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Biomedical subjects

J A David

Publications and source records attributed to J A David.

At least 19 recordsLinked to original sources
PubMed1995

Muscarinic agonists modulate calcium-dependent outward currents in an identified insect motoneurone.

The soma membrane of the fast coxal depressor (Df) motoneurone of the cockroach, Periplaneta americana possesses a population of acetylcholine receptors which respond to both nicotinic and muscarinic ligands. Activation of these 'mixed' acetylcholine receptors by McN-A-343 or oxotremorine results in the generation of an inward current at potentials positive to - 40 mV. A large proportion of the outward current induced by membrane depolarization in Df somata is due to a calcium-activated potassium conductance (IKCa) which shows a characteristic N-shape voltage-dependence. This N-shape of the membrane current-voltage relationship is suppressed by McN-A-343 or oxotremorine indicating that the agonist-induced inward current is due to a reduction in IKCa.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1994

Objective assessment for exercise treatment on the B-200 isostation as part of work tolerance rehabilitation. A random prospective blind evaluation with comparison control population.

The purpose of this study was to assess repeated exercise on the B-200 Isostation as part of rehabilitation work tolerance for nonsurgical patients with lumbar spine disorders. For a consecutive 7-month period, treatment subjects were randomly assigned according to birth date for participation in two groups: a standard work tolerance program only or standard work tolerance program plus inclusion of exercise on the B-200 Isostation. Each patient had similar referral diagnosis requiring conservative treatment. Treatment groups were compared with a control population of volunteers who had neither back pain nor known underlying spinal pathology. All study patients had objective measurement of range of motion, isometric strength, and velocity of motion, on the B-200 Isostation before treatment and at follow-up 3 weeks after treatment. The data showed no significant difference of percent improvement when comparing patients in either of the randomized assigned treatment groups. There was a higher percentage of improvement for each treatment group as compared with the control individuals, however. Based on our study using the B-200 Isostation, there is little objective justification for including exercise on the B-200 dynametric Isostation as part of the rehabilitation routine for improvement of functional physical capacity.

Analysis of Variance↗
PubMed1991

The effects of x-irradiation on hematopoietic stem cell compartments in the mouse.

The sensitivity for x-irradiation of a series of hematopoietic stem cell populations has been determined. The most primitive cells identified, cells with marrow-repopulating ability (MRA), showed the highest degree of radioresistance. These MRA cells which generate many secondary day-twelve spleen colony-forming units (MRA[CFU-S-12]) or colony-forming units in culture (MRA[CFU-C]) in the marrow of primary recipients had Do values equal to 1.18 and 1.13 Gy, respectively. The more mature CFU-S-12 had intermediate radiosensitivity (Do = 0.94 Gy), whereas the less primitive CFU-S-7 were the most radiosensitive (Do = 0.71 Gy). The in vitro colony-forming precursor cells (CFU-C) showed low radiosensitivity. These data clearly show that the most primitive hematopoietic stem cell measured is less sensitive to ionizing radiation than generally has been assumed on the basis of measurements on CFU-S-7 or CFU-S-12.

Animals↗
PubMed1990

Spinal rehabilitation by work tolerance based on objective physical capacity assessment of dysfunction. A prospective study with control subjects and twelve-month review.

A work tolerance program was used for rehabilitation treatment of 45 patients with spinal dysfunction. Patients entering the treatment group were prospectively evaluated by objective physical capacity assessment (PCA). Treatment patients averaged 4 weeks of three, one half day sessions per week. These patients were compared with a control group of 33 patients who did not participate in the rehabilitation program but were evaluated by PCA. A telephone review of all patients in each group was carried out at 6- and 12-month follow-up. Results demonstrated that 78% of the rehabilitation treatment group were discharged with an improved functional work capacity. Most importantly, at 6-month follow-up, 73.0% of patients in the treatment group were productively working while only 38% of control group patients were actively employed. In addition, 84.4% showed an improvement in spinal range of motion. The subjective pain scale ratings of these treatment patients demonstrated only 44.4% decreased pain, while 51.1% stayed the same, and two patients increased discomfort. Further medical diagnostics or intervention was required in 24.4% of treatment patients. These findings definitely show that a spinal rehabilitation work-tolerance program based on objective measurement will enhance an increased rate of return to productive employment activity. There is poor correlation of subjective pain assessment when compared to objective PCAs. Therefore, recommendations of patients for return-to-productive work should be based pain ratings. When adjusted for nonselection patients, the authors community-based hospital program showed similar results to other programs. The work tolerance and rehabilitation program in Concord, New Hampshire, demonstrated a significant cost-effective approach; being less expensive, less time-consuming, and less psychologically oriented.

