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)

Calmodulin is a major Ca2+ -binding protein that may mediate many Ca2+ -regulated processes in neuronal function. Calmodulin is present in the presynaptic nerve terminal in association with synaptic vesicles and in postsynaptic density fractions. Several calmodulin-regulated synaptic biochemical processes have been identified. These results indicate that calmodulin may modulate some aspects of neuronal excitability. Phenytoin, carbamazepine, and the benzodiazepines inhibit Ca2+ -calmodulin-regulated protein phosphorylation and neurotransmitter release by synaptic vesicles. A saturable, stereospecific membrane binding site has been identified for the benzodiazepines. The potency of the benzodiazepines to bind to these sites correlates with their ability to inhibit maximal electroshock-induced seizures. Phenytoin and carbamazepine can displace benzodiazepine binding from these binding sites. Binding to these "anticonvulsant" sites regulates Ca2+ -calmodulin-stimulated membrane protein phosphorylation and depolarization-dependent Ca2+ uptake in intact synaptosome preparations. These results provide evidence that major anticonvulsant drugs regulate Ca2+ -calmodulin systems at the synapse. Kindling alters Ca2+ -calmodulin protein phosphorylation in brain membrane. In addition, alterations in Ca2+ -calmodulin kinase systems have been associated with some strains of seizure-susceptible mice. Thus, evidence from multiple sources suggests that calmodulin-mediated processes may play a role in the development of altered neuronal excitability and in some forms of seizure disorders.
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PMID:Calmodulin systems in neuronal excitability: a molecular approach to epilepsy. 615 Jun 80

Haemophilus influenzae type b (HIb) is the most common cause of bacterial meningitis in children with a mortality rate ranging from 1.6% to 14%. Most patients have a 2-3 day history of symptoms prior to admission. A few have fulminating disease with rapid neurological deterioration. Review of 191 cases of HIb meningitis revealed a mortality rate of 2.1% but all who died had fulminating meningitis (FM). Four of six patients with FM died. FM patients had symptoms for less than 24 hours before rapid neurological deterioration with increased ICP, seizures, coma and/or respiratory arrest. Review of 10 FM cases revealed that on admission, 5 had hypotension, 3 had thrombocytopenia, and 8 had coma. Typical CSF changes were seen in only 7. All fatal cases died within 24 hours. Brain swelling and tonsillar herniation were found at autopsy. SDS-PAGE outer membrane protein subtyping did not show one "killer strain". Animal and autopsy data suggest that diminished CSF outflow and cerebral edema contribute to increased ICP. To improve survival of FM patients, initial treatment must (1) decrease ICP below levels impairing cerebral perfusion, (2) maintain adequate ventilation and blood pressure, and include (3) LP when stable, (4) antibiotics, and (5) close monitoring. Utilizing these principles, two FM patients survived without major sequelae.
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PMID:Fulminating haemophilus influenzae b meningitis. 670 99

El mouse is a mutant strain with genetic epileptogenicity. Epileptic convulsion of El mouse has been shown to be related to metabolical and structural abnormalities in the hippocampal neuron. Gamma-globulin purified from the human serum has a marked anti-convulsive effect in El mouse. Human IgG, 80% of the gamma-globulin, has the reactivity indicating the presence of Lewis-x structure in the sugar chain. In the present study, the author found that 3'-fucosyllactose, the terminal structure of Lewis-x, suppressed the tonic-clonic convulsion of El mouse. Lewis-x is a ligand of granular membrane protein-140 on the surfaces of the vascular endothelial cell and platelet. The vascular endothelial cell and platelet produce platelet-derived growth factor-BB, which prolongs the life-span of the hippocampal neuron and accelerates the formation of its axon and dendrite. The vascular endothelial cell and platelet in El mouse may be activated by 3'-fucosyllactose, and may secrete platelet-derived growth factor-BB, which, in turn, may reduce the sensitivity to have epileptic convulsions in El mouse. Moreover, the author found that the fraction having Lewis-x reactivity obtained from the serum of El mouse had much reactivity of NeuAc alpha 2-6Gal. The sialic acid in Lewis-x structures of El mouse may reduce the ability of the Lewis-x structure to activate the endothelial cell and platelet. The findings in this study indicate that sugar chain structures and their metabolisms are closely related to the mechanism of genetic seizure susceptibility of El mouse.
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PMID:[Lewis-x, a sugar chain structure, suppresses the epileptic seizure in El mouse]. 748 Mar 56

