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)

A 1-month-old boy was admitted because of failure to thrive. He was floppy and had bilateral ptosis, diminished reflexes, and poor suck. He had aspiration pneumonia, developed seizures, and died at age 3 1/2 months. Laboratory data showed lactic acidosis, proteinuria, glycosuria and generalized aminoaciduria. He was an only child, and family history was negative. Muscle biopsy showed large clumps of granules positive with oxidative enzyme stains and increased lipid droplets. Ultrastructural studies showed large aggregates of mitochondria, many of which were greatly enlarged and contained disoriented or concentric whorls of cristae and paracrystalline inclusions. Cytochrome c oxidase was absent in fresh frozen sections by histochemical staining. By biochemical assay, cytochrome c oxidase (cytochrome aa3) was 6% of normal in muscle biopsy and undetectable in autopsy muscle; spectra and content of cytochromes showed lack of cytochrome aa3, decreased cytochrome b and normal cytochrome cc1. In kidney, cytochrome-c-oxidase activity was 38% of normal and spectra showed decreased cytochromes aa3 and b. The association of fatal infantile mitochondrial myopathy, lactic acidosis and renal dysfunction was previously reported by Van Biervliet et al and appears to be a distinct nosologic entity, one of the few biochemically defined mitochondrial myopathies.
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PMID:Fatal infantile mitochondrial myopathy and renal dysfunction due to cytochrome-c-oxidase deficiency. 625 6

We present two unrelated patients, a boy and a girl, with a progressive neurologic disorder, characterized by psychomotor retardation, seizures and paresis, the illness being exacerbated during stressful periods. Lactate levels in serum and cerebrospinal fluid were elevated in both patients. Histopathologic studies of muscle tissue revealed mitochondrial abnormalities in the boy; in the girl, slight neuronal degeneration was observed. A cerebral biopsy in the girl showed abnormalities compatible with progressive poliodystrophy. Autopsy in the boy demonstrated progressive poliodystrophy. Biochemical studies in muscle tissue showed a defect of cytochrome aa3 in both patients, connected with a defect of cytochrome b in the girl. The association of defective pyruvate metabolism and progressive poliodystrophy is discussed.
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PMID:Progressive poliodystrophy (Alpers' disease) with a defect in cytochrome aa3 in muscle: a report of two unrelated patients. 630 65

A novel G-to-A transition at nucleotide 15915 in mtDNA is described. The patient showed a combination of muscle weakness, hearing loss, mental retardation, and seizures. Muscle biopsy showed RRFs and focal COX deficiency. We sequenced all mtDNA, and found 5 novel nucleotide substitutions. Three of them were synonymous mutations, one was a missense mutation in cytochrome b gene (A-->G at nt 15422), and the last one was the 15915 mutation in tRNA(Thr) gene. We screened for the 15422 and the 15915 mutations with mismatch primers and found that one of 104 normal individuals carried the former one and none of 175 had the latter one. The 15422 mutation existed in homoplasmic states both in the patient and the normal individual, suggesting that this is a polymorphism. In contrast the 15915 mutation resided in heteroplasmic states in muscle, skin fibroblast and blood. The nucleotide substitution at nt 15915 disrupts a highly conserved base pair in anticodon stem of the tRNA(Thr). Our data suggest that the 15915 mutation is an additional mtDNA mutation responsible for mitochondrial encephalomyopathies.
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PMID:A novel mutation in the mitochondrial tRNA(Thr) gene associated with a mitochondrial encephalomyopathy. 876 14

A 32-year-old woman developed chronic progressive hearing impairment, trunkal ataxia, bilateral ptosis and external ophthalmoplegia. She also showed slowly progressive mild to moderate proximal dominant muscle weakness and atrophy. ECG showed incomplete right bundle branch block. An aerobic exercise test showed abnormal blood lactate elevation and muscle biopsy revealed ragged-red fibers in addition to the myopathic change. Analysis of mitochondrial DNA extracted from biopsied muscle and fibroblast samples revealed a 1,758bp deletion from the cytochrome b to ND6 coding regions. Common mutations in tRNALeu(UUR) coding region to the mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) were not present. She was diagnosed as having incomplete Kearns-Sayre syndrome (KSS). Since the age of 35, she developed complex partial seizure attacks with secondary generalization frequently and at the age of 42, she had a severe generalized seizure with delayed consciousness loss followed by left hemiplegia. MRI showed wide T2-high signal lesions in the right temporo-parieto-occipital area. The proton MR-spectroscopy showed prominent increase of lactate beyond the lesions detected by MRI, indicating diffuse aerobic metabolic dysfunction in the central nervous system. We reviewed two other KSS cases with a stroke like episode, who also had epilepsy and large deletion but no tRNALeu(UUR) mutation, in mitochondrial DNA. Patients with KSS who have seizure may develop the stroke-like episode as seen in MELAS patients.
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PMID:[A case of incomplete Kearns-Sayre syndrome with a stroke like episode]. 940 43

