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Biomedical subjects

L M Harrison

Publications and source records attributed to L M Harrison.

At least 37 records · Page 2Linked to original sources
PubMed1999

A neurophysiological study of mirror movements in adults and children.

The mechanism underlying mirrored activity/movements in normal individuals is unknown. To investigate this, we studied 11 adults and 39 children who performed sequential finger-thumb opposition or repetitive index finger abduction. Surface electromyographic (EMG) activity recorded from the left and right first dorsal interosseous muscles (1DI) during unilateral sequential finger-thumb opposition (voluntarily activated muscle, 1DIvol) showed mirrored EMG activity (homologous muscle of the opposite hand, 1DImm) that decreased with increasing age. The time of onset of involuntary compared with voluntary EMG activity was variable but could start at the same time. A significant increase in E2 (transcortical component) size of the cutaneomuscular reflex recorded from the 1DImm indicated increased excitability of the motor cortex ipsilateral to the 1DIvol during active index finger abduction compared with the 1DIvol relaxed. Transcranial magnetic stimulation, using the Bistim technique, indicated that the transcallosal inhibitory pathway in children may not operate in the same way as in the adult. Cross-correlation analysis did not detect shared synaptic input to motoneuron pools innervating homologous left and right hand muscles. We conclude that the mirrored movements/activity observed in healthy adults and children are produced by simultaneous activation of crossed corticospinal pathways originating from both left and right motor cortices.

Adolescent↗
PubMed1999

Cutaneomuscular reflex responses recorded from the lower limb in children and adolescents with cerebral palsy.

Cutaneomuscular reflex (CMR) responses were recorded from lower-limb and trunk muscles in 27 subjects with cerebral palsy (CP) (spastic, 21; athetoid, six) and in neurologically healthy (control) subjects, aged 3 to 15 years, while standing. In the 21 subjects with spastic CP, but not in the six subjects with athetoid CP, CMR responses were more widely distributed between ipsilateral lower-limb and trunk muscles compared with age-matched control children. CMR responses in older subjects with CP were similar to younger control subjects, lacking supraspinally mediated, long-latency components. Short-latency, spinally-mediated, excitatory CMR components were seen simultaneously in pairs of distal, antagonistic lower-limb muscles in half of the subjects with spastic CP, but in none of the control children. In subjects with spastic-type CP, the abnormal reflex responses indicate disordered spinal and supraspinal inputs to motor neurones, although there was no convincing correlation between these responses and the severity of spasticity.

Adolescent↗
PubMed1999

Does abnormal branching of inputs to motor neurones explain abnormal muscle cocontraction in cerebral palsy?

The common synaptic drive shared between two groups of motor neurones synchronizes the timing of discharges between the motor-neurone groups. Recordings were made of motor-unit discharges during cocontraction of ipsilateral pairs of thumb muscles in eight subjects with cerebral palsy (CP) aged 4 to 13 years and eight neurologically healthy subjects aged 4 to 12 years, and in pairs of lower-limb muscles in 21 subjects with CP and 21 control subjects, both aged 3 to 15 years. Common synaptic drive, likely to be derived at least partly from activity in branched corticospinal-tract neurones, produced motor-unit synchronization between pairs of thumb muscles in control subjects but was absent in all subjects with CP. Motor unit synchronization was not found between lower-limb antagonist muscles that cocontract abnormally in CP, nor was synchronization present in more widely separated muscle pairs. Therefore, abnormal patterns of muscle activation and more widespread muscle reflex responses do not result from an abnormal distribution of common synaptic drive in CP.

Adolescent↗
PubMed1998

Differential effects of endomorphin-1, endomorphin-2, and Tyr-W-MIF-1 on activation of G-proteins in SH-SY5Y human neuroblastoma membranes.

Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), peptides recently isolated from bovine and human brain, have high affinity and selectivity for mu opiate receptors. They share sequence similarity with the endogenous opiate-modulating peptide Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2). The efficacies of these endogenous peptides and of the enkephalin analog DAMGO were compared by measuring their effects on the binding of guanosine-5'-O-(-gamma-[35S]thio)triphosphate ([35S]GTPgammaS) to G-proteins in membranes from SH-SYSY human neuroblastoma cells. DAMGO, endomorphin-1, and endomorphin-2 stimulated [35S]GTPgammaS binding dose dependently, with maximal effects of 60 +/- 9%, 47 +/- 9%, and 43 +/- 6% stimulation above basal and ED50 of 49 +/- 8 nM, 38 +/- 8 nM, and 64 +/- 13 nM, respectively. Tyr-W-MIF-1 showed only a small stimulation of binding (5% stimulation above basal, ED50 = 2 microM). When given in combination with the other opioids, however, Tyr-W-MIF-1 attenuated their ability to activate G-proteins. Thus, the endogenous opioids endomorphin-1 and endomorphin-2 activate G-proteins similarly to the synthetic agonist DAMGO, but the structurally similar peptide Tyr-W-MIF-1 produces only minimal stimulation of G-proteins.

Cell Membrane↗
PubMed1998

Opiate tolerance and dependence: receptors, G-proteins, and antiopiates.

Despite the existence of a large body of information on the subject, the mechanisms of opiate tolerance and dependence are not yet fully understood. Although the traditional mechanisms of receptor down-regulation and desensitization seem to play a role, they cannot entirely explain the phenomena of tolerance and dependence. Therefore, other mechanisms, such as the presence of antiopiate systems and the coupling of opiate receptors to alternative G-proteins, should be considered. A further complication of studies of opiate tolerance and dependence is the multiplicity of endogenous opiate receptors and peptides. This review will focus on the endogenous opioid system--peptides, receptors, and coupling of receptors to intracellular signaling via G-proteins--in the context of their roles in tolerance and dependence. Opioid peptides include the recently discovered endomorphins and those encoded by three known genes--pro-opiomelanocortin, pro-enkephalin, and pro-dynorphin. They bind to three types of receptors--mu, delta, and kappa. Each of the receptor types is further divided into multiple subtypes. These receptors are widely known to be coupled to G-proteins of the Gi and Go subtypes, but an increasing body of results suggests coupling to other G-proteins, such as Gs. The coupling of opiate receptors to Gs, in particular, has implications for tolerance and dependence. Alterations at the receptor and transduction level have been the focus of many studies of opiate tolerance and dependence. In these studies, both receptor down-regulation and desensitization have been demonstrated in vivo and in vitro. Receptor down-regulation has been more easily observed in vitro, especially in response to morphine, a phenomenon which suggests that some factor which is missing in vitro prevents receptors from down-regulating in vivo and may play a critical role in tolerance and dependence. We suggest that antiopiate peptides may operate in vivo in this capacity, and we outline the evidence for the antiopiate properties of three peptides: neuropeptide FF, orphanin FQ/nociceptin, and Tyr-W-MIF-1. In addition, we provide new results suggesting that Tyr-W-MIF-1 may act as an antiopiate at the cellular level by inhibiting basal G-protein activation, in contrast to the activation of G-proteins by opiate agonists.

Drug Tolerance↗
PubMed1998

Molecular evolution of dengue type 2 virus in Thailand.

Dengue is a mosquito-borne viral infection that in recent years has become a major international public health concern. Dengue hemorrhagic fever (DHF), first recognized in Southeast Asia in the 1950s, is today a leading cause of childhood death in many countries. The pathogenesis of this illness is poorly understood, mainly because there are no laboratory or animal models of disease. We have studied the genetic relationships of dengue viruses of serotype 2, one of four antigenically distinct dengue virus groups, to determine if viruses obtained from cases of less severe dengue fever (DF) have distinct evolutionary origins from those obtained from DHF cases. A very large number (73) of virus samples from patients with DF or DHF in two locations in Thailand (Bangkok and Kamphaeng Phet) were compared by sequence analysis of 240 nucleotides from the envelope/nonstructural protein 1 (E/NS1) gene junction of the viral genome. Phylogenetic trees generated with these data have been shown to reflect long-term evolutionary relationships among strains. The results suggest that 1) many different virus variants may circulate simultaneously in Thailand, thus reflecting the quasispecies nature of these RNA viruses, in spite of population immunity; 2) viruses belonging to two previously distinct genotypic groups have been isolated from both DF and DHF cases, supporting the view that they arose from a common progenitor and share the potential to cause severe disease; and 3) viruses associated with the potential to cause DHF segregate into what is now one, large genotypic group and they have evolved independently in Southeast Asia for some time.

