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)

beta-N-Oxalylamino-L-alanine (BOAA) and beta-N-methylamino-L-alanine (BMAA) are chemically related excitant amino acids isolated from the seed of Lathyrus sativus (BOAA) and Cycas circinalis (BMAA), consumption of which has been linked to lathyrism (an upper motor neuron disorder) and Guam amyotrophic lateral sclerosis (ALS), respectively. Both diseases are associated with degeneration of motor neurons. Experimentally, single doses of BOAA or BMAA induce seizures in neonatal mice and postsynaptic neuronal oedema and degeneration in explants of mouse spinal cord and frontal cortex. Preliminary studies show that these behavioural and pathological effects are differentially blocked by glutamate-receptor antagonists. In macaques, several weeks of daily oral doses of BOAA produce clinical and electrophysiological signs of corticospinal dysfunction identical to those seen in comparably well-nourished animals receiving a fortified diet based on seed of Lathyrus sativus. By contrast, comparable oral dosing with BMAA precipitates tremor and weakness, bradykinesia and behavioural changes, with conduction deficits in the principal motor pathway. BOAA and BMAA (or a metabolite thereof) are the first members of the excitotoxin family to have been shown to possess chronic motor-system toxic potential. These observations provide a rational basis for searching for comparable endogenous neurotoxins in sporadic and inherited forms of human motor neuron disease.
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PMID:Discovery and partial characterization of primate motor-system toxins. 310 39

Beta-N-methylamino-L-alanine (BMAA) and beta-N-oxalylamino-L-alanine (BOAA) are chemically related amino acids present in the seeds of Cycas circinalis and Lathyrus sativus, respectively. Consumption of these seeds has been linked to Guam amyotrophic lateral sclerosis (BMAA) and lathyrism (BOAA; a form of primary lateral sclerosis). A single large dose of BOAA or BMAA causes seizures in newborn mice and postsynaptic neuronal edema and degeneration in CNS explants. We report that the acute neurotoxic actions of these amino acids are blocked selectively by specific glutamate-receptor antagonists (administered intracerebroventricularly) (i.c.v.) prior to the amino acid. Administration of BOAA i.c.v. to neonatal mice (ED100 = 50 micrograms) elicits a spectrum of time-dependent behavioral states including arm and leg rigidity, convulsions, and resting tremor. These are blocked in a dose-dependent manner by cis-2,3-piperidine dicarboxylic acid (PDA), an antagonist of quisqualate (QA)-preferring (A2) and kainate (KA)-preferring (A3) glutamate receptors (ED50s; 2.8 micrograms, rigidity; 1.4 micrograms, convulsions; 2.4 micrograms, resting tremor). BMAA induces a transitory hyperexcitable state followed by a long-lasting whole-body shake/wobble (ED100 = 1,000 micrograms, i.c.v.). These responses are antagonized selectively and dose-dependently by 2-amino-7-phosphonoheptanoic acid (AP7), an N-methyl-D-aspartate (NMDA) or A1 glutamate-receptor antagonist (ED50 = 0.45 microgram). Taken collectively, our data indicate that the acute neuronotoxic actions of BOAA and BMAA (or a metabolite) operate through different glutamate-receptor species. BMAA likely exerts most of its action indirectly via the A1 glutamate receptor, while BOAA acts principally at the A2 and/or A3 receptor.
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PMID:Specific antagonism of behavioral action of "uncommon" amino acids linked to motor-system diseases. 314 80

Regional amino acid concentrations were measured in rat brain fixed by microwave irradiation at three levels of elevated atmospheric pressure corresponding to different phases of the high-pressure neurological syndrome [20 atmospheres absolute (ATA), no clinical signs; 60 ATA, tremor; 85 ATA, severe tremor and myoclonic jerks]. No changes in amino acid content occurred at 20 or 60 ATA. At 85 ATA glutamine content increased in hippocampus, striatum, cerebellum, and substantia nigra, and gamma-aminobutyric acid content increased in hippocampus. It is suggested that enhanced glutamate release in various subcortical structures contributes to the myoclonic activity observed at 85 ATA.
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PMID:Regional amino acid concentration in the brains of rats exposed to high pressures. 371 8

