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)

Adoptive immunotherapy using OK-432-activated mononuclear cells (OK-MCs) offers cell-mediated and cytokine-mediated pathways for antitumor activity. The effectiveness of direct intratumoral administration of OK-MCs via a catheter/reservoir system was studied in patients with malignant brain tumors. Seventeen patients, 12 with malignant glioma, four with metastatic adenocarcinoma, and one with primary sarcoma of the brain, were treated by OK-MC therapy (1.0 to 11.2 x 10(7) cells/person) between June 1989 and April 1999. The OK-MC therapy was given to patients with tumors progressing despite previous cytoreductive surgery, radiation, or chemotherapy. Adverse effects seen after the therapy were fever in 10 patients, seizure in two patients, and hypotension in one patient. Evaluation by computed tomography or magnetic resonance imaging revealed that seven patients showed no change including three with minor response, and 10 showed progressive disease. Adoptive immunotherapy using OK-MC was safe and well tolerated, but the therapeutic potential is limited.
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PMID:Adoptive immunotherapy for malignant brain tumors using human peripheral blood mononuclear cells activated by the Streptococcal preparation OK-432. 1156 49

Muromonab-CD3 is widely used for immunosuppression in patients undergoing solid organ transplant. We report two siblings with oligomeganephronia and end-stage renal disease who developed encephalopathy and seizures from muromonab-CD3 following renal transplant. The first case is a 13-year-old girl who developed encephalopathy, seizure, and triparesis following renal transplant while muromonab-CD3 was used for immunosuppression. The second case was the 6-year-old sister of the first case, who also developed recurrent focal seizures while she was on muromonab-CD3 for renal transplant immunosuppression. In both cases, a sequential brain magnetic resonance image (MRI) showed progression of abnormalities from the cerebral cortex to the white matter. In the first case, the MRI normalized after muromonab-CD3 was discontinued. In the second case, the patient developed a leukoencephalopathy following cyclosporin administration. The pathophysiology of muromonab-CD3 encephalopathy is believed to be a disturbance to the blood-brain barrier mediated by cytokine release from lymphocyte stimulation by muromonab-CD3. Because the major histocompatibility complex genes are known to regulate cytokine responses, it is possible that the excessive production of cytokines that causes encephalopathy may occur in patients who share close major histocompatibility complex genes. Muromonab-CD3 in a patient whose sibling has developed cerebral complications from its use should be administered with caution. The second case suggests that muromonab-CD3 encephalopathy predisposes patients to develop cyclosporin neurotoxicity. Because the pathogenesis of muromonab-CD3 encephalopathy and cyclosporin-related cerebral complications are both potentially mediated through a disturbance of the blood-brain barrier, it is possible that one agent may predispose a patient to the complication of the other.
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PMID:Muromonab-CD3-induced neurotoxicity: report of two siblings, one of whom had subsequent cyclosporin-induced neurotoxicity. 1173 68

In the present study, the interaction between epileptogenesis and the immune system were studied in a kindling model. First, the effects of a single administration of TNF-alpha (5.0 microg/kg, i.p.) on seizure and EEG activity were investigated in amygdala-kindled rats. TNF-alpha treated rats showed more prolonged epileptiformic discharges than control rats. TNF-alpha also induced a decrease in the power of delta band and an increase in theta and alpha activity. In addition, a marked increase in the power of beta and gamma band was observed. The EEG changes were most numerous in the frontal cortex and amygdala. All effects were registered 24 h after TNF-alpha administration. Finally, electrical stimulation enhanced the level of TNF-alpha in blood serum from 1.9 +/- 1.5 to 12.7 +/- 3.8 pg/ml and in brain tissue 56.8 +/- 6.0 to 109.2 +/- 6.0 pg/mg, as was determined via the ELISA method. It can be concluded that there is a mutual facilitative interaction of both epileptogenic and cytokine-derived mechanisms on this type of seizure. The changes in the power spectrum of the EEG after TNF-alpha might contribute to intensify thalamic-derived facilitation of epileptic discharge in cortical structures.
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PMID:The role of TNF-alpha in amygdala kindled rats. 1184 34

