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J C Barnes

Publications and source records attributed to J C Barnes.

34 records · Page 2Linked to original sources
PubMed1992

Preparation of right-side-out plasma membrane vesicles from Penicillium cyclopium: a critical assessment of markers.

A plasma membrane fraction was obtained by the combined use of differential centrifugation and aqueous polymer two-phase partitioning techniques. Vanadate-inhibited ATPase and glucan synthase activities were highly enriched in this fraction, although the presence of ATPase activity which was not inhibited by vanadate, nitrate, molybdate, anyimycin A or azide was also detected. Other intracellular membrane marker activities were present at very low or undetectable levels. A further separation step using Percoll density gradient centrifugation resulted in the separation of a fraction which exclusively contained vanadate-inhibited ATPase activity, and was enriched with silicotungstic-acid-staining membrane material. Latency tests performed on the plasma membrane markers showed that the membrane vesicles were in the right-side-out orientation.

5'-Nucleotidase↗
PubMed1992

Pharmacological characterization of angiotensin-induced depolarizations of rat superior cervical ganglion in vitro.

1. The depolarizing responses to angiotensin II and angiotensin III of the rat superior cervical ganglion have been characterized in vitro, by the use of peptidase inhibitors, peptide and non-peptide antagonists and dithiothreitol (DTT). 2. Angiotensin II and III depolarized the ganglion in a concentration-related manner. Angiotensin II was approximately 30 fold more potent than angiotensin III. 3. The endopeptidase inhibitor, bacitracin, increased the potency of angiotensin II and III by approximately 4 and 20 fold respectively. The aminopeptidase inhibitor, amastatin, further increased the potency of angiotensin III (but not angiotensin II) by approximately 4 fold. In the presence of bacitracin and amastatin, angiotensin II and III were equipotent. 4. The peptide antagonist [Ile7]angiotensin III (0.01-0.3 microM) produced a non-parallel rightward displacement of the angiotensin II concentration-response curve, with a suppression of the maximum response. The potency of [Ile7]angiotensin III was increased by bacitracin and amastatin. 5. The AT1-selective non-peptide antagonist losartan (DuP 753; 0.03 and 0.1 microM) produced a parallel rightward displacement of the angiotensin II concentration-response curve, with an apparent pKB of 8.3 +/- 0.1. A higher concentration of losartan (0.3 microM) depressed the maximum agonist response by 32 +/- 6.5%, possibly reflecting non-competitive behaviour of the antagonist. The potency of losartan was not influenced by bacitracin. 6. The AT2-selective non-peptide antagonist, PD123177 (3 microM) failed to antagonize the angiotensin II-induced depolarizations. 7. DTT (1 mM) produced a 22% reduction of the maximum response to angiotensin II.8. We conclude that the angiotensin II-induced depolarizations of the rat superior cervical ganglion are mediated by angiotensin II receptors of the AT1 subclass. The ability of peptidase inhibitors to modify the potency of peptide agonists and antagonists highlights the difficulties associated with the use of peptide agents to characterize angiotensin II receptors in this preparation.

Angiotensin II↗
PubMed1992

Pharmacological profile of GR117289 in vitro: a novel, potent and specific non-peptide angiotensin AT1 receptor antagonist.

