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Biomedical subjects

J Butterworth

Publications and source records attributed to J Butterworth.

At least 55 records · Page 3Linked to original sources
PubMed1993

Sustained focal effects of low-dose intramuscular succinylcholine.

We studied low-dose intramuscular succinylcholine in 9 subjects as part as an ongoing investigation of its potential to predict responses to botulinum toxin. We measured compound muscle action potentials (CMAPs) from the extensor digitorum brevis (EDB) muscles in each foot before and after intramuscular injections of 2.5 mg of succinylcholine into the EDB. Succinylcholine reduced mean CMAP amplitudes to 42% of baseline; the maximal reduction occurred at 19 +/- 6 (mean +/- standard deviation) minutes. Recovery to 73% of the baseline CMAP amplitude (approximately 50% recovery from block) occurred at 105 +/- 49 minutes after injection. Repetitive (train-of-four) stimulation at 2 Hz produced mild CMAP decrements (5-25%), but only during the recovery phase. Varying the succinylcholine concentrations (10, 20, or 50 mg/mL) while holding the total drug dose constant did not change the rate of onset or the extent of block. No systemic complications occurred. We conclude that: (1) 2.5 mg intramuscular succinylcholine can safely induce selective muscle weakness with a time course that differs from intravenously administered succinylcholine; and (2) further clinical studies comparing intramuscular succinylcholine and botulinum toxin are warranted.

Action Potentials↗
PubMed1993

Selecting an inotrope for the cardiac surgery patient.

Although a wide variety of positive inotropic agents have been administered to cardiac surgery patients, few of them have been carefully studied in controlled clinical trials, in surgical patient populations. The limited data available suggest that one of the more widely used agents, calcium, may lack efficacy and possibly inhibit the actions of catecholamines. Dopamine, dobutamine, and dopexamine are highly effective agents, but more prone to produce tachycardia than epinephrine. Amrinone is an effective agent by itself, but is especially useful in combination with a beta-adrenergic agonist for patients with severe left-ventricular dysfunction.

Adrenergic beta-Agonists↗
PubMed1993

Inhibition of brain cell excitability by lidocaine, QX314, and tetrodotoxin: a mechanism for analgesia from infused local anesthetics?

Local anesthetic infusions have been used to provide analgesia in a variety of painful conditions. The mechanism for this drug effect remains unknown. To better define the electrical effects of lidocaine concentrations comparable to those obtained during analgesic infusions, lidocaine (0.05-3 mmol.l-1), QX314 (an obligatorily charged, quaternary lidocaine derivative applied within the cells), and tetrodotoxin (10 mmol.l-1) were applied to rat hippocampal pyramidal cells. The three drugs, which inhibit Na+ currents by varying mechanisms, produced tonic increases in (firing) current threshold, and decreases in the amplitude of action potentials measured using an intracellular microelectrode technique. Lidocaine inhibited action potential spikes and increased current threshold in a concentration-dependent fashion. Lidocaine 50 and 100 mumol.l-1 did not inhibit action potentials, but increased firing threshold by nearly 100%. Lidocaine 1-3 mmol.l-1 significantly inhibited action potential amplitude and increased threshold by as much as 800%. Similarly, QX314 and tetrodotoxin produced greater increases in current threshold than in action potential amplitude. QX314 produced phasic (or frequency-dependent) block during trains of stimuli at 1 Hz, even when almost no tonic block was present. Lidocaine produced less phasic block than QX314, and required both greater tonic block and more frequent stimulation to produce the phenomenon. Tetrodotoxin demonstrated no phasic block. Increases in current threshold occurred in lidocaine concentrations associated with analgesia and toxicity; inhibition of action potentials occurred scarcely at all at these concentrations. Thus, tonic increases in current threshold may underlie analgesia and supplementation of general anesthesia by intravenous lidocaine.

Analgesia↗
PubMed1990

Enzyme activities in relation to pH and lactate in postmortem brain in Alzheimer-type and other dementias.