Dengue↗
PubMed1998

Tyr-W-MIF-1 attenuates down-regulation of opiate receptors in SH-SY5Y human neuroblastoma cells.

Down-regulation of opiate receptors is demonstrated more easily in vitro than in vivo. The possible role of endogenous opiate-modulating peptides in preventing such down-regulation was investigated by addition of Tyr-W-MIF-1 to an in vitro preparation, the human neuroblastoma cell line SH-SY5Y, in which down-regulation of opiate receptors has been demonstrated previously. Although both morphine and Met-enkephalin down-regulated mu and delta receptors after chronic (24 h) exposure in serum-free medium, Tyr-W-MIF-1, at doses of up to 100 microM, did not affect receptor number when administered alone. This lack of effect could not be attributed to degradation of the peptide during chronic treatment because high-performance liquid chromatography showed that 79% of the peptide remained intact after a 24-h incubation. When coadministered with 3 microM morphine, Tyr-W-MIF-1 dose-dependently attenuated morphine-induced down-regulation of both mu and delta receptors. Down-regulation of mu receptors by the selective agonist PL017 was also attenuated by Tyr-W-MIF-1, but down-regulation of delta receptors by the selective agonist DPDPE was not. These studies indicate that endogenous opiate modulators may play a role in opiate tolerance at the level of receptor down-regulation.

Culture Media↗
PubMed1997

Origins of dengue type 2 viruses associated with increased pathogenicity in the Americas.

The recent emergence and spread of dengue hemorrhagic fever in the Americas have been a major source of concern. Efforts to control this disease are dependent on understanding the pathogenicity of dengue viruses and their transmission dynamics. Pathogenicity studies have been hampered by the lack of in vitro or in vivo models of severe dengue disease. Alternatively, molecular epidemiologic studies which associate certain dengue virus genetic types with severe dengue outbreaks may point to strains with increased pathogenicity. The comparison of nucleotide sequences (240 bp) from the E/NS1 gene region of the dengue virus genome has been shown to reflect evolutionary relationships and geographic origins of dengue virus strains. This approach was used to demonstrate an association between the introduction of two distinct genotypes of dengue type 2 virus and the appearance of dengue hemorrhagic fever in the Americas. Phylogenetic analyses suggest that these genotypes originated in Southeast Asia and that they displaced the native, American genotype in at least four countries. Vaccination and other control efforts should therefore be directed at decreasing the transmission of these "virulent" genotypes.

Base Sequence↗
PubMed1997

Cross-correlation analysis of motor unit activity recorded from two separate thumb muscles during development in man.

1. Multi-unit surface EMG signals were recorded from the short and long thumb abductor muscles of seventy-five children aged from 4 to 15 years and from nine adults during simultaneous abduction and extension of the left and right thumb. Ability to perform independent finger movements was investigated by timing a series of sequential finger-to-thumb oppositions. 2. Cross-correlograms were constructed from the discharges of motor units recorded from the long and short abductor muscles acting on the same thumb. In the majority of subjects, short duration central peaks were present indicating the presence of a common drive to the motoneurone pools innervating these two muscles. Except for those subjects aged 4 and 5 years, the size of these central correlogram peaks did not differ significantly between the dominant and non-dominant hands. 3. The prevalence of central cross-correlogram peaks in different subjects increased from the age of 4 years to 15 years. The size of the central cross-correlogram peak increased with age up to 10 years but did not alter significantly after this age. The duration of the central peak steadily decreased over the age range of 4 to 15 years. 4. Multilinear regression analysis of data recorded from children revealed that there was a positive, but weak, correlation between the size of the cross-correlogram peak and the rate of performance of sequential finger movements after having controlled for age.

Adult↗
PubMed1997

Mirror movements in X-linked Kallmann's syndrome. I. A neurophysiological study.

