Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The epilepsies affect at least 1 to 2 million people in the United States and 20 to 40 million people worldwide. Because the causes and basic mechanisms of the epilepsies have only started to unravel, there is still no cure for the disease. The purpose of this chapter is to present the new routes of navigation in epilepsy research, the salient theories on mechanisms of epilepsies, and their cogency to cause (generation of seizures) and effects (epileptic cell damage). In particular, it advances a comprehensible picture of the major cellular events involved in the generation, arrest, or spread of partial epileptic seizures; it also questions the major molecular events involved in the transmission and use of genetic information in the generalized epilepsies. In reviewing the many theories on mechanisms of epilepsies, this chapter establishes the connections between neurosciences, molecular genetics, and the epilepsies. The knowledge gained from such connections will certainly bear on the diagnosis of the subvarieties of epilepsies and is already promoting new methods of treatment of the disease. Indeed, it is this fusion between molecular genetics, neurosciences, and the clinical epilepsies that provides the excitement and new ferment in research of the epilepsies. This chapter also advances a conceptual blueprint for priority challenges in epilepsy research. It calls attention to the primary goal, namely, understanding the mechanisms of human epilepsies. In the most common of human epilepsies, namely, temporal lobe epilepsy, a priority challenge is to analyze paroxysmal depolarization shifts in hippocampal slices in vitro, slices excised from known sites of epileptogenicity. Parallel experiments exploring biochemical membrane abnormalities in neuronal and glial membranes isolated from the hippocampal seizure focus would be especially valuable. The role of kindling and the mirror focus in human temporal lobe epilepsy must be resolved. A second important goal is the search for polymorphisms of restriction endonuclease patterns in monogenic epilepsies in order to localize the abnormal gene to a specific chromosome. Because of the recent successful applications of positron emission tomography (PET), single-photon-emission computed tomography, and nuclear magnetic resonance computed tomography (NMR-CT), ion transport pathways, neurotransmitter systems, and metabolic processes may be constructed within the functioning brains of epileptic patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:New wave of research in the epilepsies. 287 20

In addition to yielding new routes of navigation, the workshops from which the material in this supplement comes developed a conceptual blueprint for priority challenges in epilepsy research. All participants called attention to the ultimate goal, namely, understanding the mechanisms of human epilepsies. And, foremost to achieving this goal is the search for polymorphisms of restriction endonuclease patterns in monogenic forms of epilepsies in an attempt to localize the abnormal gene, or genes, to a specific chromosome. In human temporal lobe epilepsy, a priority challenge is to record paroxysmal depolarization shifts in hippocampal slices in vitro, slices excised from the known site of epileptogenicity. Parallel experiments exploring biochemical membrane abnormalities in neuronal and glial membranes isolated from the hippocampal seizure focus are especially valuable. Together with genetic studies using restriction-fragment-length polymorphisms, these experiments should distinguish between the respective contributions of genetic and environmental factors in multifactorial forms of partial epilepsies, such as temporal lobe epilepsy. In the genesis and spread of human temporal lobe epilepsy, the role of kindling and the mirror focus must be resolved. Recent successful applications of positron emission tomography, single-photon-emission computed tomography, and nuclear magnetic resonance computed tomography show promise in finally constructing the ion transport pathways, neurotransmitter systems, and metabolic processes within the functioning brains of epileptic patients.
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PMID:The new wave of research in the epilepsies. 615 Jun 83

The distribution of human herpesvirus 6 (HHV-6) and varicella-zoster virus (VZV) was examined in autopsy samples from a fatal case with both virus infections. A 9-month-old boy developed convulsive seizures followed by macular skin rashes, rapidly progressed to brain death, and died 15 days after the onset, when signs of varicella were noted. An isolation of HHV-6 from blood and evaluation of antibody activities to various viral agents including HHV-6 were performed before his death. Postmortem examinations included: (i) isolation of HHV-6 and VZV from tissues or organs; (ii) detection of both virus antigens in tissues or organs by an indirect immunofluorescent assay using monoclonal antibodies to both viruses; (iii) amplification of both viruses and human herpesvirus 7 DNA sequences by a nested polymerase chain reaction assay; and (iv) endonuclease digestion of amplified products of HHV-6 DNA for differentation of variants A and B. Human herpesvirus 6 DNA was detected in peripheral blood mononuclear cells (PBMC) and plasma obtained at the eruptive stage but present only in PBMC 15 days after, indicating the primary infection with HHV-6, although the virus was not isolated from the same blood sample and a significant rise in the antibody titers to HHV-6 was not observed. Both virus antigens and DNA were detected in various tissues or organs obtained at autopsy, but only VZV was isolated from these samples, suggesting disseminated infection with both viruses in an infant. All the amplified products of HHV-6 DNA were variant B. Among the findings for the distribution of virus antigens, it was noteworthy that HHV-6 antigen was demonstrated in the endothelial cells of small vessels in the frontal lobe of the brain. There was no evidence of HHV-7 infection. These data indicate that the primary HHV-6 infection closely followed by the primary VZV infection had the potential hazard of an unexpected and apparently life-threatening event, in which disseminated infections with both viruses were noted in multiple tissues or organs including the brain.
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PMID:Distribution of human herpesvirus 6 and varicella-zoster virus in organs of a fatal case with exanthem subitum and varicella. 900 91

Canavan disease (CD), an autosomal recessive neurodegenerative disorder, is caused by mutations in the aspartoacylase (ASPA) gene. In the present study, the ASPA gene was analyzed in 24 non-Jewish patients with CD from 23 unrelated families. Within this cohort, we found three large novel deletions of approximate 92, 56, and 12.13 kb in length, using both self-ligation of restriction endonuclease-digested DNA fragments with long-distance inverse PCR and multiplex dosage quantitative PCR analysis of genomic DNA. The 92 kb large deletion results in complete absence of the ASPA gene in one homozygous and one compound heterozygous patient, respectively. The 56 kb large deletion causes absence of the majority of the ASPA gene except for exon 1 alone in a compound heterozygous patient. The 12.13 kb deletion involves deletion of the ASPA gene from intron 3 to intron 5 including exons 4 and 5 (I3 to E4E5I5) in a compound heterozygous patient. Patients with the three large deletions clinically manifested severe symptoms at birth, including seizures. Our study showed that the combined use of long-distance inverse PCR and multiplex dosage quantitative PCR analysis of genomic DNA is a helpful and rapid technique to search for large deletions, particularly for detection of large deletions in compound heterozygous patients.
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PMID:Rapid detection of three large novel deletions of the aspartoacylase gene in non-Jewish patients with Canavan disease. 1685 7