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

Fibroblasts (NRK-49F) were transfected with human type 2 tyrosine hydroxylase (TH; EC 1.14.16.29) cDNA, to clarify the mechanism involved in amelioration of parkinsonism by intracerebral grafting of catecholaminergic neurons and to investigate its possible use as a donor material. These genetically manipulated fibroblasts did not develop into a mass of tissue, and survived well in the host striatum. Expression of the TH minigene in the cells was successful even when they were transplanted into the host brain. Intracerebral microdialysis revealed that a measurable amount of L-3,4-dihydroxyphenylalanine (L-DOPA) was not spontaneously released from the implanted cells into the host striatum. However, release of a large amount of L-DOPA from the cells was observed when (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) was perfused through a dialysis probe. Finally, we investigated whether these BH4-dependent L-DOPA-secreting fibroblasts are able to ameliorate the abnormal behavior of 6-hydroxydopamine-treated rats. Apomorphine-induced rotating behavior was not reversed by the grafting alone, whereas a marked reduction in drug-induced circling was observed temporarily after BH4 was perfused around the implanted cells. These findings indicate that TH cDNA-transfected non-neuronal cells might be able to be used as donor material for intracerebral grafting and ameliorate the abnormal behavior of rats with experimental Parkinson's disease.
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PMID:Tetrahydrobiopterin-dependent functional recovery in 6-hydroxydopamine-treated rats by intracerebral grafting of fibroblasts transfected with tyrosine hydroxylase cDNA. 135 49

Patients with depressive motor retardation, neuroleptic induced parkinsonism or Parkinson's disease were tested on movement tasks requiring control of simultaneous movements. This was in order to determine whether these three groups of patients, who all show slowing of movements, also share the distinctive impairment of simultaneous movement control that is observed in Parkinson's disease. Though all three patient groups showed equivalent slowing on the motor tasks that were studied, the patterns of impairment were different. Only the patients with parkinsonism, either neuroleptic induced or from Parkinson's disease, showed additional slowing of a rapid ballistic elbow flexion movement when it was performed simultaneously with a rapid squeeze of the ipsilateral hand. Only patients with parkinsonism showed a significant increase in dual task interference on a bimanual bead and tapper task, compared with controls. The bead and tapper interference in patients with depressive motor retardation was between that of controls and parkinsonism. Having a bimanual skill had a large effect on the subjects' dual task interference on this task. The measures of dual task interference for the two tasks did not correlate with one another; difficulty running simultaneous motor programs does therefore not explain the interference that is observed when tapping is performed while the other hand simultaneously performs a dextrous motor task. Only patients with parkinsonism showed increased fatigue on the tapping task. The patients with depressive motor retardation did have elevated scores on a clinical rating of parkinsonism. Nevertheless there are clearly defined differences between the movement disorder observed in patients with depression, and that observed in in parkinsonism. The patterns of impairments in patients with neuroleptic parkinsonism were very similar to those of Parkinson's disease.
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PMID:Control of simultaneous movements distinguishes depressive motor retardation from Parkinson's disease and neuroleptic parkinsonism. 135 98

Deprenyl, a monoamine oxidase B inhibitor, appears to slow the progression of neurological deficits in Parkinson's disease and cognitive decline in Alzheimer's disease. The mechanisms for the slowing of the diseases are unknown. Deprenyl can reduce the death of murine substantia nigra neurons when administered after the neurons are damaged in MPTP parkinsonism by increasing the neurons' survival after they are damaged, rather than by just protecting the neurons against damage by blocking the conversion of MPTP to its active form as was previously thought. The death of immature motoneurons after separation from their muscle targets by axotomy provides a model for assessing trophically dependent neuronal survival. To determine whether deprenyl can alter the survival of neurons other than those in the substantia nigra, we examined the survival of rat facial motoneurons after axotomy at 14 days of age. Using a combination of immunocytochemistry for choline acetyl transferase and Nissl staining, we found that deprenyl treatment (10 mg/kg every second day) increased by 2.2 times the number of motoneurons surviving 21 days after the axotomy. This finding showed that deprenyl treatment can rescue neurons other than those in the substantia nigra and can compensate in part for the loss of target-derived trophic support caused by axotomy.
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PMID:Deprenyl reduces the death of motoneurons caused by axotomy. 137 34

