver stain. Also, examination of lectin-stained sections did not reveal any reactive microglia. At the same time, reactive astrocytes, as judged by an increase in glial fibrillary acidic protein immunoreactivity and a de novo vimentin immunoreactivity, were prominent in amygdala, piriform cortex, entorhinal cortex and hippocampus. These results suggest that loss of neurones is not a prerequisite for establishment of epilepsy-prone state, that seizures of short duration do not necessarily result in neuronal death, and that in kindling, astrocytes are activated by factors that are not related to neuronal degeneration, but which are likely associated with abnormal neuronal activity.
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PMID:Activation of astrocytes during epileptogenesis in the absence of neuronal degeneration. 898 6

Seizures evoked by kainic acid and a variety of experimental methods induce sprouting of the mossy fiber pathway in the dentate gyrus. In this study, the morphological features and spatial distribution of sprouted mossy fiber axons in the dorsal dentate gyrus of kainate-treated rats were directly shown in granule cells filled in vitro with biocytin and in vivo with the anterograde lectin tracer Phaseolus vulgaris leucoagglutinin (PHAL). Sprouted axon collaterals of biocytin-filled granule cells projected from the hilus of the dentate gyrus into the supragranular layer in both transverse and longitudinal directions in kainate-treated rats but were not observed in normal rats. The sprouted axon collaterals projected into the supragranular region for 600-700 microm along the septotemporal axis. Collaterals from granule cells in the infrapyramidal blade crossed the hilus and sprouted into the supragranular layer of the suprapyramidal blade. Sprouted axon segments in the supragranular layer had more terminal boutons per unit length than the axon segments in the hilus of both normal and kainate-treated rats but did not form giant boutons, which are characteristic of mossy fiber axons in the hilus and CA3. Mossy fiber axons in the hilus of kainate-treated rats had more small terminal boutons, fewer giant boutons, and there was a trend toward greater axon length compared with mossy fibers in the hilus of normal rats. With the additional length of supragranular sprouted collaterals, there was an overall increase in the length of mossy fiber axons in kainate-treated rats. The synaptic and axonal remodeling of the mossy fiber pathway could alter the functional properties of hippocampal circuitry by altering synaptic connectivity in local circuits within the hilus of the dentate gyrus and by increasing the divergence of the mossy fiber terminal field along the septotemporal axis.
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PMID:Synaptic and axonal remodeling of mossy fibers in the hilus and supragranular region of the dentate gyrus in kainate-treated rats. 945 May 37

In order to evaluate the putative role of Cu,Zn-superoxide dismutase (SOD-1) in the antioxidant defense mechanism during the neurodegenerative process, we examined the level of mRNA, the specific activity and immunocytochemical distribution for SOD-1 in the rat hippocampus after systemic injection of kainic acid (KA). Hippocampal SOD-1 mRNA levels were significantly increased by the seizure intensity 3 and 7 days after KA. These enhanced mRNA levels for SOD-1 were consistent with the increased specific activities for SOD-1, suggesting that the superoxide radical generated in neurotoxic lesion, induced SOD-1 mRNA. The CA1 and CA3 neurons lost their SOD-1-like immunoreactivity, whereas SOD-1-positive glia-like cells mainly proliferated throughout the CA1 sector and had an intense immunoreactivity at 3 and 7 days after KA. This immunocytochemical distribution for SOD-1-positive non-neuronal elements was similar to that for glial fibrillary acidic protein (GFAP)-positive cells. Each immunoreactivity for SOD-1-positive non-neuronal cell or GFAP in the layers of CA1 and CA3 disappeared 3 and 7 days after a maximal stage 5 seizure. On the other hand, activated microglial cells as selectively marked with the lectin occurred in the areas affected by KA-induced lesion. Double-labeling immunocytochemical analysis demonstrated the co-localization of SOD-1-positive glia-like cells and reactive astrocytes as labeled by GFAP or S-100 protein immunoreactivity. This finding suggested that the mobilization of astroglial cells for the synthesis of SOD-1 protein is a response to the KA insult designed to decrease the neurotoxicity induced by oxygen-derived free radicals. Therefore, these alterations might reflect the regulatory role of SOD-1 against oxygen-derived free radical-induced neuronal degeneration after systemic KA administration.
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PMID:Changes of hippocampal Cu/Zn-superoxide dismutase after kainate treatment in the rat. 1064 Jun 19

