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Biomedical subjects

M G Evans

Publications and source records attributed to M G Evans.

At least 73 records · Page 4Linked to original sources
PubMed1986

Chloride channels activated by hyperpolarization in Aplysia neurones.

The outside-out configuration of the patch-clamp technique was used in order to characterize the elementary events underlying the previously described hyperpolarization-activated Cl current of Aplysia neurones. A few membrane patches bathed with K-free internal and external solutions showed channels characterized by long duration (up to several seconds) bursts of activity which were clearly activated by hyperpolarization. I-V curves of elementary current obtained for three different values of the Cl equilibrium potential show that these channels are selective for Cl ions. During the bursts, the current fluctuates between three levels: the resting (closed) level, a level of maximum conductance (10-15 pS) and a half-conductance level. This behaviour is similar to that of the Cl channels extracted from Torpedo electroplaques.

Animals↗
PubMed1986

Blockage of Ca-activated Cl conductance by furosemide in rat lacrimal glands.

Single cells isolated from rat lacrimal glands were studied with the tight-seal whole-cell recording technique. It was found that furosemide (1 mM, applied externally) selectively blocked one part of the electrical response elicited by muscarinic agonists. This component of the response had been shown in a previous work (Marty et al. 1984) to be due to Ca-dependent Cl channels. The action of furosemide was further studied on cells which were dialysed with a high-Ca, high-Na solution, and which mainly displayed the Ca-dependent Cl conductance. In these experiments, furosemide (1 mM) was again found to depress the Ca-dependent Cl current. The present findings offer an explanation for previous reports that furosemide blocks ion fluxes and electrolyte secretion in exocrine glands without necessarily involving the neutral Na-K-Cl carrier usually assumed to be affected by the drug.

Animals↗
PubMed1986

Nonselective ionic channels in Aplysia neurones.

Single-channel recordings from outside-out patches of Aplysia neurones in K-free solutions revealed the presence in most membrane patches of ionic channels showing surprising selectivity properties, as deduced from reversal potential measurements. After complete substitution of external NaCl by mannitol (in the presence of internal CsCl), these channels are more permeable to Cl than to Cs, but are also slightly permeable to Cs: PCl/PCs = 4. Furthermore, in the presence of external NaCl, their ability to discriminate cations from anions seems lower than in external mannitol. Substitutions of external Cl by various anions showed that the channels are more permeable to NO3 than to Cl, and that they are appreciably permeable to isethionate, SO4 and methanesulfonate. Their elementary conductance is about 100 pS in 600 mM symmetrical Cl. However, different conductance states (usually 2 or 3) can often be detected in the same membrane patch. By using voltage ramps, we established the I-V curves corresponding to each of these states and found small but significant differences between the reversal potentials of each state.

Animals↗
PubMed1986

Aortic body tumour with adjacent ectopic thyroid tissue in a dog.

A 12-year-old neutered male Husky dog had a neoplasm at the base of the heart which did not invade surrounding tissues. Microscopically, the neoplasm was composed of nests and sheets of polyhedral cells subdivided into lobules by trabeculae of fine fibrovascular stroma. Adjacent to the neoplasm was a rim of ectopic thyroid tissue that appeared histologically normal. The possible differential diagnoses for the neoplasm were aortic body tumour, ectopic thyroid tumour and ectopic parathyroid tumour; the ultrastructural characteristics revealed it to be an aortic body tumour.

Animals↗
PubMed1986

Potentiation of muscarinic and alpha-adrenergic responses by an analogue of guanosine 5'-triphosphate.

Ca2+-dependent K+ and Cl- currents were recorded in isolated and dialyzed rat lacrimal gland cells by use of the tight-seal whole-cell recording technique. Under control conditions, application of acetylcholine (0.5-1.0 microM) resulted in the full activation of both types of current. When 50-200 microM guanosine 5'-[gamma-thio]triphosphate (GTP[S], a nonhydrolyzable GTP analogue) was added to the intracellular solution, activation of both currents was seen with 1 nM acetylcholine, a dose 1/100th that needed under control conditions. Dialysis with solutions containing 200 microM GTP or cAMP had no, or only slight, potentiation effects. The effects of GTP[S] were obtained only when ATP was included in the intracellular solution. The potentiated responses to acetylcholine were blocked by increasing 10-fold the intracellular Ca2+-buffering capacity and were not dependent on external Ca2+. Thus, the potentiated responses appeared to result from a release of Ca2+ from internal stores. GTP[S] also greatly potentiated the Ca2+-dependent adrenergic (norepinephrine) response of this preparation. In addition, GTP[S] elicited in some cells transient responses without application of acetylcholine or norepinephrine. Finally, rapid and sustained responses were seen as soon as the cells were dialyzed with inositol trisphosphate (20 microM). These findings are discussed in terms of a possible role of a GTP-binding protein as a link between activation of muscarinic or adrenergic receptors and initiation of Ca2+ release by inositol trisphosphate.