To clarify the molecular mechanism of neuronal bursting activity of seizures, we have constructed a cDNA library from mouse cerebrum cortex-derived cells treated with pentylentetrazole (PTZ), one of the convulsant drugs. Using a differential screening technique, several cDNA clones whose expressions change with PTZ-treatment were obtained. Among these clones, SEZ-6 was characterized by increased expression with PTZ. Detailed northern analysis showed that expression of SEZ-6 was limited to the brain and increased by the administration of PTZ not only in in vitro cultured cells but also in vivo. Analysis of SEZ-6 cDNA revealed multiple motifs, including typical signal sequence, threonine-rich domain, five copies of short consensus repeats (SCRs) or sushi domain (complement C3b/C4b binding site), two repeated sequences which were partially similar to the CUB domain or complement C1r/s-like repeat, one transmembrane domain and a short cytoplasmic segment in the C-terminal region. Although many proteins with multiple SCRs or CUB domains other than complement-related proteins have been found, this is the first report about a brain-specific cDNA which encodes membrane protein with both SCRs and CUB domain-like segments. Based on these findings, it is evident that SEZ-6 encodes a novel type of protein which may be related to seizure.
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PMID:Cloning and expression of SEZ-6, a brain-specific and seizure-related cDNA. 772 19

A study was undertaken to assess the receptor binding characteristics of [3H]4-benzylpempidine to an allosteric site on calf brain membranes associated with nicotinic cholinergic receptors and to compare the binding affinity of novel arylpempidine analogs with their ability to antagonize the behavioral effects of nicotine in mice. Scatchard analysis of the binding yielded a K(d) of 20 nM and a B(max) of 330 fmols/mg membrane protein. [3H]4-benzylpempidine appears to be a more satisfactory ligand than [3H]mecamylamine, since it possessed a 50-fold greater affinity and its binding was far less sensitive to inorganic ions and Tris. Among the arylpempidine analogs 4-m-chlorobenzylidenepempidine and 4-benzylidenepempidine had the lowest K(i) values (1.4 nM and 5.0 nM, respectively) and were the most potent in antagonizing nicotine-induced seizures in mice. Although the K(i) values for pempidine and mecamylamine were 1-2 orders of magnitude greater than any of the arylpempidines, the dose required to antagonize nicotine-induced seizures in mice was comparable to the arylpempidines. One explanation for this apparent discrepancy in the correlation of binding affinity and nicotine antagonism is the lower brain penetration of arylpempidines compared to mecamylamine, following their systemic administration to mice.
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PMID:[3H]benzylpempidine, a new radioligand for probing a putative channel site on nicotinic cholinergic receptors. 909 44

Taking into consideration the significance of glutamate receptors in epileptic focus forming, the authors studied the level of autoantibodies (Glu aAB) to fragment of glutamate receptors, quisqualate membrane protein with molecular mass 56 kDa in blood serum. The study employed the diagnostic kit "Paroxysmal activity test" (PAT) elaborated in Institute of Human Brain, RAS (St-Petersburg), 140 children from 2 months to 16 years with epilepsy, epileptic syndrome, paroxysmal states of nonepileptic genesis and with other neurologic diseases as well as 32 practically healthy children were examined. Significant increase of Glu aAB level was found in children with epilepsy and epileptic syndrome as compared with healthy children. Glu aAB level was decreased in patients which were treated by adequate anticonvulsant therapy that resulted in relief of convulsive fits for 6 months and normalization of EEG. In patients with paroxysmal disorders Glu aAB content was lower than in patients with epilepsy and epileptic syndrome, but higher than in healthy children; 5 children from this group with high level of Glu aAB had seizures in aged. It was proposed to introduce the described method into clinic for the study of the processes of brain's epileptization in process of development of diseases of nervous system, accompanied by convulsions or paroxysmal states.
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PMID:[Paroxysmal activity test in pediatric neurology]. 950 2

Migration disorders cause neurons to differentiate in an abnormal heterotopic position. Although significant insights have been gained into the etiology of these disorders, very little is known about the anatomy of heterotopias. We have studied heterotopic masses arising in the hippocampal CA1 region after prenatal treatment with methylazoxymethanol (MAM) in rats. Heterotopic cells were phenotypically similar to neocortical supragranular neurons and exhibited the same temporal profile of migration and neurogenesis. However, they did not express molecules characteristic of CA1 neurons such as the limbic-associated membrane protein. Horseradish peroxidase injections in heterotopia demonstrated labeled fibers not only in the neocortex and white matter but also in the CA1 stratum radiatum and stratum lacunosum. To study the pathophysiological consequences of this connectivity, we compared the effects of neocortical and limbic seizures on the expression of Fos protein and on cell death in MAM animals. After metrazol-induced seizures, Fos-positive cells were present in CA1 heterotopias, the only hippocampal region to be activated with the neocortex. By contrast, kainic acid-induced seizures caused a prominent delayed cell death in limbic regions and in CA1 heterotopias. Together, these results suggest that neocortical heterotopias in the CA1 region are integrated in both the hippocampal and neocortical circuitry.
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PMID:Neocortex in the hippocampus: an anatomical and functional study of CA1 heterotopias after prenatal treatment with methylazoxymethanol in rats. 959 May 59

