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A Butler

Publications and source records attributed to A Butler.

At least 19 recordsLinked to original sources
PubMed1992

An essential 'set' of K+ channels conserved in flies, mice and humans.

The molecular genetic approach to studying K+ channels has revealed that at least four subfamilies of voltage-gated K+ channels originally discovered in Drosophila are conserved in mice and humans. This conservation of the K+ channel subfamilies Shaker, Shal, Shab, and Shaw suggests that not only the broad outlines of membrane electrical properties but also many molecular details as well evolved in the parent species ancestral to both invertebrate and vertebrate life. Shaker, Shal, Shab, and Shaw K+ channels have similar structures, but appear to be independent channel systems: when co-expressed in Xenopus oocytes, all four function independently. These four K+ channel subfamilies may be part of an essential 'set' of excitable channels required by most nervous systems. The task now remaining is to understand the functions of each member of the set.

Animals↗
PubMed1991

Mechanism of dioxygen formation catalyzed by vanadium bromoperoxidase from Macrocystis pyrifera and Fucus distichus: steady state kinetic analysis and comparison to the mechanism of V-BrPO from Ascophyllum nodosum.

Vanadium bromoperoxidase (V-BrPO) catalyzes the oxidation of bromide by hydrogen peroxide, which results in the bromation of appropriate organic substrates or the formation of dioxygen, in the absence of an organic substrate and under certain other conditions. The mechanism of the bromide-assisted disproportionation of hydrogen peroxide catalyzed by V-BrPO, which is the reaction that forms dioxygen, has been investigated for V-BrPO isolated from two new marine algal sources, Macrocystis pyrifera and Fucus distichus. The steady state kinetic studies have been performed under conditions of 0.02-40 mM H2O2, 1-500 mM Br- and pH 4.0-8.0. The rate data is consistent with a substrate-inhibited bi bi ping pong mechanism, in which the substrate bromide, is also an inhibitor by a noncompetitive-type mechanism. Bromide inhibits V-BrPO from M. pyrifera most strongly at pH 5.0-5.5 and V-BrPO from F. distichus most strongly at pH 5.5-6.0. The steady state mechanism of the Macrocystis and the Fucus enzymes are compared to the mechanism of the bromide-assisted disproportionation of hydrogen peroxide catalyzed by V-BrPO from Ascophyllum nodosum. In addition, the substrate hydrogen peroxide can also inhibit V-BrPO.

Catalysis↗
PubMed1991

mShal, a subfamily of A-type K+ channel cloned from mammalian brain.

We have cloned and expressed a mouse brain cDNA, mShal, that encodes a transient, A-type K+ current. mShal, the vertebrate homolog of the Drosophila Shal gene, defines a distinct subfamily of voltage-gated K+ channels. The Shal deduced proteins are more highly conserved between mouse and Drosophila than other presently known K+ channels. mShal carries a "low-threshold" A-type current with a hyperpolarized steady-state inactivation midpoint. Marked similarity was observed between mShal and its Drosophila homolog, fShal, with regard to voltage sensitivity of activation, macroscopic inactivation, steady-state inactivation, and 4-aminopyridine sensitivity. Sequence conservation for Shal proteins is unusually high at the amino terminus, an area considered important for inactivation. Removal of conserved amino-terminal residues from mShal modifies macroscopic inactivation but the transient nature of the current is preserved. Underlying the very high conservation of mShal and fShal may be a role in the nervous system that is conserved in widely divergent species.

Amino Acid Sequence↗
PubMed1991

A dose ranging study of ibuprofen suspension as an antipyretic.

A double blind trial was conducted to determine the dose of ibuprofen suspension, which is effective in reducing the body temperature. The principal measure of efficacy was a reduction in axillary temperature of 1 degree C or more three hours after dosing. A second objective of the trial was to compare the incidence and severity of side effects and the palatability of a range of ibuprofen doses. Ninety three children were included in the analysis. All four doses of ibuprofen studied (0.625 mg/kg-5 mg/kg) were associated with temperature reduction and only the lowest dose failed to satisfy the principal measure of efficacy. The influence of dose on the magnitude of the body temperature reduction was significant and the 5 mg/kg dose achieved the largest mean reduction in body temperature (2 degrees C). The tolerability and palatability of all doses studied were excellent. These findings suggest that ibuprofen is a good alternative to paracetamol as an antipyretic.