Mitochondrial function is a key determinant of both excitability and viability of neurons. Present studies were carried out to decipher cerebral mitochondrial oxidative energy metabolism and membrane function in the chronic condition of generalized seizures induced by picrotoxin (PTX) in rats. PTX-induced convulsions resulted in decreased respiration rates (14-41%) with glutamate, pyruvate + malate, and succinate as substrate. The ADP phosphorylation rates were drastically reduced by 44-65%. An opposite trend was observed with ascorbate + N,N,N',N'-tetramethyl-p-phenylenediamine [corrected] (TMPD) as substrate. In general, uncoupling of the mitochondrial electron transport was observed after PTX treatment. Malate dehydrogenase (MDH) and succinate dehydrogenase (SDH) activities were decreased by 20-80%; also, there was significant reduction in cytochrome b content after PTX treatment, while the F(o)F(1) ATPase (complex V) activity increased in basal and 2,4-dinitrophenol (DNP)-stimulated condition, indicating increased membrane fragility. The substrate kinetics analysis had shown that K(m) and V(max) of the higher affinity kinetic component of ATPase increased significantly by 1.2- to 1.4-fold in epileptic condition. Temperature kinetic analysis revealed 1.2-fold increase in energies of activation with decreased transition temperature. The total phospholipid (TPL) and cholesterol (CHL) contents decreased significantly with lowering of diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidylserine (PS), while lysophospholipid (lyso), sphingomyelin (SPM), and phosphatidylcholine components were found to be elevated. Brain mitochondrial membrane was somewhat more fluidized in epileptic animals. Possible consequences of mitochondrial respiratory chain (MRC) dysfunction are discussed. In conclusion, impairment of MRC function along with structural alterations suggests novel pathophysiological mechanisms important for chronic epileptic condition.
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PMID:Structural and functional alterations in mitochondrial membrane in picrotoxin-induced epileptic rat brain. 1569 21

We previously reported that magnesium sulfate (MgSO(4)) increases the threshold dose of bupivacaine in inducing seizure in rats. Cytochrome P450 (P450) isoforms involved in the biotransformation of bupivacaine to three oxidative metabolites and the effects of MgSO(4) in vivo on the P450 activities in rats were investigated. Of six cDNA-expressed rat P450 isoforms tested, CYP3A2 and CYP2C11 had high rates for N-debutlylation and 3'-hydroxylation of bupivacaine, respectively. The liver microsomes prepared from male rats pretreated with intravenous administration of MgSO(4) (a bolus dose of 25 mg/kg, followed by infusion of 2.0 mg/kg/min for 6 h) showed increased V(max) values for N-debutylation and 3'-hydroxylaiton of bupivacaine compared to the liver microsomes from control rats. Administration of MgSO(4) also increased the activities of testosterone 6beta- and 16alpha-hydroxylation. Although the level of expression of CYP3A and CYP2C isoforms in the liver microsomes were unchanged, NADPH-P450 reductase and cytochrome b(5) were found to be induced by intravenous administration of MgSO(4). These results suggest that CYP3A and CYP2C isoforms are activated by MgSO(4) in vivo as a consequence of enhanced microsomal electron transfer due to induction of NADPH-P450 reductase and cytochrome b(5), leading to the increased metabolism and clearance of bupivacaine.
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PMID:Activities of rat cytochrome P450 3A and 2C isoforms are increased in vivo by magnesium sulfate as evidenced by enhanced oxidation of bupivacaine and testosterone in liver microsomes. 1685 23

Survey on secondary data of taeniasis/cysticercosis was carried out in Mongolia in 2002-2006. A total of 118 taeniid proglottids, a diphyllobothriid segment, and 59 serum samples from 118 taeniasis cases were collected at National Center for Communicable Diseases, Ulaanbaatar, Mongolia. In 2006, 14 serum samples were collected from local people who had histories of epileptic seizures in Selenge Province where pig husbandry was the main business. The 118 proglottids were confirmed to be Taenia saginata by mitochondrial DNA analysis using cytochrome c oxidase subunit 1 and cytochrome b genes. T. saginata taeniasis was widely distributed at least in 10 of 21 provinces. No variation in the nucleotide sequences of the two genes was observed among T. saginata isolates from Mongolia. There was no evidence of Taenia solium taeniasis/cysticercosis or Taenia asiatica taeniasis. A diphyllobothriid segment was confirmed to be Diphyllobothrium latum by mitochondrial DNA analysis.
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PMID:Taeniasis in Mongolia, 2002-2006. 1769 Apr 9

Forensic investigations are an important area in the regulation of food mis-description, wildlife seizures and the international trade in wildlife and its products. An early, but important stage in dealing with many biological materials that are submitted for forensic scrutiny is species identification. We describe a method and new primers to amplify three small DNA fragments of the cytochrome b region of the mitochondrial DNA that are suitable for marsupial species identification from degraded sources, such as wildlife seizures. They were designed as consensus sequences from a comparison of 21 marsupial species. The primers also contained sequences intended specifically not to amplify human DNA, thereby reducing the likelihood of amplifying contaminants. Examples of the utility of these primers are given using a range of conditions that may be applied using such an approach, including (1) field-collected sub-fossil bones, (2) an example of museum mis-identification from a specimen collected in 1930 and (3) a skull collected from Bernier Island, in the harsh mid-west of Western Australia.
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PMID:Identification of historical specimens and wildlife seizures originating from highly degraded sources of kangaroos and other macropods. 1989 Jul 38