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)

Down syndrome (DS) is associated with mental retardation, immune disorders and congenital heart diseases. Although it is usually caused by the presence of an extra chromosome 21, a subset of the diagnostic phenotypic features may be caused by the presence of the band 21q22, called the "Down syndrome region". Many proteins important for the immune and nervous systems as CuZn-superoxide dismutase (SOD-1), CD18-beta chain of LFA-1, interferon receptor, APP-amyloid precursor protein, protein S-100 beta are coded by chromosome 21. Overexpression of these molecules may contribute to the thymic derangement that results in anomalous maturation leading to functionally impaired T cells. Many factors have been shown to contribute to the immune deficiency which results in high susceptibility to infections, high rate of malignancies, and autoimmune phenomena in persons with DS. The main disorders in the immune system include thymus abnormalities, changes in cell-mediated immunity, phagocytosis, antibodies-mediated immunity and a high prevalence of autoantibodies in persons with DS. Furthermore, the duplication of chromosome 21 genes may generate most of the pathological changes in the central nervous system. There is an increased prevalence of seizure disorders. Such widespread alterations in the cortical areas seem to account for specific impairments observed in short-term and long-term memory, language skills, and cognitive and learning processes. If all principles of optimal health care and adequate education were followed without exception for persons with DS, then the quality of their life could be improved significantly and they would be able to become productive citizens in the society. (Tab. 5, Fig. 3, Ref. 42.)
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PMID:[Down's syndrome--effect of increased gene expression in chromosome 21 on the function of the immune and nervous system]. 926 31

The tissue non-specific alkaline phosphatase (TNAP) knock-out mouse is a model of infantile hypophosphatasia displaying impaired bone mineralization, epileptic seizures, apnoea, abnormal apoptosis in the thymus, abnormal lumbar nerve roots, and postnatal death. Administration of vitamin B6 suppresses the epileptic seizures in TNAP-/- mice. This paper examines to what extent the diverse abnormalities seen in these mice are due to impaired utilization of vitamin B6, using two complementary approaches: administration of vitamin B6 to TNAP null mice and deprivation of vitamin B6 in wild-type and TNAP heterozygous mice. Administration of exogenous pyridoxal HCl delayed the onset of epileptic attacks and increased the life span of TNAP-/- mice. The episodes of apnoea ceased and the appearance of lumbar nerve roots improved, but hypomineralization and accumulation of osteoid continued to worsen with age. Control mice fed a vitamin B6-depleted diet developed epileptic seizures indistinguishable from those observed in TNAP-/- mice, abnormal apoptosis in the thymus, and thinning of the nerve roots, but showed no evidence of bone mineralization abnormalities. Depletion of vitamin B6 did not affect the ability of primary cultures of osteoblasts to deposit bone mineral in vitro. While abnormal metabolism of vitamin B6 explains many of the abnormalities in this mouse model of infantile hypophosphatasia, it is not the basis of the abnormal mineralization that characterizes this disease.
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PMID:Abnormal vitamin B6 metabolism in alkaline phosphatase knock-out mice causes multiple abnormalities, but not the impaired bone mineralization. 1116 25

Estrogens change the susceptibility to seizures in humans and experimental animals. In this study, the effect of estrone and 17 beta-estradiol on kainate-induced seizures and neurotoxicity was investigated in male mice. Pre-treatment with estrone (250-1000 micrograms/kg) at 24 and 2 hours before kainate (40 mg/kg) administration significantly decreased both the percentage of animals with clonic seizures and their mortality (the latter at a dose of 1000 micrograms/kg only). On the other hand, 17 beta-estradiol (10-500 micrograms/kg) had no effect on seizures, and its dose of 10 micrograms/kg increased mortality. When given alone at a dose of 1 mg/kg, tamoxifen, an antagonist at estrogene receptors, did not affect the kainate-induced seizures, but prevented the anticonvulsant effect of estrone. A histological analysis showed that 73% of mice injected with vehiculum and kainate incurred hippocampal damage. Estrone (2000 micrograms/kg) decreased the percentage of animals with hippocampal neuronal loss down to 43%, and that effect was not antagonized by tamoxifen. Pretreatment of mice with 17 beta-estradiol had no effect on the kainate-induced neuronal loss. Additionally, we found that kainate injected i.p. had a profound effect on the immune system of mice, as reflected by a decrease in the thymus weight and an increased metabolic activity of splenocytes. The anticonvulsive dose of estrone (1000 micrograms/kg) did not change the immunoreactivity of either control or kainate-treated mice. In conclusion, the obtained data indicate that estrone, but not 17 beta-estradiol, attenuates the kainate-induced seizures, mortality and excitotoxicity in male mice. Moreover, it is suggested that the suppressive effect of estrone on clonic seizures involves intracellular receptors, whereas its antineurotoxic activity seems to depend on a non-genomic mechanism.
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PMID:Estrone, but not 17 beta-estradiol, attenuates kainate-induced seizures and toxicity in male mice. 1140

