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)

A mutant mitochondrial DNA (mtDNA) with a 4,977-bp deletion was detected in the parkinsonian brain by using the polymerase chain reaction. Although the deleted mtDNA was detectable even in the brain of aged controls, the proportion of deleted mtDNA to normal mtDNA in the striatum was higher in the parkinsonian patients than in the controls. In both the parkinsonian patients and the aged controls, the proportion was higher in the striatum than in the cerebral cortex. These results indicate that age-related accumulation of deleted mtDNA is accelerated in the parkinsonian striatum and suggest that the deletion contributes to pathophysiological processes underlying Parkinson's disease.
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PMID:Increase of deleted mitochondrial DNA in the striatum in Parkinson's disease and senescence. 239 73

The etiology of Parkinson's disease remains an enigma. Yet substantial progress toward its elucidation has been made in recent years. This disease has emerged as a particular morbid entity with a characteristic pathology and clinical expression. Viral encephalitis and heredity, which have long dominated discussions of the possible causes of the disease, appear to have been excluded. However, the possibility of a viral or subviral pathogen as the causative factor has not been excluded. The discovery of a selective dopaminergic neurotoxin, MPTP, which is active via any portal of entry, has raised the question of a toxic etiology. Current attention has focused on the search for an environmental agent. Recent studies of the Lewy body, the pathologic hallmark of Parkinson's disease, point to possible defects in neurofilament synthesis or transport. The finding that cultured cells from patients with Parkinson's disease have an abnormal radiosensitivity suggests that an acquired defect in DNA repair mechanisms may play a role.
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PMID:Etiology of Parkinson's disease: current concepts. 242 34

In juvenile parkinsonism (JP), unlike naturally occurring Parkinson's disease, high frequency of familial onset is observed, which suggests the involvement of some genetic factor(s) in the pathogenesis of the disease. In an attempt to conduct a molecular genetic approach to JP, we tried to isolate tyrosine hydroxylase (TH) cDNA from human pheochromocytoma, and demonstrated the existence of four types of cDNA (type 1, 2, 3 and 4), differing in the 5'-terminal region. All four cDNAs had the same sequence in common from ATG of the translation start codon to 90th nucleotide. However, in types 2, 3 and 4, characteristic sequences were inserted between 90th and 91 st nucleotides of type 1 cDNA. TH genomic DNA cloning showed that the multiple form of mRNA were produced from a single gene through alternative splicing. Four types of cDNA was expressed in COS cells. They exhibited different homospecific activities: type 1 TH having the highest activity, others less than 40% of type 1 TH. The question whether possible change in TH gene is related to the pathogenesis of JP is now being pursued based on these molecular biological understanding of TH gene.
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PMID:[Pathogenesis of Parkinson's disease, a molecular genetic approach]. 257 27

The cerebrospinal-fluid copper concentration, measured by electrothermal atomisation/atomic absorption spectrophotometry, was significantly higher in 24 patients with untreated, idiopathic Parkinson's disease than in a control population of 34 patients (p less than 0.001). The difference in the in-vitro capacity of copper to damage DNA, measured by the phenanthroline assay was even greater. The high phenanthroline-copper concentration correlated with disease severity (p = 0.02) and with the rate of progression of disease (p less than 0.05). A possible role is suggested for copper-catalysed oxidative mechanisms in the pathogenesis of Parkinson's disease.
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PMID:Raised cerebrospinal-fluid copper concentration in Parkinson's disease. 288 15

In situ hybridization (ISH) to detect and to quantitate viral nucleic acid sequences in cryopreserved central nervous system (CNS) tissue is a reliable, valid and sensitive molecular technique. On the other hand, utilization of formaldehyde fixed paraffin embedded (FFPE) tissue to improve cytomorphology requires fundamental changes in the procedure since it is necessary to cleave the elaborate protein network cross-linked by formaldehyde using elevated concentrations of proteinases in order to permit diffusion of complementary DNA probes to the targets (genomic viral nucleic acid sequences and/or viral mRNA). Adversely, this procedure hydrolyzed the proteinaceous glues generally used to fix tissue to glass slides resulting in loss of tissue sections during the ISH protocol. This report describes the application of a novel procedure utilizing a silano-organic compound to covalently bond to glass slides FFPE sections as well as cryopreserved tissue sections and cultured cells with and without virus infections. This covalent bonding procedure has permitted optimization of the ISH procedure for virus detection and quantification, especially for exploratory studies of specificity and wash stringency in relation to the Tm of the hybridized product. Progressive multifocal leucoencephalopathy (PML) caused by an opportunistic papovavirus (JC) was chosen because of the ready availability of tissue, stability of papovavirus nucleic acids, and specificity of 3H- and 35S-radiolabeled JC cloned DNA probes. Further, this laboratory is utilizing the optimized sensitive procedure to search for several virus etiologies in human diseases such as multiple sclerosis, temporal lobe epilepsy, Alzheimer's disease, schizophrenia, and Parkinson's disease, as well as normal aging.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quest for a reliable, valid, and sensitive in situ hybridization procedure to detect viral nucleic acids in the central nervous system. 329 27