Possible mechanisms underlying the pathological mirror movements that are seen in the majority of patients with X-linked Kallmann's syndrome have been investigated using neurophysiological techniques. An EMG was recorded from the first dorsal interosseous muscle (1DI) during voluntary self-paced abduction of one indexed finger; EMG activity could also be recorded simultaneously from the contralateral 1DI. There was no significant difference between the time of onset of the bursts of voluntary and involuntary mirroring EMG. Focal magnetic stimulation of the hand area of the motor cortex revealed the presence of fast conducting bilateral corticospinal projections from each motor cortex in all subjects. However, both inter- and intra-subject differences exist when considering the ratio of ipsilaterally to contralaterally projecting axons. Cross-correlation analysis of multi-unit EMGs recorded during simultaneous voluntary sustained activation of homologous left and right pairs of distal upper limb muscles was performed. A short duration central peak was seen in the cross-correlograms indicating the presence of a common drive to left and right homologous motor neuron pools. This common drive may result from the synchronous activation of intermingled ipsilaterally and contralaterally projecting corticospinal neurons in the motor cortex. Cutaneomuscular reflexes were recorded from the 1DI following stimulation of the digital nerves of the index finger. Typically each reflex comprises spinal and longer latency trans-cortical components. In these subjects, the long latency components of the reflex response could, in addition, be recorded from the 1DI of the non-stimulated side. We conclude that these subject have a novel ipsilateral at least in part, for the pathological mirroring.

Adolescent↗
PubMed1997

Mirror movements in X-linked Kallmann's syndrome. II. A PET study.

To investigate the mechanism of mirror movements seen in X-linked Kallmann's syndrome, we measured changes of regional cerebral blood flow with H2 15O-PET. We studied six right-handed Kallmann male subjects and six matched, right-handed control subjects during an externally paced finger opposition task. The analyses were done both on a single subject and a group basis. The Kallmann group showed a strong primary motor cortex (M1) activation contralateral to the voluntarily moved hand, but there was also a significant degree of M1 activation ipsilateral to the voluntarily moved hand, i.e. contralateral to the mirroring hand. However, when comparing contralateral to ipsilateral M1 activation, the M1 activation contralateral to the voluntarily moved hand was significantly stronger. In the controls, significant increases in rCBF were seen in the contralateral M1 during voluntary movement of either hand; a small ipsilateral M1 activation was found in two out of six normal subjects when they moved their left hand. In a second experiment it was shown that, in two out of two Kallmann subjects, passive movements of the right hand resulted in left M1 activation that was similar to the activation in the left M1 when subjects made mirror movements with their right hand. This suggests, but does not prove, that the small but significant activation of the ipsilateral M1 in Kallmann's subjects may be due to sensory feedback from the involuntarily mirroring hand.

Adolescent↗
PubMed1996

A comparison of the effects of frontal cortical and thalamic lesions on measures of spatial learning and memory in the rat.

Two experiments were conducted to compare the effects of radiofrequency lesions of thalamus and frontal cortex on three measures of spatial learning and memory: delayed non-matching to sample (DNMTS), radial arm maze with imposed delays, and serial reversal learning. Thalamic lesions were aimed at the lateral internal medullary lamina (L-IML) and cortical lesions at the projection areas of the mediodorsal nucleus along the medial wall (MW) and dorsal to the rhinal sulcus (RS) in frontal cortex. In Experiment 1 rats were trained on DNMTS prior to surgery. After recovery, rats with MW lesions showed persistent deficits on DNMTS that were significantly greater than for RS lesions. The deficits observed in MW lesioned animals were comparable to the effects of L-IML lesions on this task that have been described in previous studies. In Experiment 2 animals were trained to perform the radial arm maze task prior to treatment. After recovery, animals with L-IML lesions were impaired on the radial arm maze and on subsequent acquisition of the serial reversal task. Rats with RS and MW lesions showed transient impairments on the radial arm maze task, but otherwise performed as well as controls on both these tasks.

Animals↗
PubMed1995

Cutaneomuscular reflexes recorded from the lower limb in man during different tasks.