Seizure-related changes in function of the peripheral immune system, especially in its cell component are poorly recognized. In the present study, we examined the effect of seizures induced by intraperitoneal injection of kainate to mice and rats on weight of central and secondary immunological organs and metabolic activity of splenocytes (MTT test). In kainate-injected mice the production of cytokines: interleukin 2 (IL-2) and IL-10 was also estimated. Seventy two hours after kainate administration, the mice and rats showed a marked decrease in the thymus weight by 36% and 50%, respectively, whereas the spleen weight tended to decrease in rats only. Splenocytes of kainate-injected mice and rats showed significant increase in metabolic activity. The ability of splenocytes of kainate-injected mice to produce IL-2 and IL-10 was reduced but only the former effect reached statistical significance. The results suggest a decrease in T helper-cell dependent immunoreactivity and enhanced phagocytic activity of macrophages in kainate-treated rodents.
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PMID:Immunoreactivity in kainate model of epilepsy. 1199 75

Cerebral cavernous malformations (CCM) are vascular malformations, mostly located in the central nervous system, which occur in 0.1-0.5% of the population. They are characterized by abnormally enlarged and often leaking capillary cavities without intervening neural parenchyma. Some are clinically silent, whereas others cause seizures, intracerebral haemorrhage or focal neurological deficits. These vascular malformations can arise sporadically or may be inherited as an autosomal dominant condition with incomplete penetrance. At least 45% of families affected with cerebral cavernous malformations harbour a mutation in Krev interaction trapped-1 (Krit1) gene (cerebral cavernous malformation gene-1, CCM1). This gene contains 16 coding exons which encode a 736-amino acid protein containing three ankyrin repeats and a FERM domain. Neither the CCM1 pathogenetic mechanisms nor the function of the Krit1 protein are understood so far, although several hypotheses have been inferred from the predicted consequences of Krit1 mutations as well as from the identification of Krit1 as a binding partner of Rap1A, ICAP1A and microtubules. Here, we report the identification of Krit1B, a novel Krit1 isoform characterized by the alternative splicing of the 15th coding exon. We show that the Krit1B splice isoform is widely expressed in mouse cell lines and tissues, whereas its expression is highly restricted in human. In addition, we developed a real-time PCR strategy to accurately quantify the relative ratio of the two Krit1 alternative transcripts in different tissues, demonstrating a Krit1B/Krit1A ratio up to 20% in mouse thymus, but significantly lower ratios in other tissues. Bioinformatic analysis using exon/gene-prediction, comparative alignment and structure analysis programs supported the existence of Krit1 alternative transcripts lacking the 15th coding exon and showed that the splicing out of this exon occurs outside of potentially important Krit1 structural domains but in a region required for association with Rap1A, suggesting a subtle, yet important effect on the protein function. Our results indicate that maintenance of a proper ratio between Krit1A and Krit1B could be functionally relevant and suggest that the novel Krit1B isoform might expand our understanding of the role of Krit1 in CCM1 pathogenesis.
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PMID:Identification of Krit1B: a novel alternative splicing isoform of cerebral cavernous malformation gene-1. 1469 11

Topiramate, a new anticonvulsant, has been reported to possess neuroprotective effects in both in vivo and in vitro experiments. In the present study, the effect of topiramate (40 and 80 mg/kg ip) on the fully developed kainate-induced status epilepticus was evaluated in the rat. Injection of kainate (15 mg/kg ip) evoked recurrent limbic seizures which lasted several hours. Topiramate injected 1.5 h after kainate administration had no effect on the seizures and mortality of the animals. Biochemical study revealed that at 80 mg/kg ip, topiramate significantly attenuated the kainate-induced lipid peroxidation in the piriform cortex and showed similar tendency in the frontal cortex. Besides the central nervous system, the kainate-induced seizures evoked significant changes in immunoreactivity, such as reduction in thymus weight and the proliferative activity of splenocytes, and the splenocyte-increased production of interleukin-10, but not interferon-gamma. Topiramate did not affect the kainate-induced reduction in thymus weight, but attenuated changes in the proliferative activity of splenocytes. It is concluded that topiramate, when given during the fully developed kainate-induced status epilepticus in rats, has no effect on seizures, but attenuates lipid peroxidation in piriform cortex and prevents certain changes in immunoactivity.
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PMID:Effect of topiramate on the kainate-induced status epilepticus, lipid peroxidation and immunoreactivity of rats. 1559 43