Levodopa-carbidopa has been widely used in the treatment of Parkinson's disease. We are currently investigating the effectiveness of this combination for the treatment of patients with advanced malignant melanoma. As part of this study, we have examined the effects of this combination on the phytohemagglutinin-induced transformation of human lymphocytes, isolated from patients with malignant melanoma prior to undergoing treatment. Levodopa, as well as carbidopa and 3 additional levodopa synthetic analogs, inhibited the transformation of phytohemagglutinin-stimulated DNA synthesis at pharmacologically attainable levels. These results confirm our earlier preclinical observations suggesting that catechols have profound intracellular metabolic effects in a variety of cells other than melanoma cells. It is possible that some of the effects of catechols in other diseases might also be mediated by similar intracellular metabolic effects, and effects on human melanoma might be mediated in part through effects on the immune system. We are currently awaiting introduction of synthetic catechols, including 3,4-dihydroxybenzylamine (NSC 263475), to extend these observations to our clinical studies in patients with advanced metastatic disease.
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PMID:Inhibition of transformation by levodopa-carbidopa in lymphocytes derived from patients with melanoma. 357 25

Nonhuman primates are excellent animal models for human diseases because of their close relationship to humans. Indeed, comparisons of the chromosomes and DNA homologies between primates and humans testify to the commonality of the genetic material between these phylogenetically related species. Not surprisingly, this close relationship at the genotypic level extends to the phenotypic level. Thus, the patho-physiological responses of humans and nonhuman primates to internal and external insults are remarkably similar. Two types of human diseases for which nonhuman primates are paramount animal models are discussed. One type includes diseases with defined, single agent etiologies and to which all members of the species are genetically susceptible. Examples of these are leprosy, AIDS, hepatitis and Parkinson's disease. A second type represents diseases that have a substantial genetic component, but are multifactorial and are greatly influenced by the environment. Examples of these are diabetes, lymphoma, atherosclerosis, alcoholic cirrhosis and anxiety disorders. Nonhuman primates are also ideally suited to the role of animal models in the new area of human gene therapy. In the future, biomedical research will focus increasingly on genetic manipulations such as the transfer of genes from one individual to another to correct genetic diseases, particularly those diseases caused by single recessive gene defects. Before gene transfers are attempted in humans, they should be done in nonhuman primates. In a real sense, nonhuman primates, as animal models, represent the "step to man."
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PMID:Genetic significance of some common primate models in biomedical research. 360 96

Fibroblast and/or lymphoblastoid lines from patients with several inherited primary neuronal degenerations are hypersensitive to DNA-damaging agents. Therefore, lymphoblastoid lines were irradiated from patients with sporadic Parkinson's disease (PD), Alzheimer's disease, and amyotrophic lateral sclerosis. The mean survival values of the eight Parkinson's disease and of the six Alzheimer's disease lines, but not of the five amyotrophic lateral sclerosis lines, were less than that of the 28 normal lines. Our results with Parkinson's disease and Alzheimer's disease cells can be explained by a genetic defect arising as a somatic mutation during embryogenesis, causing defective repair of the X-ray type of DNA damage. Such a DNA repair defect could cause an abnormal accumulation of spontaneously occurring DNA damage in Parkinson's disease and Alzheimer's disease neurons in vivo, resulting in their premature death.
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PMID:Parkinson's disease and Alzheimer's disease: hypersensitivity to X rays in cultured cell lines. 387 9

The contribution of genetic differences to variation in ageing and the relationship of ageing to certain types of dementia are discussed. Neuropathological changes commonly found in the ageing brain are present in more severe form in Alzheimer-type dementia, Down's syndrome, multi-infarct dementia, and a substantial number of patients with Parkinson's disease. An increased frequency of ageing-associated changes outside the brain have been reported in Alzheimer-type dementia, Down's syndrome, and multi-infarct dementia, although the evidence is generally meagre and in many cases requires further corroboration. Genetic studies of Alzheimer-type dementia support the existence of heterogeneity on the basis of family history and age of onset; early onset is associated with greater genetic risk and severity of abnormality. The increasing evidence of an association between DNA damage, premature ageing, and neuronal cell loss may provide insights into the aetiology of these and other forms of dementia.
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PMID:Genetics, ageing and dementia. 623 64

Among the white races, the prevalence rates of Parkinson's disease range from 66 to 187 per 100,000 population, through without any obvious geographical pattern. A similar variation is found in the annual incidence rates with estimates from 5 to 24 per 100,000 population. The black races may be partially protected against the disease. Both sexes are probably equally affected by the disease. Parkinson's disease usually begins after the age of 50 years, and the risk of the disease steeply rises with advancing age. Parkinson's disease is often omitted in death certificates; mortality rates with Parkinson's disease as an underlying cause of death vary from 0.5 to 3.8 per 100,000. Levodopa treatment, by reducing the excess mortality accompanying the natural course of Parkinson's disease, may increase the number of patients living with this disease in the near future. Postencephalitic Parkinson's disease, developing as a sequel to lethargic encephalitis and accounting for some two thirds of parkinsonian cases shortly after the epidemic, has probably been a transient phase in the epidemiology of Parkinson's disease and is now disappearing. Data from epidemiological investigations have advanced our understanding of the cause of Parkinson's disease only to a small extent. No other characteristic than race has been found to influence the susceptibility to the disease. The environmental risks for Parkinson's disease have not been unequivocally demonstrated. Highly conflicting information is available as to the contribution of hereditary to the pathogenesis of Parkinson's disease. Seroepidemiological investigations have shown an increased antibody response against herpes simplex virus in parkinsonian patients, but attempts to detect herpes virus specific products or DNA sequences in the brain material have been unsuccessful.
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PMID:Epidemiology of Parkinson's disease--an overview. 726 26


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