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)

We analyzed the 1986-1997 mortality in a cohort of 2065 residents of an Italian municipality which had been exposed to drinking water with a high content of inorganic selenium over a long period of time, and compared it with mortality in the remainder of the municipal population. Mortality from malignant neoplasms increased [standardized mortality ratio (SMR) 1.17, 95% confidence interval (CI) 0.96-1.42], mainly due to an excess mortality from melanoma and colorectal cancer in both sexes, kidney cancer in men, and lymphoid malignancies in women. Overall cardiovascular mortality changed little (SMR 1.05, 95% CI 0.89-1.23), despite the higher cerebrovascular mortality (SMR 1.43, 95% CI 1.03-1.93). Coronary disease mortality slightly decreased (SMR 0.87, 95% CI 0.63-1.16), due to a low mortality among women. We also noted an excess mortality from Parkinson's disease in men and from motor neuron disease in women. Evaluation of these findings is, however, hampered by the lack of information about potential lifestyle confounders, the fact that the exposure could only be characterized by a simple dichotomization, and the inconsistencies of most estimates between the two sexes.
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PMID:Mortality in a population with long-term exposure to inorganic selenium via drinking water. 1102 40

Recently a breakthrough in research was reported in the Dutch press. The results were considered of major importance for the treatment of patients with Parkinson's disease, motor neuron disease and Alzheimer's disease. Thereafter societies of patients and neurologists were overloaded with questions. They had to explain again and again that false expectations had been aroused. The road from basic research to a proven beneficial therapy is long. Promising results are at many phases of the development of a treatment at risk of disappearing. Reports from the laboratory on new treatments are always too early. In order to prevent false expectations, submissions to the press ought to be based on firm evidence as is usual with publications in professional journals, editors of the press should scrutinize the claims made by researchers, and, in addition, the general public should be educated on the diagnostic process and the assessment of treatment efficacy.
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PMID:['Another breakthrough': general news reports raise false hopes]. 1103 83

Motor neurons are among some of the most unusual cells in the body becaue of their immense size and their role as the critical link between the motor centers of the brain and the muscles. In addition to their intrinsic biological interest, it is vital that we gain a better understanding of these cells and their pathology, since motor neuron degenerative diseases are lethal disorders that affect young and old and are relatively common. For example, one form of spinal muscular atrophy (SMA) is the most common genetic killer of children in the developed world. Amyotrophic lateral sclerosis (ALS), another form of motor neuron degeneration, is the third most common neurodegenerative cause of adult death, after Alzheimer's disease and Parkinson's disease, and is significantly more common than multiple sclerosis (Motor Neurone Disease Association 1998). Currently, approximately 1 in 500 people in England and Wales who die have a form of motor neuron disease (Motor Neurone Disease Association 1998). Each year, 5000 Americans are diagnosed with ALS, and of these, 10% are under 40 years old. Mouse models of motor neuron degeneration are essential for understanding the causes and mechanisms of motor neuron pathology. These mice are yielding important information that will ultimately lead to treatments and potentially cures for these diseases.
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PMID:Mice, the motor system, and human motor neuron pathology. 1113 Sep 70

Advances in molecular biology have increased our understanding of both inherited and sporadic forms of neurological disease. In this review, the impact of these advances is discussed in relation to specific neurological conditions. These include the hereditary neuropathies and ataxias, Huntington's disease, and the muscular dystrophies, as well as Alzheimer's disease, Parkinson's disease, and motor neuron disease. Genetic channelopathies, such as familial hemiplegic migraine, are also described. Although knowledge in this area overall is still relatively scant, current advances in molecular biology have helped in the reclassification of some neurological disorders, thereby providing a further step towards the development of rational therapies to treat these conditions.
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PMID:The impact of molecular biology on clinical neurology. 1140 75

The role of xenobiotic metabolising enzymes (XMEs) in disease aetiology has been under investigation by numerous researchers around the world for the last two decades. The association of a number of defects in both phase I and phase II reactions with Parkinson's disease (PD) and motor neuron disease (MND) have been extensively studied. This review of the work of the group based initially at the University of Birmingham into the functional genomics of XMEs and neurodegenerative diseases has indicated that: 1. Sub-groups of patients with PD and MND can be identified with problems in xenobiotic metabolism by in vivo or in vitro methods. 2. 38-39% of the patients with MND/PD have a defect in the S-oxidation of the mucoactive drug, carbocysteine, by an unknown cytosolic oxidase(s). The odds risk ratio for the association of this defect with these diseases was calculated to be 10.21 for MND and 10.50 for PD. 3. Patients with PD appear to have an altered substrate specificity for monoamine oxidase B substrates in an in vitro platelet assay. 4. Patients with MND have an increased capacity to S-methylate aliphatic sulphydryl compounds in an in vivo challenge as well as an in vitro erythrocyte thiol methyltransferase assay. The results of over a decade of investigations into both PD and MND indicate that these are diseases with mutifactorial origins that encompass both genetic predisposition and environmental insult.
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PMID:A review of xenobiotic metabolism enzymes in Parkinson's disease and motor neuron disease. 1146 Aug 78