The effect of arotinolol, a peripherally acting beta-adrenergic-blocking agent, on postural or kinetic tremor was studied in monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Male cynomolgus monkeys (Macaca fascicularis) were treated with three injections of MPTP hydrochloride (0.3 mg/kg, i.v.) at an interval of 3-4 days, followed by several injections of the same dose every 7 days. Four monkeys with persistent parkinsonian symptoms manifested for greater than 1 year were used. The animals developed mild to moderate degrees of postural or kinetic tremor, and their motor activity was reduced. Arotinolol (20-30 mg/kg, s.c.) significantly suppressed postural tremor in a dose-dependent manner. Propranolol (20-30 mg/kg) was also effective in suppressing the tremor. However, the application of propranolol induced emesis, whereas arotinolol had no adverse effects. These results suggest that arotinolol is a useful adjunct to dopaminergic therapy for tremor in Parkinson's disease.
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PMID:Therapeutic effects of arotinolol, a beta-adrenergic blocker, on tremor in MPTP-induced parkinsonian monkeys. 138 70

We investigated the prevalence of Parkinson's disease and other types of parkinsonism in a Sicilian population using a door-to-door two-phase approach. This design called for the administration of a brief screening instrument to all subjects who, on November 1, 1987, were residents of Terrasini (Palermo Province), Santa Teresa di Riva (Messina Province), and Riposto (Catania Province), Sicily (N = 24,496). Study neurologists using specified diagnostic criteria extensively investigated those subjects who screened positive. We found 63 subjects affected by Parkinson's disease, 21 with secondary parkinsonism, and seven with unspecified parkinsonism. The crude prevalence per 100,000 population was 371.5 for all types of parkinsonism and 257.2 for Parkinson's disease; for both entities, prevalence increased steeply with age and showed an inconsistent sex pattern. Our prevalence figures for Parkinson's disease are higher than those previously reported in Italy or elsewhere, which may be due, in part, to more complete case-ascertainment.
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PMID:Prevalence of Parkinson's disease and other types of parkinsonism: a door-to-door survey in three Sicilian municipalities. The Sicilian Neuro-Epidemiologic Study (SNES) Group. 140 70

The pathogenesis of Parkinson's disease (PD) has been linked to oxidative-mediated events including increased monoamine oxidase (MAO) and free-radical generation. We are investigating the ability of the MAO inhibitor, selegiline (deprenyl), and of the free-radical scavenger, tocopherol, to delay the onset of disability requiring levodopa therapy (primary end point) in patients with early PD. Eight hundred patients with early, untreated PD were enrolled in the multi-center placebo-controlled, double-blind clinical trial 'Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP)'. Subjects were assigned by 2 x 2 factorial design to receive selegiline (10 mg/day), tocopherol (2,000 IU/day), a combination of both drugs, or placebo, and followed to determine if and when disability occurred requiring levodopa therapy. After 12 +/- 5 months of observation, independent monitoring prompted a preliminary analysis indicating that selegiline 10 mg/day significantly extended the time to the primary end point. Selegiline therapy, alone or in combination with tocopherol, resulted in a 57% reduction in the rate of developing disability requiring levodopa therapy (p < 10(-10)) and a 50% reduction in the rate of loss of full-time employment (p = 0.01). Deterioration of motor and mental features was significantly less in selegiline-treated subjects. Adverse effects were minor and infrequent. We conclude from these preliminary results that selegiline (10 mg/day) delays the onset of disability associated with early, otherwise untreated PD. It remains unclear whether these benefits derive from mechanisms that are symptomatic (dopaminergic), protective (anti-neurotoxic), or both. The DATATOP study is ongoing to examine the long-term effects of selegiline and the independent and interactive effects of tocopherol.
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PMID:An interim report of the effect of selegiline (L-deprenyl) on the progression of disability in early Parkinson's disease. The Parkinson Study Group. 142 20

74 inpatients and outpatients (mean age 71.9 years) with idiopathic Parkinson's disease, a vascular pseudo-parkinsonian syndrome or a Parkinson-associated dementia were analysed by present-state clinical rating with regard to use and needs of physical and speech therapy. 55% of the patients had physical therapy whatsoever, 32% of them on a daily schedule. 58% of patients without everyday physical therapy indicated to do less physical therapy than one year ago or that they have quite any exercise. This item showed significant correlations with: age of disease onset over 70 years, Hoehn-Yahr stage of 3 and over, activities of daily living according to Schwab-England of less than 60%, diagnosis of vascular pseudoparkinsonian syndrome or Parkinson-associated dementia, more frequent use of community support services for the ambulatory elderly. Only 8% of the patients had ever had speech therapy. Using both ratings of complaints and clinical findings, about 30% of patients had moderate to severe impairment of speech, 80% of these had also considerable memory disturbances. The study suggests that the need for physical therapy might be derived more from patient's assessment of reduced daytime motor activities than from a scaled item rating of an external observer. Use and continuity of physical and speech therapy in Parkinsonism seems to be limited largely by cognitive disturbances and social variables. Speech therapy appears to be useful only for a subgroup of Parkinsonian patients.
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PMID:[Physical therapy and speech therapy in Parkinson syndrome--a status assessment]. 142 53

