Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors present the results of examining the content of 4-hydroxy-3-methoxy-phenylacetic or homovanillic acid (the principal end metabolite of dopamine) in the ventricular fluid of patients suffering from various extrapyramidal diseases. A considerable lowering of the homovanillic acid (HVA) concentration is demonstrated in patients with parkinsonism: this reflects the degeneration of the dopamine-containing pathways and the lowering of the dopamine synthesis in the basal ganglia in that disease. The treatment with L-DOPA leads to a considerable rise of the HVA level in the ventricular fluid, the fact, that points to an intensification of dopamine metabolism in the brain, when its precursor, i.e. L-DOPA is given to the patients. In patients with deforming muscular dystonia, statistically significant differences of the HVA concentration in the cerebrospinal fluid were noted. These differences correlated with the clinical manifestations of the disease. The concentration was found to be much higher in patients with local muscular rigidity, than in those in whose clinical picture the dystonic hyperkinesis was prevalent. It is concluded that in phenotypically different forms of the deforming muscular dystonia the character of the pathology of the central dopaminergic system is also different. Patients with Huntington's chorea showed a low level of the HVA in the intraventricular fluid. It is supposed that this is an evidence of either a fall of the dopamine total content in the brain because of the degeneration of the respective neurons, or of a deterioration of cerebral dopamine catabolism because of enzymatic insufficiency. The data obtained are of importance for understanding the pathogenesis, and for developing methods of treating extrapyramidal motor disturbances.
 ...
PMID:[Approaches to the study of dopamine metabolism in various extrapyramidal diseases]. 645 76

The authors report an experiment undertaken with trazodone in the treatment of different forms of pathological involuntary movements. Forty-five subjects were treated for two months; 15 were affected with L-DOPA + decarboxylase inhibitor induced dyskinesias, 9 with choreic or choreoathetosic syndromes, 6 with primary buccolingual dyskinesias, 4 with ticks, 9 with tremors--3 of whom had delirium tremens--and 1 case of Wilson's disease with severe postural dystonia. At the end of treatment there was a considerable improvement in 40 cases (88.9%), 17 of whom (37.8%) had a reduction of over 65% of symptoms. The results were good in all the groups considered; particularly interesting were those obtained in delirium tremens, alcoholic induced tremor, primary buccolingual dyskinesias, L-DOPA + decarboxylase inhibitor induced dyskinesias. Emphasis is placed on the efficacy of the drug in inhibiting postural dystonia in the one case of Wilson's disease. The good tolerance of the drug was confirmed.
 ...
PMID:[Trazodone in involuntary pathologic movements]. 671 59

The hypothalamus was examined in cases of sudden heart death in 50 persons of both sexes whose ages ranged from 25 to 55. The microscopic and biochemical findings were compared with those in cases of heart death which had not occurred suddenly in patients with myocardial infarction of different duration (50 cases). It is shown that in sudden heart death diffuse edema of the white matter and dystonic changes in the microcirculation vessels develop in the hypothalamus. Biochemical examination discloses in the tissue of the hypothalamus in such cases a sharp decrease in the content of noradrenalin and the precursor of catecholamine synthesis DOPA and a marked increase in the level of adrenalin. It is assumed that there is a causative connection between vascular dystonia and the decrease in the noradrenalin level. An increase in the adrenalin content may be conducive to the intensification of cerebral hydrophilism.
 ...
PMID:[Hypothalamic characteristics in sudden human cardiac death]. 740 43

A woman and her son had progressive dystonia and chronic insomnia at 32 and 19 years of age respectively. Levodopa was markedly effective at low dose both for dystonia and insomnia without dyskinesia over a 5-year follow-up period.
 ...
PMID:[L-dopa-responsive dystonia: 2 familial cases of adult onset with sleep disorders]. 748 95

GTP cyclohydrolase I is the first and rate-limiting enzyme for the biosynthesis of tetrahydrobiopterin in mammals. Previously, we reported three species of human GTP cyclohydrolase I cDNA in a human liver cDNA library (Togari, A., Ichinose, H., Matsumoto, S., Fujita, K., and Nagatsu, T. (1992) Biochem. Biophys. Res. Commun. 187, 359-365). Furthermore, very recently, we found that the GTP cyclohydrolase I gene is causative for hereditary progressive dystonia with marked diurnal fluctuation, also known as DOPA-responsive dystonia (Ichinose, H., Ohye, T., Takahashi, E., Seki, N., Hori, T., Segawa, M., Nomura, Y., Endo, K., Tanaka, H., Tsuji, S., Fujita, K., and Nagatsu, T. (1994) Nature Genetics 8, 236-242). To clarify the mechanisms that regulate transcription of the GTP cyclohydrolase I gene and to generate multiple species of mRNA, we isolated genomic DNA clones for the human and mouse GTP cyclohydrolase I genes. Structural analysis of the isolated clones revealed that the GTP cyclohydrolase I gene is encoded by a single copy gene and is composed of six exons spanning approximately 30 kilobases. We sequenced all exon/intron boundaries of the human and mouse genes. Structural analysis also demonstrated that the heterogeneity of GTP cyclohydrolase I mRNA is caused by an alternative usage of the splicing acceptor site at the sixth exon. The transcription start site of the mouse GTP cyclohydrolase I gene and the 5'-flanking sequences of the mouse and human genes were determined. We performed regional mapping of the mouse gene by fluorescence in situ hybridization, and the mouse GTP cyclohydrolase I gene was assigned to region C2-3 of mouse chromosome 14. We identified missense mutations in patients with GTP cyclohydrolase I deficiency and expressed mutated enzymes in Escherichia coli to confirm alterations in the enzyme activity.
 ...
PMID:Characterization of mouse and human GTP cyclohydrolase I genes. Mutations in patients with GTP cyclohydrolase I deficiency. 773 Mar 9

