Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chromatographic separation and biochemical characterization of a beta-bungarotoxin is described. This toxin is isolated as the most basic eluting protein of Bungarus multicinctus venom when separated by column chromatography on CM-Sephadex C-25. The protein migrated as a single band on pH 4.3 and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The molecular weight of this toxin was estimated to be 10 000 +/- 1000 by analytical sedimentation analysis. This value was consistent with the electrophoretic mobility of the toxin in SDS-polyacrylamide gels. The amino acid composition of this 11 000-dalton beta-bungarotoxin was similar to that of the 22 000-dalton beta-bungarotoxin previously reported (Lee et al. (1972) J. Chromatogr. 72, 71--82; Kelly, R.B. and Brown, III, F.R. (1974) J. Neurobiol. 5, 135--150; Kondo et al. (1978) J. Biochem. Tokyo 83, 91--99), suggesting that the 11 000-dalton toxin may be one of the polypeptide chains of the larger toxin. The 11 000-dalton beta-bungarotoxin was toxic to mice when injected intravenously. Animals that received lethal doses exhibited hyperexcitability followed by ataxia, convulsions, and death. The minimum lethal dose was 0.12 microgram/g body weight. This beta-bungarotoxin exhibited Ca2+-dependent phospholipase A activity comparable to that of the 22 000-dalton beta-bungarotoxin. The enzyme exhibited phospholipid substrate specificity in the rank order of phosphatidyl-choline, phosphatidylserine, phosphatidylethanolamine, and phosphatidyl-inositol. The enzyme activity was destroyed by boiling for 3 min at pH 8.6. In addition, an enzymatically inactive quantity of the 11 000-dalton toxin, equivalent to five times the minimum lethal dose of enzymatically active toxin, was not lethal when injected into mice. To test whether phospholipase A activity is responsible for lethality, bee venom phospholipase A2 was injected into mice at similar and greater concentrations with no toxic effect. Thus, while phospholipase A activity may be required for the lethal effect of the 11 000-dalton beta-bungarotoxin, the specificity of action of the toxin is not determined by its enzyme activity.
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PMID:Purification and biochemical characterization of an 11 000-dalton beta-bungarotoxin. 56

1 The effect of altering the ionic balance of the cerebrospinal fluid (CSF) on cloacal temperature of unanesthetized pigeons kept at room temperature (20-25 degrees C) was examined by injection or infusion of solutions of different ionic composition into a cannulated lateral cerebral ventricle. 2 An increase in the concentration of calcium ions caused a fall in temperature and behavioural sedation. The effects were the same whether the calcium was present as calcium chloride or as the calcium disodium salt of ethylenediamine tetra-acetic acid (CaNa2EDTA). 3 When the concentration of sodium ions in the CSF perfusate was increased by addition of NaCl or that of calcium ions was decreased by addition of Na2EDTA a rise in temperature was often produced but this was not consistent. NaCl sometimes had either no effect or lowered the temperature. Na2EDTA while producing a rise when first injected failed to do so when repeated a few hours, 24 h and often 72 h later. Prolonged infusion of either agent caused intense behavioural excitement leading to death. 4 Potassium ions, like sodium ions, caused a rise in temperature but only when infused continuously. Behavioural excitement was only rarely observed. 5 Magnesium produced a fall in temperature. The concentration required was much higher than that of calcium but the hypothermia was more prolonged suggesting a slower elimination of the magnesium ions from the CSF. Magnesium ions caused tremors, nystagmus and ataxia as opposed to sedation caused by calcium. 6 All these were central effects as they were not obtained when the substances were injected intravenously. 7 Since changes in body temperature of the pigeon produced by injection of calcium or sodium ions into the CSF were similar to those seen in various species of mammal, it is concluded that the relative concentration of these ions within the brain plays an important role in establishing the temperature setpoint in both birds and mammals.
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PMID:Sodium and calcium ions in the control of temperature set-point in the pigeon. 81 41

