Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diagnosis of Parkinsonism is made in two steps: 1. identification of the Parkinson syndrome, a combination of rest tremor, hypertonia, akinesia and postural disturbances; 2. then essentially on the basis of clinical observations, relation to Parkinson's disease. The main risks during the course with L-dopa treatment are, on the one hand, the appearance of akinetic changes and movement disorders, more common in the younger affected patients, and on the other hand, disorders that do not respond to L-dopa, especially postural and cognitive, that are favoured by old age. Anxiety, depression pain, autonomic disorders and insomnia increase the repercussions of the disease and complicate its management.
 ...
PMID:[Diagnosis and course (under treatment) of Parkinson disease]. 920 68

Recent evidence has questioned the view that the increased muscle tone of Parkinson's disease results solely from reduced release of dopamine in the striatum, by emphasising the important role of the substantia nigra. The aim of the current study was to compare the effects on muscle tone of inactivating D1 and D2 dopamine receptors throughout the brain with those seen following their inactivation only in the substantia nigra. Inactivation of dopamine receptors by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline injected either intraperitoneally, or bilaterally into the substantia nigra, resulted in similar increases in muscle tone, measured as changes in tonic electromyographic (EMG) activity. The magnitude and onset of EMG increases was related to the level of dopamine receptor inactivation. The results are consistent with the hypothesis that nigral dopamine mechanisms play a key role in the maintenance of muscle tone.
 ...
PMID:The effects of an irreversible dopamine receptor antagonist, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), on the regulation of muscle tone in the rat: the role of the substantia nigra. 971 78

The purpose of this study was to quantify response variations during isokinetic passive movements of the knee in subjects with Parkinson's disease. Parkinsonian patients demonstrated a greater decrease of resistive torque compared to healthy control subjects, particularly in tests at higher velocities and during knee flexion movements. Responses were influenced by electromyographic activity in stretched and shortened muscle groups and also by mechanical factors. The results indicate that repetition of movements needs to be taken into account when measuring hypertonia in parkinsonian subjects.
 ...
PMID:Torque variations during repeated passive isokinetic movements of the knee in subjects with Parkinson's disease and healthy control subjects. 1069 89

Parkinson's disease related to degeneration of the extrapyramidal structures is characterized in its typical form by the classic triad of tremors, rigidity and akinesia, constituting Parkinson's syndrome. These are combined with neurovegetative disorders, responsible for sexual and bladder sphincter dysfunction. The Latter occurs in from 30% to 90% of cases, depending on the stage of progression of the disease. The dopamine deficiency in the nigrostriataL tract leads to a lifting of the inhibition which is probably the cause of the bladder hyperreflexia. Irritative signs are most frequently observed. The flowmetry data are contradictory, depending on the publication whereas the bladder overactivity, objectified by cystomanometry, is described in most of the studies although certain authors report, on the contrary, bladder hypoactivity. Conflicting data have also been published on bladder sphincter dyssynergia although in most studies, micturition was described as synergic in Parkinson's disease patients. L-dopa, the main drug for Parkinson's disease, has, according to the publication, either no action, or contradictory effects with bladder hypoactivity or hyperactivity. Anticholinergics are effective on overactive bladder, the alphablockers on the urethral hypertonia at the price of a higher risk of arterial hypotension in this diathesis. The indication for prostatic surgery must be carefully considered and preceded by precise clinical, urodynamic and sometimes electromyography evaluation. There is a high risk of post surgical incontinence. Endourethral prostheses provide an attractive alternative in the case of prostatic obstruction.
 ...
PMID:[Bladder sphincter disorders in Parkinson's disease]. 1565 93