Acetylcholine↗
PubMed1986

Calcium-dependent chloride currents in isolated cells from rat lacrimal glands.

Isolated cells from rat lacrimal glands were studied with the tight-seal whole-cell recording technique. Cells were dialysed with K-free solutions containing a high concentration of Ca2+ buffer in order to record Ca-dependent Cl- currents at a Ca2+ level fixed between 0.1 and 10 microM. HEDTA was preferable to EGTA as a Ca2+ buffer, even under conditions of equivalent equilibrium buffering power. After replacement of all internal K+ with Na+, the cells displayed a small conductance component which could be abolished by removal of external K+ or by external application of 2 mM-tetraethylammonium. It is suggested that this conductance is due to Ca-dependent K+ channels. The main part of the cell current was Cl selective. The Cl- conductance was negligible at 0.5 microM-Ca2+, and fully activated at 2 microM-Ca2+. The dose-response curve relating Cl- currents to the internal Ca2+ concentration, [Ca]i, was steeper than predicted by a simple binding isotherm reaction. Relaxations observed in response to voltage jumps could, in most cases, be fitted with single exponentials. At [Ca]i 0.5 microM, the curve relating the relaxation time constant, tau, to the membrane potential, displayed a maximum near +20 mV and 250 ms. At hyperpolarized potentials, tau varied by an e-fold factor in 130 mV. At [Ca]i 1 microM, tau decreased from 100 ms at -120 mV to 60 ms at +60 mV. Relaxation analysis gave an estimate of the variation of the channel open state probability, Po, with potential. At [Ca]i 0.5 microM, Po varied by an e-fold factor in 50-70 mV at hyperpolarized potentials, and saturated above +60 mV. At [Ca]i 1 microM, Po varied e-fold in 100 to 110 mV at hyperpolarized potentials, and saturated near +20 mV. External Cl- was substituted with various anions. From reversal potential measurements, the following permeability sequence was obtained: I- greater than NO3- greater than Br- greater than Cl- greater than F- greater than isethionate, methanesulphonate greater than glutamate. The corresponding normalized permeability coefficients were 2.7, 2.4, 1.6, 1, 0.2, 0.1, 0.1, 0.05. Replacement of external Cl- with Br-, isethionate, methanesulphonate or glutamate did not alter current kinetics as obtained during or after a depolarizing voltage jump.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

Muscarinic response in rat lacrimal glands.

A large variety of responses has been uncovered by recent investigations of conductance changes elicited by muscarinic agonists. In exocrine glands, the permeability to K+, Cl- and Na+ ions is increased, and internal Ca2+ serves as a second messenger. Patch-clamp analysis of the secreting cells has revealed three types of Ca2+-dependent channels, which are respectively selective for K+, for Cl-, and for monovalent cations. The channels differ in their sensitivity to the internal Ca2+ concentration, Cai. K+-selective channels are partially activated at rest, with Cai approx. 10 nmol l-1; Cl(-)-selective channels are activated between 100 nmol l-1 and 1 mumol l-1; activation of cationic channels requires micromolar Cai levels. Cell-attached recordings, performed either on isolated cells or on cell clusters, show an activation of all three channel types upon application of acetylcholine. In whole-cell recordings, mostly K+- and Cl(-)-selective channels are activated. The cell currents display slow oscillations linked to variations of Cai. Whole-cell currents rise after a delay of approx. 1 s, and decay with a time constant of approx. 0.7 s upon removal of acetylcholine. They do not depend on extracellular Ca2+. The recent demonstration that Ca2+-dependent currents can also be obtained when dialysing the cells with inositoltrisphosphate or with GTP gamma S, a non-hydrolysable analogue of guanosine triphosphate, opens promising leads to an analysis of intracellular events regulated by acetylcholine.

Acetylcholine↗
PubMed1986

Prevalence of K88, K99, and 987P pili of Escherichia coli in neonatal pigs with enteric colibacillosis.

One hundred nineteen live neonatal pigs with diarrhea less than or equal to 2 weeks old were euthanatized, and frozen sections of their ilea were submitted to an indirect fluorescent antibody technique to identify K88, K99, and 987P pili (also referred to as F-4, F-5, and F-6 pili, respectively) in Escherichia coli. Ten-centimeter ileal sections were used to determine numbers of lactose-fermenting bacteria. Of 52 pigs in which E coli pili were found, 14 had K88 (27%), 23 had K99 (44%), 13 had 987P (25%), and 2 had K88 and K99 simultaneously (4%). Numbers of lactose-fermenting bacteria were significantly (P less than or equal to 0.05) higher in pigs with piliated E coli than in pigs without piliated E coli. Results of this study indicated that piliated E coli are a major cause of enteric disease in neonatal swine in Michigan, and that in pigs less than or equal to 2 weeks of age, K99 was the most frequently encountered pilus antigen.

