Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effects of conventional antiepileptic drugs (AEDs) on absence-like seizures in homozygous tremor rats (tm/tm) to determine if they corresponded pharmacologically to human absence seizures and absence-like seizures in spontaneously epileptic rats (SER: zi/zi, tm/tm) with both tonic convulsive and absence-like seizures. Cortical and hippocampal EEG activity was recorded with chronically implanted electrodes. The effects of AEDS on seizures of the tremor rat showed profiles similar to those observed in human absence seizures and also in absence-like seizures of SER. The absence-like seizures, associated with paroxysmal bursts of 5-7-Hz spike-wave complexes, were inhibited by trimethadione (TMO 200 mg/kg intraperitoneally, i.p.), ethosuximide (ESM 100 and 200 mg/kg, i.p.), valproate (VPA 100 mg/kg, i.p.), and phenobarbital (PB 10 and 20 mg/kg, i.p.). Phenytoin (PHT 20 mg/kg, i.p.) was ineffective. These results are consistent with the conclusion that the tremor rat is a useful model for evaluating new AEDS for human absence seizures.
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PMID:Effect of antiepileptic drugs on absence-like seizures in the tremor rat. 764 34

We measured the binding of [3H]3-[(+/-)2-carboxypiperazin-4-yl] propyl-1-phosphonic acid ([3H]CPP), a competitive ligand for N-methyl-D-aspartate (NMDA) receptors, in double mutant spontaneously epileptic rats (SER: zi/zi, tm/tm) and their parent strains, zitter rats and tremor rats, and WTC rats (control rats from tremor rats derived from Kyoto:Wistar rats) before and after the onset of seizures in tremor rats and SER. Significantly lower [3H]CPP binding receptor density (Bmax) was found in the cortex of SER and zitter rats at 12-15 weeks of age than in that of WTC rats and tremor rats, and at 4 weeks of age the Bmax in zitter rats was lower than that in the other strains. The reduction of Bmax in SER at 12-15 weeks of age may reflect a down regulation of NMDA receptors due to repetitive tonic seizures in SER.
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PMID:Changes of NMDA receptor binding in spontaneously epileptic rat and parent strains. 825 69

Dopamine (DA) and norepinephrine (NE) brain levels and turnover rate were examined in the spontaneously epileptic rat (SER: zi/zi, tm/tm), a double mutant rat obtained by mating tremor heterozygotes (tm/+) with zitter homozygotes associated with epileptic seizures composed of spontaneously occurring tonic convulsion and absence-like seizure. DA and NE levels were also determined in age-matched male zitter, tremor and Kyo: Wistar rats. DA levels in caudate nucleus were significantly lower in adult age (10-12 weeks) SER, which showed epileptic seizures, and zitter rats than in adult Kyo: Wistar and tremor rats. DA levels in other areas such as thalamus-hypothalamus, midbrain, and pons medulla were not different among SER, zitter, tremor, and Kyo: Wistar rats at age 10-12 weeks. Except in cerebral cortex and hippocampus, there were no differences in brain DA levels between young seizure-free SER (age 5 weeks) and young Kyo: Wistar rats. Furthermore, the turnover rate of DA was significantly lower in caudate nucleus of adult SER than of Kyo: Wistar rat, whereas in pons-medulla there was no difference between the two strains. In contrast, NE levels in the thalamus-hypothalamus, midbrain, cerebellum and pons-medulla were higher in SER and zitter rats at age 10-12 weeks than in age-matched tremor and Kyo: Wistar rats. Higher NE levels were also observed in midbrain, cerebellum, and pons-medulla of young SER as compared with young Kyo: Wistar rats. Turnover rates of NE were significantly lower in pons-medulla and cerebellum of the adult SER than in those of Kyo: Wistar rat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased dopamine and increased norepinephrine levels in the spontaneously epileptic rat, a double mutant rat. 850 78

The concentrations of amino acids in the cerebrospinal fluid (CSF) (n = 20) and serum (n = 20) taken from patients with essential tremor were measured by HPLC and compared with those of controls (n = 10). Reduced concentrations of some amino acids (asparagine, glutamine, glycine, threonine, isoleucine, leucine) were observed in serum taken from patients with tremor. Significant increases were detected in the concentrations of glutamate (p < 0.001) and aspartate (p < 0.01). The general tendency of the changes in CSF and serum was similar; although the highest differences were observed in amino acid concentrations in the serum of patients with essential tremor. Opposite shifts of some amino acids were detected, in the concentrations of aspartate, serine, tyrosine, leucine, and isoleucine, which may indicate the independence of the changes in the serum from those in the CSF. This study raises the possibility that a genetically determined metabolic disorder is involved in the etiology of essential tremor that appears peripherally and, partly, centrally. The slight increase in the concentration of glutamate together with the reduced levels of GABA, glycine, and serine in CSF may form the neurochemical basis of the central oscillation observed in essential tremor.
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PMID:Change in the concentrations of amino acids in CSF and serum of patients with essential tremor. 881 1