Positron emission tomography (PET) has enabled us to study the human brain with unrivalled sensitivity, and has already established its place in the research of neurological conditions such as Parkinson's disease and epilepsy. PET has been used as a tool in the study of patients with motor neuron disease (MND) for well over ten years now, but its potential in diagnosis and to identify surrogate markers of disease expression (phenotype) and progression has yet to be fully realized. The early studies using 2-18fluoro-2-deoxy-D-glucose to measure regional changes in cerebral metabolic rate for glucose gave the first clues to the more widespread involvement of the brain in MND. Later studies exploited the development of activation studies using 15O-containing tracers, which allowed correlation with neuropsychological measures, and the refinement of mapping techniques to delineate the extra-motor areas involved in the disease process. More recently, studies involving ligands such as 11C-flumazenil have allowed the exploration of functional reorganisation in MND, and inhibitory interneuronal pathways which may be crucial in modulation of disease expression. In the future new ligands will be applied in combination with other modalities of investigation (multimodal magnetic resonance imaging; neurophysiological studies) in order to understand the pathophysiology of this heterogeneous condition. Although the potential of PET has not yet been realized in ALS, it is likely to play a part in defining new diagnostic and surrogate markers of disease extent and severity.
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PMID:Positron emission tomography (PET)--its potential to provide surrogate markers in ALS. 1146 36

Dementia of motor neuron disease type (DMND) is a variety of frontotemporal dementia (FTD) which is pathologically defined by characteristic neuronal ubiquitinated, tau- and synuclein-negative intracytoplasmic inclusions. Many cases with this pathology, however, do not have motor neuron disease. In the present study, we document the presence of ubiquitinated neuronal intranuclear inclusions in a sub-population of cases of neuropathologically verified DMND. Immunohistochemical localization of ubiquitin was performed on sections of post-mortem brain from 12 patients with DMND as well as from cases with other neurodegenerative diseases including amyotrophic lateral sclerosis, Parkinson's disease, dementia with Lewy bodies, corticobasal degeneration, progressive supranuclear palsy, and multiple system atrophy. All of the cases of DMND showed ubiquitinated, tau-negative intracytoplasmic inclusions in dentate granule cells and cortical neurons. Of these 12 cases of DMND, 3 also showed neuronal ubiquitinated intranuclear inclusions. In 1 of these cases, CAG repeat expansions in the genes known to harbor these mutations were excluded. Cases with intranuclear inclusions displayed striatal atrophy and reduced brain weight relative to non-inclusion-bearing cases. In addition, patients with intranuclear inclusions tended to have a younger age of onset, a prolonged duration of disease, absence of motor neuron symptoms, and a family history of dementia. Intranuclear inclusions were not identified in the control cases with other neurodegenerative diseases. Ubiquitinated neuronal intranuclear inclusions have not been reported previously in DMND. The presence of ubiquitinated intranuclear inclusions along with striatal atrophy in a subset of cases of DMND may signify the existence of a neuropathologically distinct subset of this unique form of FTD.
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PMID:Frontotemporal dementia with ubiquitinated cytoplasmic and intranuclear inclusions. 1154 57

This study concerns an autopsy case of motor neuron disease with dementia (MND-D) that exhibited unusual clinical and neuropathological findings. The patient was a Japanese man without any relevant family history who was 60 years old at the time of death. His clinical manifestation included character change at the age of 54, followed by frozen gait, dysarthria and bradykinesia and he was diagnosed with Parkinson's disease. He gradually developed spastic paresis and died of respiratory failure 6 years after onset of the illness. Neuropathological examinations showed prominent degeneration in the striatonigral and pallidoluysian systems in addition to the neuronal loss and microvacuolation in the second to third layers of the frontal and temporal cortex, the involvement of the upper and lower motor neuron systems and the presence of ubiquitinated neuronal inclusions. To our knowledge, five cases of motor neuron disease (MND) combined with pallido-nigro-luysian atrophy (PNLA) have been reported previously, but the present case is the first report of MND-D combined with the degeneration of the striatonigral and pallidoluysian systems. Such an association may represent more than a coincidental occurrence, and it suggests that MND-D is not simply a disease of the motor neuron system but a multisystem degeneration.
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PMID:Motor neuron disease with dementia combined with degeneration of striatonigral and pallidoluysian systems. 1193 70

