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PubMed2004

A novel Tctex2-related light chain is required for stability of inner dynein arm I1 and motor function in the Chlamydomonas flagellum.

Tctex1 and Tctex2 were originally described in mice as putative distorters/sterility factors involved in the non-Mendelian transmission of t haplotypes. Subsequently, these proteins were found to be light chains of both cytoplasmic and axonemal dyneins. We have now identified a novel Tctex2-related protein (Tctex2b) within the Chlamydomonas flagellum. Tctex2b copurifies with inner arm I1 after both sucrose gradient centrifugation and anion exchange chromatography. Unlike the Tctex2 homologue within the outer dynein arm, analysis of a Tctex2b-null strain indicates that this protein is not essential for assembly of inner arm I1. However, a lack of Tctex2b results in an unstable dynein particle that disassembles after high salt extraction from the axoneme. Cells lacking Tctex2b swim more slowly than wild type and exhibit a reduced flagellar beat frequency. Furthermore, using a microtubule sliding assay we observed that dynein motor function is reduced in vitro. These data indicate that Tctex2b is required for the stability of inner dynein arm I1 and wild-type axonemal dynein function.

Amino Acid Sequence↗

PubMed2002

p53 inhibitors preserve dopamine neurons and motor function in experimental parkinsonism.

Drugs currently used for patients with Parkinson's disease provide temporary relief of symptoms but do not halt or slow the underlying neurodegenerative disease process. Increasing evidence suggests that neurons die in Parkinson's disease by a process called apoptosis, which may be triggered by mitochondrial impairment and oxidative stress. We report that two novel synthetic inhibitors of the tumor suppressor protein p53, pifithrin-alpha (PFT-alpha) and Z-1-117, are highly effective in protecting midbrain dopaminergic neurons and improving behavioral outcome in a mouse model of Parkinson's disease. Mice given intraperitoneal injections of PFT-alpha or Z-1-117 exhibited improved motor function, reduced damage to nigrostriatal dopaminergic neurons and reduced depletion of dopamine and its metabolites after exposure to the toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP caused an increase in the level of the proapoptotic protein Bax, which was prevented by giving mice PFT-alpha and Z-1-117. PFT-alpha and Z-1-117 also suppressed Bax production and apoptosis in cultured dopaminergic cells exposed to MPP(+). Our findings demonstrate a pivotal role for p53 in experimental parkinsonism and identify a novel class of synthetic p53 inhibitors with clinical potential.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2002

Modification of a functional motor task by non-consciously perceived sensory stimuli.

In recent years it has been suggested that processing of visual information is divided between a ventral stream, responsible for object recognition and conscious processing of object properties, and a dorsal stream mediating automatic integration of visual information into a motor task. We used metacontrast masking to prevent conscious perception of visual cues concerning the load of an object to be lifted in a precision grip. It was found that when such non-consciously perceived cues warned of a load change, they allowed the subjects to produce the grip force profile appropriate to the new load. It is concluded that non-consciously perceived visual information can be utilised to adapt a functional motor task to actual conditions.

Adult↗

PubMed1996

The inhibitory effect of substance P on gastric motor function in the nucleus raphe obscurus is mediated via nitric oxide in the dorsal vagal complex.

We have previously shown that substance P (SP), microinjected into the caudal nucleus raphe obscurus (nROb) of the rat decreases intragastric pressure via a vagally mediated pathway. Recent studies from this laboratory demonstrated that nitric oxide (NO) synthase is present in the dorsal vagal complex (DVC) and NO synthase blockade in the DVC of the rat with NG-nitro-L-arginine methyl ester (L-NAME) evokes increases in intragastric pressure. Since the nROb controls gastric vagal outflow through the DVC, we tested the hypothesis that NO in the DVC is a mediator of inhibitory effects of SP on gastric motor function in the nROb. Substance P (135 pmol) was microinjected into the nROb 3-6 min after bilateral microinjections of L-NAME (45 nmol per site) into the DVC of chloralose-anesthetized rats were started. Changes in the area of the response for intragastric pressure on microinjection of SP after L-NAME did not differ from the effect of vehicle microinjected after L-NAME and were significantly lower when compared with the effect of SP microinjected after vehicle. We conclude that SP in the nROb release NO in the DVC to mediate the inhibitory effect on intragastric pressure.

Animals↗

PubMed1997

Motor function, olfactory threshold, and hematological indices in manganese-exposed ferroalloy workers.