Animals↗
PubMed1984

Acid influx into snail neurones caused by reversal of the normal pHi-regulating system.

Intracellular pH (pHi), and Na+ and Cl- activities were measured with ion-sensitive micro-electrodes in Helix aspersa neurones, and the effects of reducing external pH (pHo) were investigated. When pHo was changed from 7.5 to 6.5 keeping CO2 constant, there was a slow fall in pHi, a rise in internal Cl and a fall in internal Na. These ionic changes are opposite to those caused by normal operation of the pHi-regulating system. These effects of external acidification were inhibited by the application of SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid) or by the removal of external Cl. Raising intracellular Na activity by inhibiting the Na pump increased the rate of fall of pHi in acid solutions. In acid solutions the average rate of acid uptake attributable to reversed pHi-regulation was about three times the rate of loss of internal Na, and about twice the rate of Cl uptake. We conclude that these intracellular ion changes in acid solutions were largely due to a reversal of the pHi-regulating mechanism, so that it carried acid into, rather than out of, the cell interior.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1984

Use of nifedipine as an adjunct to current antihypertensive therapy.

Ten hypertensive patients with poor responses to standard antihypertensive therapy were treated with the calcium channel antagonist nifedipine in an attempt to obtain better BP control. The drug was highly effective in significantly lowering BP immediately (average decrease, 58/29 mm Hg) and after three to eight weeks of maintenance therapy (average decrease, 49/27 mm Hg), with no significant change in heart rate observed at either time. No adverse interactions between nifedipine and other concurrent medications, including digoxin and beta-adrenergic blockers, were noted. Drug-related side effects of tachycardia or flushing necessitated the withdrawal of nifedipine therapy in two patients. We conclude that nifedipine may be safely employed in an outpatient setting as a useful adjunct to current antihypertensive drug regimens.

Adrenergic beta-Antagonists↗
PubMed1982

Effect of phencyclidine on [3H]QNB binding.

Intraperitoneal injection of phencyclidine before intravenous injection of [3H] Quinuclidinyl benzilate (QNB, 1.6 micrograms/kg) significantly increased the amount of radioactivity found in the brains of female C57BL/6J mice one hour after the 3H-QNB administration. This effect was found in hypothalamus, cortex, hippocampus and striatum and was decreased by pretreatment of the animal with atropine. The magnitude of the enhancement varied as a function of dose but did not change across the time span studied. These data are in contrast to our findings and those of others of inhibition of the specific binding of 3H-QNB to muscarinic cholinergic receptors by PCP in vitro. When atropine or PCP was administered in vivo and the tissue later analyzed in vitro, no effects of the drugs were observed on 3H-QNB binding. The reasons for the differences remain a matter of speculation.

Animals↗
PubMed1981

A controlled prospective trial of adjuvant razoxane in resectable colorectal cancer.

Following resection of their tumour, 162 patients with colorectal cancer entered a prospective randomized controlled clinical trial of adjuvant oral razoxane. Thirty-one patients were Duke's group A; 49 group B; 61 group C; and 17 group D; an additional four patients were randomized in error. The adjuvant group received the usual clinical care and 125 mg razoxane twice daily for 5 consecutive days (monday-friday) every week indefinitely. Control patients received the same clinical care as the adjuvant group, but no razoxane. At 3 years, 134 patients (84%) are evaluable. The recurrence rate in the first 6 months was 20% and 28% respectively in the Duke's B and C controls compared with 4% and 9% in the corresponding razoxane treated patients. Most recurrences occurred within the first 6 months from randomization. When all patients as randomized are included in the analysis of survival, irrespective of whether they were cured by surgery (Duke's A), had advanced cancer (Duke's D), or took no razoxane when randomized to take it, then as might be expected any differences there may be between the razoxane-treated and control patients with minimal residual disease (Duke's B and C) are so distorted that the p value of the difference in survival was 0.93. If however only patients with Duke's group B or C are taken (49 controls and 47 treated), log-rank analysis reveals a difference in the cancer mortality curves (p = 0.07). If patients who had been randomized to take razoxane, but who had not taken it at any time (and therefore received the same treatment as controls) are analysed with the controls, the difference between the two groups increases further, with p less than 0.05. The razoxane-treated patients experienced no significant toxicity apart from a readily reversible mild leukopenia in 52% while gastrointestinal symptoms necessitated stopping the drug in only four patients. These four all took the drug for less than 4 weeks. Because there was no toxicity to subtract from any benefit razoxane adjuvant treatment produced and the quality of life was not impaired, the therapeutic benefit of surgery wsa increased to the extent that razoxane increased survival of patients with Duke's B and C tumours.

Clinical Trials as Topic↗