Adult↗
PubMed1988

GABA receptors on the cell-body membrane of an identified insect motor neuron.

The pharmacology of a gamma-aminobutyric acid (GABA) receptor on the cell body of an identified motor neuron of the cockroach (Periplaneta americana) was investigated by current-clamp and voltage-clamp methods. Iontophoretic application of GABA increased membrane conductance to chloride ions, and prolonged application resulted in desensitization. Hill coefficients, determined from dose-response data, indicated that binding of at least two GABA molecules was required to activate the chloride channel. Differences between vertebrate GABAA receptors and insect neuronal GABA receptors were detected. For the GABA receptor of motor neuron Df, the following rank order of potency was observed: isoguvacine greater than muscimol greater than or equal to GABA greater than 3-aminopropanesulphonic acid. The GABAB receptor agonist baclofen was inactive. Of the potent vertebrate GABA receptor antagonists (bicuculline, pitrazepin, RU5135 and picrotoxin), only picrotoxin (10(-7) M) produced a potent, reversible block of the response to GABA of motor neuron Df. Both picrotoxinin and picrotin also blocked GABA-induced currents. Bicuculline hydrochloride (10(-4) M) and bicuculline methiodide (10(-4) M) were both ineffective when applied at resting membrane potential (-65 mV), although at hyperpolarized levels partial block of GABA-induced current was sometimes observed. Pitrazepin (10(-4) M) caused a partial, voltage-independent block of GABA-induced current. The steroid derivative RU5135 was inactive at 10(-5) M. In contrast to the potent competitive blockade of vertebrate GABAA receptors by bicuculline, pitrazepin and RU5135, none of the weak antagonism caused by these drugs on the insect GABA receptor was competitive. Flunitrazepam (10(-6) M) potentiated GABA responses, providing evidence for a benzodiazepine site on an insect GABA-receptor-chloride-channel complex.

Androstanes↗
PubMed1988

Ionic events following GABA receptor activation in an identified insect motor neuron.

The ionic events underlying gamma-aminobutyric acid (GABA) receptor activation on the cell body of a cockroach identified motor neuron were investigated by using current-clamp and voltage-clamp techniques. The reversal potential for GABA-induced hyperpolarization was -77.0 +/- 2.4 mV (mean +/- s.e.m.; n = 22). The reversal potential for GABA was highly sensitive to changes in external chloride, only weakly affected by changes in external potassium, and independent of changes in either sodium or calcium ion concentration. Intracellular ion-sensitive microelectrodes confirmed that an influx of chloride ions mediated the GABA response. Intracellular injection of acetate, citrate, sulphate, fluoride or ammonium caused no change in the reversal potential for GABA. Intracellular injection of chloride, bromide, chlorate, bromate, or methyl sulphate shifted the reversal potential for GABA to values more positive than resting membrane potential. Evidence for chloride accumulating and for extrusion mechanisms was examined by using putative inhibitors. However, internal application of ammonium ions, and external application of 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid (SITS), 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS), acetazolamide, furosemide, ammonium, zinc and copper ions, were all without effect on the reversal potential for GABA.

Animals↗
PubMed1987

Beds.

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Adolescent↗
PubMed1987

Tools of the trade.

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Electronics, Medical↗
PubMed1986

Relaxation studies on the interaction of hexamethonium with acetylcholine-receptor channels in Aplysia neurons.

