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)

We recorded cortical frontal, central, and parietal somatosensory evoked potentials (SEPs) in 9 patients with hemiparkinsonism and in a group of 25 healthy volunteers. No differences were observed in the SEPs recorded after stimulation of the asymptomatic and symptomatic sides in the patients. Likewise, comparison with the healthy controls did not reveal significant group differences or abnormal waveforms in the patients. Even frontal N30 deflection, which has been reported to be diminished in Parkinson's disease (PD), was normal and symmetric in the patients. Therefore, no evidence was found for altered sensory input to the motor or premotor and supplementary motor cortices in PD.
 ...
PMID:Pre- and postcentral cortical somatosensory evoked potentials in hemiparkinsonism. 823 52

The association of free radicals and particularly free iron in the pathogenesis of idiopathic Parkinson's disease and MPTP-induced parkinsonism remains controversial. Whereas the actual cause of dopamine cell death in the substantia nigra compacta (SNc) remains unknown, disturbances in lipid peroxidation and subsequent mitochondrial and cell membrane disruption has been demonstrated. In a genetically susceptible host, abnormal elimination of oxygen and trace metal free radicals may further damage dopamine cells. Using a unilaterally MPTP-treated African Green monkey, which showed obvious contralateral hemiparkinsonism, the total free iron concentration was measured. Iron, Fe2+ and Fe3+, but not other trace elements, was significantly elevated in the SNc compared with the opposite unlesioned side, which was similar to separate control animals. Iron content in the SNc, periaqueductal gray area, and crus cerebri was 228-270 ppm. Normal control SNc was 285 (+/- 59) ppm, whereas iron levels of 532 (+/- 151) ppm were found in the MPTP-lesioned SNc. These animals were drug naive and not on long-term levodopa maintenance. Proton microprobe elemental analysis was matched against adjacent immunocytochemically stained tissue slices to ensure the cells studied were in the SNc. Iron was found not only in the degenerating dopamine cells themselves but also in the surrounding matrix and glial cells. Whether free iron that is not bound to neuromelanin is responsible for dopamine cell death as suggested by these experiments remains to be proved.
 ...
PMID:Increased iron in the substantia nigra compacta of the MPTP-lesioned hemiparkinsonian African green monkey: evidence from proton microprobe elemental microanalysis. 826 13

We report findings on brain glucose metabolism and dopamine D2 receptors generated by positron emission tomography (PET) in a 67-year-old woman with right hemiparkinsonism-hemiatrophy syndrome (HP-HA). PET with [18F]-fluorodeoxyglucose (FDG) showed marked glucose metabolism asymmetry. There were significant reductions in glucose uptake at the level of the basal ganglia and, to lesser extent, in the fronto-parietal cortex contralateral to the clinically involved side. These changes were different from those found in a patient with hemi-Parkinson's disease who was scanned under similar conditions. Because the patient with HP-HA had only minimal response to levodopa therapy, we evaluated post-synaptic dopaminergic structures using PET with [18F]-fluoroethylspiperone (FESP). No striatal binding asymmetry was found in FESP/PET, which suggests a sparing of striatal dopamine D2 receptors. The changes in FDG uptake which we found were in brain areas relevant to the clinical features of HP-HA syndrome. In addition, our study provides evidence that FDG/PET may help to differentiate HP-HA syndrome from hemi-Parkinson's disease. In most instances, since HP-HA is associated with a more benign clinical course than Parkinson's disease, this distinction is of clinical important.
 ...
PMID:Brain glucose metabolism and dopamine D2 receptor analysis in a patient with hemiparkinsonism-hemiatrophy syndrome. 834 11

Regional cerebral blood flow was assessed in 19 patients with early idiopathic Parkinson's disease (PD) and 12 control subjects of similar age by single-photon emission tomography using technetium-99m hexamethylpropylene amine oxime (HMPAO). Of the patients with PD, seven were mildly demented and 15 presented with hemiparkinsonism. Mean HMPAO cortical or basal ganglia/cerebellum activity ratios were calculated. Mean cortical and regional uptake ratios in non-demented PD patients were not significantly different from values in the controls. In contrast, besides generalized cortical hypoperfusion, demented PD patients had significantly lower HMPAO uptake in the frontal and basal ganglia regions than non-demented patients. These observations support the hypothesis of impaired neuronal activity in both cortical and subcortical regions of the brain in demented PD patients. In hemiparkinsonian patients, the only asymmetrical finding was a relative hypoperfusion in the contralateral parietal region. This may be due to deafferentation of the thalamoparietal pathways. The lack of asymmetrical uptake in basal ganglia in our PD patients may be explained by their staging at the time of the investigation (stage I and II, Hoehn and Yahr scale).
 ...
PMID:Technetium-99m hexamethylpropylene amine oxime single photon emission tomography of the brain in early Parkinson's disease: correlation with dementia and lateralization. 849 Dec 27