A cross-sectional study was conducted in 35 male subjects randomly selected from workers of a ferroalloy production plant and exposed to manganese (Mn) oxides; the objective was to detect early signs of neurologic impairment. The subjects' mean age was 39.4 years (SD, 8. 4); the average exposure duration was 14.5 years (range, 5-29 years). A control group of industrial workers not exposed to neurotoxic chemicals and comparable in age and confounding factors was recruited. The intensity of Mn exposure was moderate, as reflected by airborne Mn concentrations in total dust averaging 193 [corrected] micro g/m3. Mn levels in blood (MnB) and urine (MnU) were significantly higher in the Mn-exposed workers than in control workers. A relationship (not found with MnU) was found between MnB and a cumulative exposure index calculated on the basis of air concentration and exposure history for each subject (r = 0.52; r2 = 0.27; P = 0.002). Psychomotor function scores were lower among Mn-exposed subjects. The Aiming score was negatively correlated with MnB in the exposed group. The olfactory threshold did not differ between the two groups, although it was negatively associated with MnU in the exposed group. The white blood cell count results were significantly higher in Mn-exposed subjects than in controls. These findings show that an increase in Mn body burden is associated with an impairment of motor functions, whereas the increased excretion of Mn is related to an increased olfactory perception. Changes in numbers of leukocytes could indicate possible interferences of Mn with the immunological system.

Air Pollutants, Occupational↗

PubMed2004

The effects of the delta-opioid agonist SNC80 on hind-limb motor function and neuronal injury after spinal cord ischemia in rats.

Recent investigation suggested neuroprotective efficacy of a delta-opioid agonist in the brain. We investigated the effects of intrathecal treatment with a delta-opioid agonist (SNC80) on spinal cord ischemia (SCI) in rats. SCI was induced with an intraaortic balloon catheter. The animals were randomly allocated to one of the following five groups: 1) SNC80 before 9 min of SCI (SNC-9; n = 12), 2) vehicle before 9 min of SCI (V-9; n = 12), 3) SNC80 before 11 min of SCI (SNC-11; n = 10), 4) vehicle before 11 min of SCI (V-11; n = 12), or 5) sham (n = 12). SNC80 (400 nmol) or vehicle was administered 15 min before SCI. Forty-eight hours after reperfusion, hind-limb motor function was assessed by using the Basso, Beattie, Bresnahan (BBB) scale (0 = paraplegia; 21 = normal) and histological assessment of the L4 and L5 spinal segments was performed. BBB scores in the SNC-9 group were higher compared with those in the V-9 group (P < 0.05), whereas there were no differences in BBB scores between the SNC-11 and V-11 groups. There were significantly more normal neurons in the SNC-9 and SNC-11 groups than in the V-9 and V-11 groups (P < 0.05). The results indicate that intrathecal treatment with the delta-opioid agonist SNC80 can attenuate hind-limb motor dysfunction and neuronal injury after SCI in rats.

Animals↗

PubMed2006

Sensory-motor function of human periodontal mechanoreceptors.

Natural teeth are equipped with periodontal mechanoreceptors that signal information about tooth loads. In the present review, the basic force-encoding properties of human periodontal receptors will be presented along with a discussion about their likely functional role in the control of human mastication. Microneurographic recordings from single nerve fibres reveal that human periodontal receptors adapt slowly to maintained tooth loads. Most receptors are broadly tuned to the direction of force application, and about half respond to forces applied to more than one tooth. Populations of periodontal receptors, nevertheless, reliably encode information about both the teeth stimulated, and the direction of forces applied to the individual teeth. Information about the magnitude of tooth loads is made available in the mean firing rate response of periodontal receptors. Most receptors exhibit a markedly curved relationship between discharge rate and force amplitude, featuring the highest sensitivity to changes in tooth load at very low force levels (below 1 N for anterior teeth and 4 N for posterior teeth). Thus, periodontal receptors efficiently encode tooth load when subjects contact and gently manipulate food using the teeth. It is demonstrated that signals from periodontal receptors are used in the fine motor control of the jaw and it is clear from studies of various patient groups (e.g. patients with dental implants) that important sensory-motor functions are lost or impaired when these receptors are removed during the extraction of teeth.

Adaptation, Physiological↗

PubMed1996

Progressive deterioration of intellect and motor function occurring several decades after cranial irradiation. A new facet in the clinical spectrum of radiation encephalopathy.