The chronic treatment of Parkinson's disease with L-dopa is often associated with fluctuations of motor response and dyskinesias. Therefore, to overcome the adverse effects of the long-term use of L-dopa, directly acting dopamine receptor agonists have been introduced. However, L-dopa remains the most effective treatment of the slowness of movement, increased muscle tone, and tremor that are typical of Parkinson's disease. Why is this so? In this article, we discuss evidence that suggests that dopamine produced from L-dopa has a larger number of actions compared with dopamine receptor agonists. In addition to stimulating D1- and D2-like dopamine receptors, dopamine might also activate adrenoceptors, novel dopamine sites, the dopamine transporter and trace amine receptors, all of which might contribute to the superior effect of L-dopa in Parkinson's disease.
 ...
PMID:The 'magic' of L-dopa: why is it the gold standard Parkinson's disease therapy? 1593 32

Hypertonia, which results from motor pathway defects in the central nervous system (CNS), is observed in numerous neurological conditions, including cerebral palsy, stroke, spinal cord injury, stiff-person syndrome, spastic paraplegia, dystonia and Parkinson disease. Mice with mutation in the hypertonic (hyrt) gene exhibit severe hypertonia as their primary symptom. Here we show that hyrt mutant mice have much lower levels of gamma-aminobutyric acid type A (GABA(A)) receptors in their CNS, particularly the lower motor neurons, than do wild-type mice, indicating that the hypertonicity of the mutants is likely to be caused by deficits in GABA-mediated motor neuron inhibition. We cloned the responsible gene, trafficking protein, kinesin binding 1 (Trak1), and showed that its protein product interacts with GABA(A) receptors. Our data implicate Trak1 as a crucial regulator of GABA(A) receptor homeostasis and underscore the importance of hyrt mice as a model for studying the molecular etiology of hypertonia associated with human neurological diseases.
 ...
PMID:Trak1 mutation disrupts GABA(A) receptor homeostasis in hypertonic mice. 1638 Jul 13

Postural abnormalities and increased muscle tone in Parkinson's disease (PD) may cause back pain. In this controlled study, we analyzed features of back pain in PD patients. The prevalence of back pain was 74% in PD patients (n = 101) when compared with 27% in control patients (n = 132; P < 0.0001, fisher's exact test), but did not correlate with disease severity or duration. The mean back pain intensity (visual analog scale of 0-10) was 4.3 for PD patients, and 1.3 for controls. Both radicular and nonradicular types of back pain were more frequent, and back pain caused more impairment in PD patients. However, it is noteworthy that the PD patients in our study did not receive more pain medication than control patients. This suggests that back pain in PD patients is often neglected and insufficiently treated. Our results argue for the routine evaluation of back pain in every patient suffering from PD.
 ...
PMID:Radicular and nonradicular back pain in Parkinson's disease: a controlled study. 1735 31

The most hazardous manganese exposures occur in mining and smelting of ore. Recently, the poisoning has been frequently reported to be associated with welding. In occupational exposure, manganese is absorbed mainly by inhalation. Manganese preferentially accumulates in tissues rich in mitochondria. It also penetrates the blood brain barrior and accumulate in the basal ganglia, especially the globus pallidus, but also the striatum. Manganese poisoning is clinically characterized by the central nervous system involvement including psychiatric symptomes, extrapyramidal signs, and less frequently other neurological manifestations, Psychiatric symptomes are well described in the manganese miners and incrude sleep disturbance, disorientation, emotional lability, compulsive acts, hallucinations, illusions, and delusions. The main characteristic manifestations usually begin shortly after the appearance of these psychiatric symptomes. The latter neurological signs are progressive bradykinesia, dystonia, and disturbance of gait. Bradykinesia is one of the most important findings. There is a remarkable slowing of both active and passive movements of the extremities. Micrographia is frequently observed and a characteristic finding. The patients may show some symmetrical tremor, which usually not so marked. The dystonic posture of the limbs is often accompanied by painfull cramps. This attitudal hypertonia has a tenndency to decrease or disappear in the supine position and to increase in orthostation. Cog-wheel rigidity is also elisited on the passive movement of all extremities. Gait disturbance is also characteristic in this poisoning. In the severe cases, cook gait has been reported. The patient uses small steps, but has a tendency to elevate the heels and to rotate them outward. He progress without pressing on the flat of his feet, but only upon the metatarsophalangeal articulations, mainly of the fourth and fifth toes. Increased signal in T1-weighted image in the basal ganglia has been reported in patients with the poisoning. Thus, increasd signal intensities as a target site dose can be a more useful biomakers of the manganese than other biological indicies such as ambient manganese concentration or blood manganese concentration on individual basis. Manganese poisoning ultimately becomes chronic. However, if the disease is diagnosed while still at the early stages and the patient is removed from exposure, the course may be reversed. Once well established, it becomes progressive and irreversible, even when exposure is terminated. Levodopa therapy is not effective for the management of manganese poisoning. Levodopa unresponsiveness may be usefull to distinguish manganese-induced parkinsonism from Parkinson disease.
 ...
PMID:[Occupational neurotoxicology due to heavy metals-especially manganese poisoning]. 1758 89

