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Biomedical subjects

M B Jackson

Publications and source records attributed to M B Jackson.

At least 109 records · Page 6Linked to original sources
PubMed1986

Hormonal responses to treatment of high blood pressure with low-salt diet alone and combined with added potassium.

One week strict sodium depletion in essential hypertensive men (n = 17) decreased blood pressure and body weight. Plasma renin concentration increased four-fold (p less than 0.001), plasma noradrenaline with 38% (p less than 0.001), plasma dopamine with 58% while plasma adrenaline remained unchanged. The urinary excretion of vasopressin was reduced with 50% (p less than 0.001). Extra potassium induced only small changes when already sodium depleted. Thus, vasopressin was the only pressor hormone which varied directly with sodium intake, blood pressure and body weight during sodium depletion.

Arginine Vasopressin↗
PubMed1986

Seasonal variations in cryptorchidism.

The month of birth of boys undergoing orchidopexy in the Oxfordshire Health District during the years 1974-83 was analysed. A significant seasonal variation with a peak in April was found for those boys operated upon by paediatric surgeons at a young age (0-4). Possible causes of this variation and its relationship to the aetiology of cryptorchidism are discussed.

Adolescent↗
PubMed1986

Toward a mechanism of gating of chemically activated channels.

Chemically activated channels are membrane proteins that have various functions, including the generation of postsynaptic responses. Receptor activation of channels produces excitation, inhibition, or modulation of the responsiveness of a neuron. Synaptic transmission can be altered by many drugs that act on receptors or channels, and many such drugs are important to epilepsy research and treatment. The analysis of channel-gating mechanisms proceeds by the identification of conformations of the receptor channel complex with high or low conductance. These "open" and "closed" states are correlated with the state of occupancy of the receptor binding sites. The patch-clamp technique is ideally suited for the study of channel gating, since it permits the detection of different conductance states of a single channel. Analysis of single-channel current data yields information about the number of such conformations available to channels. Single-channel current analysis of the nicotinic acetylcholine (Ach) receptor of skeletal muscle has shown that there are several different open and closed states. Two of the closed states open very rapidly and are probably activated closed states with bound agonists. The ACh receptor channel can open spontaneously at a very low rate in the absence of bound agonist. Work with other chemically activated channels offers hope that channels activated by neurotransmitters in the mammalian central nervous system can be understood. Glutamate-activated channels can be studied in arthropod muscle and GABA-activated channels can be studied in mammalian spinal cord and hippocampus. In addition, the action of serotonin can be studied in molluscan neurons. One goal of such studies is to understand the mechanisms of responses to neurotransmitters well enough to test for the normal and defective activity of receptor channels as hypotheses for epilepsy. Another goal is to understand the molecular mechanism of action of drugs that are relevant to epilepsy.

Animals↗
PubMed1985

Stochastic behavior of a many-channel membrane system.

A stochastic theory of channel-gating transitions is developed for a stationary system with many channels, with applications to patch-clamp single-channel experiments. Exact probability density and distribution functions for closed times, open times, and first transit times in an N-channel system are obtained in terms of N and the solutions for a one-channel system. Once N is determined, the expressions derived here can be used to analyze data records that are crowded by many channel openings and where multilevel events are common. The three-state model is treated as a specific example. Computer simulations of three-state models indicate that the equations derived here can be used to recover useful information from crowded single-channel current records. The simulations also revealed some of the limitations to the usefulness of these equations. The probability that a channel that has not opened is in a particular closed state was examined as a function of time. This analysis led to a useful limit where the distribution of unopened channels between various closed states is constant in time. This limit simplifies the mathematical treatment of closed-time probabilities, and provides a general method for the analysis of many-channel systems when channels open infrequently.

Animals↗
PubMed1985

Adenosine-activated potassium conductance in cultured striatal neurons.