OBJECTIVE: To report the cases of 2 patients who developed the features of radiation encephalopathy 33 and 28 years after cranial irradiation. DESIGN: Case reports; clinical data were available for 2 years in each instance. CONCLUSION: Latent intervals approaching 2 decades have been reported in cases of radiation necrosis following cranial irradiation, but a similar or greater delay before the onset of radiation encephalopathy has not been described previously. This report indicates that a diagnosis of radiation encephalopathy must be considered when any individual who has received cranial irradiation presents with deterioration in intellectual or motor function, whatever the interval.

Adult↗

PubMed1998

Hemolink-induced effects on intestinal motor function and attenuation of these effects by selected agents.

Hemolink, an oxidized, ring-opened raffinose-crosslinked hemoglobin-based oxygen carrier produced by Hemosol Inc., stimulates esophageal peristalsis, possibly by interference with neural NO-mediated effects. The effects of Hemolink on jejunal tone and contractions, arterial pressure and heart rate were measured in anesthetized rats, and the effect of selected agents in attenuating or reversing these effects was studied. Infusion of L-NAME was used to validate the study model; it caused an immediate increase in tone and initiated phasic contractions indicating that the model was responsive to NO-mediated effects. Hemolink administration caused effects on intestinal motor function similar to those caused by L-NAME, including increases in basal tone and contraction amplitude. Rat whole blood caused none of these changes. The Hemolink-induced effects were less immediate in some animals compared to those observed after L-NAME. As well there was greater inter-animal variability on the effects. Hemolink administration also caused a mild increase in arterial blood pressure and a reciprocal decrease in heart rate in some animals. Co-administration of morphine, a common analgesic that has been reported to influence the motility of the GI tract; L-arginine, a substrate for NO synthesis; and glycopyrrolate, an anti-cholinergic agent, did not significantly modulate the Hemolink effects, whereas nitroglycerin, an NO donor; and nifedipine, a slow calcium-channel blocker, attenuated or reversed these effects.

Analgesics, Opioid↗

PubMed1990

Electroencephalographic and magnetoencephalographic studies of motor function.

Although a great deal has been learned from the study of scalp-recorded movement-related potentials, the exact origin of the various components described above remains unclear, mainly because of the limited spatial resolution of the EEG and the consequent difficulty in predicting sources from the surface distribution of these components. The introduction of the MEG and source localization methods based on neuromagnetic recordings has provided a new means by which to study the cortical activation during movement in humans. The study of movement-related magnetic fields of the brain is still at an early stage of development. However, the data reviewed to date indicate that the MEG offers a promising means by which to study (noninvasively) cortical motor function. With regard to the data reviewed here, the following conclusions can be made: 1. Slow "readiness" magnetic fields can be recorded prior to a variety of voluntary movements and display a topography which indicates the activation of bilateral sources, even if the instructed movement is unilateral. Sources in the contralateral hemisphere appear as early as 0.5 sec before the movement and appear to be localized in the sensorimotor cortex. Consequently, the assumption of a contralateral source being the only or primary generator of the readiness potential, based on EEG data, must be tempered. 2. A large-amplitude "movement-evoked field" (occurring at a post-EMG-onset latency of about 110 msec for finger movements) is probably the counterpart of the MP and appears to be the result of a dipolar source localized to the contralateral sensorimotor area. This source is probably the first sign of movement reafferent input to cortex. 3. Variability in the movement-evoked field across individuals, which are much more evident in MEG than in EEG, may reflect the summation of multiple sources active in the region of the sensorimotor cortex during movement onset (i.e., both pre- and postcentral generators). In some instances, it may be possible to extract simpler elements of these complex sources based on assumptions of temporal overlapping of pre-movement and movement-evoked activity.

Brain Mapping↗

PubMed1986

Early effects of bethanechol on the esophageal motor function of infants with gastroesophageal reflux.

Lower esophageal sphincter (LES) pressure, as well as esophageal peristaltic amplitude, duration, and velocity were measured in 16 infants with gastroesophageal reflux before administration of subcutaneous bethanechol, and at 10, 20, and 30 min after. Seven infants received 0.1 mg/kg, and 9 received 0.2 mg/kg. Significant increases in LES pressure occurred at both doses and lasted for 20 min. The amplitude and duration of peristaltic contractions were increased only after the larger bethanechol dose, and the increases were of greater magnitude in the distal esophagus than in the middle esophagus. The velocity of peristalsis decreased significantly in both the lower and middle esophagus, but only after the larger dose of bethanechol. Bethanechol had no effect on any motor function of the upper third of the esophagus. The changes in esophageal peristalsis produced by bethanechol may improve the efficiency of distal esophageal acid clearance and thus may be responsible in part for the therapeutic effect of bethanechol in infants with gastroesophageal reflux.