Twenty-seven dogs with lead poisoning were admitted to the University of Pennsylvania Veterinary Hospital from July, 1963, to April, 1975. The major source of the lead was paint. A common history was ingestion of plaster or paint scrapings during room renovation. Most of the dogs were less than 1 year old and had clinical signs referable to the gastrointestinal or the nervous system, or both. The gastrointestinal signs, in order of frequency, were vomiting, anorexia, tender abdomen, diarrhea, and constipation. The neurologic signs, in order of frequency, were hysteria, convulsions, ataxia, blindness, and mydriasis. The finding of many nucleated erythrocytes without severe anemia was nearly pathognomonic for lead poisoning. Of 14 affected dogs subjected to abdominal radiography, 9 had evidence of ingested radiopaque material. A mean blood lead concentration of 18.8 mug/100 ml, with a range of 0 to 50 mug/100 ml, was found for 26 dogs that were hospitalized for problems unrelated to lead poisoning. Of the 27 dogs with lead poisoning, 22 had their blood analyzed for lead. This group had blood lead values ranging from 40 to 530 mug/100 ml. Seven of the affected dogs were monitored throughout their period of treatment with calcium ethylenediaminetetraacetate. The concentration of lead in the blood decreased quickly after the initiation of treatment but leveled off after 2 or 3 days. The initial rapid phase probably corresponded to the removal of weakly bound or extracellular lead, whereas the slow phase probably corresponded to strongly bound or intracellular lead.
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PMID:Lead poisoning in dogs at the University of Pennsylvania Veterinary Hospital. 81 31

Injection of endothelin-1 (9 pmol) into the lateral cerebral ventricle of rats produced barrel-rotations, convulsions, tonic hindlimb extensions, facial clonus, and kinetic ataxia for up to 45 min. Quantitative metabolic autoradiographs produced from the [14C]deoxyglucose method and analyzed over 60 individual brain structures or subregions revealed intense hypermetabolism in periventricular tissues close to the injection site and in many of their efferent projection sites. Histological examination of these areas proved that this dose of endothelin was without toxic or ischemic effects on neurons or glial cells. Structures metabolically affected ipsilateral to injection were caudate nucleus (+164%), lateral septal nucleus (+270%), and two white matter tracts--corpus callosum (+236%) and hippocampal fimbria (+318%). Distant stimulated structures included cerebellar cortical layers, but not cerebellar nuclei or white matter. Increased rates of glucose metabolism among many other nuclei, particularly distinct subunits of the hippocampal formation and structures in contact with the ventricular system, signify that endothelin induced widespread metabolic stimulation over much of the neuraxis. Furthermore, although the 9 pmol concentration of endothelin produced convulsive movements and diverse metabolic stimulation, it did not evoke detectable electroencephalographic seizure activity assessed by intra- or extracerebral electroencephalography. Both the convulsions and hypermetabolic activation were inhibited by intraventricular pretreatment with the dihydropyridine calcium-channel antagonist, nimodipine. The results identify endothelin-1 as a calcium-mediated 'convulsive' peptide with selective stimulatory effects on cerebral glucose metabolism.
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PMID:Cerebral hypermetabolism produced by intraventricular endothelin-1 in rats: inhibition by nimodipine. 132 10

Calcium- and calmodulin-regulated protein phosphorylation has been suggested to play a role in the pathogenesis of organophosphorus compound-induced delayed neurotoxicity (OPIDN). This condition is characterized by ataxia that progresses to paralysis concurrent with a central-peripheral distal axonopathy after a delay period of 1-2 weeks following exposure to an organophosphorus compound causing delayed neurotoxicity, such as tri-o-cresyl phosphate (TOCP). Calcium/calmodulin (CaM) kinase II is involved in the increased phosphorylation of brain microtubule and spinal cord neurofilament triplet proteins following treatment of animals with organophosphorus compounds that are capable of producing OPIDN. In this study, chickens were given a single oral neurotoxic dose of 750 mg TOCP/kg body weight and killed after 1, 6, 14 or 21 days following treatment. Protein kinase-mediated phosphorylation of cytoskeletal proteins was studied in proximal and distal parts of sciatic nerves of control and treated hens. Peripheral nerve proteins were phosphorylated in vitro using [gamma-32P]ATP as a phosphoryl group donor. Phosphorylated proteins were separated by one- and two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Protein phosphorylation was detected by autoradiography and quantified by laser microdensitometry. The extent of Ca2+-calmodulin dependent phosphorylation of five cytoskeletal proteins was significantly increased in TOCP treated animals, particularly at 1 and 6 days after treatment, in both the proximal and distal portion of the nerve. The identity of these proteins was confirmed by 2-D PAGE as tubulin, the neurofilament triplet proteins and microtubule associated protein-2 (MAP-2). These results confirm earlier observation of the close temporal relationship between increased cytoskeletal protein phosphorylation and the development and OPIDN.
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PMID:Biochemical changes in sciatic nerve of hens treated with tri-o-cresyl phosphate: increased phosphorylation of cytoskeletal proteins. 133 13

