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Biomedical subjects

L M Jordan

Publications and source records attributed to L M Jordan.

At least 19 recordsLinked to original sources

Purification and partial characterization of phospholipase A2 isoforms from human placenta.

Five isoforms of the human placental phospholipase A2 were identified and purified to near homogeneity. The purification of these enzymes involved gel permeation, ion-exchange and affinity chromatography. The apparent relative molecular mass of these proteins is 70,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These enzymes have pH optima of 7 and 8. Two-dimensional gel electrophoresis of these enzymes revealed distinct pH optima for each of the isoforms with values ranging from 4.0 to 6.5. Three of the isoforms require calcium for activity whereas the other two forms exhibit 50% of their maximum activity without the presence of calcium.

Calcium

On the regulation of repetitive firing in lumbar motoneurones during fictive locomotion in the cat.

Repetitive firing of motoneurones was examined in decerebrate, unanaesthetised, paralysed cats in which fictive locomotion was induced by stimulation of the mesencephalic locomotor region. Repetitive firing produced by sustained intracellular current injection was compared with repetitive firing observed during fictive locomotion in 17 motoneurones. During similar interspike intervals, the afterhyperpolarisations (AHPs) during fictive locomotion were decreased in amplitude compared to the AHPs following action potentials produced by sustained depolarising current injections. Action potentials were evoked in 10 motoneurones by the injection of short duration pulses of depolarising current throughout the step cycles. When compared to the AHPs evoked at rest, the AHPs during fictive locomotion were reduced in amplitude at similar membrane potentials. The post-spike trajectories were also compared in different phases of the step cycle. The AHPs following these spikes were reduced in amplitude particularly in the depolarised phases of the step cycles. The frequency-current (f-I) relations of 7 motoneurones were examined in the presence and absence of fictive locomotion. Primary ranges of firing were observed in all cells in the absence of fictive locomotion. In most cells (6/7), however, there was no relation between the amount of current injected and the frequency of repetitive firing during fictive locomotion. In one cell, there was a large increase in the slope of the f-I relation. It is suggested that this increase in slope resulted from a reduction in the AHP conductance; furthermore, the usual elimination of the relation is consistent with the suggestions that the repetitive firing in motoneurones during fictive locomotion is not produced by somatic depolarisation alone, and that motoneurones do not behave as simple input-output devices during this behaviour. The correlation of firing level with increasing firing frequency which has previously been demonstrated during repetitive firing produced by afferent stimulation or by somatic current injection is not present during fictive locomotion. This lends further support to the suggestion that motoneurone repetitive firing during fictive locomotion is not produced or regulated by somatic depolarisation. It is suggested that although motoneurones possess the intrinsic ability to fire repetitively in response to somatic depolarisation, the nervous system need not rely on this ability in order to produce repetitive firing during motor acts. This capability to modify or bypass specific motoneuronal properties may lend the nervous system a high degree of control over its motor output.

Action Potentials

Control of functional systems in the brainstem and spinal cord.

Progress has been made in the identification of cells, circuits, and networks involved in certain important subcortical functional systems, including swallowing, chewing, posture and locomotion, and in the shared mechanisms for selecting the network for specific motor tasks, including a role for excitatory amino acids for network activation, the shaping of the network by inhibitory control, and the selection of inputs and modulation of outputs by monoamines and other agents.

Afferent Pathways

The effect of selective brainstem or spinal cord lesions on treadmill locomotion evoked by stimulation of the mesencephalic or pontomedullary locomotor regions.

The descending pathways from the brainstem locomotor areas were investigated by utilizing reversible cooling (to block synaptic or fiber transmission) and irreversible subtotal lesions of the brainstem or spinal cord (C2-C3 level). Experiments were conducted on decerebrate cats induced to walk on a treadmill by electrical stimulation of the brainstem. Locomotion produced by stimulation of the mesencephalic locomotor region (MLR) was not abolished by caudal brainstem lesions that isolated the lateral tegmentum or by extended rostral/caudal dorsal hemisections of the spinal cord. These results demonstrate that the MLR does not require a pathway projecting through the lateral tegmentum of the brainstem or the dorsal half of the spinal cord, as previously suggested (Mori et al., 1977, 1978b; Shik and Yagodnitsyn, 1978; Shik, 1983). Rather, the results indicate that the descending pathway originating from the MLR projects through the medial reticular formation (MedRF) and the ventral half of the spinal cord. Locomotion produced by stimulation of the pontomedullary locomotor region (PLR) was blocked by reversible cooling of either the MedRF or the ventrolateral funiculus of the spinal cord. In some cases, locomotion could be produced by stimulation of the PLR following extended dorsal hemisections of the spinal cord. These results demonstrate that the PLR can also produce locomotion by activation of cells in the MedRF that project caudally through the ventral half of the spinal cord. Stimulation of the PLR could also elicit locomotion following its surgical isolation from the MedRF of the brainstem. Furthermore, lesions of the dorsal spinal cord resulted in the loss of PLR-evoked locomotion in some, but not all, cases. Thus, an alternative projection of the PLR through the dorsal half of the spinal cord (Kazennikov et al., 1980, 1983a,b; Shik, 1983) cannot be ruled out. Overall, these results demonstrate that the PLR is not an essential component of the motor pathway originating from the MLR. The organizational scheme of "brainstem locomotor regions" is discussed in the context of recent information demonstrating a link between the sensory component of the trigeminal system and locomotor pathways (Noga et al., 1988).