The striatal D2 receptor was investigated for variability of behavior in 16 patients with Parkinson disease by means of SPECT using 123I-IBZM, a recently synthesized radioligand with high affinity and specificity for this type of receptor. All the patients underwent routine laboratory tests, EEG and cranial CT scanning as well as SPECT. To ensure accurate clinical assessment we used the Hoehn and Yahr, and Webster scales, NUDS and Mini Mental State examination. Our preliminary data indicate: increased uptake by the striatal dopamine receptor in untreated patients with early PD compared with controls (striatum/cerebellum ratio of 1.77 +/- 0.12 vs 1.59 +/- 0.13); a slight but significant lowering of D2 receptor binding when L-Dopa is started (1.49 +/- 0.09); low D2 uptake values in the more severely affected patients; absence of asymmetries in hemiparkinsonism.
 ...
PMID:Dopamine D2 receptor imaging with SPECT using IBZM in 16 patients with Parkinson disease. 850 71

Signs of attentional dysfunction mimicking spatial neglect have been described both in humans with lateralised Parkinson's Disease (PD) and in animals with MPTP-related hemiparkinsonism. Such deficits have been attributed to dopamine loss in basal ganglia and cortical targets. However, in previous studies the existence of neglect was assumed from behavioural tests which needed a motor output, thus entailing interpretation ambiguities due to effects of directional hypokinesia. We recorded brain event-related potentials (ERPs) evoked by the presentation of target somatic stimuli to the affected and non-affected sides in 44 patients with unilateral or asymmetrical PD. The N2 and P3 ERP components were specifically analysed, since (a) they are triggered selectively by task-relevant, attended sensory stimuli; (b) their latency reflects stimulus evaluation time, independently from the execution of a motor response, and (c) they have proved to be abnormal in hemineglect syndromes due to focal brain lesions. Irrespective of the side (left or right) of motor symptom predominance there were no significant ERP differences to stimulation of the affected and non-affected limbs, nor was there any correlation between ERP latencies and the degree of dopamine-related motor impairment. The P3 latency was abnormally delayed in 23% of the patients, but there was no trend for abnormalities to concentrate on the affected side. This study does not confirm the existence of a significant attentional impairment toward the affected limb in lateralised PD, and suggests that previous clinical evidence of "neglect' behaviour in PD might be linked to directional hypokinesia, thus reflecting intentional, rather than attentional lateralised deficits.
 ...
PMID:Brain responses to detection of right or left somatic targets are symmetrical in unilateral Parkinson's disease: a case against the concept of "parkinsonian neglect'. 895 46

A variety of tests are available for the evaluation of behavioural deficits in rat models of hemiparkinsonism; many, however, are of limited applicability or insufficiently objective. The drug-induced turning behaviour test is widely used. A disadvantage of this test is that the use of drugs may lead to misleading results. Here, we describe a drug-free rotarod test that was used to evaluate the effects of unilateral 6-hydroxydopamine lesions, nigral grafts, and subrotational doses of apomorphine. The rotarod unit was automated and interfaced to a personal computer allowing automatic recording of the time that each rat was able to stay on the rod at different rotational speeds (i.e., progressively increasing the difficulty of the task). A combination of lesion-induced deficits resembling those of Parkinson's disease appears to be involved in falling from the rod. The test shows high effectiveness for identifying rats with maximal dopaminergic lesions, but is also effective for identifying partial lesions. Rotarod performance profiles were useful for investigating the effects of intrastriatal nigral grafts, since low rotation speeds revealed differences from lesioned rats (i.e., improvements) while higher speeds revealed differences from normal rats (i.e., remaining deficits and partial lesions). The test was effective regardless of whether rats were trained on the rod before lesion, after lesion, or after grafting. Injections of apomorphine (0.0125 and 0.0250 mg/kg) did not induce consistent improvements. These results indicate that the rotarod test is a useful drug-free procedure for overall evaluation of basic motor abilities in rat models of parkinsonism and treatment-induced changes.
 ...
PMID:Drug-free evaluation of rat models of parkinsonism and nigral grafts using a new automated rotarod test. 913 18