Child, Preschool↗
PubMed1990

Mechanism of dioxygen formation catalyzed by vanadium bromoperoxidase. Steady state kinetic analysis and comparison to the mechanism of bromination.

The steady state kinetic mechanism of the bromide-assisted disproportionation of hydrogen peroxide, forming dioxygen, catalyzed by vanadium bromoperoxidase has been investigated and compared to the mechanism of monochlorodimedone (MCD) bromination under conditions of 0.0125-6 mM H2O2, 1-500 mM Br-, and pH 4.55-6.52. Under these conditions, 50 microM MCD was sufficient to inhibit at least 90% of the dioxygen formation during MCD bromination. The rate data is consistent with a substrate-inhibited Bi Bi Ping Pong mechanism, in which the substrate bromide, is also an inhibitor at pH 4.55 and 5.25, but not at pH 5.91 and 6.52. The kinetic parameter KmBr, KmH2O2, KisBr, and KiiBr determined for the reactions of bromide-assisted disproportionation fo hydrogen peroxide and MCD bromination are similar, indicating that the mechanisms of both reactions occur via the formation of a common intermediate, the formation of which is rate-limiting. Fluoride is a competitive inhibitor with respect to hydrogen peroxide in both reactions at pH 6.5. At high concentrations of hydrogen peroxide, the bromide-assisted disproportionation of hydrogen peroxide occurs during the bromination of MCD. The sum of the rates of MCD bromination and dioxygen formation during MCD bromination is equal to the rate of dioxygen formation in the absence of MCD. The apportionment of the reaction through the MCD bromination and dioxygen formation pathways depends on pH, with much lower hydrogen peroxide concentrations causing significant dioxygen formation at higher pH.

Hydrogen Peroxide↗
PubMed1990

Characterization of vanadium bromoperoxidase from Macrocystis and Fucus: reactivity of vanadium bromoperoxidase toward acyl and alkyl peroxides and bromination of amines.

Vanadium bromoperoxidase (V-BrPO) has been isolated and purified from the marine brown algae Fucus distichus and Macrocystis pyrifera. V-BrPO catalyzes the oxidation of bromide by hydrogen peroxide, resulting in the bromination of certain organic acceptors or the formation of dioxygen. V-BrPO from F. distichus and M. pyrifera have subunit molecular weights of 65,000 and 74,000, respectively, and specific activities of 1580 units/mg (pH 6.5) and 1730 units/mg (pH 6) for the bromination of monochlorodimedone, respectively. As isolated, the enzymes contain a substoichiometric vanadium/subunit ratio; the vanadium content and specific activity are increased by addition of vanadate. V-BrPO (F. distichus, M. pyrifera, and Ascophyllum nodosum) also catalyzes the oxidation of bromide using peracetic acid. In the absence of an organic acceptor, a mixture of oxidized bromine species (e.g., hypobromous acid, bromine, and tribromide) is formed. Bromamine derivatives are formed from the corresponding amines, while 5-bromocytosine is formed from cytosine. In all cases, the rate of the V-BrPO-catalyzed reaction is much faster than that of the uncatalyzed oxidation of bromide by peracetic acid, at pH 8.5, 1 mM bromide, and 2 mM peracetic acid. In contrast to hydrogen peroxide, V-BrPO does not catalyze formation of dioxygen from peracetic acid in either the presence or absence of bromide. V-BrPO also uses phenylperacetic acid, m-chloroperoxybenzoic acid, and p-nitroperoxybenzoic acid to catalyze the oxidation of bromide; dioxygen is not formed with these peracids. V-BrPO does not catalyze bromide oxidation or dioxygen formation with the alkyl peroxides ethyl hydroperoxide, tert-butyl hydroperoxide, and cuminyl hydroperoxide.