Foscarnet (Foscavir) is an antiviral drug for intravenous (i.v.) treatment of cytomegalovirus (CMV) retinitis in immunocompromised patients. The drug forms complexes with divalent metal ions such as Ca2+ and serum calcium levels may be affected during its i.v. infusion. In this study, the effect on calcium homeostasis was investigated during daily 8-hr infusions of foscarnet in dogs. After priming infusions of 40 or 80 mg/kg administered during 0.5 hr, maintenance infusion rates were 46 or 91 mg/kg/hr (total daily doses of 410 or 810 mg/kg). At the low infusion rate, foscarnet was administered for 5 consecutive days. The mean plateau serum concentration was 0.56 mmol/liter and the main clinical sign was vomiting. Total serum calcium was reduced from about 2.5 to 2.0 mmol/liter and ionized calcium from 1.3 to 0.9 mmol/liter. Parathyroid hormone (PTH) levels in serum were elevated three to six times while calcitriol (1,25-(OH)2D3) levels were unaffected. At the high infusion rate, treatment was discontinued after 1-2 days of dosing due to pronounced adverse clinical signs such as extensive vomitings, apathy, ataxia, and muscle spasms. The mean serum plateau concentration of foscarnet at this dose level was 1.2 mmol/liter. Total serum calcium was reduced from 2.5 to 1.6 mmol/liter and ionized calcium from 1.3 to 0.7 mmol/liter. PTH as well as 1,25-(OH)2D3 levels in serum were elevated. Total and ionized calcium levels were normalized within 16 hr after stopping drug treatment. The results showed that foscarnet infusion affects calcium homeostasis and that calcium monitoring might be considered in the clinical use of the drug.
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PMID:Hypocalcemia induced by foscarnet (Foscavir) infusion in dogs. 153 76

We examined protein kinase C (PKC) activity and inositol 1,4,5-trisphosphate (InsP3) binding in frontal cortex (FC) and cerebellar cortex (CC) of normal humans, patients with dominant ataxia ("C" kindred) and in Lurcher mutant mouse brain (LMB), a suggested animal model for olivopontocerebellar atrophy (OPCA). PKC activity and [3H]InsP3 binding were decreased in CC of human OPCA by 70% and 90% respectively. The decreases were specific to CC as there were no changes in FC. PKC activity and [3H]InsP3 binding in cerebellum (CB) of LMB were similarly decreased as compared to normal littermate controls. The LMB decrease of PKC and [3H]InsP3 binding was evident on the 15th day of age, the day of onset of ataxia. InsP3-mediated calcium release was also decreased significantly in the cerebellar microsomes of 25-day-old LMB and human OPCA when compared with their respective controls. These data indicate that the decrease of second messenger linked PKC activity and InsP3 receptor binding in CB may be a biochemical marker that reflects neuronal degeneration in dominant cerebellar ataxia.
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PMID:Inositol 1,4,5-trisphosphate receptors and protein kinase C in olivopontocerebellar atrophy. 165 68

The effects of the dihydropyridine calcium antagonist, nitrendipine and the calcium channel activator, Bay K 8644, have been compared on the anaesthetic, ataxic and anticonvulsant effects of benzodiazepines. Possible interactions between the peripheral benzodiazepine receptor antagonist, PK11195, and the classical benzodiazepines were also examined. Nitrendipine considerably potentiated the anaesthetic effects of benzodiazepines and increased their ataxic effects but had no effect on the anticonvulsant actions. Clonazepam did not produce anaesthesia, at doses up to 1 g kg-1 or when given with nitrendipine. When given alone, nitrendipine did not cause general anaesthesia. Nitrendipine did not appear to alter the metabolism of midazolam. The calcium channel activator, Bay K 8644, reduced the anaesthetic potency of midazolam and, when given alone, produced ataxia. It did not significantly alter central concentrations of midazolam. The "peripheral" benzodiazepine antagonist, PK11195, did not affect the ataxic or anaesthetic actions of benzodiazepines. These results suggest that dihydropyridine-sensitive calcium channels may be more important to the general anaesthetic than to the anticonvulsant actions of benzodiazepines. The "peripheral" benzodiazepine site did not appear to play a role in either of these properties.
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PMID:Differential interactions between benzodiazepines and the dihydropyridines, nitrendipine and Bay K 8644. 171 26

