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 population-based case-control study was conducted to examine the effects of past and recent physical activity on the risk of hip fracture in women. Cases included females aged 55-84 years with a first diagnosis of hip fracture in 1989 in metropolitan Toronto, Canada. Controls were a population-based random sample frequency matched by 5-year age groups. Data were collected on 381 cases and 1,138 controls by self-administered mailed questionnaires or telephone interviews. Past activity was calculated as a compilation of activity scores at ages 16, 30, and 50 years. Recent activity was defined as activity in the past year for controls and activity in the year before fracture for cases. Multiple logistic regression was used to control for age, previous fracture, obesity, smoking, osteoporosis, epilepsy, stroke or Parkinson's disease, daily intake of dietary calcium, and duration of use of supplemental calcium, fluoride, and estrogen. After recent activity was adjusted for, statistically significant effects were found for women who in the past had been active (odds ratio estimate (OR) = 0.66, 95% confidence interval (CI) 0.45-0.96) or very active (OR = 0.54, 95% CI 0.33-0.88). After past activity was adjusted for, a similar protective effect was found for women who were moderately active recently (OR = 0.61, 95% CI 0.41-0.90), but women who were very active recently were not protected from hip fracture (OR = 1.15, 95% CI 0.72-1.83). This study showed evidence of independent protective effects of past physical activity and of moderate levels of recent physical activity on the risk of hip fracture in postmenopausal women.
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PMID:Past and recent physical activity and risk of hip fracture. 834 29

Methionine metabolism and transmethylation are central to the metabolism and differentiation of all known cells. In enkaryotic organisms, methionine metabolism and transmethylation are of paramount importance in modification and regulation of proteins, lipids, and nucleic acids. The differential methylation of genes regulates their expression in the myriad of cells in eukaryotic organisms. Disruption and abnormalities in methionine metabolism and transmethylation seems to be associated with the major diseases of mankind, including cancer, heart disease, aging, obesity, and Parkinson's disease. In this review, we describe how aberrant and abnormal methionine metabolism and transmethylation are related to these major diseases. Most importantly, we review and hypothesize how the developing therapeutic recombination methioninase (rMETase) can be utilized to cure or prevent all of these diseases.
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PMID:Methioninase: a therapeutic for diseases related to altered methionine metabolism and transmethylation: cancer, heart disease, obesity, aging, and Parkinson's disease. 923 67

Virtual Reality Environments for Psychoneurophysiological Assessment and Rehabilitation-is an European Community funded project (Telematics for health-HC 1053 http:/(/)www.etho.be/ht_projects/vrepar/) whose aim is: to develop a PC based virtual reality system (PC-VRS) for the medical market that can be marketed at a price which is accessible to its possible end-users (hospitals, universities and research centres) and which would have the modular, connectability and interoperability characteristics that the existing systems lack; to develop three hardware/software modules for the application of the PC VRS in psychoneurophysiological assessment and rehabilitation. The chosen development areas are eating disorders (bulimia, anorexia and obesity), movement disorders (Parkinson's disease and torsion dystonia) and stroke disorders (unilateral neglect and hemiparesis). This paper presents the rationale of the different approaches and the methodology used.
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PMID:Virtual reality environments for psycho-neuro-physiological assessment and rehabilitation. 1016 30

The TaqIA D2 dopamine receptor (DRD2) minor (A1) allele was first associated with severe alcoholism a decade ago. Since then, studies both confirming and not confirmnning this finding were reported. However, a meta-analysis of a large number of Caucasian alcoholics (both more severe and less severe) and controls (both assessed and unassessed for substance use disorders) revealed a significantly higher frequency (p < 10(-6)) and prevalence (p < 10(-8)) of the DRD2 A1 allele in the alcoholics. Further analysis showed that the more severe alcoholics had a 3-fold higher prevalence of the DRD2 A1 allele than the assessed controls (p < 10(-10)), whereas no difference was found between the less severe alcoholics and the unassessed controls. DRD2 exonic or promoter mutations have not yet been associated with alcoholism, although two intronic variants at the TaqIB and intron 6 sites, which are in linkage disequilibrium with the TaqIA site, were associated with this disorder. Variants of the DRD2 gene have also been associated with cocaine, nicotine and opioid dependence, obesity and gambling. It is hypothesised that the DRD2 is a reinforcement or reward gene. Although less intensively studied than substance use disorders, the DRD2 gene has been implicated in Tourette's syndrome (TS), post-traumatic stress disorder (PTSD) and certain symptoms associated with affective disorders and schizophrenia. Further, DRD2 variants have been implicated in Parkinson's disease (PD) and in iatrogenically-induced movement disorders, as well as in certain migraineurs. Phenotypic differences have been associated with DRD2 variants. These include reduced D2 dopamine receptor numbers and diminished glucose metabolism in the brain of subjects who carry the DRD2 A1 allele. In addition, phenotypic differences have been found in neurocognitive and personality characteristics, and in treatment outcome of DRD2 variants. The involvement of the DRD2 gene in certain neuropsychiatric disorders opens up the potential of a targeted pharmacogenomic approach to the prevention and treatment of these disorders.
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PMID:The DRD2 gene in psychiatric and neurological disorders and its phenotypes. 1125 81