Amines↗
PubMed1990

1-(m-chlorophenyl)-biguanide, a potent high affinity 5-HT3 receptor agonist.

1-(m-Chlorophenyl)-biguanide (mCPBG) was examined and compared with three 5-HT3 receptor agonists in three 5-HT3 receptor models. mCPBG inhibited [3H]GR67330 binding to 5-HT3 receptors with high affinity (IC50 1.5 nM). mCPBG depolarized the rat vagus nerve with an EC50 one tenth of that for 5-HT (0.05 vs. 0.46 microM); the maximum depolarization was approximately half that for 5-HT. The mCPBG depolarization was potently blocked by the selective 5-HT3 antagonist, ondansetron (pKB 8.6 +/- 0.1). In anaesthetised cats, mCPBG potently evoked the Bezold-Jarisch reflex which was blocked by low doses of ondansetron (10 micrograms/kg i.v.). It is concluded that mCPBG is a potent, high affinity 5-HT3 receptor agonist.

Anesthesia↗
PubMed1990

K+ current diversity is produced by an extended gene family conserved in Drosophila and mouse.

The Drosophila Shaker gene on the X chromosome has three sister genes, Shal, Shab, and Shaw, which map to the second and third chromosomes. This extended gene family encodes voltage-gated potassium channels with widely varying kinetics (rate of macroscopic current activation and inactivation) and voltage sensitivity of steady-state inactivation. The differences in the currents of the various gene products are greater than the differences produced by alternative splicing of the Shaker gene. In Drosophila, the transient (A current) subtype of the potassium channel (Shaker and Shal) and the delayed-rectifier subtype (Shab and Shaw) are encoded by homologous genes, and there is more than one gene for each subtype of channel. Homologs of Shaker, Shal, Shab, and Shaw are present in mammals; each Drosophila potassium-channel gene may be represented as a multigene subfamily in mammals.

Amino Acid Sequence↗
PubMed1990

Mechanistic investigations of the novel non-heme vanadium bromoperoxidases. Evidence for singlet oxygen production.

Three newly discovered non-heme bromoperoxidases isolated from marine algae were found to catalyze the production of singlet oxygen in reactions composed of the bromoperoxidase, hydrogen peroxide, and bromide. The bromoperoxidases studied were vanadium bromoperoxidase (V-BrPO) from Ascophyllum nodosum, native non-heme bromoperoxidase from Corallina vancouveriensis (which contains vanadium and iron), and the vanadium-reconstituted bromoperoxidase derivative from C. vancouveriensis. These enzyme systems generated near infrared emission, characteristic of singlet oxygen. The emission had a peak intensity near 1268 nm, was greatly increased in 2H2O-containing buffers, and was greatly decreased by the singlet oxygen quenchers, histidine and azide. The yield of singlet oxygen was approximately 80% of the theoretical yield. A unique feature of the non-heme bromoperoxidases distinct from the iron heme haloperoxidases, was the remarkable stability of the non-heme enzymes in the presence of singlet oxygen and oxidized bromine species. V-BrPO turned over multiple aliquots of 2 mM hydrogen peroxide without losing efficiency. In contrast, iron heme lactoperoxidase was completely inactivated after turnover of the first aliquot of 2 mM hydrogen peroxide, and iron heme chloroperoxidase was 50% deactivated. The profile of singlet oxygen formation by V-BrPO and the near stoichiometric yield of singlet oxygen suggest that the mechanism of singlet oxygen formation is the same as the mechanism of dioxygen formation determined by oxygen probe measurements.

Azides↗
PubMed1990

[3H] GR67330, a very high affinity ligand for 5-HT3 receptors.