Animals

Does the employed technique of endotracheal extubation reduce the risk of aspiration?

Aspiration of gastric contents continues to be one of the most serious complications of general anesthesia. Laryngeal competence may be reduced immediately following endotracheal extubation, which may increase the risk of aspiration. An evaluation research design was used in 20 adult canines to compare the techniques of positive pressure extubation and extubation at the height of inspiration employing radiopaque barium. Evaluation of radiographs from both groups revealed that no aspirate of barium was detected in the tracheobronchial trees of any of the dogs. This study establishes that there is no difference in the risk of aspiration following endotracheal extubation using the canine model regardless of the clinical technique employed.

Animals

Locomotion produced in mesencephalic cats by injections of putative transmitter substances and antagonists into the medial reticular formation and the pontomedullary locomotor strip.

The purpose of this study was to determine the distribution of cells in the medial reticular formation (MRF) and the pontomedullary locomotor strip (PLS), which can induce locomotion when activated. Controlled microinjections of neuroactive substances (Goodchild et al., 1982) into the MRF or PLS were made in order to activate cell bodies in those areas. The ability of trigeminal receptive field stimulation to induce locomotion before and after drug infusion into the PLS was also assessed since the PLS and the spinal nucleus of the trigeminal nerve are similar in their anatomical distribution. Experiments were performed on precollicular-postmamillary decerebrate cats walking on a treadmill. Injections of glutamic acid (GA; 500 nmol) into the MRF produced locomotion that was antagonized by infusion of glutamic acid diethyl ester into the same spot. Decreases in the current threshold for locomotion produced by electrical stimulation of the MRF were observed when the MRF was infused with either GA (40-80 nmol), DL-homocysteic acid (DL-HCA; 200 nmol), or picrotoxin (PIC; 15 nmol). Injections of GA (100 nmol), DL-HCA (700 nmol), PIC (10-50 nmol), and substance P (2 nmol) into the PLS also produced locomotion. Locomotion produced by injections of PIC into the PLS was blocked by infusion of equal amounts of muscimol or GABA. Effective PLS injection sites were all confined to the trigeminal spinal nucleus or immediately ventral and medial to this in the adjacent lateral reticular formation. Trigeminal nerve peripheral field stimulation evoked locomotion after microinjection of PIC into the PLS, although this same facial stimulus was not effective prior to drug injection. We conclude that the MRF and PLS regions of the cat brain stem contain cells that produce locomotion when chemically stimulated, and we suggest that the PLS is closely related to or synonymous with the spinal nucleus of the trigeminal nerve. Furthermore, we suggest that stimulation of trigeminal afferents is analogous to stimulation of segmental afferent pathways in the production of locomotion (Sherrington, 1910; Jankowska et al., 1967; Afelt, 1970; Budakova, 1972; Grillner and Zangger, 1979).

Animals

The role of Renshaw cells in locomotion: antagonism of their excitation from motor axon collaterals with intravenous mecamylamine.

The contribution of Renshaw cell (RC) activity to the production of fictive locomotion in the mesencephalic preparation was examined using the nicotinic antagonist mecamylamine (MEC). After the i.v. administration of 3 doses of MEC (1.0 mg/kg) the following observations were made: 1) ventral root (VR) evoked discharge of RCs was decreased by up to 87.7%, 2) recurrent inhibitory postsynaptic potentials recorded in alpha motoneurons were greatly reduced or abolished, and 3) the rhythmic firing of RCs during the fictive step cycle was abolished in 83% of the cells examined. Locomotor drive potentials (LDPs) in motoneurons persisted during the fictive step cycle after MEC administration. Bursts of motoneuron firing during each fictive step cycle were characterized by increased frequency and number of spikes after MEC, although the burst duration was unaltered for similar step cycle lengths. A greater number and frequency of spikes per burst was also observed in Ia inhibitory interneurons (IaINs), which remained rhythmically active after MEC administration. It is concluded that Renshaw cells are not an integral part of the spinal central pattern generator for locomotion, nor do they control the timing of the motoneuron or IaIN bursts of firing during fictive locomotion. The data are consistent with a role for RCs in limiting the firing rates of motoneurons and IaINs during each burst.