We are currently sequencing the entire mitochondrial genome from 600 persons, including centenarians, patients with Parkinson's disease or diabetes, and young adults with or without obesity to search for single nucleotide polymorphisms (SNPs) associated with longevity or diseases. To test the hypothesis that centenarians are free from deleterious mitochondrial variations, we analyzed amino acid variations in cytochrome b of 64 Japanese centenarians. Although the frequencies of some variations, such as N260D and G251S, differed significantly between centenarians and patients with Parkinson's disease, the most striking feature of centenarian cytochrome b was the much greater scarceness of amino acid variations in contrast with the variety of amino acid replacements in patients with Parkinson's disease. Particular deviations from the standard amino acid sequence may be associated with increased production by mitochondria of reactive oxygen species. The absence of certain variations in centenarians and their presence in patients with Parkinson's disease indicate that these variations do not benefit long-term survival but do predispose to adult-onset diseases and that centenarians are genetically hitting the "golden mean."
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PMID:Mitochondrial genotypes and cytochrome b variants associated with longevity or Parkinson's disease. 1237 58

The major psychoactive constituent of Cannabis sativa, delta(9)-tetrahydrocannabinol (delta(9)-THC), and endogenous cannabinoid ligands, such as anandamide, signal through G-protein-coupled cannabinoid receptors localised to regions of the brain associated with important neurological processes. Signalling is mostly inhibitory and suggests a role for cannabinoids as therapeutic agents in CNS disease where inhibition of neurotransmitter release would be beneficial. Anecdotal evidence suggests that patients with disorders such as multiple sclerosis smoke cannabis to relieve disease-related symptoms. Cannabinoids can alleviate tremor and spasticity in animal models of multiple sclerosis, and clinical trials of the use of these compounds for these symptoms are in progress. The cannabinoid nabilone is currently licensed for use as an antiemetic agent in chemotherapy-induced emesis. Evidence suggests that cannabinoids may prove useful in Parkinson's disease by inhibiting the excitotoxic neurotransmitter glutamate and counteracting oxidative damage to dopaminergic neurons. The inhibitory effect of cannabinoids on reactive oxygen species, glutamate and tumour necrosis factor suggests that they may be potent neuroprotective agents. Dexanabinol (HU-211), a synthetic cannabinoid, is currently being assessed in clinical trials for traumatic brain injury and stroke. Animal models of mechanical, thermal and noxious pain suggest that cannabinoids may be effective analgesics. Indeed, in clinical trials of postoperative and cancer pain and pain associated with spinal cord injury, cannabinoids have proven more effective than placebo but may be less effective than existing therapies. Dronabinol, a commercially available form of delta(9)-THC, has been used successfully for increasing appetite in patients with HIV wasting disease, and cannabinoid receptor antagonists may reduce obesity. Acute adverse effects following cannabis usage include sedation and anxiety. These effects are usually transient and may be less severe than those that occur with existing therapeutic agents. The use of nonpsychoactive cannabinoids such as cannabidiol and dexanabinol may allow the dissociation of unwanted psychoactive effects from potential therapeutic benefits. The existence of other cannabinoid receptors may provide novel therapeutic targets that are independent of CB(1) receptors (at which most currently available cannabinoids act) and the development of compounds that are not associated with CB(1) receptor-mediated adverse effects. Further understanding of the most appropriate route of delivery and the pharmacokinetics of agents that act via the endocannabinoid system may also reduce adverse effects and increase the efficacy of cannabinoid treatment. This review highlights recent advances in understanding of the endocannabinoid system and indicates CNS disorders that may benefit from the therapeutic effects of cannabinoid treatment. Where applicable, reference is made to ongoing clinical trials of cannabinoids to alleviate symptoms of these disorders.
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PMID:Therapeutic potential of cannabinoids in CNS disease. 1261 97

Little is known about body composition in Parkinson's disease (PD). We studied 35 patients (20 male, 15 female subjects; mean age 69.7+/-5.8 years) with advanced PD by anthropometry, dual-energy X-ray absorptiometry (DEXA), and serum 25-OH vitamin D measurement. Over 70% of patients had a disease duration of more than 4 years; all were on L-dopa treatment. Low levels of serum 25-OH vitamin D were present in 41% of the patients. The mean body mass index (BMI) was 25.3+/-4.3 kg/m(2) (range 17.1-37.3). Mid-arm muscle circumference was below the 10th percentile in 23%. For whole-body mean (+/-SD) bone mineral density, the T score was below -1 SD in 35% of patients, and the Z score was below -1 SD in 24%. Percent fat mass measured with DEXA was 30.6+/-11.4% (range 10.1-45.5) in the overall sample; it was 21.1+/-8.8% (range 10.1-30.4) in male subjects and 38.1+/-9.2% (range 25.8-45.5) in female subjects. We conclude that advanced-stage PD may show excess adiposity coexisting with depletion of lean body mass (sarcopenic obesity), in addition to decreased whole-body bone mineral density associated with low serum 25-OH vitamin D. A low level of physical activity and inadequate exposure to sunlight are likely to be among the putative causes.
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PMID:Body composition in advanced-stage Parkinson's disease. 1461 69