The present study sought to determine the effects of long-term kindled seizures of the basal amygdala upon immune function in rat, utilizing the thymus, as a principal target for study. Histopathology from kindled Sprague-Dawley rats revealed the presence of epithelial cell thymoma in 70% of these rats. The results revealed an increased rate of apoptosis and proliferation in thymic epithelial cells. Analysis of thymocytes indicated a decrease in the ratio of CD4 to CD8 positive T cells and reduced proliferative response to T-cell mitogens. To determine whether these effects were mediated through the sympathetic nervous system, animals were treated with guanethidine, which blocked the development of epithelial cell thymomas, while mifepristone treatment, employed to determine the possible role of the hypothalamic-pituitary axis, was ineffective in attenuating thymoma development. Thus, the present study demonstrated that functional and pathological changes in the thymus during kindled seizures are mediated through the sympathetic nervous system.
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PMID:Amygdaloid kindled seizures can induce functional and pathological changes in thymus of rat: role of the sympathetic nervous system. 1608 31

Extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) lymphomas are a well-described type of low-grade B-cell non-Hodgkin lymphoma. They typically arise adjacent to mucosal surfaces in the gastrointestinal tract, lung and conjunctiva, and, less frequently, in the skin, salivary gland and thyroid gland. Unusual locations, such as the genitourinary tract, thymus and meninges, have also been reported. We recently encountered a case of an intracranial MALT lymphoma in a 53-year-old man who presented with persistent headaches and a seizure. The lesion developed as a mass within the lateral ventricle, appeared to be arising from the choroid plexus, and was not associated with meninges. Histologically, there was a vaguely nodular, dense lymphoid infiltrate with occasional benign follicles colonized by marginal zone lymphoma, suggesting derivation from a focus of prior inflammation. Translocations involving the MALT1 gene were not identified but karyotypic evaluation highlighted a complex cytogenetic profile with many chromosomal abnormalities. This rare case provides insight into the pathophysiology of MALT lymphomas.
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PMID:Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue arising in the lateral ventricle. 1619 87

X-linked cyclin-dependent kinase-like 5 (CDKL5 or STK9) has recently been implicated in atypical Rett and X-linked West syndromes, severe neurological disorders associated with mental retardation, loss of communication and motor skills and infantile spasms and seizures in predominantly females. Besides CDKL5, these disease phenotypes are also linked to mutations in the MECP2 and ARX genes. Here, we have expressed and characterized CDKL5 and its mutant forms. CDKL5 is a 118 kDa protein that is widely distributed in all tissues, with highest levels in brain, thymus and testes. Whole mount embryo staining reveals CDKL5 to be ubiquitous. Within cells, CDKL5 is localized primarily in the nucleus. Removal of the C-terminal domain increases CDKL5 expression, enhances autophosphorylation activity and causes perinuclear localization, indicating that the C-terminus regulates CDKL5 function. Although we detect MeCP2 but not ARX binding to CDKL5, our results suggest that neither of these proteins are direct substrates of the CDKL5 kinase. Finally, the CDKL5 mutations associated with the disease phenotype cause loss of kinase activity as assessed by autophosphorylation. These results suggest that inactivation of the CDKL5 kinase can lead to severe neurodevelopmental disorders.
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PMID:CDKL5/Stk9 kinase inactivation is associated with neuronal developmental disorders. 1633 Apr 82

High levels of stress or stress hormones have been reported to exacerbate a variety of human disorders of the cardiovascular, gastrointestinal, immune, reproductive, and nervous systems. In rats, high glucocorticoid levels have been reported to cause neuronal death and injury as well as enhance susceptibility to neurotoxic agents and attenuate repair mechanisms; however, the impact of high dosages of CORT in mice has not been fully evaluated. We investigated the ability of supraphysiological levels of CORT to cause hippocampal neuronal death, and to modulate the neurotoxicity of kainic acid (KA) in male C57BL/6J mice. Timed-release CORT pellets (10, 35, 100 mg/21 d) were implanted subcutaneously in the back of mice, and the sustained release of glucocorticoid caused involution of the thymus and decreased the weight of the spleen. Kainic acid caused stage 1 seizures that were unaffected by CORT; however, steroid treatment decreased KA-associated mortality. Little neuronal damage was detected by the cupric-silver neurodegeneration stain. Neurotoxicity caused by an intraperitoneal injection of 25mg/kg KA was attenuated by seven days of CORT pre-treatment. The KA-induced increase in cupric-silver staining, reactive gliosis, microglial activation, and blood-brain barrier disruption was attenuated indicating neuroprotection. Our data indicate supraphysiological levels of CORT do not cause neuronal death or injury in hippocampus of C57BL/6J mice and provide neuroprotection against KA-induced neural damage.
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PMID:Protracted exposure to supraphysiological levels of corticosterone does not cause neuronal loss or damage and protects against kainic acid-induced neurotoxicity in the hippocampus of C57BL/6J mice. 1961 23


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