Febrile seizures can be the first sign of epilepsy. In a recent study, patients with temporal lobe epilepsy were reported to carry the interleukin-1beta allele 2 at position -511 more often than healthy control subjects. Because pro-inflammatory cytokines, such as interleukin-1, are well-known inducers of fever and therefore could play an important part in the pathogenesis of febrile seizures, we have, in this study, analyzed the cytokine gene polymorphism of interleukin-1beta at position -511 in children with febrile seizures and control subjects. We found a statistically significant increase in the frequency and the carriage of interleukin-1beta (-511) allele 2 in children with febrile seizures (n = 35) compared with healthy blood donors (n = 400) (P = 0.03 and P = 0.05, respectively). In previous studies, this allele has been connected to increased in vitro production of interleukin-1. Children with febrile seizures may therefore have an increased pro-inflammatory reaction during fever. This pro-inflammatory reaction may also predispose some children to the development of epilepsy.
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PMID:Increased frequency of interleukin-1beta (-511) allele 2 in febrile seizures. 1195 25

Glycogen storage disease (GSD) is a rare autosomal-recessive disorder characterized by hypoglycemia, hepatosplenomegaly, seizures, and failure to thrive in infants. Neutropenia and/or neutrophil dysfunction develops in GSD1b, but not in other types. GSD1b results from a deficiency of the glucose-6-phosphate translocase enzyme and the genetic defect maps to chromosome 11q23. Patients with GSD1b are susceptible to recurrent bacterial infections, commonly involving the perirectal area, ears, skin, and urinary tract, although life-threatening infections, such as septicemia, pneumonia, and meningitis occur less frequently. Although the exact mechanism of neutropenia in patients with GSD1b is not known, treatment with recombinant human granulocyte colony-stimulating factor (G-CSF) has reduced the incidence of infections and has improved the quality of life of these patients. Defects in neutrophil chemotaxis and intracellular bacterial killing have been described and appear to be corrected by the use of G-CSF. To date, no cases of myelodysplasia or acute myeloid leukemia have been observed in patients with GSD1b treated with G-CSF. A significant complication of cytokine therapy is the development of hypersplenism, requiring either a reduction in the dosage of G-CSF or splenectomy.
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PMID:Glycogen storage disease. 1195 92

Neurocysticercosis, a parasitic infection of the human central nervous system caused by Taenia solium, is a leading cause of seizures. Seizures associated with neurocysticercosis are caused mainly by the host inflammatory responses to dying parasites in the brain parenchyma. We previously demonstrated sequential expression of Th1 cytokines in early-stage granulomas, followed by expression of Th2 cytokines in later-stage granulomas in murine cysticercosis. However, the mechanism leading to this shift in cytokine response in the granulomas is unknown. Neuropeptides modulate cytokine responses and granuloma formation in murine schistosomiasis. Substance P (SP) induces Th1 cytokine expression and granuloma formation, whereas somatostatin inhibits the granulomatous response. We hypothesized that neuropeptides might play a role in regulation of the granulomatous response in cysticercosis. To test this hypothesis, we compared expression of SP and expression of somatostatin in murine cysticercal granulomas by using in situ hybridization and immunohistochemistry. We also compared expression with granuloma stage. Expression of SP mRNA was more frequent in the early-stage granulomas than in the late-stage granulomas (34 of 35 early-stage granulomas versus 1 of 13 late-stage granulomas). By contrast, somatostatin was expressed primarily in later-stage granulomas (13 of 14 late-stage granulomas versus 2 of 35 early-stage granulomas). The median light microscope grade of SP mRNA expression in the early-stage granulomas was significantly higher than that in the late-stage granulomas (P = 0.008, as determined by the Wilcoxon signed rank test). By contrast, somatostatin mRNA expression was higher at later stages (P = 0.008, as determined by the Wilcoxon signed rank test). SP and somatostatin are therefore temporally expressed in granulomas associated with murine cysticercosis, which may be related to differential expression of Th1 and Th2 cytokines.
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PMID:Sequential expression of the neuropeptides substance P and somatostatin in granulomas associated with murine cysticercosis. 1211 65