Bethanechol↗

PubMed2005

Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor.

OBJECT: Glial cell line-derived neurotrophic factor (GDNF) has demonstrated significant antiparkinsonian actions in several animal models and in a recent pilot study in England in which four of five patients received bilateral putaminal delivery. In the present study the authors report on a 6-month unilateral intraputaminal GDNF infusion in 10 patients with advanced Parkinson disease (PD). METHODS: Patients with PD in a functionally defined on and off state were evaluated 1 week before and 1 and 4 weeks after intraputaminal catheter implantation in the side contralateral to the most affected side. Each patient was placed on a dose-escalation regimen of GDNF: 3, 10, and 30 microg/day at successive 8-week intervals, followed by a 1-month wash-out period. The Unified Parkinson's Disease Rating Scale (UPDRS) total scores in the on and off states significantly improved 34 and 33%, respectively, at 24 weeks compared with baseline scores (95% confidence interval [CI] 18-47% for off scores and 16-51% for on scores). In addition, UPDRS motor scores in both the on and off states significantly improved by 30% at 24 weeks compared with baseline scores (95% CI 15-48% for off scores and 5-61% for on scores). Improvements occurred bilaterally, as measured by balance and gait and increased speed of hand movements. All significant improvements of motor function continued through the wash-out period. The only observed side effects were transient Lhermitte symptoms in two patients. CONCLUSIONS: Analysis of the data in this open-label study demonstrates the safety and potential efficacy of unilateral intraputaminal GDNF infusion. Unilateral administration of the protein resulted in significant, sustained bilateral effects.

Aged↗

PubMed2003

[Dynamics of clinical symptoms, indices of quality of life, and the state of motor function of the esophagus and rectum in patients with functional dyspepsia and irritable bowel syndrome after Helicobacter pylori eradication].

94 patients with irritable bowel syndrome and functional dyspepsia were included in the study. To confirm the diagnosis of H. pylori infection, all patients underwent fibroesophagogastroduodenoscopy with histological and urea tests before and 5 weeks after treatment. Standard eradication was performed. 25 patients underwent intraesophageal and anorectal manometry using the Polygraf device, Sweden. The dynamics of clinical symptoms, life quality (SF-36), manometry data and data of the histological examination of the stomach mucous coat was assessed. 63.5% of patients had clinical improvements following the eradication. The threshold of rectal sensitivity rose in 40% of patients. The esophageal motor function normalized in 48% of patients. An improvement of the morphological picture of chronic gastritis was recorded in 58.7% of patients.

Adult↗

PubMed1997

Tolcapone improves motor function in parkinsonian patients with the "wearing-off" phenomenon: a double-blind, placebo-controlled, multicenter trial.

We studied the new catechol-O-methyltransferase inhibitor tolcapone, 100 and 200 mg, three times daily (tid) in a randomized, double-blind, parallel-group trial involving 202 parkinsonian patients who were experiencing the "wearing-off" phenomenon on levodopa therapy. After 3 months, patients receiving tolcapone had a significant decrease in mean daily levodopa dose requirement compared with placebo-treated patients (p < 0.01). In patients treated with tolcapone 200 mg tid, daily "off" time, measured using patient diaries, was reduced from baseline by 3.25 hours; this reduction was significantly different from that seen in the placebo group (p < 0.01). Moreover, the number of daily levodopa intakes was reduced significantly in each tolcapone group compared with placebo (p < 0.01). We found significant improvements in motor function and overall efficacy in the tolcapone groups (p < 0.01). The most frequent adverse events were associated with levodopa treatment. Dyskinesia developed or worsened in 18% of patients receiving placebo, in 51% receiving tolcapone 100 mg tid, and in 64% receiving 200 mg tid, with most cases occurring within the first 30 days of the study. Diarrhea was the most frequent nondopaminergic event, occurring in 14% on placebo, 13% on tolcapone 100 mg tid, and 19% on 200 mg tid. Overall 18% of patients withdrew because of adverse events: 15% on placebo, 17% on tolcapone 100 mg tid, and 22% on 200 mg tid. We conclude that tolcapone as an adjunct offers promise for the relief of the "wearing-off" phenomenon in levodopa-treated parkinsonian patients.