1. This paper describes the effects of GR117289 (1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzo-furanyl]methyl ]-2-butyl-4-chloro-1H-imidazole-5-carboxylic acid) at angiotensin receptors and binding sites in rabbit aorta, rat liver and bovine cerebellum preparations in vitro. 2. In rabbit isolated aortic strips, GR117289 (0.3, 1 and 3 nM) caused a concentration-related, insurmountable suppression of the concentration-response curve to angiotensin II (AII). When the contact time was increased, a greater degree of antagonism of AII was observed, suggesting that GR117289 is slow to reach equilibrium. A pKB of 9.8 +/- 0.1 was calculated for GR117289 after 3 h incubation. GR117289 (1 microM) did not affect contractile responses to phenylephrine or 5-hydroxytryptamine (5-HT) in the rabbit aorta. 3. GR117289 (1 nM) alone caused a marked suppression and a slight rightward displacement of the AII concentration-response curve. Co-incubation with the competitive, surmountable AT1 receptor antagonist, losartan (10 nM, 100 nM and 1 microM), resulted in a concentration-related upward and rightward displacement of the concentration-response curve to subsequently administered AII. In separate experiments in which preparations were pre-incubated with GR117289 (1 nM), subsequent addition of losartan (1 microM) for 2, 15 or 45 min caused a further, but similar, rightward displacement of the concentration-response curve to subsequently administered AII with a time-dependent increase in the maximum response.4. Suppression of All-induced contractile responses, caused by superfusion with GRI17289 (0.3, 1 or 3 nM) was not reversed by continuously washing the tissues for 3 h; in fact, the potency of GRI 17289 was slightly enhanced after this period.5. In rat liver membranes, GRI17289 was a potent competitor with [3H]-AII for AT, binding sites(pKi = 8.7 +/- 0.1) but in bovine cerebellum membranes, it was a very weak competitor for AT2 binding sites (pKi<6). Pre-incubation of rat liver membranes with GRI17289 had little effect on its affinity(pKi = 9.1 +/- 0.21), but increasing the concentration of bovine serum albumen in the assay buffer from 0.001% to 0.1% w/v decreased affinity (pKi= 7.5 +/- 0.1).6. In saturation binding experiments in rat liver membranes, GRI 17289 (12 nM) increased the Kd of[3H]-AII from 0.28 +/- 0.06 nM to 0.37 +/- 0.02 nM, and decreased Bm. from 10.0 +/- 0.1 to 5.6 +/-0.3 fmol mg' tissue. In other experiments, GR1 17289 (1 jIM) did not alter the rate of dissociation of[3H]-AII from AT1 binding sites, following addition of excess unlabelled All.7. In rabbit aorta vascular smooth muscle membranes, GR1 17289 competed with ['25I]-Sar'1le8 All for binding to AT, binding sites. In the presence of 0.1% w/v bovine serum albumen, a pIC50 of 7.6 +/- 0.1 was calculated. Under the same conditions, but with rat liver membranes, a pIC50 of 7.8 +/- 0.1 was determined.8. Taken together, these results show that GRI17289 is a potent, specific, selective and insurmountable antagonist at angiotensin AT, receptors. Its profile in the rabbit aorta is consistent with the proposalthat GRI17289 is a slowly reversible (pseudo-irreversible) antagonist at these receptors.

Angiotensin II↗
PubMed1991

Central effects of muscarinic agonists and antagonists on hippocampal theta rhythm and blood pressure in the anaesthetised rat.

The in vivo central effects of a range of full and partial muscarinic receptor agonists have been investigated on hippocampal theta rhythm and blood pressure. In the isoflurane-anaesthetised rat, pretreated with N-methylscopolamine, i.v. administration of arecoline, oxotremorine, arecaidine propargyl ester, aceclidine and pilocarpine produced dose-dependent increases in the frequency of hippocampal theta rhythm and blood pressure, with an order of potency of arecoline = oxotremorine = arecaidine propargyl ester greater than aceclidine greater than or equal to pilocarpine. To increase theta wave frequency, pilocarpine showed a low maximum response and possessed antagonist activity against arecoline, indicating that pilocarpine was acting as a partial agonist. AF102B failed to alter blood pressure or theta rhythm. Intraventricular injections of scopolamine and the M1 receptor-selective antagonist, pirenzepine, produced dose-dependent antagonism of the enhanced theta wave frequency and hypertensive response produced by arecoline. The differences in antagonist potency for the two responses was less than 6-fold, which indicated that both the increase in hippocampal theta wave activity and increase in blood pressure may have been mediated through muscarinic receptors of the M1 subtype. Further studies using a wider range of antagonists will be required to confirm this conclusion.

Anesthesia↗
PubMed1989

Adenine and pyridine nucleotide levels during calcium-induced conidiation in Penicillium notatum.

Concentrations of adenine and pyridine nucleotides and the associated charge values were examined in extracts of mycelium of Penicillium notatum during vegetative growth and reproductive development promoted by the addition of Ca2+ (10 mmol dm-3). The significant increase in adenylate energy charge promoted by Ca2+ was due to a fall in intracellular AMP and a concomitant rise in ATP concentration. Intracellular concentrations of NADH and NAD fell within 1 h of the addition of Ca2+. The catabolic reduction charge was unchanged by Ca2+ whilst the anabolic reduction charge increased in Ca2+-induced mycelium due to lowered intracellular NADP concentration. Reduced concentration of NADPH in Ca2+-induced mycelium, relative to the vegetative controls, lowered the phosphorylated nucleotide fraction. The results are discussed in relation to metabolic economy during morphogenesis in P. notatum.

Adenine Nucleotides↗
PubMed1987

Actions of opioids on the dorsal root potential of the isolated spinal cord preparation of the neonate rat.