A cardinal feature of Parkinson's disease (PD) is muscle hypertonicity, i.e. rigidity. Little is known about the axial tone in PD or the relation of hypertonia to functional impairment. We quantified axial rigidity to assess its relation to motor symptoms as measured by UPDRS and determine whether rigidity is affected by levodopa treatment. Axial rigidity was measured in 12 PD and 14 age-matched controls by directly measuring torsional resistance of the longitudinal axis to twisting (+/-10 degrees ). Feet were rotated relative to fixed hips (Hip Tone) or feet and hips were rotated relative to fixed shoulders (Trunk Tone). To assess tonic activity only, low constant velocity rotation (1 degrees /s) and low acceleration (<12 degrees /s(2)) were used to avoid eliciting phasic sensorimotor responses. Subjects stood during testing without changing body orientation relative to gravity. Body parts fixed against rotation could translate laterally within the boundaries of normal postural sway, but could not rotate. PD OFF-medication had higher axial rigidity (p<0.05) in hips (5.07 N m) and trunk (5.30 N m) than controls (3.51 N m and 4.46 N m, respectively), which did not change with levodopa (p>0.10). Hip-to-trunk torque ratio was greater in PD than controls (p<0.05) and unchanged by levodopa (p=0.28). UPDRS scores were significantly correlated with hip rigidity for PD OFF-medication (r values=0.73, p<0.05). Torsional resistance to clockwise versus counter-clockwise axial rotation was more asymmetrical in PD than controls (p<0.05), however, there was no correspondence between direction of axial asymmetry and side of disease onset. In conclusion, these findings concerning hypertonicity may underlie functional impairments of posture and locomotion in PD. The absence of a levodopa effect on axial tone suggests that axial and appendicular tones are controlled by separate neural circuits.
 ...
PMID:Axial hypertonicity in Parkinson's disease: direct measurements of trunk and hip torque. 1769 15

Hypertonia, which is characterized by stiff gait, abnormal posture, jerky movements, and tremor, is associated with a number of neurological disorders, including cerebral palsy, dystonia, Parkinson's disease, stroke, and spinal cord injury. Recently, a spontaneous mutation in the gene encoding trafficking protein, kinesin-binding 1 (Trak1), was identified as the genetic defect that causes hypertonia in mice. The subcellular localization and biological function of Trak1 remain unclear. Here we report that Trak1 interacts with hepatocyte-growth-factor-regulated tyrosine kinase substrate (Hrs), an essential component of the endosomal sorting and trafficking machinery. Double-label immunofluorescence confocal studies show that the endogenous Trak1 protein partially colocalizes with Hrs on early endosomes. Like Hrs, both overexpression and small-interfering-RNA-mediated knockdown of Trak1 inhibit degradation of internalized epidermal growth factor receptors through a block in endosome-to-lysosome trafficking. Our findings support a role for Trak1 in the regulation of Hrs-mediated endosomal sorting and have important implications for understanding hypertonia associated with neurological disorders.
 ...
PMID:Hypertonia-associated protein Trak1 is a novel regulator of endosome-to-lysosome trafficking. 1867 23


<< Previous 1 2 3 4 Next >>