Aged↗

PubMed2001

D(3) dopamine receptors in rat spinal cord: implications for sensory and motor function.

Quantitative autoradiography was used to determine the distribution of D(3) receptors in rat spinal cord and compare it with the distribution of D(1)-like and D(2) (and D(4)) receptors. [(3)H]PD 128907-labeled D(3) sites were observed in roughly 6-fold lower density than [(3)H]spiperone-labeled D(2) (D(4)) sites and 60-fold lower density than [(3)H]SCH 23390-labeled D(1)-like sites. Highest densities of D(3) binding were observed in the superficial layers of the dorsal horn at cervical and lumbar levels followed by the pars centralis and dorsal horn. Lowest densities of D(3) sites were detected in the ventral horn. These observations suggest that spinal D(3) receptors may play a role in sensory and/or motor function or contribute to the pharmacological effects of dopaminergic drugs.

Animals↗

PubMed1996

The topographic representation of esophageal motor function on the human cerebral cortex.

BACKGROUND & AIMS: Corticofugal pathways to the human esophagus have been recently identified in humans using transcranial magnetic stimulation. The aim of this study was to determine the topographic representation of the esophagus on the cerebral cortex. METHODS: Focal magnetic stimulation of 1-cm areas was performed over both hemispheres in 10 healthy subjects. Esophageal electromyographic responses were recorded 2 cm below the upper esophageal sphincter. The studies were repeated to determine reproducibility in 3 subjects; in 2 subjects, esophageal topography was compared with thenar muscle topography. RESULTS: In all subjects, esophageal electromyographic responses were evoked by stimulation of either the right or left hemisphere. Largest amplitude responses were obtained anterior to those of the thenar muscles, indicating that the esophagus may be represented on either the anterior aspect of the motor cortex or on the premotor cortex. In all subjects, the area of response was asymmetric, being more extensive on the right hemisphere than on the left hemisphere in 8 subjects. In 2 subjects, the area of response on the left hemisphere was more extensive than on the right. Repeat studies showed that this asymmetry was consistent. CONCLUSIONS: Esophageal motor function shows bilateral cortical representation with consistent interhemispheric asymmetry.

Adult↗

PubMed1980

Abnormal gastric motor function in viral gastroenteritis.

Nausea and vomiting occur commonly with gastroenteritis caused by parvovirus-like agents. Infection results in histologic injury to the small bowel mucosa, but the gastric mucosa remains unaffected. We have studied gastric emptying of liquids serially in 10 volunteers before and after ingestion of the parvovirus-like agents, Norwalk and Hawaii viruses. The five subjects who developed illness all showed marked delays in gastric emptying, while the five well subjects had no alteration of emptying. Five addition volunteers who developed Norwalk virus gastroenteritis underwent serial studies of gastric secretion of hydrochloric acid, pepsin, and intrinsic factor. No change was detected in either basal or betazole-stimulated secretion of these three substances during the course of illness. The nausea and vomiting accompanying this type of viral gastroenteritis may result from abnormal gastric motor function.

Adult↗

PubMed1977

Effect of dopamine on esophageal motor function.

Intravenous administration of dopamine produced a dose-dependent decrease in lower esophageal sphincter pressure and a dose dependent increase in contractile activity of the body of the esophagus. The threshold dose of dopamine was 0.25 mug/kg, and the effect reached a plateau at about 6 mug/kg. A dose of 6 mug/kg of dopamine produced 83%+/-3 (SE) reduction in the lower esophageal sphincter pressure and 12+/-1 (SE) contractions in the body of the esophagus within 5 min of the bolus injection. Atropine, phentolamine, propranolol, and bilateral cervical vagotomy did not modify the effect of dopamine. Both haloperidol and bulbocapnine potently antagonized the effect of dopamine. The amplitude of esophageal contraction in the lower esophagus in response to pharyngeal stimulation and esiogageal distention was significantly increased after administration of haloperidol. It is concluded that intravenous administration of dopamine has potent effects on the motor function of the lower esophageal sphincter and the body of the esophagus. The effect of dopamine is not mediated via the vagal centers in the brain or cholinergic muscarinic and adrenergic receptors. The response of the smooth muscle segment of opossum esophagus to intravenous dopamine is mediated via specific dopamine receptors. The inhibitory dopamine receptors may play a physiological role in controlling the amplitude of esophageal contractions.

Animals↗