Animals

Ia inhibitory interneurons and Renshaw cells as contributors to the spinal mechanisms of fictive locomotion.

The activity of selected single alpha-motoneurons, Renshaw cells (RCs), and Ia inhibitory interneurons (IaINs) during fictive locomotion was recorded via microelectrodes in decerebrate (precollicular-postmammillary) cats in which fictive locomotion was induced by stimulation of the mesencephalic locomotor region. The interrelationships in the timing and frequency of discharge among these three interconnected cell types were determined by comparing their averaged step cycle firing histograms, which were normalized in reference to motoneuron activity recorded in ventral root filaments. Previous findings that RCs are rhythmically active during locomotion and discharge in phase with the motoneurons from which they are excited were confirmed, and further details of the phase relationships between RC and alpha-motoneuron activity during fictive locomotion were obtained. Flexor and extensor RCs became active after the onset of flexor and extensor motoneuron activity, respectively. Maximal activity in extensor RCs occurred at the end of the extension phase coincidental with the onset of hyperpolarization and a decrease in activity in extensor motoneurons. Maximal flexor RC activity occurred during middle to late flexion and was temporally related to the onset of reduced flexor motoneuron activity. The IaINs recorded in the present experiments were rhythmically active during fictive locomotion, as previously reported. The quadriceps IaINs were mainly active during the extension phase of the step cycle, along with extensor RCs. Thus the known inhibition of quadriceps IaINs by RCs coupled to quadriceps and other extensor motoneurons is obviously not sufficient to interfere with the appropriate phasing of IaIN activity and reciprocal inhibition during fictive locomotion, as had been speculated. Most of the quadriceps IaINs analyzed exhibited a decrease in discharge frequency at the end of the extension phase of the step cycle, which was coincidental with increased rates of firing in extensor RCs. These data are consistent with the possibility that extensor RCs contribute to the reduction in quadriceps IaIN discharge at the end of the extension phase of the step cycle. The possibility that IaIN rhythmicity during fictive locomotion arises from periodic inhibition, possibly from Renshaw cells, was tested by stimulating the reciprocal inhibitory pathway throughout the fictive step cycle. The amplitude of Ia inhibitory postsynaptic potentials (IPSPs) varied significantly throughout the fictive step cycle in 14 of the 17 motoneurons tested, and, in 11 of these 14 motoneurons, the Ia IPSPs were maximal during the phase of the step cycle in which the motoneuron was most

Animals

Initiation of locomotion from the mesencephalic locomotor region: effects of selective brainstem lesions.

The effects of selected brainstem lesions on controlled treadmill locomotion produced by stimulation of the mesencephalic locomotor region (MLR) in postmamillary cats were determined in these experiments. The importance for the initiation of locomotion of projections from the MLR to rostral brainstem structures, described in a preceding paper, were examined by selective lesioning or by adjusting the level of the decerebration. The role played by the lateral vestibulospinal tract (LVST) in the initiation of locomotion was examined by lesioning Deiters' nucleus bilaterally. Contrary to previous claims, the results of the present experiments show that areas of the brainstem rostral to the MLR are not required for the initiation of locomotion by MLR stimulation. This finding eliminates the ventral tegmental area of Tsai and the substantia nigra, both implicated in the initiation of locomotion, as required participants in MLR stimulated locomotion. Bilateral Deiters' nucleus (DN) lesions did not significantly affect the initiation of locomotion from the MLR, nor did such lesions alter in a systematic fashion the amplitude or timing of EMG activity in flexor or extensor muscles of the hindlimb during MLR evoked walking. Joint angle changes during the locomotor cycle were also essentially unaltered by DN lesions. The significance of these findings regarding the brainstem structures which must be involved in the initiation of locomotion are discussed.

Animals

Excitatory and inhibitory postsynaptic potentials in alpha-motoneurons produced during fictive locomotion by stimulation of the mesencephalic locomotor region.