An 8-year-old male Tibetan Terrier showed prolonged astasia, complete paralysis, ticlike signs, and seizure and died 2 months after the onset of symptoms. Histopathologically, there was moderate to severe infiltration of pleomorphic histiocytic mononuclear cells bilaterally in the basiarachnoidal and ventricular areas of the brain. The spinal dura mater, arachnoidal space, and leptomeninges were also affected by infiltrative proliferation of these mononuclear cells. The infiltrating cells had the morphologic characteristics of histiocytes but exhibited moderate pleomorphism and atypia, with abundant mitotic figures. With immunohistochemistry and lectin histochemistry, most of the infiltrating cells were positive for lysozyme and lectin RCA-1 and negative for glial fibrillary acid protein, suggesting that they were of monocytic/histiocytic-origin. Positive proliferating cell nuclear antigen immunostaining demonstrated that most nuclei of the histiocytic cells were in the S phase of the cell cycle, consistent with a proliferating population of cells. Based on these findings, the case was diagnosed as diffuse leptomeningeal malignant histiocytosis.
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PMID:Diffuse leptomeningeal malignant histiocytosis in the brain and spinal cord of a Tibetan Terrier. 1128 Mar 79

Sensitive indices of neural injury were used to evaluate the time course of kainic acid (KA)-induced hippocampal damage in adult C57BL/6J mice (4 months), a strain previously reported to be resistant to kainate-induced neurotoxicity. Mice were injected systemically with saline or kainate, scored for seizure severity (Racine scale), and allowed to survive 12 h, one, three, or seven days following which they were evaluated for neuropathological changes using histological or biochemical endpoints. Most kainate-treated mice exhibited limited seizure activity (stage 1); however, cupric-silver and Fluoro-Jade B stains revealed significant damage by 12 h post-treatment. Immunohistochemistry and immunoassay of glial fibrillary acidic protein and lectin staining revealed a strong treatment-induced reactive gliosis and microglial activation. Immunostaining for immunoglobulin G revealed a kainate-induced breach in the blood-brain barrier. Nissl and hematoxylin stains provided little information regarding neuronal damage, but revealed the identity of non-resident cells which infiltrated the pyramidal layer. Our data suggest sensitive indicators of neural injury evaluated over a time course, both proximal and distal to treatment, are necessary to reveal the full extent of neuropathological changes which may be underestimated by traditional histological stains. The battery of neuropathological indices reported here reveals the C57BL/6J mouse is sensitive to excitotoxic neural damage caused by kainic acid, in the absence of tonic-clonic seizures.
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PMID:Sensitive indicators of injury reveal hippocampal damage in C57BL/6J mice treated with kainic acid in the absence of tonic-clonic seizures. 1545 67

Possible central nervous system effects of the gymnosperm lectin from Araucaria angustifolia seeds were studied in seizure and open field tests. Male Swiss mice were administered saline (control), lectin (0.1, 1, and 10 mg/kg), flumazenil (1 mg/kg), or diazepam (1 mg/kg) intraperitoneally. Lectin at the highest dose increased time to death in the pentylenetetrazole- and strychnine-induced seizure models as compared with control, but not in the pilocarpine model. In the open field test, lectin reduced locomotor activity at all doses tested, as did diazepam, when compared with control. These locomotor effects were reversed by flumazenil pretreatment. In conclusion, A. angustifolia lectin had a protective effect in the pentylenetetrazole- and strychnine-induced seizure models, suggestive of activity in the GABAergic and glycinergic systems, respectively, and also caused a reduction in animal movements, which was reversed by flumazenil, pointing to a depressant action mediated by a GABAergic mechanism.
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PMID:Central action of Araucaria angustifolia seed lectin in mice. 1944 42