Conditions influencing the survival of Campylobacter jejuni in the natural aquatic environment have been determined. Release of Campylobacter spp. into natural waters by animal hosts is postulated to play a key role in the maintenance of viability and transmission of the organism in the environment. Laboratory flask microcosms containing filter-sterilized stream water were used to test C. jejuni for the ability to remain viable in simulated natural systems. The microcosms were compared with the biphasic and shaking broth procedures used routinely for growth of Campylobacter spp. in the research laboratory. The stream-water microcosms were analyzed to determine effects of temperature and aeration on the survival of a well-characterized C. jejuni strain isolated originally from a human campylobacteriosis patient. Morphological characteristics were evaluated by phase-contrast microscopy and scanning or transmission electron microscopy. Survival curves were quantified on the basis of plate counts, epifluorescent microscopy, optical density measurements, and direct viable counts associated with protein synthesis in the absence of DNA replication. A significant difference was observed between results of direct enumeration, i.e., direct viable counts or acridine orange direct counts, and those from spread plate cultures. In all cases, increasing temperature of cultivation resulted in decreased recoverability on laboratory media, due possibly to an increased metabolic rate, as analyzed by CO2 evolution in the presence of radiolabeled glutamate. Stream water held at low temperature (4 degrees C) sustained significant numbers of campylobacters for greater than 4 months. Microcosms, aerated with shaking, exhibited logarithmic decline in recoverable C. jejuni, while stationary systems underwent a more moderate rate of decrease to the nonculturable state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Viable but nonculturable stage of Campylobacter jejuni and its role in survival in the natural aquatic environment. 376 58

Glutamate excretion by colonies of Citrobacter intermedium C3 was detected by using the auxotrophic strain Leuconostoc mesenteroides P-60. A constant ratio of strain C3 colonies did not excrete glutamate. These colonies were subcultured, and colonial analysis of their descendants established that the change from non-excretor to excretor (Sg(-) --> Sg(+)) is a spontaneous and random process with occurs at a high rate, and that an equilibrium state results from the back-transition Sg(+) --> Sg(-) in large populations. Acridine orange, ethidium bromide, and shaking have a strong influence on Sg(+)-to-Sg(-) interconversion, which suggests that a genetic element like an episome is implicated (S factor). Various auxotrophic mutants of bacterial strain C3 have been cured of the S factor. Strains lacking the S factor (S(-) strains) do not excrete glutamate and lose their fermentative metabolism completely. Consequently, the S factor is different from other extrachromosomal genetic factors whose elimination does not modify central metabolism. The gain of the S factor by infectious transfer has been shown with different C3 auxotrophic mutant strains. Also, the S factor has been transferred to Paracolobactrum intermedium ATCC 11606. These findings suggest that phenotypic changes observed are a consequence of elimination or infectious gain of the S factor, with its autonomous or integrated multiplication.
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PMID:A new episomic element controlling fermentative metabolism and excretion of amino acids by Citrobacter intermedium C3. 460 Jun 93

Clifton, C. E. (Stanford University, Stanford, Calif.), and John Cherry. Influence of glutamic acid on the endogenous respiration of Bacillus subtilis. J. Bacteriol. 91:546-550. 1966.-Amino acids serve as the major initial endogenous substrate for Bacillus subtilis. The endogenous activity of freshly harvested washed cells is high and falls off rapidly with time of shaking at 30 C to lower but still significant levels. The rate of O(2) consumption after the addition of glutamic acid also decreases as the cells age, but more slowly than noted for endogenous respiration. When cells were fed glutamate as soon as possible after harvesting, an apparent stimulation of endogenous respiration was noted. However, endogenous activity was inhibited if the cell suspensions were shaken for at least 1 hr before addition of the glutamate. Similar results were obtained with glycerol or glucose as exogenous substrates. Variation in rates of respiration with age of the cells, inherent instability of B. subtilis, and possible utilization of substances initially excreted by the cells appear to account for the variations noted regarding the influence of an exogenous substrate on endogenous respiration.
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PMID:Influence of glutamic acid on the endogenous respiration of Bacillus subtilis. 495 54