Phosphate-activated glutaminase, glutamic acid decarboxylase, pyruvate dehydrogenase, succinic dehydrogenase, pH, and lactate were measured in frontal cortex and caudate nucleus of postmortem brains from cases of Alzheimer-type dementia (ATD), Down's syndrome, Huntington's disease, and one case of Pick's disease, as well as from sudden death and agonal controls. Lactate levels were higher and pH, phosphate-activated glutaminase, and glutamic acid decarboxylase levels were lower in the agonal controls than in the sudden death controls. Phosphate-activated glutaminase and glutamic acid decarboxylase were correlated with tissue pH and lactate, and also were reduced by in vitro acidification, suggesting that the low activities of these enzymes in agonal controls were related to decreased pH consequent upon lactate accumulation. Compared with control tissues at the same pH, phosphate-activated glutaminase and glutamic acid decarboxylase were unaltered in ATD and Down's frontal cortex and reduced in Huntington's caudate nucleus, and glutamic acid decarboxylase was reduced in Huntington's frontal cortex. These data suggest that GABAergic neurons are not affected in ATD and confirm the GABAergic defect in Huntington's disease. Pyruvate dehydrogenase and succinic dehydrogenase activities were the same in agonal controls and sudden death controls and were unaffected by acid pH and lactate in vitro, and pyruvate dehydrogenase was not correlated with pH or lactate. Reduced pyruvate dehydrogenase in frontal cortex of individual ATD, Down's, and Pick's cases, and in the caudate nucleus of Huntington's and Down's cases, was accompanied by gliosis/neuron loss. We conclude that decreased pyruvate dehydrogenase reflects neuronal loss.

Alzheimer Disease↗
PubMed1989

Postmortem human brain pH and lactate in sudden infant death syndrome.

Lactate and pH were measured in frontal and temporal cortex, cingulate gyrus, and caudate nucleus in brains from sudden infant death syndrome (SIDS) cases, control infants, and control adults. Both the lactate levels and the pH values were significantly correlated (p less than 0.001) between the four brain areas, whereas lactate and pH values were significantly correlated within each brain area (p less than 0.001) with a value of pH 7.2 for zero lactate. The lactate concentration in heart blood was significantly correlated with brain lactate (p less than 0.001). Adult sudden death cases (heart attacks) had low lactate and high pH values, whereas agonal state cases had high lactate and low pH values. Control infants who had died because of accidents also had low lactate and high pH values, but infants who might have been exposed to hypoxia before death had high lactate and low pH values. SIDS cases fell into two groups: the first, consisting of all victims over 30 weeks of age and about one-half to two-thirds of those aged less than 30 weeks, had low lactate and high pH values; the second group, consisting of about one-third to one-half of those less than 30 weeks old, had high lactate and low pH values. The changes in lactate levels and pH values indicate that the majority of SIDS cases had died suddenly, but that a sizeable minority had been exposed to hypoxia prior to death.

Brain↗
PubMed1986

Changes in nine enzyme markers for neurons, glia, and endothelial cells in agonal state and Huntington's disease caudate nucleus.

Enzymes considered to be markers for neurons (angiotensin converting enzyme, thermolysin-like metalloendopeptidase, alanine aminopeptidase, and glutamate-oxaloacetate transaminase), glia (glutamine synthetase, pyruvate carboxylase, and beta-glucuronidase), and endothelial cells (alkaline phosphatase and plasminogen activator) were measured in caudate nucleus from 10 sudden death controls, eight agonal state controls, and 16 Huntington's disease patients. Glutamate-oxaloacetate transaminase was slightly reduced by agonal state. The four enzymes with a neuronal distribution were all correlatively reduced in Huntington's disease caudate nucleus. Glutamine synthetase activity was reduced and beta-glucuronidase mean activity increased over twofold in Huntington's disease caudate nucleus, with the two enzyme activities being inversely related. Pyruvate carboxylase was markedly affected by agonal state and was very variable in Huntington's disease caudate nucleus. The two endothelial enzymes were unaltered in Huntington's disease caudate nucleus. The findings are indicative of neuronal loss, an increased proportion of altered glia, and also of maintained vasculature in Huntington's disease caudate nucleus. Measurement of enzyme activities can help to delineate the types of cell altered in Huntington's disease.