Dopaminergic nigrostriatal neurons, degeneration of which causes Parkinson's disease, are known to receive excitatory input almost exclusively from the pedunculopontine tegmental nucleus (PPN). We report here that excitotoxic lesions of the PPN produce abnormal motor signs relevant to hemiparkinsonism in the macaque monkey. Under the guidance of extracellular unit recordings, the electrophysiologically identified PPN was injected unilaterally with kainic acid. These PPN-lesioned monkeys exhibited mild to moderate levels of flexed posture and hypokinesia in the upper and lower limbs contralateral to the lesion. In most of the monkeys, such pathophysiological events were gradually improved and became stationary in 1-2 weeks. The hemiparkinsonian symptoms observed after PPN destruction might be ascribed to a decrease in nigrostriatal neuron activity due to excitatory input ablation.
 ...
PMID:Excitotoxic lesions of the pedunculopontine tegmental nucleus produce contralateral hemiparkinsonism in the monkey. 915 2

Neural tissue transplantation has become an alternative treatment for Parkinson's disease (PD) and other neurodegenerative disorders. The clinical use of neural grafts as a source of dopamine for Parkinson's disease patients, although beneficial, is associated with logistical and ethical issues. Thus, alternative graft sources have been explored including polymer-encapsulated cells and nonneural cells (that is, adrenal chromaffin cells) or genetically modified cells that secrete dopamine and/or trophic factors. Although progress has been made, no current alternative graft source has ideal characteristics for transplantation. Emerging evidence suggests the importance of trophic factors in enhancing survival and regeneration of intrinsic dopaminergic neurons. It would be desirable to transplant cells that are readily available, immunologically accepted by the central nervous system and capable of producing dopamine and/or trophic factors. Sertoli cells have been shown to secrete CD-95 ligand and regulatory proteins, as well as trophic, tropic, and immunosuppressive factors that provide the testis, in part, with its "immunoprivileged" status. The present study demonstrated that transplantation of rat testis-derived Sertoli cells into adult rat brains ameliorated behavioral deficits in rats with 6-hydroxydopamine-induced hemiparkinsonism. This was associated with enhanced tyrosine hydroxylase (TH) immunoreactivity in the striatum in the area around the transplanted Sertoli cells. Furthermore, in vitro experiments demonstrated enhanced dopaminergic neuronal survival and outgrowth when embryonic neurons were cultured with medium in which rat Sertoli cells had been grown. Transplantation of Sertoli cells may provide a useful alternative treatment for PD and other neurodegenerative disorders.
 ...
PMID:Testis-derived Sertoli cells have a trophic effect on dopamine neurons and alleviate hemiparkinsonism in rats. 933 25

The pathophysiology of dystonia is unclear, but several clues implicate striatal dopamine dysfunction. In contrast, the causal relationship between striatal dopamine deficiency and parkinsonism is well defined. We now suggest that parkinsonism or dystonia may occur following striatal dopamine deficiency. Baboons treated with intracarotid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) developed transient hemidystonia prior to hemiparkinsonism. The day after MPTP treatment, most animals had spontaneous ipsilateral turning. Within a few days, all developed contralateral hemidystonia, with the arm and leg extended and externally rotated. This transient dystonia preceded hemiparkinsonism with flexed posture, bradykinesia, and postural tremor that persisted for up to 1.5 years. Dystonia corresponded temporally with a decreased striatal dopamine content and a transient decrease in D2-like receptor number. The time course of dystonia and parkinsonism is analogous to lower limb dystonia as the first, frequently transient, symptom of Parkinson's disease in humans. The association of striatal dopamine deficiency with dystonia and parkinsonism implies that other factors influence clinical manifestations.
 ...
PMID:MPTP induces dystonia and parkinsonism. Clues to the pathophysiology of dystonia. 937 34


<< Previous 1 2 3 4 5 6 7 8 9 Next >>