GR67330 potently inhibited 5-hydroxytryptamine (5-HT)-induced depolarizations of the rat isolated vagus nerve. At the higher concentrations used (0.3 nmol/l-1 nmol/l) this was accompanied by a marked reduction in the maximum response to 5-HT. The calculated pKB value was 10.2. The binding of the tritiated derivative of GR67330 to homogenates of rat entorhinal cortex was examined. Kinetic analysis revealed that specific [3H] GR67330 (0.1 nmol/l) binding was rapid and reversible. Association and dissociation rate constants were 1.48 +/- 0.36 x 10(8) mol/l-1 s-1 and 7.85 +/- 0.41 x 10(-3) s-1 respectively. Equilibrium saturation analysis revealed specific binding was to a single site (Bmax 22.6 +/- 0.21 fmol/mg protein) of high affinity (Kd 0.038 +/- 0.003 nmol/l). At low ligand concentrations, specific binding was up to 90% of total binding. If unlabelled GR67330 was used to define non-specific binding two sites were evident (Kd1 0.066 +/- 0.007 nmol/l, Kd2 20.1 +/- 9.7 nmol/l; Bmax1 31.5 +/- 3.2 fmol/mg protein, Bmax2 1110 +/- 420 fmol/mg protein). [3H] GR67330 binding was inhibited potently by 5-HT3 antagonists and agonists. Ligands for other 5-HT receptors and other neurotransmitter receptors were either only weakly active or inactive at inhibiting binding. Hill numbers for antagonist inhibition of binding were close to unity, except for quipazine which was significantly greater than one. In common with other 5-HT3 binding studies, all 5-H-agonist tested had Hill numbers greater than one (1.51-1.71). GR38032 and GR65630 inhibited a greater proportion of binding than other 5-HT3 antagonists, this additional binding was interpreted as inhibition from a second saturable site unrelated to the 5-HT3 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Mortality associated with captopril and enalapril: a report from the DHSS Hypertension Care Computing Project.

In 1986, the Committee on Safety of Medicines published a report suggesting that enalapril may have an adverse effect on renal function. The prescription event monitoring scheme subsequently published figures on adverse drug reactions and mortality for patients treated with enalapril. They concluded that enalapril did not have an adverse effect on renal function and survival. Similar data were not available for captopril, as the drug was marketed before prescription event monitoring had been developed. In the Department of Health and Social Security (DHSS) Hypertension Care Computing Project (DHCCP), 368 hypertensive patients treated with captopril and 371 treated with enalapril were followed for an average of 3.1 and 1.6 years, respectively. Thirty-two patients died; none had renal failure as an underlying cause of death. The death rate was similar in both drug groups, at 17.5 (enalapril) and 24.0 (captopril) per 1000 patient-years. The present report shows that, for patients treated for high blood pressure, the relative risk of mortality with captopril compared with enalapril was 1.37, an insignificant difference (95% confidence interval 0.63, 2.98).

Acute Kidney Injury↗
PubMed1990

The pharmacological characterization of 5-HT3 receptors in three isolated preparations derived from guinea-pig tissues.