We have examined the effect of adenosine on the membrane properties of cultured embryonic mouse striatal neurons using patch electrode techniques. Adenosine at 50 microM effectively blocked spontaneous action potential activity. Adenosine or 2-chloroadenosine caused a slow hyperpolarization of the membrane potential and, under voltage clamp, an outward current that was blocked by 1 mM theophylline. ATP also caused a hyperpolarization that was slower and weaker than the adenosine response and could be blocked by 1 mM theophylline. The current induced by adenosine appears to be carried by potassium since (i) an inward current was generated by adenosine when the cells were internally perfused with cesium salts and (ii) the reversal potential of the outward current shifted 57 mV with a 10-fold change in extracellular potassium concentration. The adenosine response is voltage dependent in that the current evoked by adenosine is reduced at holding potentials more positive than -55 mV, despite a larger driving force. Though calcium influx is not required for adenosine to activate the potassium conductance, some components of the cytosol may be essential, since the response is lost during intracellular perfusion.

2-Chloroadenosine↗
PubMed1984

Chemically activated channels in muscle and spinal cord.

The patch clamp can be used to record single chemically activated channel currents in a variety of cell culture preparations. In the case of the gamma-aminobutyric acid (GABA) response in spinal cord cell culture, the channel is Cl - selective. Cl- can be made to flow into or out of a cell by changing the direction of the electrochemical driving force for Cl-; as a result, positive or negative channel currents are produced. Channel currents generated by GABA and the GABA agonists muscimol and pentobarbital have the same amplitude. The kinetics of channel gating are studied by analyzing distributions of dwell times in conducting and nonconducting states. Such analyses of the GABA-activated channel and the acetylcholine-activated channel reveal that gating is complex. More elaborate procedures of data analysis have been used in an attempt to elucidate detailed molecular gating mechanisms.

Acetylcholine↗
PubMed1984

Spontaneous openings of the acetylcholine receptor channel.

Patch clamp recordings from embryonic mouse muscle cells in culture revealed spontaneous openings of the acetylcholine receptor channel in the absence of exogenously applied cholinergic agent. The conductance of the spontaneous channel currents was, within experimental error, identical with the conductance of suberyldicholine-activated channel currents. The comparison of channel conductance was made with sodium and with cesium, each at two concentrations, with the same result. Treatment of the cells with alpha-bungarotoxin blocked the spontaneous channel currents. To determine whether the spontaneous openings were caused by an endogenous agent with cholinergic activity a reactive disulfide bond near the receptor binding site was reduced with dithiothreitol and alkylated with N-ethylmaleimide. This chemical modification reduced the effectiveness with which suberyldicholine and curare activated channel currents but did not reduce the frequency of spontaneous openings. These experiments indicate that the acetylcholine receptor briefly and infrequently fluctuates into an active state in the absence of agonist. Agonist activation of the receptor presumably accelerates this spontaneously occurring process.

Animals↗
PubMed1984

Episiotomy: who gets one and why.

Data was collected about the mother, the infant and the pregnancy in women who had an episiotomy performed at delivery, and those who did not, in one district hospital and two community hospitals. Factors predisposing mothers to episiotomy were sought and compared in the different hospitals. Traditional indications for episiotomy, such as a large baby and a small mother, were found to be less important than the occurrence of fetal distress, prolongation of the second stage of labour and the presence of pupil midwives at delivery. Current practice in the use of episiotomy is discussed.

Adult↗
PubMed1983

Connections of the mesencephalic locomotor region (MLR) I. Substantia nigra afferents.

These studies were designed to determine whether or not substantia nigra (SN) neurons project to the mesencephalic locomotor region (MLR). An attempt was made to activate SN neurons antidromically from the same site which induced locomotion on a treadmill following a precollicular-postmammillary transection in the same animal. Less than 10% of posterior SN neurons were activated antidromically from the physiologically-identified MLR. These results support previous anatomical findings describing a sparse projection from the SN to the MLR [5]. Locomotion on a treadmill was elicited at low current strengths (20-50 muA) from an area around the cuneiform nucleus in the posterior mesencephalon. This area included the lateral central gray, mesencephalic trigeminal root, dorsal brachium conjunctivum and nucleus tegmenti pedunculopontinus (NTPP) and perhaps anterodorsal locus coeruleus. Stimulation of the area just described induced a complete stepping cycle with a flexion phase and a three-part extension phase. Stimulation of the posterior SN produced spastic locomotion on a treadmill at higher current strengths (70 muA) in cats with a precollicular-postmammillary transection.