Alkaline Phosphatase↗
PubMed1985

Prolinase and non-specific dipeptidase of human kidney.

Human kidney prolinase, assayed with Pro-Ala, and non-specific dipeptidase, assayed with Gly-Leu, were purified by using DEAE-cellulose, gel-filtration, metal-ion-chelate, hydrophobic and adsorption chromatography and chromatofocusing. Both enzymes gave single peaks of activity that were congruent and the ratio of their activities was constant throughout the purification. Gel filtration indicated an Mr of 100 000 and chromatofocusing a pI of 5.4. Ni2+-chelate chromatography demonstrated the presence of exposed histidine residues on the enzyme and was an effective separative procedure. Polyacrylamide-gel electrophoresis of the final preparation showed the two enzyme activities to be coincident. Both enzyme activities decayed at the same rate at 53 degrees C and were inhibited to the same extent by p-hydroxymercuribenzoate. Of six non-specific dipeptidase substrates tested Gly-Leu gave the highest activity, and of six prolinase substrates Pro-Leu had the highest activity. Gly-Leu was hydrolysed at double the rate of Pro-Leu. Pro-Ala was a competitive inhibitor of activity towards Gly-Leu, and Gly-Leu was a competitive inhibitor of activity towards Pro-Ala. Mixed-substrate studies strongly suggested that Gly-Leu and Pro-Ala were hydrolysed at a common active site. The data are consistent with prolinase and non-specific dipeptidase activity in human kidney being due to a single enzyme.

Dipeptidases↗
PubMed1985

Presence in human cells and tissues of two prolidases and their alteration in prolidase deficiency.

Two forms of prolidase can be separated for all the human cells and tissues examined by DEAE-cellulose column chromatography or batch methods. Serum had a very low prolidase activity eluting as a single peak prior to tissue peak I prolidase. Analysis of the two peaks can readily be carried out using white blood cells, cultured skin fibroblasts and amniotic fluid cells. Dialysis inactivated peak II prolidase although the loss can be prevented by the presence of dithiothreitol. The two peaks differed in their response to Mn(2+), substrate specificity, heat stability and inhibition by p-hydroxymercuribenzoate. In two unrelated cases of prolidase deficiency, fibroblast peak I was markedly reduced, although still detectable, whereas peak II was active against all the substrates, except for a 90% reduction against glycyl-L-proline. The properties of peak II were altered in the disease. The results imply that the two forms of prolidase are structurally related.

Cells, Cultured↗
PubMed1985

Distribution of phosphate-activated glutaminase, succinic dehydrogenase, pyruvate dehydrogenase and gamma-glutamyl transpeptidase in post-mortem brain from Huntington's disease and agonal cases.

The activity of phosphate-activated glutaminase was reduced throughout the brain of cases with longstanding illnesses (agonal controls) compared to cases dying suddenly. The reduction was less marked in cortical than sub-cortical areas, with the caudate nucleus occupying an intermediate position. In control brains succinic dehydrogenase and pyruvate dehydrogenase were little affected by the ante-mortem clinical state. Of 9 brain areas studied, only the caudate nucleus showed a reduction of phosphate-activated glutaminase and succinic dehydrogenase in Huntington's disease greater than in agonal controls. The levels of succinic dehydrogenase and pyruvate dehydrogenase were highly correlated in frontal cortex and in caudate nucleus of Huntington's disease and control brains. There was a significant reduction in pyruvate dehydrogenase mean activity and a significant increase in gamma-glutamyl transpeptidase mean activity in Huntington's disease caudate nucleus. The level of pyruvate dehydrogenase significantly decreased and the level of gamma-glutamyl transpeptidase significantly increased with increasing duration of illness, possibly due to a progressive loss of neurons and increase in the density of glia in Huntington's disease caudate nucleus.