Lacunes on brain MRI, causal blood pressure, 24-hour ambulatory blood pressure and common carotid blood flow measured by the doppler method were studied in 31 elderly patients with Parkinson's disease (mean age 67.5 +/- 7.3 years). Nineteen patients with Parkinson's disease (61%) had at least one lacune. Patients with lacunes (P(+)) were significantly higher in age than patients without lacune (P(-)). The difference of casual blood pressure between patients in the two groups was not significant. On the other hand, the average of ambulatory blood pressure measurements during a 24-hour period was significantly higher in the P(+) group than in the P(-) group. The average of carotid blood flow was also significantly lower in the P(+) group than in the P(-) group, however, after adjustment for age, the difference between them became insignificant. In conclusion, the incidence of silent lacunes on brain MRI was fairly common in elderly patients with Parkinson's disease. A high average 24-hour ambulatory blood pressure was suggested to be one of the risk factors of lacunar stroke in elderly cases of Parkinson's disease. The concept of "combine type" in Parkinsonism was supposed to be suitable as well as in senile dementia of Alzheimer type.
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PMID:[Silent lacunes in the elderly Parkinson's disease correlated with ambulatory blood pressure]. 143 50

Some elderly patients with chronic illness such as stroke, or Parkinsonism cannot take food orally because of dysphagia. In such cases, tube feeding can be used as a supplement to oral intake when malnutrition is present. This route allows for easier nursing care and decreases the frequency of aspiration pneumonia. Complications of tube feeding include nutrient deficiency states, pulmonary aspiration, gastrointestinal and metabolic disorders. We report two cases with complications of acute gastric ulcer which was thought to be induced with long-term tube feeding. Case 1 was a 61-year-old male patient with Parkinson's disease for ten years. L-DOPA had been administered with good control of his condition. However, his ability to swallow has deteriorated gradually. As he often suffered from aspiration pneumonia, nasogastric tube feeding was performed. After three years of tube feeding, he suddenly vomited much bloody material. He died from massive bleeding with acute gastric dilatation. Autopsy showed giant acute gastric ulcer covered with coagulated blood. UL3, 50 mm in maximum diameter, was observed in the middle portion of the greater curvature, where the top of tube probably came in contact with the gastric wall. Case 2 was an 83-year-old female patient with stroke and chronic heart failure. She had been hospitalized for about one year because of the intermittent deterioration of her cardiac condition. Furthermore, her inability to swallow increased during her hospitalization. She also suffered from aspiration pneumonia. Nasogastric tube feeding was performed to prevent aspiration pneumonia and malnutrition. She died of acute heart failure after twelve months. Autopsy revealed heart dilatation, old myocardial infarction and stroke. In addition, two acute gastric ulcers (UL3.10 and 30 mm in diameter) were recognized; one was in the upper portion of the greater curvature, the other in the lower portion of the greater curvature. The location of these gastric ulcers was unusual. Moreover, they coincided with location of top of the nasogastric tube. From these two cases, we conclude that in long-term tube feeding the tip of the tube often comes in contact with the gastric wall, and gastric ulcer could be produced by repeated mechanical stimulus of the wall. Reports of acute gastric ulcer induced by tube feeding have not been published previously. Therefore, we should pay much attention to this complication in the care of the elderly people with long-term tube feeding.
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PMID:[Long-term nasogastric feeding and complications of acute gastric ulcer in two elderly patients]. 143 62

Death certificates were reviewed to observe trends in the number of persons on Guam reported to have chronic degenerative motor neuron diseases (amyotrophic lateral sclerosis, parkinsonism-dementia or Parkinson's disease) at the time of death. Additional data, including age and race of the deceased and the name of the certifying physician were also collected. The number of persons having been diagnosed with amyotrophic lateral sclerosis is apparently decreasing while their mean age is increasing suggesting that the etiologic agents or factors causing this disease are less prevalent on Guam today than they have been in the past. Trends with regard to parkinsonism-dementia and Parkinson's disease are less clear.
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PMID:Are the endemic motor neuron diseases of Guam really disappearing? 143 82


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