Transsynaptic movement of endogenous zinc may play a key role in selective neuronal death after brain ischemia and prolonged seizures. As to the mechanism, we have reported recently that zinc-induced neuronal death occurs mainly by oxidative stress in cortical cultures. Here we present evidence supporting the idea that activation of membrane protein kinase C (PKC) in neurons is likely to play a key role in zinc-induced oxidative neuronal injury. Exposure of cortical cultures to 300 microM zinc for 15 min induced increases in the activity, without changing the amount, of membrane PKC to two- to threefold of control values, followed by neuronal death over the next day. Addition of a zinc chelator, Ca-EDTA, or PKC inhibitors with zinc completely abolished the zinc-induced increase in the membrane PKC activity. Indicating the participation of PKC in zinc-induced oxidative stress and neuronal death, the selective PKC inhibitor GF109203X attenuated both. Furthermore, as in zinc-induced neuronal death, activation of PKC with phorbol esters induced free radical generation and neuronal death, which were blocked by GF109203X or an antioxidant, Trolox. The present results support the idea that zinc influx activates PKC in the membrane, which contributes to free radical generation and neuronal death. As an increasing body of evidence suggests that zinc neurotoxicity is an important mechanism of pathological neuronal death, timely prevention of PKC activation after acute brain insult may prove useful in ameliorating this type of neuronal death.
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PMID:Mediation by membrane protein kinase C of zinc-induced oxidative neuronal injury in mouse cortical cultures. 1009 68

The cyanobacterium Synechocystis sp. PCC 6803 is an ideal model organism for the proteome study of light-induced gene expression because the whole genomic sequence has been determined. The soluble proteins extracted from light- and dark-cultured cells were separated by two-dimensional polyacrylamide gel electrophoresis. Light-induced protein spots electroblotted on a polyvinyldiene difluoride membrane were analyzed by N-terminal Edman sequence determination and followed by CyanoBase. The tryptic digests of some proteins were also confirmed by matrix-assisted laser desorption ionization/time-of-flight (MALDI-TOF) and MS-Fit search. Interestingly, eight proteins were related to photosynthesis and respiration (RbcS/L, CbbA, Gap2, AtpB, CpcB, PsbO, and PsbU). Four proteins (SodB, DnaK, GroEL2, and Tig) were involved in cellular processes and the functions of another two proteins (rehydrin and membrane protein) were unknown. The proteome analysis by N-terminal Edman sequencing and MALDI-TOF enabled us to characterize one-shot protein profiles expressed under different physiological conditions.
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PMID:Proteome analysis of light-induced proteins in Synechocystis sp. PCC 6803: identification of proteins separated by 2D-PAGE using N-terminal sequencing and MALDI-TOF MS. 1121 77

1. Cellular prion (PrPc) is a plasma membrane protein involved with copper uptake, protection against oxidative stress, cell adhesion, differentiation, signaling, and survival in the central nervous system. 2. Deletion of PrPc gene (Pmp) in mice enhances sensitivity to seizures in vivo and neuronal excitability in vitro which can be related to: (i) disrupted Ca(+2)-activated K+ currents, with loss of IHAP conductance in hippocampus; (ii) abnormal GABA-A inhibition in the hippocampus; (iii) mossy fiber reorganization in the hippocampus; (iv) changes in ectonucleotidases in both hippocampus and neocortex; and (v) higher levels of neocortical and subcortical oxidative stress. Moreover, postnatal Prnp knockout mice showed a significant reduction of after hyperpolarization potentials in hippocampal CA1 cells. 3. Taken together, these findings suggest that loss of PrPc function contributes to the hyperexcitable and synchronized activities underlying epileptic seizures generated in neocortex and hippocampus. Hence, the role of PrPc on human symptomatic, cryptogenic or idiopathic epileptic syndromes deserves further investigation.
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PMID:Cellular prion protein: implications in seizures and epilepsy. 1246 68


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