Adult↗
PubMed1984

Substrate specificity of manganese-activated prolidase in control and prolidase-deficient cultured skin fibroblasts.

Skin fibroblasts have a single enzyme, Mn2+-activated prolidase, that hydrolyses a range of amino acid-proline dipeptides. Two cases of prolidase deficiency showed a marked loss of activity against glycyl-proline irrespective of Mn2+ conditions. However, the abnormal enzyme showed only moderate reductions in activity against phenylalanyl-, alanyl-, and leucyl-proline following preincubation with Mn2+ or addition of Mn2+ with the substrate. Control prolidase was stable to prolonged preincubation with Mn2+, whereas the abnormal prolidase was progressively inactivated. The findings indicate, for at least the present two cases, that prolidase deficiency results from an altered rather than a marked reduction in the amount of normal enzyme.

Amino Acid Metabolism, Inborn Errors↗
PubMed1983

Fluorimetric assay of phosphate-activated glutaminase.

A fluorimetric assay for the estimation of phosphate-activated glutaminase is presented. The liberated glutamate is separated from glutamine using a Dowex centrifugation technique allowing multiple samples to be rapidly analyzed. Glutamate is estimated fluorimetrically by reaction with o-phthaldialdehyde. Parameters for the assay were worker out based upon characterization of human frontal cortex glutaminase. High phosphate-activated glutaminase was found in cultured human skin fibroblasts and amniotic fluid cells and rat frontal cortex and striatum. Human caudate nucleus and frontal cortex activity was variable, but related in an exponential manner. Human and rat liver activity was markedly lower than brain activity.

Animals↗
PubMed1983

Phosphate-activated glutaminase in relation to Huntington's disease and agonal state.

Involvement of phosphate-activated glutaminase in Huntington's disease and agonal state was investigated in caudate nucleus and frontal cortex from postmortem brains. In Huntington's disease the activities of phosphate-activated glutaminase, glutamic acid decarboxylase, succinic dehydrogenase, choline acetyltransferase, and acetylcholinesterase were significantly reduced in the caudate nucleus, but not in the frontal cortex. The activity of phosphate-activated glutaminase, and to a lesser extent of glutamic acid decarboxylase, was reduced in cases of terminal illness, as compared with cases of sudden death. Succinic dehydrogenase and choline acetyltransferase were reduced only in the few cases of prolonged and severe terminal illness. Enzyme activities of the caudate nucleus were more affected by agonal state than were those of frontal cortex. Results indicate that phosphate-activated glutaminase could be a useful marker of neuronal damage due to agonal state, and that phosphate-activated glutaminase and succinic dehydrogenase are reduced in Huntington's disease.

Acetylcholinesterase↗
PubMed1982

Effects of Econazole, Fungizone and Pimafucin on cell growth, lysosomal enzyme activity and sulphate metabolism of cultured human skin fibroblasts and amniotic fluid cells.

Human skin fibroblasts and amniotic fluid cells showed sensitivity to antifungal agents in the order Econazole less than Pimafucin less than Fungizone, with the last initially reducing cell growth 10-20%, even at the level recommended for cell culture. The activities of the lysosomal enzymes alpha-L-fucosidase, beta-D-glucuronidase and alpha-D-mannosidase were unaffected, even by high concentrations of all three antifungal agents. Sulphate incorporation by cultured fibroblasts was increased by removal of sulphate salts and Crystamycin (contains streptomycin sulphate) from the culture medium. Sulphate incorporation into and degradation from macromolecules was only slightly reduced by antifungal agents. Human skin fibroblasts and amniotic fluid cells can be cultured long term in the presence of Econazole or Fungizone and used for lysosomal enzyme assay and sulphate kinetic studies.

Amniotic Fluid↗