The tremorgenic mycotoxin verruculogen was administered directly into the brain of freely moving rats by the use of cannula systems that superfused either the cortical surface or the lateral ventricular space. The tremor produced by these CNS routes was compared with that produced by i.p. administration of the toxin or the dried mycelium of the fungus that synthesizes the verruculogen. The nature and degree of tremor produced by the central vs peripheral routes suggest that the site of action of verruculogen is not immediately adjacent to the cannula sites in the brain. Measures of the amino acids in the superfusates collected during the verruculogen-induced tremor showed an increase in the excitatory neurotransmitters, glutamate and aspartate in superfusates from the lateral ventricle but not in superfusates from the cortical surface. The differential effect on transmitter release suggests that a subcortical action of verruculogen is responsible for its tremorgenic activity.
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PMID:Actions of a tremorgenic mycotoxin on amino acid transmitter release in vivo. 612 4

The excitatory amino acid analogues kainate, quisqualate, domoic acid, 4-fluoroglutamate, homocysteic acid and N-methylaspartate as well as the tremor-inducing drugs harmaline and oxotremorine all induced significant elevations in cyclic guanosine monophosphate (cGMP) levels in the cerebellum in vivo. The putative antagonists of excitatory amino acids, 2-amino-5-phosphonovalerate (APV) and piperidine dicarboxylate (PDA) both blocked the actions of the tremorogens. Piperidine dicarboxylate also blocked the in vivo activity of all the amino acid analogues except homocysteic acid and N-methylaspartate. 2-Amino-5-phosphonovalerate (APV) was inactive against kainate, quisqualate and homocysteic acid. It therefore appears that PDA and APV are useful tools for the further study of the function of glutamate and asparatate receptors.
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PMID:Antagonists of excitatory amino acids and cyclic guanosine monophosphate in cerebellum. 613 Apr 88

The purpose of this study was to correlate the chlordecone-elicited tremor activity with alterations of brain neurotransmitters. A single injection of chlordecone (80 mg/kg, ip) significantly increased the brain levels of 5-hydroxyindoleacetic acid (5-HIAA) but did not affect the concentrations of dopamine, dihydroxphenylacetic acid, aspartate, taurine, glutamate, glycine, and gamma-aminobutyric acid (GABA). There was a dose- and time-related correlation between the increases in striatal 5-HIAA levels and tremor after chlordecone treatment. A subsequent study with pargyline indicated that the increase in striatal 5-HIAA level represented an increase in the turnover of serotonin. This study plus the previous finding that pizotifen (BC-105), a serotonin receptor blocker, attenuated chlordecone-elicited tremor strongly suggests a possible involvement of the serotonin system in mediating the tremor elicited by this insecticide.
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PMID:Effects of chlordecone exposure on brain neurotransmitters: possible involvement of the serotonin system in chlordecone-elicited tremor. 620 Sep 57

Thirty-four chemicals-diverse in structure, postulated mechanisms of action, and primary target organs--were tested for cytotoxic response in isolated hepatocyte suspensions from young male Sprague-Dawley rats. Hepatocytes were incubated in the presence and absence of the test chemicals in closed vessels fitted with side arms for serial sampling for up to 5 h at 37 degrees C with gentle shaking under an O2:CO2 (95:5) atmosphere. The parameters evaluated were glutamate-oxaloacetate transaminase and lactate dehydrogenase release from the cells, Trypan blue exclusion, cell count, urea synthesis capability, and steady-state ATP levels. All chemicals cytotoxic in animals following single or short-term repeated exposures caused statistically significant changes in one or more of these parameters in the 0.01-10-mM concentration range. Dimethylnitrosamine and thioacetamide were not as potent in the isolated cell system as expected from their in vivo hepatotoxicity, and the quantitative changes produced with thioacetamide in the hepatocytes were marginal, even at 10 mM. The solvents tested--ethanol, acetone, dimethyl sulfoxide (DMSO), and propylene glycol--were without effect. These results indicate that isolated hepatocyte suspensions are useful for the identification of cytotoxins in general and hepatotoxins in particular, but that their capability for yielding a quantitative index of cytotoxic potential for diverse chemical species remains to be demonstrated.
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PMID:Response of isolated hepatocytes to organic and inorganic cytotoxins. 662 Mar 99


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