We tested the hypothesis that stimulation of the mesencephalic locomotor region (MLR) activates polysynaptic pathways that project to lumbar spinal motoneurons and are involved in the initiation of locomotion. Fictive locomotion was produced by MLR stimulation, and intracellular records of evoked postsynaptic potentials (PSPs) in alpha-motoneurons were computer analyzed. Stimulation of sites in the MLR that were maximally effective for the initiation of locomotion produced excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) in all the motoneurons examined. The amplitudes of the PSPs increased as locomotion commenced. The EPSPs were largest during the depolarized phase of the step cycle, and in 17 of our 22 cells the EPSP was replaced by an IPSP of slightly longer latency during the hyperpolarized phase. The mean latency of the EPSPs measured from the stimulus artifact produced by stimulation of the MLR was 5.1 ms (3.0-7.0 ms). In all cases, the IPSP occurred 0.6 ms or more after the onset of the EPSP in the same cell. Later PSPs were sometimes observed as well. The effects of constant current injection on the membrane potential oscillations associated with fictive locomotion (locomotor drive potentials) were examined. The results showed that the amplitudes of the locomotor drive potentials (LDPs) could be affected by depolarizing and hyperpolarizing current injection. The data is consistent with the LDP having a predominant inhibitory component, which is more readily altered by current injection than is the excitatory component. The effect of constant current injections on the MLR-evoked PSPs was also examined, and it was observed that both EPSPs and IPSPs could be affected by the injected currents. The EPSPs increased in amplitude with constant hyperpolarizing current injection, and this fact rules out the possibility that the EPSP is actually a reversed IPSP. The IPSP was decreased in amplitude by hyperpolarizing current injection. Combined stimulation of the MLR and the ipsilateral high-threshold muscle or cutaneous afferents produced facilitation of both short- and long-latency MLR-evoked PSPs, suggesting that the two pathways share common interneurons. The possibility that the long-latency PSPs are produced by rapid oscillation in the locomotor central pattern generator is discussed. We concluded that MLR stimulation that evokes fictive locomotion produces both excitation and inhibition of spinal motoneurons. Spinal interneuronal systems are implicated and may be those involved in the initiation and control of locomotion. The probable relay sites for the descending pathway from the MLR to motoneurons are discussed.

Animals

Motoneuron input-resistance changes during fictive locomotion produced by stimulation of the mesencephalic locomotor region.

Input-resistance changes during fictive locomotion were monitored in a variety of extensor and flexor hindlimb alpha-motoneurons in precollicular, postmammillary decerebrate cats induced to "walk" by electrical stimulation of the mesencephalic locomotor region (MLR). Using intracellular recording techniques and injected hyperpolarizing current pulses, the changes in the motoneuron input resistance recorded at the motoneuron soma were examined during nonlocomoting control periods as well as during the depolarized and hyperpolarized phases of the membrane potential oscillations (locomotor drive potentials, or LDPs) of fictive locomotion. In 28 of the 52 motoneurons examined, no change in the input resistance between the control and locomotor periods was observed. The remainder of the cells displayed a decrease (less than 20%) in input resistance when fictive stepping commenced. Over 80% of all the motoneurons depolarized (mean depolarization 4 mV), whereas only one LG motoneuron hyperpolarized (2 mV) with the onset of stimulation of the MLR. The remaining motoneurons did not display such changes. In 43 out of 52 motoneurons examined, no significant change in the input resistance could be observed between the depolarized and hyperpolarized phases of the step cycle. A decrease in the input resistance during the depolarized phase of the LDP was observed in four LG motoneurons, whereas five other motoneurons (2 LG, 1 TA, 1 PB, and 1 ST) displayed an increased input resistance during the depolarized phase compared with the hyperpolarized phase of locomotion. The data are consistent with the presence of an excitatory synaptic input alternating with an inhibitory input to the motoneuron during the fictive step cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Differential projections of cat medullary raphe neurons demonstrated by retrograde labelling following spinal cord lesions.

Neurons of the medullary raphe nuclei in cats were retrogradely labelled following injection of horseradish peroxidase (HRP) into the L6 spinal cord segment. Brainstems were cut in sagittal section to facilitate examination of the rostral-caudal extent of raphe neurons projecting to the spinal cord. Large numbers of HRP-labelled neurons were found in nucleus raphe magnus, nucleus raphe pallidus, and nucleus raphe obscurus (as well as a few neurons in nucleus raphe pontis). Dorsal or ventral hemisections at the T12-L1 level restricted HRP retrograde transport to those pathways within the intact portion of spinal cord, allowing a determination of the part of the cord through which raphe neurons project to the lumbar enlargement. Neurons of nucleus raphe magnus were found to project primarily in dorsolateral fasciculus. A significant number of neurons of nucleus reticularis gigantocellularis also project in dorsolateral fasciculus. Nucleus raphe obscurus neurons were found to project primarily in ventral funiculus, while nucleus raphe pallidus neurons project in the ventrolateral fasciculi and ventral funiculus. The serotonergic (5HT) fibers described by Dahlström and Fuxe ('65) to terminate in the dorsal horn, intermediolateral cell column, and ventral horn are likely to coincide with the raphe-spinal projections documented in this work.

Animals