The purpose of this study is to verify the features of the power spectrum of postural tremors for neuromuscular disease patients and to classify the postural tremors. The subjects were 88 neuromuscular disease patients (30 Parkinson disease (PD), 25 cerebellar disease (CER), 7 multiple sclerosis (MS), 7 neuropathy (NEU), 10 motor neuron disease (MND), 9 myopathy (MYO)). The control subjects were 12 normal young persons and 10 normal aged persons. Postural tremor was detected by accelerator sensor. Postural tremor was recorded under the two postural conditions: The subjects maintained the index finger without or with a weight load of 50 g in a horizontal position while looking at a visual target in front of the tip of the index finger. The power spectrum was calculated by an auto-regressive model (AR model). The peak frequency and the peak power were evaluated under the two conditions. Two frequency components of 8-12 Hz and 20-25 Hz appeared in the postural tremor of both normal subjects and neuromuscular disease patients. The difference of the postural tremor between the subjects mainly appeared in the 8-12 Hz component during the postural tremor with a weight load. MYO patients belonged to one group (called as group P1) due to lower peak power, CER patients belonged to one group (called as group P2) due to higher peak power, and PD and MS patients belonged to one group (called as group P3) due to lower peak frequency and higher peak power. NER and MND patients belonged to one group (called as group N which meant normal group). These results suggested that the peak frequency and the peak power of the 8-12 Hz component were changed by the conditions of both spinal reflex system and central nervous system. An oscillator within the central nervous system produced the underlying frequency of 8-12 Hz component, while the amplitude of 8-12 Hz component was governed by both spinal reflex system and central nervous system. In conclusion, the classification of postural tremor for neuromuscular disease patients was a useful index to elucidate the mechanism of tremor oscillation and to assist in clinical diagnosis of neuromuscular disease.
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PMID:Evaluation of postural tremor of finger for neuromuscular diseases and its application to the classification. 1205 36

Parkinson's disease is a progressively debilitating motor neuron disease that affects the dopaminergic neurons within the nigral-striatal and surrounding pathways and which is characterized clinically by rigidity, resting tremor and bradykinesia with or without postural imbalance. Levodopa is the "gold standard" for the treatment and management of Parkinson's disease worldwide. However, following prolonged use of the drug, the "honey-moon" which was once enjoyed by patients on levodopa begins to wane. The clinical as well as the socio-economic costs associated with such failure in response to levodopa is enormous. Various approaches in the management of Parkinson's disease patients experiencing motor fluctuations with levodopa treatment have been suggested and include both pharmacologic and non-pharmacologic strategies involving invasive surgical intervention. Currently, the non-pharmacological approach, which is invasive, remains to be fully perfected and is associated with high morbidity and mortality. The use of the non-invasive, pharmacological approach is currently the most widely accepted approach but would require a review of all possible drug regimens used. This entails evaluating the pharmacokinetics and pharmacodynamic actions of the drug regimens used and possibly, dosage form and route of administration of the drugs. The use of levodopa formulated for transdermal or intranasal administration might help improve the ease of use and compliance. Controversy abounds as to the role of plasma pharmacokinetics of levodopa in the management of Parkinson's patients, vis a vis its dynamics at the central nerve terminal and its receptor site. However, it is worthy of mention that an integrated optimal pharmacological approach involving the peripheral, and central pharmacokinetics of levodopa as well as its central pharmacodynamics would ensure better treatment and management of this disease. In addition, the choice of alternate formulations and routes of administration will not only improve on the bioavailability and overall pharmacokinetics of levodopa, but also increase compliance. Furthermore, monitoring of both plasma and central concentrations of levodopa and its metabolites might play a major role in individualization of pharmacotherapy in special Parkinsonian patients experiencing motor fluctuations with levodopa.
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PMID:Role of integrative pharmacokinetic and pharmacodynamic optimization strategy in the management of Parkinson"s disease patients experiencing motor fluctuations with levodopa. 1220 67


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