The effects of opioids were studied on the dorsal root-dorsal root evoked potential (DRP) of the neonatal hemisected spinal cord of the rat in vitro. Applications of [D-Ala2,Met5]enkephalinamide (DAME), [D-Ala2,D-Leu5]enkephalin (DADL), Leu5 enkephalin, Met5 enkephalin, Dynorphin 1-9 and normorphine produced dose-dependent depressions of the dorsal root potential. The depressant effects of these agents were antagonised by naloxone but not by the highly selective delta-opioid receptor antagonist ICI 174864. Compounds acting on the kappa opioid receptor had only weak and inconsistent inhibitory effects on the dorsal root potential. Morphine had antagonist properties on the dorsal root potential, as did the kappa agonists ethylketocyclazocine and bremazocine, but not U50488 and tifluadom. The depressant actions of opioids on the dorsal root potential thus appeared to be mediated by actions on the mu receptor type. However, only mu agonists with relatively high intrinsic activity were able to reduce the dorsal root potential. Other mu agonists, including morphine, acted as antagonists. Actions on receptors for the delta and kappa agonists, in contrast, appeared to have little influence on this response. The antagonist actions of certain kappa agonists were probably due to their high affinity for, but low efficacy at mu receptors.

Animals↗
PubMed1987

Ketotifen can antagonise changes in sensitivity of cerebral dopamine receptors: behavioural correlates in rodent and primate.

Rats preselected as "low responders" to the hyperactivity-inducing action of (-)N-n-propylnorapomorphine [(-)NPA] responded to an infusion of dopamine into the nucleus accumbens (25 micrograms/24 hr for 13 days) with hyperactivity during the infusion and long-term increased sensitivity to (-)NPA administered after the infusion. Both effects were antagonised by ketotifen (intraperitoneal infusion, 1 mg/kg/day), administered during the period of infusion of dopamine. Animals subject to infusion of dopamine also showed enhanced hyperactivity to L-DOPA (plus benserazide): this enhanced response was also antagonised by ketotifen, given acutely as a single dose (1 mg/kg i.p.). When haloperidol was given concurrently with the infusion of dopamine, spontaneous locomotor activity was markedly increased after the infusion for a period of at least 7 weeks: this long-term change was antagonised by ketotifen (1 mg/kg/24 hr), given during the period of treatment with dopamine/haloperidol or by a single acute injection of ketotifen (0.1-1.0 mg/kg i.p.) on an established response. Ketotifen, in doses up to 20 mg/kg (i.p.) did not reduce spontaneous locomotor activity, cause catalepsy or antagonise amphetamine-induced stereotypy in normal rats. In the marmoset, an enhanced sensitivity to the locomotor-stimulant effects of L-DOPA was induced 5 to 8 weeks after a treatment for 4 days with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which led to the development of akinesia and severe depletion of dopamine in the striatum. Treatment with a single dose of ketotifen (1 mg/kg i.p.) 60 min before L-DOPA antagonised the enhanced locomotor responsiveness to the L-DOPA/benserazide regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Congenital rectovesical fistula in the absence of imperforate anus.

Two neonates with multiple congenital anomalies presented with contamination of the urinary tract with fecal organisms. Both patients had normal anorectal areas but in both, a work-up of the urinary tract infection including cystogram and barium enema revealed a rectovesical fistula. This is highly unusual and as far as can be determined, no reports similar to this could be found. Patient 1 succumbed from severe cardiovascular disease after colostomy so that no further diagnostic or therapeutic measures could be taken. Patient 2 underwent sigmoid colostomy to divert the fecal contamination of the bladder. He then underwent successful surgical division of the rectovesical fistula from an abdominal approach and subsequently had his colostomy closed. Intraoperatively, a catheter placed in the fistula via the rectum was quite helpful in identification of the fistula. This very unique lesion in this second patient was one of a constellation of anomalies including megalourethra, epispadiac urethral fistula, undescended testes, bilaterally, a floppy lower abdominal wall, and absent left kidney. This patient could be construed as a variant of the prune belly syndrome.

Abnormalities, Multiple↗
PubMed1986

Lithium and bupropion antagonise the phasic changes in locomotor activity caused by dopamine infused into the rat nucleus accumbens.