The Osteogenic Disorder Shionogi (ODS) rat, Clea Inc., Tokyo, Japan lacks the ability to synthesize L-ascorbic acid (AA). As with man, monkey and the guinea pig, this rat lacks L-gulonolactone oxidase necessary for the synthesis of AA from glucose. This study shows this animal to be an alternative to the guinea pig in AA studies. The anti-scorbutic potency of Ester C (EC), a calcium ascorbate and calcium threonate mixture, was compared with an AA dose of equal ascorbate activity equivalents (AAE) for anti-scorbutic activity in the ODS rat. The minimal anti-scorbutic dose of EC was determined to be 0.44 mg/kg/day (AAE), while an AA dose of 0.51 mg/kg/day (AAE) was not anti-scorbutic in a 24 day study. At 24 days EC rats gained 125% of initial body weight (BW) and the AA rats only 45% BW. Scorbutic signs at 24 days were scored on a 0 (min) to 3 (max) scale. The EC/AA ratio scores were: hemorrhage 0/1.4, behavior change 0/2.0, piloerection 0/2.2, mobility 0.4/2.2, dysbasia 0.6/2.8 and ataxia 0.4/1.0. Pearson's correlation coefficient for BW versus AAE was r = .34 for the AA group and r = .90 for the EC group. The morbidity index for EC was 0/5 and for the AA group 2/5. The AAE dose of AA which was 16% higher/day than the EC AAE dose was not anti-scorbutic, while the EC dose was anti-scorbutic. EC rats had 3.5X greater weight gain, a sensitive indicator of scurvy, than the AA rats. EC rats had 3-4 times less, if any, scorbutic signs than AA rats. The results clearly show that, based on ascorbate activity equivalents, EC has more available ascorbate activity/potency than AA. The mechanism of this increased potency is believed to be due to the facilitated transport of AAE into the cell by the threonate (a normal in vivo metabolite of AA) present in the EC product. In addition, previous studies have shown EC (AAE) to be higher in plasma and excreted less rapidly than the AAE derived from AA administered orally.
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PMID:Comparison of the anti-scorbutic activity of L-ascorbic acid and Ester C in the non-ascorbate synthesizing Osteogenic Disorder Shionogi (ODS) rat. 190 22

Idiopathic hypoparathyroidism was diagnosed in five young to middle-aged cats of mixed breeding. Three of the cats were male and two were female. Historic signs included lethargy (n = 5), anorexia (n = 5), muscle tremors (n = 4), weakness (n = 4), generalized seizures (n = 3), ataxia (n = 3), mental dullness or disorientation (n = 3), panting (n = 2), pruritus (n = 1), ptyalism (n = 1) and dysphagia (n = 1). Weakness (n = 4), dehydration (n = 2), cataracts (n = 2), hypothermia (n = 1), and bradycardia (n = 1) were found on physical examination. Results of electrocardiography revealed a prolonged Q-T interval in two cats. Results of initial laboratory tests revealed profound hypocalcemia and severe hyperphosphatemia with normal renal function. The diagnosis of hypoparathyroidism was made on the basis of the history, clinical signs, and results serum biochemical testing (i.e., severe hypocalcemia and hyperphosphatemia); in two cats, the diagnosis was also confirmed by histologic examination of parathyroid glands. Initial treatment included intravenous administration of 10% calcium gluconate and oral administration of large loading doses of calcium and vitamin D (dihydrotachysterol). Successful long-term management with dihydrotachysterol and calcium was achieved in all cats. The final dosage of dihydrotachysterol required to maintain normocalcemia in the five cats ranged from 0.004 to 0.04 mg/kg/day (mean = 0.015 mg/kg/day). Long-term calcium supplementation was given to three of the cats in dosages ranging from 29 to 53 mg/kg/day (mean = 42 mg/kg/day) of elemental calcium. One cat died after 28 months of therapy from widely metastatic hemangiosarcoma; the other three cats are still alive and well after 5 to 37 months of treatment.
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PMID:Idiopathic hypoparathyroidism in five cats. 202 14


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