Gangliosides, sialic acid-bearing glycosphingolipids, are expressed at high abundance and complexity in the brain. Altered ganglioside expression results in neural disorders, including seizures and axon degeneration. Brain gangliosides function, in part, by interacting with a ganglioside-binding lectin, myelin-associated glycoprotein (MAG). MAG, on the innermost wrap of the myelin sheath, binds to gangliosides GD1a and GT1b on axons. MAG-ganglioside binding ensures optimal axon-myelin cell-cell interactions, enhances long-term axon-myelin stability and inhibits axon outgrowth after injury. Knowledge of the molecular interactions of brain gangliosides may improve understanding of axon-myelin stability and provide opportunities to enhance recovery after nerve injury.
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PMID:Brain gangliosides in axon-myelin stability and axon regeneration. 1982 44

Circulating endothelial cells (CECs) are nonhematopoetic mononuclear cells in peripheral blood that are dislodged from injured vessels during cardiovascular disease, systemic vascular disease, and inflammation. Their occurrence during cerebrovascular insults has not been previously described. Epileptic seizures cause the long-term loss of cerebrovascular endothelial dilator function. We hypothesized that seizures cause endothelial sloughing from cerebral vessels and the appearance of brain-derived CECs (BCECs), possible early indicators of cerebral vascular damage. Epileptic seizures were induced by bicuculline in newborn pigs; venous blood was then sampled during a 4-h period. CECs were identified in the fraction of peripheral blood mononuclear cells by the expression of endothelial antigens (CD146, CD31, and endothelial nitric oxide synthase) and by Ulex europeaus lectin binding. In control animals, few CECs were detected. Seizures caused a time-dependent increase in CECs 2-4 h after seizure onset. Seizure-induced CECs coexpress glucose transporter-1, a blood-brain barrier-specific glucose transporter, indicating that these cells originate in the brain vasculature and are thus BCECs. Seizure-induced BCECs cultured in EC media exhibited low proliferative potential and abnormal cell contacts. BCEC appearance during seizures was blocked by a CO-releasing molecule (CORM-A1) or cobalt protoporphyrin (heme oxygenase-1 inducer), which prevented apoptosis in cerebral arterioles and the loss of cerebral vascular endothelial function during the late postictal period. These findings suggest that seizure-induced BCECs are injured ECs dislodged from cerebral microvessels during seizures. The correlation between the appearance of BCECs in peripheral blood, apoptosis in cerebral vessels, and the loss of postictal cerebral vascular function suggests that BCECs are early indicators of late cerebral vascular damage.
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PMID:Epileptic seizures increase circulating endothelial cells in peripheral blood as early indicators of cerebral vascular damage. 2036 95

The pancreatitis-associated protein (PAP) family (also known as the regenerating gene (Reg) family) is a group of 16 kDa secretory proteins structurally classified as the calcium dependent-type lectin superfamily. Some PAP family members are expressed in neurons following peripheral nerve injury and traumatic brain injury. To determine whether PAP family members are expressed in non-traumatic brain injury, expressions were analyzed following kainic acid (KA)-induced seizure. PAP-I (also known as Reg2 in rat and RegIII-beta in mouse) and pancreatitis associated protein-III (PAP-III; RegIII-gamma in mouse) messenger ribonucleic acid (mRNA) was transiently expressed in some restricted areas, such as the hippocampus and parahippocampal area; expression was observed immediately at a maximal level 1 day after seizure. Expression disappeared within 3 days after seizure. In situ hybridization (ISH) and immunohistochemistry revealed neuronal PAP-I and PAP-III expression in the hippocampal dentate gyrus, perirhinal and entorhinal cortices, and the posterior cortical nucleus of the amygdala. The number of PAP-III mRNA-positive neurons was significantly greater than PAP-I mRNA-positive neurons. The majority of positive neurons co-localized with c-Jun, but not with glutamic acid decarboxylase (GAD). These results may suggest that PAP-I and PAP-III induction in non-GABAergic neurons would protect neurons against damage following seizure.
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PMID:Pancreatitis-associated protein-I and pancreatitis-associated protein-III expression in a rat model of kainic acid-induced seizure. 2109 49


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