1. The pharmacological characterization of the 5-HT3 receptors in guinea-pig isolated tissues is described. The tissues used were ileum (longitudinal muscle-myenteric plexus), colon and vagus nerve. The guinea-pig isolated colon is a novel preparation. 2. In the guinea-pig isolated ileum, 5-hydroxytryptamine (5-HT, 1 x 10(-8)-3 x 10(-5) M) and the selective 5-HT3 receptor agonist 2-methyl-5-HT (3 x 10(-7)-1 x 10(-4) M) caused concentration-related contractions. The 5-HT concentration-response curve was biphasic whilst the 2-methyl-5-HT curve was monophasic. The EC50 value for the low potency portion of the 5-HT curve was 4.1 x 10(-6) M. The EC50 for 2-methyl-5-HT was 1.23 x 10(-5) M. Selective 5-HT3 receptor antagonists caused rightward shifts of the 2-methyl-5-HT curve and the lower potency portion of the 5-HT curve. Neither ketanserin (1 x 10(-6) M) nor methysergide (1 x 10(-5) M) antagonized the responses to 5-HT or 2-methyl-5-HT. 3. In the guinea-pig isolated colon, 5-HT (3 x 10(-7)-3 x 10(-5) M; EC50 2.4 x 10(-6) M) caused contractions which were mimicked by 2-methyl-5-HT (1 x 10(-6)-1 x 10(-4) M; EC50 7.2 x 10(-6) M). Selective 5-HT3 receptor antagonists caused rightward displacements of the 5-HT concentration-response curves. Neither ketanserin (1 x 10-6 M) nor methysergide (1 x 10- 5M) had any effect on responses to 5-HT or 2-methyl- 5-HT. 4. In the guinea-pig isolated vagus nerve, 5-HT (1 x 10-6-3 x 1O-4M) and 2-methyl-5-HT (1 x i0-S- 1 X 10-3m; EC50 7.6 x 10- M) caused depolarizations; at higher concentrations there were afterhyperpolarizations. The maximum response to 2-methyl-5-HT was less than half that to 5-HT. Selective 5-HT3 receptor antagonists caused rightward displacements of the 5-HT concentration-response curves. Antagonists at other 5-HT receptors (ketanserin, 1 x 10- M and methysergide, 1 x 10-6 M) had no effect. 5. The estimated affinity values of 5-HT3 receptor antagonists correlated well between the three models. Phenylbiguanide was inactive as an agonist or antagonist (up to 1 x 1O-4M) in each preparation. 6. Comparisons with antagonist affinity values obtained in the rat isolated vagus nerve revealed marked differences. Antagonists were generally more potent on the rat isolated vagus nerve, although the differences varied considerably between antagonists. 7. The results are discussed in terms of species-related receptor differences.

Animals↗
PubMed1989

A family of putative potassium channel genes in Drosophila.

Mutant flies in which the gene coding for the Shaker potassium channel is deleted still have potassium currents similar to those coded by the Shaker gene. This suggests the presence of a family of Shaker-like genes in Drosophila. By using a Shaker complementary DNA probe and low-stringency hybridization, three additional family members have now been isolated, Shab, Shaw, and Shal. The Shaker family genes are not clustered in the genome. The deduced proteins of Shab, Shaw, and Shal have high homology to the Shaker protein; the sequence identity of the integral membrane portions is greater than 50 percent. These genes are organized similarly to Shaker in that only a single homology domain containing six presumed membrane-spanning segments common to all voltage-gated ion channels is coded by each messenger RNA. Thus, potassium channel diversity could result from an extended gene family, as well as from alternate splicing of the Shaker primary transcript.

Amino Acid Sequence↗
PubMed1989

Castleman's disease manifesting in the central nervous system: case report with immunological studies.

Castleman's disease is an uncommon lymphoproliferative disorder that manifests itself as a local or generalized tumor-like condition affecting both lymph nodes and nonnodal tissues, usually in the chest or abdomen. Only two prior examples involving the central nervous system had been reported when this patient was encountered. Very recently, three additional cases have been reported by Severson et al. We report the sixth case of Castleman's disease affecting the central nervous system, which occurred in a 63-year-old woman in whom the diagnosis was made after craniotomy for a mass lesion involving the dura over the frontal regions. Neuroradiological, clinical, and immunopathological characteristics of the case are presented. The lesion was treated with cranial irradiation and the patient is alive and symptom free three years after initial treatment.

Brain Diseases↗
PubMed1989

The effects of anti-hypertensive drugs on sexual function in men and women: a report from the DHSS Hypertension Care Computing Project (DHCCP).

One thousand, two hundred and eighty-five men and 1,080 women being followed in the DHSS Hypertension Care Computing Project answered the questions on sexual activity included in a self-administered questionnaire. In men, both impotence and sexual inactivity were increased in patients receiving hydralazine. No gross excess of these complaints could be determined in patients receiving either beta-adrenoceptor blocking drugs or methyldopa, nor was failure of ejaculation increased with these drugs. The survey could not exclude any deterioration in sexual function occurring uniformly across all treatment groups. However, the rates of complaint were similar in men taking a diuretic alone, a beta-adrenoceptor blocking drug alone and those taking the combination of these two drug groups. In women with hypertension, frequency of sexual intercourse and the achievement of orgasm was not associated with the giving of hydralazine, beta-adrenoceptor blocking drugs or methyldopa.

Adult↗