Five patients presented in infancy or early childhood with various combinations of pyramidal and extrapyramidal signs with normal cognitive function. Their perinatal courses were unremarkable. In each patient, initial impressions listed by several examiners included spastic diplegia or cerebral palsy. Later in each course, either extrapyramidal features or progression suggested dopa-responsive dystonia. In 4 of the 5 children, cerebrospinal fluid was obtained and disclosed reduced levels of biopterin, neopterin, and homovanillic acid in all 4. Levodopa therapy resulted in prompt improvement with normal function returning within 6 months. The disappearance of the "spasticity," extensor plantar responses, and extrapyramidal signs, following levodopa therapy, confirmed the diagnosis of doparesponsive dystonia in these patients. Three had apparently sporadic disease; the other 2 were siblings with an affected paternal grandmother. Three had onset in infancy with delayed sitting and walking before the appearance of overt dystonia; infantile onset is infrequent in dopa-responsive dystonia. The other 2 had normal milestones, but developed gait disorders with prominent imbalance in early childhood. The diagnosis of dopa-responsive dystonia should be considered in children with unexplained or atypical "cerebral palsy."
 ...
PMID:Dopa-responsive dystonia simulating cerebral palsy. 788 Mar 38

We report two patients with diurnally fluctuating hereditary progressive dystonia, that presented with dystonic movements and parkinsonian symptoms with marked diurnal fluctuations. There was a significant and maintained improvement of symptoms with small doses of L-Dopa. The pathogenesis of this disease could be a functional alteration of basal ganglia in the dopaminergic striatonigral region. The diurnal fluctuation of symptoms would be related to the circadian variation of tyrosine hydroxylase function.
 ...
PMID:[Progressive hereditary dystonia with diurnal fluctuations: report of 2 cases]. 790 16

Thirty-eight children with deforming muscular dystonia were treated. Eighteen of them suffered from rigid, seven from hyperkinetic, and 13 from, mixed forms of the disease. To patients with rigid condition DOPA-containing drugs (nakom) were administered in combination with cholinolytics, diphenin, midocalm. If the condition proved resistant to therapy, parlodel, remantadin, antidepressants were added. To patients with hyperkinetic forms haloperidol, clonazepam, dephenin, finlepsin were administered. In mixed forms combinations of nakom with haloperidol and clonazepam were prescribed. The best results were attained in therapy of rigid forms (77% of all rigid forms), particularly of DOPA-dependent forms and those with local involvement.
 ...
PMID:[The differentiated treatment of dystonia musculorum deformans in children]. 790 72

We report a family of parkinsonism in which the clinical feature of the constituents varied with the age of onset. The propositus was a 49-year-old woman who had developed tremor and akinesia at the age of 26 years. Levodopa markedly relieved her symptoms. The feet showed pes equinovarus with tonic extension of the great toe. The most characteristic feature was marked diural fluctuation of her symptoms; her gait was nearly normal in the morning, while she showed marked tremor and gait disturbance with parkinsonian posture in the evening. Sleep markedly improved her conditions. Her maternal uncle developed parkinsonism at the age of 60 years, and anti-parkinsonian drugs including levodopa were persistently effective. Neurological examination at the age of 75 years revealed parkinsonian features with rigidity, resting tremor, akinesia and loss of postural reflex, together with severe pes equinovarus and tonic extension of the great toe. There was no diural fluctuation in his symptoms. Several types of dystonia-parkinsonism, either familial or sporadic, have been reported in the literature, but none of them showed the same clinical and genetic features as the present family. The present family may be included in a spectrum of dystonia-parkinsonism syndrome of autosomal-dominant inheritance.
 ...
PMID:[A family of parkinsonism in which the clinical feature of constituents varied with the age of onset]. 795 37

In 58 patients with Parkinsonism or dystonia striatal dopamine D2 receptors were investigated using 123I-iodobenzamide (123I-IBZM) single-photon emission computed tomography (SPECT). The influence of SPECT reconstruction methodology on semiquantification and the clinical value of 123I-IBZM SPECT were evaluated. Delineation of the striatal uptake and striatum/frontal cortex (ST/FC) ratios were improved by the use of compensation procedures for scatter and attenuation as well as the choice of an adequate filter. Satisfactory results were achieved using a Metz prefilter with a comparatively high order number (i.e. high cut-off and low suppression of higher frequencies via roll-off). Regarding clinical diagnoses it was not possible to differentiate between advanced idiopathic Parkinson's disease (IP) and Parkinsonism of other aetiology (OP) on the basis of 123I-IBZM SPECT. But patients with IP and favourable response to L-Dopa showed significantly higher ST/FC ratios than those with fluctuating response. In patients with dystonia ST/FC ratios were significantly higher compared to patients with IP or OP.
 ...
PMID:123I-IBZM SPECT: reconstruction methodology and results in parkinsonism and dystonia. 799 77


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>