Specimens of human salivary glands have been studied by our modification of the AODO maceration method which, carried out on sections of controlled thickness, allows the analytical study of human bioptical material. Lately, our technique has been further improved and simplified by omitting the treatment with dimethylsulfoxide and by using osmium-ferrocyanide as secondary fixative. Following maceration with diluted OsO4, some of the sections also were shaken for 10-15 min with a rotating agitator. Already at low magnification, all parenchymal cells were clearly distinguishable for their complement of cytoplasmic organelles. Serous cells and mucous cells at the beginning of their secretory cycle were characterized by well developed RER and Golgi apparatus, while mature mucous cells exhibited only scanty organelles compressed among the secretory droplets. Mitochondria were tubular, and often branched and convoluted. When sectioned, these organelles, besides the usual plate-like cristae, showed tubular cristae as well. The SER of striated and excretory duct cells was well developed and consisted of a network of smooth anastomosing tubules in the apical cytoplasm where it probably represented the transcellular pathway for ion transport. In specimens subjected to shaking, cytoplasmic organelles were occasionally removed allowing a nonobstructed view of the inner side of the plasmalemma and its specializations. With this technique the intercellular canaliculi of serous cells also became appreciable from their cytoplasmic side. They appeared as ribbon-like irregular protrusions with walls fenestrated by holes, corresponding to the interior of microvilli deprived of the cytoskeleton, and, sometimes, with lateral expansions possibly related to the mechanism of exocytosis. Results reported here clearly showed the usefulness of the maceration method in providing additional data on the cytoarchitecture of epithelial cells of salivary glands. Furthermore, by allowing the visualization of internal surfaces previously hidden to direct inspection, our technique may open new horizons in morpho/functional studies of human salivary glands.
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PMID:Further data on intracellular structures of human salivary glands. A SEM study. 887 98

Haematological and serum biochemical measurements in male spontaneously epileptic rats (SER; double mutants homozygous for zitter and tremor genes) were compared with the values for related rat strains. Some haematological values were low in TRM rats and total leukocyte counts were high in ZI and TRM rats. TRM rats showed higher total cholesterol, phospholipid, high-density lipoprotein cholesterol and calcium values, and lower albumin value than Kyo: Wistar rats. Zitter homozygous rats including SER exhibited low total cholesterol, phospholipid and high-density lipoprotein cholesterol values. The SER showed an increase in urea nitrogen, aspartate aminotransferase and alanine aminotransferase values, and a decrease in glucose value, suggesting deterioration of the whole body with age.
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PMID:Haematological and serum biochemical values in spontaneously epileptic male rats and related rat strains. 958 5

Tremor rat (tm/tm), the parent strain of spontaneously epileptic rat (SER: zi/zi, tm/tm), exhibits absence-like seizures characterized by 5-7 Hz spike-wave-like complexes on cortical and hippocampal electroencephalograms (EEG) after 10 weeks of age, prior to development of convulsive seizures. Recently, this animal model has been demonstrated to display a genomic microdeletion within the critical region of tm, where aspartoacylase hydrolyzing N-acetyl-L aspartate (NAA) is located, besides showing the ability to accumulate NAA in the brain. Therefore, the present study was performed to determine the involvement of NAA in the induction of epileptic seizures. When NAA (4 micromol) was applied intracerebroventricularly (i.c.v.) to normal Wistar rats, 4-10 Hz polyspikes and/or spike-wave-like complexes followed by absence-like seizure before persistent 1-5 Hz waxing high-voltage after-discharges were observed on cortical and hippocampal EEG. At a higher dose (8 micromol), NAA induced convulsive seizures. The absence-like seizures with polyspikes and/or spike-wave-like complexes on the EEG were also observed with i.c.v. NAA in premature tremor rats without seizures. The NAA-induced seizures in normal rats were antagonized by i.c.v. glutamic acid diethyl ester, a non-selective glutamate receptor antagonist. In addition, NAA applied to the bath rapidly induced a long-lasting depolarization concomitantly with repetitive firings in hippocampal CA3 neurons of normal rat brain slice preparations. These findings suggest that NAA is involved in the induction of absence-like seizures and/or convulsion, probably via glutamate receptors.
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PMID:Epileptic seizures induced by N-acetyl-L-aspartate in rats: in vivo and in vitro studies. 1075 74