1. Cutaneomuscular reflexes have been recorded in ten adult subjects from extensor digitorum brevis (EDB), tibialis anterior (TA), soleus (Sol), quadriceps femoris (Quad) and erector spinae (ES) following electrical stimulation of the digital nerves of the second toe. 2. Recordings were made while subjects were instructed to activate voluntarily the relevant muscles and also when these muscles were active posturally. 3. Reflex responses could comprise three components: an initial increase in EMG (E1), followed by a decrease (I1), followed by a second increase (E2). E1 and I1 were confined to muscles acting at the ankle and in the foot. E2 was most pronounced in EDB but also found in TA, Sol, Quad (1 subject) and ES. No responses were recorded contralateral to the stimulus. 4. E2 was significantly larger when the reflex was recorded during voluntary contraction of the muscle, rather than when the muscle was active posturally. 5. E1 and I1 components are mediated via spinal pathways. E2 requires the integrity of the dorsal columns, sensorimotor cortex and corticospinal tract (Jenner & Stephens, 1982; Rowlandson & Stephens, 1985b). The present study suggests that one or more of these supraspinal pathways is more active during voluntary contraction of lower limb muscles than when these muscles are active posturally.

Adult↗
PubMed1995

Organization of inputs to motoneurone pools in man.

1. Surface EMGs were recorded from pairs of muscles involved in movements of the wrist and/or digits in the upper limb and from pairs of intrinsic foot muscles in the lower limb during voluntary isometric contractions. 2. EMGs were also recorded from lower limb and trunk muscles during three different tasks: lying, standing and balancing. 3. To investigate if the co-contraction of muscles was due to the presence of a common drive to each of the two motoneurone pools, cross-correlation analysis of the two multiunit EMG signals was used. 4. Evidence for a common drive was seen between pairs of muscles that share a common joint or joint complex (such as the metacarpophalangeal joints); no evidence was found for a common drive to co-contracting muscles that did not share a common joint. 5. When considering analogous hand and foot muscle pairs, the degree of synchrony was significantly greater for lower limb pairs. 6. Where a common drive was detected with lower limb muscle pairs, the degree of synchrony was significantly larger during balancing than during either lying or standing. 7. The origin of the common drive is discussed. It is concluded that activity in both last-order branched presynaptic fibers and presynaptic synchronization is involved.

Adult↗
PubMed1994

Evidence for bilateral innervation of certain homologous motoneurone pools in man.

1. Surface EMG recordings were made from left and right homologous muscle pairs in healthy adults. During each recording session subjects were requested to maintain a weak isometric contraction of both the left and right muscle. 2. Cross-correlation analysis of the two multiunit EMG recordings from each pair of muscles was performed. Central peaks of short duration (mean durations, 11.3-13.0 ms) were seen in correlograms constructed from multiunit EMG recordings obtained from left and right diaphragm, rectus abdominis and masseter muscles. No central peaks were seen in correlograms constructed from the multiunit EMG recordings from left and right upper limb muscles. 3. To investigate descending pathways to the homologous muscle pairs, the dominant motor cortex was stimulated using a focal magnetic brain stimulator whilst recording from homologous muscle pairs. 4. Following magnetic stimulation of the dominant motor cortex, a response was recorded from both right and left diaphragm, rectus abdominis and masseter muscles. In contrast, when recording from homologous upper limb muscles, a response was only seen contralateral to the side of stimulation. 5. The finding of short duration central peaks in the cross-correlograms constructed from multiunit recordings from left and right diaphragm, rectus abdominis and masseter, suggests that muscles such as these, that are normally co-activated, share a common drive. The mechanism is discussed and it is argued that the time course of the central correlogram peaks is consistent with the hypothesis that they could be produced by a common drive that arises from activity in last-order branched presynaptic fibres although presynaptic synchronization of last-order inputs is also likely to be involved. 6. The results of the magnetic stimulation experiments suggest that this common drive may involve the corticospinal tract. 7. We saw no evidence for a common drive to left and right homologous muscle pairs that may be voluntarily co-activated but often act independently.

Abdominal Muscles↗