Afferent Pathways↗
PubMed1983

Successive openings of the same acetylcholine receptor channel are correlated in open time.

Previous analysis of single-channel current records has shown that both the opening and closing transitions of chemically activated ion channels are operated by fast and slow kinetic processes. The fast component in the kinetics of channel opening has been interpreted as the reopening of a channel that has just closed. The fast component in the kinetics of channel closure has many possible explanations and is therefore more difficult to interpret. We can gain insight into the closing process by asking whether the lifetimes of successive openings of an acetylcholine receptor channel are correlated in open-state lifetime. Five kinetic models of channel closure are considered. Two of these models predict uncorrelated open-state lifetimes, one predicts correlated open-state lifetimes, and for two others a range of behavior is possible. Acetylcholine receptor channel data from cultured rat muscle are analyzed to show that open-state lifetimes are correlated, eliminating two models of channel gating.

Acetylcholine↗
PubMed1983

Action potentials and membrane ion channels in clonal anterior pituitary cells.

The electrophysiological properties of the mouse anterior pituitary cell line AtT-20/D16-16 were investigated with intracellular and patch-clamp techniques. Clonal AtT-20/D16-16 cells were found to be electrically excitable, with most cells exhibiting spontaneous bursting action potentials. The mean burst rates varied from 1.4 Hz at -55mV to 8.2 Hz at -25mV, showing an approximately linear frequency-current relationship in the low current range. The bursts consisted of one to several fast Na+ spikes superimposed on a slow pacemaker potential, followed by a Ca2+ spike and a Ca2+-sensitive afterhyperpolarization. Removal of either Na+ or Ca2+ from the bathing medium led to cessation of spontaneous activity and the appearance of arrhythmic firing patterns. Single channel recordings revealed the presence of Ca2+-dependent K+ channels with unitary conductances of approximately equal to 130 pS in physiological medium. These channels were activated by both intracellular Ca2+ and membrane depolarization. Addition of norepinephrine (10 microM) led to increases in burst frequency and beta-endorphin secretion mediated by activation of beta-adrenergic receptors. Our results, in conjunction with previous work, suggest that the Ca2+ that enters the cell during the burst may be involved in hormone secretion.

Action Potentials↗
PubMed1983

Single-channel currents activated by curare in cultured embryonic rat muscle.

Single cholinergic receptor channel currents activated by curare were recorded in tissue-cultured embryonic rat muscle, directly confirming curare's action as a weak cholinergic agonist. In embryonic muscle, curare, in addition to its classical action as a competitive cholinergic antagonist, produces small sustained depolarizations which can be blocked by alpha-bungarotoxin. The single-channel events are of short duration but otherwise exhibit the major features observed with other cholinergic agonists. The single-channel events are blocked by alpha-bungarotoxin. Two values of unit conductance, 30.4 +/- 3.5 pS and 47 +/- 6 pS, were measured in cells from different cultures. Histograms of open-state duration are well fit by a distribution which is a sum of two exponentials, with time constants of 0.33 +/- 0.08 msec for the fast component and 1.84 +/- 0.43 msec for the slow component.

Action Potentials↗
PubMed1983

Preliminary clinical and pharmacokinetic experiences in the newborn when meptazinol is compared with pethidine as an obstetric analgesic.

Preliminary results on the disposition of meptazinol in the neonate are reviewed. Meptazinol has a half-life of 3.4 hours compared with 22.7 hours for pethidine. In a randomised double blind trial of 100 patients the depressant effects in the newborn of meptazinol and pethidine were compared. There was no difference in the Apgar scores at 1 and 3 minutes. Weight loss and the incidence of neonatal jaundice were less when mothers received meptazinol although these differences did not reach statistical significance. However, the number of infants considered fit for discharge by the 6th day was significantly greater in the meptazinol groups. In 43 cases transcutaneous monitoring of arterial PO2 was carried out for 30 minutes following delivery. Although the mean PaO2 was similar for meptazinol and pethidine, significant variations in the PaO2 of 2.0 kPa or greater and significant neonatal activity as judged by episodes of crying and movement, were recorded in the meptazinol group. The results of the trial suggest that meptazinol may have less depressant effects on the newborn, and may be preferable to pethidine as an obstetric analgesic.