The mode of action of the cholinergic antagonist hexamethonium on the excitatory responses of voltage-clamped Aplysia neurons to acetylcholine (ACh) has been examined by voltage- and concentration-jump relaxation analysis. At steady-state concentrations of ACh hyperpolarizing command steps induced inward current relaxations to a new steady-state level (Iss). The time constants of these inward relaxations, tau f, which approximate the mean single-channel lifetime, were increased both by increasing the membrane potential and by lowering the bath temperature (Q10 = 3) but were not affected by increasing the ACh concentration over the dose range employed. In the presence of hexamethonium hyperpolarizing command steps produced biphasic relaxations of the agonist-induced current. tau f was reduced in a voltage-dependent manner, the degree of reduction increasing with hyperpolarization. Slow, inverse relaxations were also triggered in the presence of hexamethonium. The time constant of this relaxation was reduced by increasing membrane potential and hexamethonium concentration. Both the estimated association (kf = 5 X 10(4) M-1 . sec-1) and the estimated dissociation (kb = 0.24-0.29 sec-1) rate constants derived from a three-state sequential model for block by hexamethonium were independent of the membrane potential. Similar rate constants were estimated from experiments with the concentration-jump technique, which were also independent of the membrane potential over the range -50 to -110 mV. It is suggested that the voltage-dependent actions of hexamethonium may originate either from an alteration of the channel opening and closing rate constants through an allosteric interaction with the ACh receptor, rather than through an influence of the transmembrane electric field on the rate of drug binding, or through a fast reaction which is rate-limited by voltage-independent diffusion.

Acetylcholine↗
PubMed1983

Voltage-dependent block by histrionicotoxin of the acetylcholine-induced current in an insect motoneurone cell body.

Acetylcholine (ACh)-induced currents were recorded from the voltage-clamped cell body of the fast coxal depressor motoneurone of the cockroach Periplaneta americana, at membrane potentials in the range -120 mV to -60 mV. In the presence of histrionicotoxin (HTX) (1.0 X 10(-6) M), ACh currents were blocked. The blocking action of HTX was voltage-dependent, being more effective at more negative membrane potentials.

Acetylcholine↗
PubMed1982

Differential accessibility to two insect neurones does not account for differences in sensitivity to alpha-bungarotoxin.

The nicotinic acetylcholine receptor probe alpha-bungarotoxin (1.0 x 10(-7) M) blocks the depolarising response to ionophoretic application of acetylcholine onto the cell body membrane of the fast coxal depressor motoneurone (Df) of desheathed cockroach (Periplaneta americana) metathoracic ganglia, but at the same concentration is completely ineffective in blocking the depolarising action af acetylcholine on dorsal unpaired median (DUM) neurones in the same ganglion. The possibility that this is due to differences in accessibility of the toxin to the neurones has been tested by a combination of ionophoretic injection of horseradish peroxidase into single neurones with a study of the distribution of the exogenous tracer lanthanum, which is of similar effective size to alpha-bungarotoxin. The peripherally located cell body membranes and the fine axonal processes of Df and DUM neurones of desheathed metathoracic ganglia are equally accessible to lanthanum. Differential accessibility to the two cell types does not account therefore for the differences in sensitivity to alpha-bungarotoxin.

Acetylcholine↗
PubMed1982

The effects of axotomy upon the extrasynaptic acetylcholine sensitivity of an identified motoneurone in the cockroach Periplaneta americana.

The effects of axotomy on the sensitivity of the fast coxal depressor motoneurone (Df) of the cockroach (Periplaneta americana) to applied acetylcholine (ACh) and carbamylcholine (CCh) have been investigated. ACh and CCh applied to the soma membrane either by bath perfusion or by ionophoresis caused depolarization; repeated application of large doses of these agonists resulted in a relatively rapid desensitization and depression of the response. Axotomy performed 3-10 days before recordings were made caused an approximately threefold increase in the sensitivity to ACh but had no affect upon the sensitivity to CCh. The resting potential, input resistance and membrane time-constant remained within the normal range. In addition there was no change in the rise-times of the responses or of the ACh reversal potential, or in the apparent number of ACh molecules needed to combine with individual cholinoceptors to produce a response. The anticholinesterases physostigmine and neostigmine potentiated the ACh response at relatively low concentrations (10(-7) M-10(-6) M). This potentiation was significantly greater in the normal cells than in the axotomized cells. It is therefore concluded that the increase in ACh sensitivity of this motoneurone results at least partly from a fall in the activity of cholinesterase in the region of the applied drug.

Acetylcholine↗