Leukemia inhibitory factor (LIF) is a pluripotent cytokine which affects the survival and differentiation of various types of cells both in the hematopoietic and nervous systems. In this study, the time course and localization of LIF mRNA expression following kainic acid-induced seizures were examined by northern blot analyses and in situ hybridization. Northern blot analyses demonstrated that intraperitoneal injection of kainic acid at a convulsive dose induced LIF mRNA expression intensely in the hippocampus and moderately to weakly in the cerebral cortex, thalamus and hypothalamus. The expression peaked at 8-24 h after the injection in the hippocampus and cerebral cortex and at 8 h in the thalamus and hypothalamus. In situ hybridization revealed different time courses of LIF mRNA expression depending on the area of the hippocampus; that is, the expression peaked at 10 h in the granule cell layer of the dentate gyrus, then at 12 h in the polymorph and molecular layers of the dentate gyrus, and finally at 12-24 h in the strata oriens and radiatum of the CA1 and CA3 subfields. It is worth noting that the expression of LIF mRNA was intense in the dentate gyrus, the region where neurogenesis and aberrant network reorganization have been shown to be induced by seizures. The upregulation of LIF mRNA expression in the dentate granule cell layer followed by that in the dentate polymorph and molecular layers may be involved in activity-dependent neurogenesis in the granule cell layer and ectopic migration of granule cells to the polymorph and molecular layers in the dentate gyrus.
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PMID:Kainic acid induces leukemia inhibitory factor mRNA expression in the rat brain: differences in the time course of mRNA expression between the dentate gyrus and hippocampal CA1/CA3 subfields. 1241 22

Recently, an association between a regulatory polymorphism in the gene encoding the pro-inflammatory cytokine interleukin (IL)-1beta and febrile convulsions (FC) has been reported. In this study we attempted to confirm these findings in a sample consisting of 99 FC patients and 126 ethnically matched controls. Since about 3% of all FC patients experience unprovoked seizures (epilepsy) later during life we furthermore genotyped 43 patients with non-lesional temporal lobe epilepsy who reported a history of FC. In both samples we failed to show an association between the IL-1beta polymorphism and an increased risk for FC. We only found a trend towards an increased frequency and carriage of the putative IL-1beta susceptibility allele two in a sub-sample of 43 FC patients who reported a positive family history for seizures in first and/or second degree relatives. However, these trends did not reach statistical significance.
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PMID:Association analysis between the human interleukin 1beta (-511) gene polymorphism and susceptibility to febrile convulsions. 1243 77

Interleukin-4 (IL-4) is a cytokine with anti-inflammatory properties. This study was undertaken to investigate whether IL-4 intron 3 gene polymorphism could be used as markers of susceptibility to febrile seizures and epilepsy of children. Children were divided into three groups: group 1, febrile seizures (n = 51); group 2, epilepsy (n = 43); and group 3, normal control group (n = 83). Polymorphisms for IL-4 intron 3 were detected by polymerase chain reaction. Genotypes and allelic frequencies for IL-4 intron 3 gene polymorphism in three groups were compared. We found that proportions of different IL-4 intron 3 polymorphisms in three groups were nonsignificantly different. Proportions of RP1 homozygote/heterozygote/RP2 homozygote for IL-4 intron 3 in three groups were as follows: group 1, 56.9/41.2/1.9%; group 2, 62.8/32.6/4.6%; and group 3, 62.7/33.7/3.6%. The proportion of RP1/RP2 for IL-4 intron 3 in three groups were as follows: group 1, 77.5/22.5%, group 2, 79.1/20.9%, and group 3, 79.5/20.5%. We concluded that the association of IL-4 polymorphisms with febrile seizures and epilepsy of children does not exist. IL-4 intron 3 polymorphism is not a useful marker for prediction of the susceptibility of febrile seizure and epilepsy of children.
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PMID:Interleukin-4 intron 3 polymorphism is not related to susceptibility to febrile seizures. 1243 65

The systemic symptoms associated with influenza infection are mainly attributable to cytokines. To elucidate whether the high incidence of creatine kinase elevation and febrile seizures in influenza infection could be related to cytokines, we examined the serum levels of creatine kinase and cytokines (interferon-alpha, interleukin-6, and tumor necrosis factor-alpha) in patients with influenza and other febrile illness. Among those in the influenza group, 12 of 43 patients demonstrated elevated levels of creatine kinase (more than 200 IU/L), whereas in the control group two of 14 patients demonstrated elevated creatine kinase levels. When age was limited to under 7 years, seven of 32 patients (21.9%) in the influenza group had febrile seizures, whereas one of seven patients (14.3%) had a seizure in the control group. The influenza group demonstrated significantly high levels of interferon-alpha and interleukin-6. There was no correlation between cytokine levels and duration of fever or serum creatine kinase levels. The number of patients with high levels of interferon-alpha (>400 pg/mL) was significantly larger in the febrile seizure group than in the control group (six of seven patients in the febrile seizure group, 16 of 36 in the control group; P < 0.05). The present findings suggest the possible contribution of interferon-alpha in the pathogenesis of febrile seizures.
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PMID:Possible contribution of interferon-alpha to febrile seizures in influenza. 1243 68


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