2,5-Dimethoxy-4-iodoamphetamine (DOI), a serotonin (5-HT)2A/2C receptor agonist, elicits shaking behaviors in rodents, which have been reliably quantified as behavioral correlates of 5-HT2A receptor activation. Such studies are lacking in the rabbit. As part of our research examining the role of the 5-HT2 receptor in rabbits, we analyzed the behavioral effects of systemically administered DOI in rabbits. DOI (0.01-3 micromol/kg) or vehicle was injected, and two distinct behaviors, head bobs (vertical head movements) and body shakes (wet dog shakes), were counted for 90 min following the injection. DOI dose-dependently increased the number of head bobs and body shakes. The selective 5-HT2A receptor antagonist ketanserin (1-3 micromol/kg), 1 h before DOI (0.3 micromol/kg) challenge, significantly attenuated head bobs, but not body shakes. In contrast, the selective 5-HT2C receptor antagonists SDZ SER 082 (1-3 micromol/kg) and SB 206553 (1 micromol/kg) 30 min before challenge, significantly reduced body shakes but not head bobs produced by the same dose of DOI. This study establishes that, in rabbits, DOI mediates head bobs via 5-HT2A receptors and body shakes via 5-HT2C receptors. Thus, the rabbit provides a novel behavioral assay that discriminates between 5-HT2A and 5-HT2C receptor activation.
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PMID:A novel behavioral model that discriminates between 5-HT2A and 5-HT2C receptor activation. 1190 Aug 8

The sigmaK checkpoint coordinates gene expression in the mother cell with signaling from the forespore during Bacillus subtilis sporulation. The signaling pathway involves SpoIVB, a serine peptidase produced in the forespore, which is believed to cross the innermost membrane surrounding the forespore and activate a complex of proteins, including BofA, SpoIVFA, and SpoIVFB, located in the outermost membrane surrounding the forespore. Activation of the complex allows proteolytic processing of pro-sigmaK, and the resulting sigmaK RNA polymerase transcribes genes in the mother cell. To investigate activation of the pro-sigmaK processing complex, the level of SpoIVFA in extracts of sporulating cells was examined by Western blot analysis. The SpoIVFA level decreased when pro-sigmaK processing began during sporulation. In extracts of a spoIVB mutant defective in forespore signaling, the SpoIVFA level failed to decrease normally and no processing of pro-sigmaK was observed. Although these results are consistent with a model in which SpoIVFA inhibits processing until the SpoIVB-mediated signal is received from the forespore, we discovered that loss of SpoIVFA was insufficient to allow processing under certain conditions, including static incubation of the culture and continued shaking after the addition of inhibitors of oxidative phosphorylation or translation. Under these conditions, loss of SpoIVFA was independent of spoIVB. The inability to process pro-sigmaK under these conditions was not due to loss of SpoIVFB, the putative processing enzyme, or to a requirement for ongoing synthesis of pro-sigmaK. Rather, it was found that the requirements for shaking of the culture, for oxidative phosphorylation, and for translation could be bypassed by mutations that uncouple processing from dependence on forespore signaling. This suggests that ongoing translation is normally required for efficient pro-sigmaK processing because synthesis of the SpoIVB signal protein is needed to activate the processing complex. When translation is blocked, synthesis of SpoIVB ceases, and the processing complex remains inactive despite the loss of SpoIVFA. Taken together, the results suggest that SpoIVB signaling activates the processing complex by performing another function in addition to causing loss of SpoIVFA or by causing loss of SpoIVFA in a different way than when translation is blocked. The results also demonstrate that the processing machinery can function in the absence of translation or an electrochemical gradient across membranes.
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PMID:Forespore signaling is necessary for pro-sigmaK processing during Bacillus subtilis sporulation despite the loss of SpoIVFA upon translational arrest. 1221 26

Certain forms of seizure involve excessive glutamate transmission. We have recently identified a protein, referred to as the inhibitory protein factor (IPF), which potently inhibits glutamate uptake into isolated synaptic vesicles. In an effort to understand the mechanism underlying excessive glutamate transmission associated with seizure, we have analyzed IPF content in various brain regions of the spontaneously epileptic rat, SER (tm/tm, zi/zi), the absence-seizure tremor rat, TM (tm/tm), and the seizure-free control rats zitter ZI (zi/zi) and Wistar tremor control, each at 13 weeks of age. IPF content was found to be markedly reduced in the hippocampus, but not in the other brain regions, of SER, compared to the control and TM rats. TM rats also exhibited reduced IPF content compared to seizure-free controls. These changes appear developmentally regulated; no such alteration was observed in 8-week-old rats, which rarely show seizure. These observations indicate that an aberrant decrease in IPF is associated with certain forms of seizure; this decrease could lead to an abnormal increase in the amount of exocytotically released glutamate through its excessive accumulation in synaptic vesicles.
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PMID:Aberrant reduction of an inhibitory protein factor in a rat epileptic model. 1235 Mar 84


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