Anesthesia, Obstetrical↗
PubMed1982

Single channel currents activated by gamma-aminobutyric acid, muscimol, and (-)-pentobarbital in cultured mouse spinal neurons.

The patch electrode technique was used to record single channel current pulses in tissue-cultured mouse spinal cord neurons. In agreement with earlier noise studies, channels activated by gamma-aminobutyric acid (GABA), muscimol, and (-)-pentobarbital were found to have equal unit conductances. The kinetics of channel closing were studied by analyzing the distributions of open state lifetimes. Channels activated by (-)-pentobarbital and muscimol had longer mean open times than channels activated by GABA. As a result, the kinetics of (-)-pentobarbital- and muscimol-activated channels could be studied in greater detail. Most observed open state lifetime distributions were not exponential but contained an excess of short duration events. A sum of two exponential functions gave a much better fit than a single exponential function to most observed open state lifetime distributions. A critical comparison of noise analysis with single channel recording shows that the fast process responsible for the rapid closures would be very difficult to detect in a noise experiment. The channel noise is dominated by the slower process, and as a result, the relaxation time of the slower kinetic component derived from single channel studies is close to the mean open state lifetime derived from noise measurements. The observation of a faster process points toward either an additional population of channels or a scheme for the channel closing transition which is not a simple first order process.

Animals↗
PubMed1982

Single cholinergic receptor channel currents in cultured human muscle.

Single cholinergic channel currents were recorded in adult human muscle tissue culture. The agonists suberyldicholine and carbamylcholine produce channels with the same conductance as channels produced by acetylcholine but with different closing kinetics. The antagonist tubocurarine, alone or mixed with suberyldicholine, activates channels which close very rapidly. For agonist-activated channels, the distribution of open state lifetimes shows deviations from the usual single exponential form. An excess of short duration openings indicates the presence of an additional faster kinetic process. The lifetime distribution data can be interpreted in terms of varying proportions of slow and fast components which are present in a ratio determined by curve-fitting the appropriate two-exponential function to observed open time distributions. This ratio shows great variability in muscle from older cultures, but the fast and slow time constants are relatively constant. The observation of double exponential open time distributions indicates that the mechanism of channel closing is more complicated than earlier evidence indicated.

Acetylcholine↗
PubMed1982

Electrical development in spinal cord cell culture.

Parallel electrophysiological and neurochemical studies of development are reported for mouse spinal cord cell cultures. The time course of electrical activity and the stage-dependent effects of tetrodotoxin on levels of the neuronal enzyme choline acetyltransferase were compared to establish the presence of spontaneous electrical activity at a time when tetrodotoxin adversely affects development. The extracellular patch electrode makes it possible to examine the ongoing electrical activity of the small cells present in young cultures. A rapid increase in spontaneous electrical activity during the first 2 weeks in culture was found to correlate closely with the onset of tetrodotoxin-induced depression of choline acetyltransferase activity, supporting the idea that ongoing electrical activity plays a role in neuronal development. The development of inhibitory synaptic activity occurs gradually throughout the period of culture, whereas excitatory synaptic activity and action potentials develop in unison, reaching maximal levels during the 2nd week in culture. For all cultures tested, ranging in age from 9 to 45 days old, acute bath application of gamma-aminobutyric acid (GABA) abolished spontaneous electrical activity. Glycine is relatively ineffective in abolishing spontaneous activity in young cultures which have few inhibitory postsynaptic potentials (IPSPs), but glycine becomes as effective as GABA at a later stage of development. This suggests rather different timetables of development for GABA and glycine receptors, with glycine receptors developing in parallel with IPSPs.

Animals↗