Dopamine infused persistently (25 micrograms/24 h for 13 days) into the nucleus accumbens of rat brain caused phasic increases in spontaneous locomotor activity during the period of infusion. This phasic responding was prevented by lithium administered throughout the infusion period in divided doses (3 X daily administrations of 2.5 mg/kg IP) or as a continuous IP infusion (7.5 mg/kg/24 h), and by bupropion treatment (5-20 mg/kg 3 X daily). In contrast, imipramine, amitriptyline and nomifensine failed to prevent the phasic locomotor response to dopamine at doses which did not by themselves cause marked motor changes. Locomotor activity was measured using individual photocell cages, and rats preselected to (-)NPA were those initially showing a modest locomotor activity. Fourteen to twenty-eight days after discontinuing the dopamine infusion rats showed increased responsiveness to (-)NPA which persisted throughout the remainder of the 70-day withdrawal period. This long-term change was prevented when lithium was given continuously throughout the period of dopamine infusion, but not when lithium was given in divided doses, showing the importance of the mode of drug delivery. The long-term change caused by the dopamine infusion could also be prevented by bupropion but not by imipramine, amitriptyline or nomifensine to show again that the actions of classical antidepressant drugs may be differentiated from those of lithium and bupropion. Therefore, it is suggested that the model of phasic hyperactivity described may provide a means for more closely analysing, both behaviourally and biochemically, the site and mechanism of action of lithium (and bupropion) in the control of the short- and long-term consequences of an enhanced mesolimbic dopamine activity.

Amitriptyline↗
PubMed1986

Modulation of dopamine function by glycine in the nucleus accumbens of the brain of the rat.

The effects of glycine on the phasic changes in locomotor activity in the rat, caused by a persistent infusion of dopamine (DA) into the nucleus accumbens (ACB) were investigated. Dopamine (25 micrograms/24 hr), infused into the nucleus accumbens for 13 days, caused hyperactivity, with two peaks occurring on days 3-4 and 9-11. Glycine (12.5 or 25 micrograms/24 hr) infused into the nucleus accumbens on its own did not alter the locomotor activity, yet when infused at the same time as DA (25 micrograms/24 hr), glycine (12.5 or 25 micrograms/24 hr) inhibited the development of the first peak of hyperactivity induced by DA, with no effect on the second peak. A larger dose of glycine (50 micrograms/24 hr), infused alone, significantly increased locomotor activity, and a combination of this dose with DA (25 micrograms/24 hr), led to a temporal shift in the response to DA such that the first peak of hyperactivity was delayed to "fuse" with the second peak. The locomotor response to a threshold dose of DA (6.25 micrograms/24 hr) plus glycine (50 micrograms/24 hr) was no greater than could be accounted for by the hyperactivity response to glycine alone (50 micrograms/24 hr). Strychnine (10 micrograms/24 hr), infused into the nucleus accumbens, produced no alteration in locomotor activity. Similarly, when infused together with DA (25 micrograms/24 hr), strychnine (10 micrograms/24 hr) caused no significant alteration in the phasic hyperactivity induced by DA. However, strychnine (10 micrograms/24 hr), infused together with DA and glycine (25 and 12.5 micrograms/24 hr respectively), prevented the inhibition by glycine of the first peak of hyperactivity induced by DA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Low pressure/low flow voiding in younger men: psychological aspects.

Low pressure/low flow voiding in young and middle-aged males in the absence of outflow tract obstruction has been reported as being associated with anxiety and a high incidence of dyspepsia. To assess objectively the psychological basis of this condition, an unselected group of 50 men aged 25 to 55 years was evaluated by psychiatric interview, questionnaires and urodynamic tests. In addition, patients involved in an earlier study were psychologically evaluated. Low pressure/low flow voiding was demonstrated in three (6%) of the new patients. This voiding pattern was related to a long preceding history, stress-dependent symptoms and difficulty in voiding in public urinals. When compared with a control population, the experimental group scored significantly higher on measures of psychoneurosis. It is recommended that surgery be avoided in these patients and that simple behavioural therapy may be most appropriate.

Adult↗
PubMed1978

The VATER Association.

The VATER association is a group of congenital anomalies with a nonrandom tendency for concurrence. Defects include vertebral, vascular, anorectal malformation, tracheoesophageal fistula with esophageal atresia, radial-limb, and renal abnormalities. The critical period of organogenesis is at or before the sixth or seventh week of gestation. The VATER assoication is important in the evaluation of newborns with major congenital anomalies.

Abnormalities, Multiple↗
PubMed1978

Gastric emphysema in infants with hypertrophic pyloric stenosis.

Gastric emphysema in unusual in infants and children. Air in the wall of the stomach can rarely occur in children with gastric outlet obstruction due to hypertrophic pyloric stenosis. The clinical features and radiographic appearance of this association are described in three infants, and the value of the lateral radiograph is illustrated. The differential diagnostic considerations, importance of correct radiologic diagnosis and results of proper therapy are discussed.

Emphysema↗