Dopamine is involved in the regulation of food intake, and obese persons have decreased dopamine D2 receptor availability in the striatum. Furthermore, midlife triceps skinfold thickness has been found to be positively associated with the risk of Parkinson's disease (PD) among Japanese-American men in Hawaii. The authors prospectively investigated whether obesity was associated with PD risk in two large cohorts of US men and women. They documented 249 cases of PD in men (1986-2000) and 202 cases in women (1976-1998). Neither baseline body mass index (weight (kg)/height (m)(2)) nor early adult body mass index was associated with PD risk. The multivariate relative risk for a baseline body mass index of > or = 30 versus <23 was 0.8 (95% confidence interval (CI): 0.6, 1.2; p for trend = 0.3). Overall, waist circumference and waist-to-hip ratio were not related to PD risk. However, among never smokers, both variables showed significantly positive associations with PD risk. The relative risks for comparisons of extreme quintiles were 1.9 (95% CI: 1.0, 3.4; p for trend = 0.03) for waist circumference and 2.0 (95% CI: 1.1, 3.6; p for trend = 0.03) for waist-to-hip ratio. The results do not support a role of overall obesity in PD pathogenesis; however, central obesity may be associated with higher PD risk among never smokers, and this finding merits further investigation.
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PMID:Obesity and the risk of Parkinson's disease. 1500 58

Polymorphisms in the human mitochondrial genome have been used for the elucidation of phylogenetic relationships among various ethnic groups. Because analysis by mitochondrial genetics has detected pathogenic mutations causing mitochondrial encephalomyopathy or cardiomyopathy, most of the mitochondrial single nucleotide polymorphisms (mtSNPs) found in control subjects have been regarded as merely normal variants. However, we cannot exclude the possibility that the mitochondrial functional differences among individuals are ascribable at least in part to the mtSNPs of each individual. Human lifespan in ancient history was much shorter than that at the present time. Therefore, it is reasonable to speculate that certain mtSNPs that predispose one toward susceptibility to adult- or elderly-onset diseases, such as Parkinson's disease and Alzheimer's disease, have never been a target for natural selection in the past. Similarly, thrifty mtSNPs that had been advantageous for survival under severe famine or cold climate conditions might turn out to be related to satiation-related diseases, such as diabetes mellitus and obesity. To examine these hypotheses, we have constructed a mtSNP database by sequencing the entire mitochondrial genomes of 672 subjects: 96 in each of seven groups (i.e., centenarians, young obese or non-obese subjects, diabetic patients with or without major vascular involvement, patients with Parkinson's disease, and those with Alzheimer's disease).
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PMID:Mitochondrial genome single nucleotide polymorphisms and their phenotypes in the Japanese. 1512 79

More than 20 syndromes among the significant and increasing number of degenerative diseases of neuronal tissues are known to be associated with diabetes mellitus, increased insulin resistance and obesity, disturbed insulin sensitivity, and excessive or impaired insulin secretion. This review briefly presents such syndromes, including Alzheimer disease, ataxia-telangiectasia, Down syndrome/trisomy 21, Friedreich ataxia, Huntington disease, several disorders of mitochondria, myotonic dystrophy, Parkinson disease, Prader-Willi syndrome, Werner syndrome, Wolfram syndrome, mitochondrial disorders affecting oxidative phosphorylation, and vitamin B(1) deficiency/inherited thiamine-responsive megaloblastic anemia syndrome as well as their respective relationship to malignancies, cancer, and aging and the nature of their inheritance (including triplet repeat expansions), genetic loci, and corresponding functional biochemistry. Discussed in further detail are disturbances of glucose metabolism including impaired glucose tolerance and both insulin-dependent and non-insulin-dependent diabetes caused by neurodegeneration in humans and mice, sometimes accompanied by degeneration of pancreatic beta-cells. Concordant mouse models obtained by targeted disruption (knock-out), knock-in, or transgenic overexpression of the respective transgene are also described. Preliminary conclusions suggest that many of the diabetogenic neurodegenerative disorders are related to alterations in oxidative phosphorylation (OXPHOS) and mitochondrial nutrient metabolism, which coincide with aberrant protein precipitation in the majority of affected individuals.
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PMID:Neurodegenerative disorders associated with diabetes mellitus. 1517 61


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