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)

In the Rotterdam Study, prevalence and determinants of chronic diseases in the elderly (age > or = 55 years), were investigated in inhabitants of Ommoord, a suburb of Rotterdam. The study focused on cardiac diseases (myocardial infarction, angina pectoris, cardiovascular risk factors), glaucoma, macular degeneration, osteoporosis, osteoarthrosis and invalidity, dementia (Alzheimer's disease, vascular dementia, Parkinson's disease), epilepsy, cerebrovascular accident. The number of participants was 7983 (3105 men, 4878 women), a response of 78%. The participants were interviewed and were twice examined in an out-patient clinic. The results will be described in subsequent issues of this journal.
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PMID:[Prevalence of chronic diseases in the elderly; the ERGO study (Erasmus Rotterdam Health and the Elderly)]. 747 40

The decision to stop driving leads to severe contraction of independence, and most localities do not curtail driving privileges in impaired elders. In a population of community-based, ambulatory individuals 70-96 years old, annual medical screening showed that 276 of 1,656 (16.7 +/- 1.8%) who reported driving regularly in the past do not currently drive. The cessation of driving behavior was examined in terms of specific medical conditions occurring within the past 5 years. Retired drivers were disproportionately female, and driving cessation risk rose with age. Age-sex-adjusted logistic regression found that six conditions explained about 50 percent of the decisions to stop driving: macular degeneration; retinal hemorrhage; any deficit in Activities of Daily Living; Parkinson's disease; stroke-related residual paralysis or weakness; and syncope. Strikingly, only 1.8 percent of those who stopped driving had ever had a license revoked; 58.7 percent reported voluntarily stopping; 31.9 percent gave health or medical reasons. Clearly, the decision to cede driving privileges is complex and not dependent solely on medical problems.
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PMID:Medical conditions associated with driving cessation in community-dwelling, ambulatory elders. 831 47

A range of compounds in or derived from the diet modulates apoptosis in cell cultures in vitro. These observations have important implications concerning the mechanisms whereby dietary components affect health. Proapoptotic compounds could protect against cancer by enhancing elimination of initiated, precancerous cells, and antiapoptotic compounds could promote tumor formation by inhibiting apoptosis in genetically damaged cells. Proapoptotic compounds could also contribute to age-related degenerative diseases by activating cell death in postmitotic cells or shifting the normal balance of mitosis and apoptosis in tissues with regenerative capacity. Many age-related diseases, for example macular degeneration and Parkinson's disease, appear to have oxidative stress as an underlying component that interacts with genetic, dietary, and environmental factors to determine relative risk in an individual. Oxidative stress activates apoptosis, and antioxidants protect against apoptosis in vitro; thus, a central role of dietary antioxidants may be to protect against apoptosis. However, little in vivo data are available to directly link diet with altered apoptosis as an underlying determinant of disease. Moreover, the possible antagonistic effects of different dietary components and the uncertainty about whether proapoptotic compounds that may protect against cancer could contribute to degenerative diseases and vice versa indicate that there is a great need for better in vivo assessment of apoptosis and that caution should be exercised when extrapolating in vitro data on apoptosis to in vivo dietary recommendations.
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PMID:Diet and apoptosis. 1094 Mar 43

The role of saccadic adaptive processes in recovery from the effects of various neurological disorders, such as myasthenia gravis, extraocular muscle palsies, and age-related macular degeneration, is reviewed. Studies of clinical populations (e.g. cerebellar disease, mild closed head injury, and opsoclonus) in which intrasaccadic displacement of visual targets has been used to stimulate adaptation are also reviewed. Our own data from such a study of 12 subjects with Parkinson's disease are presented, showing that visually guided adaptation is preserved in PD while memory-guided adaptation is impaired. This supports a model in which different brain regions subserve adaptation in different tasks.
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PMID:Saccadic adaptation in neurological disorders. 1250 6

At has been reported that transplantation of appropriate cells, growth factors, and/or extracellular matrix may help the regeneration of damaged tissues or organs. Some growth factors, such as basic fibroblast growth factor(bFGF), have been successfully transferred to patients with ischemic heart disease. Embryonic dopamine neurons were also transplanted into the brains of patients with Parkinson's disease successfully. We have also performed cultured auto iris pigment epithelial cell (IPE) transplantation into the subretinal space after removal of choroidal neovascularization in patients with age-related macular degeneration (AMD). Here, we report the results of auto IPE transplantation in 35 patients, who could be followed for more than 6 months. We also tried to apply cell transplantation to other retinal diseases by managing the transplanted cells as introduced growth factor genes. Auto IPE transplantation was performed after removal of choroidal neovascular membranes (CNV). Visual acuity wes improved by more than 0.2 log MAR in 18 of 35 patients (51.5%), it was unchanged in 11 patients (31.5%), and it was worsened in 6 patients (17%). No significant difference was observed in comparison to patients who underwent CNV removal only. However, unlike the previous reports, we found no patients showing rejection. We also found that the cultured transplanted cells never showed proliferation under the retina or in the vitreous cavity and concluded that cultured auto IPE transplantation can be performed safely without complications. Next, we examined whether cell transplantation can be expanded to other degenerative retinal diseases. One of our results showed that host RPE may play an important role against the transplanted cells in the subretinal regions. When we introduced bFGF gene into the cells, we found synexpression cluster of the genes in the cells. One of the most prominent movements among the genes was lysyl oxidase like-1 gene, which plays an important role in the maturation of the extracellular collagen and in cell attachment. However, when we examined the cell attachment on the culture plates after 12 hours of culture, no significant difference was observed between the cells with or without bFGF. Further, when we examined the area of the cells transplanted into the subretinal space of rats during successive follow-up using fluorescein marker (EGFP), no statistical significance was observed. The gene expression pattern may be different when we introduce different growth factor gene. No antibody production was generated against the growth factor gene introduced cells after cell transplantation. Further, when we made transgenic mice expressing bFGF or Axokine cDNA in the RPE of rd mice, no photoreceptor degeneration was observed. One of the reasons was suspected to be that bFGF was expressed systemically by the promoter of tyrosinase related-protein 1 gene and may lead to lethality. Another reason was suspected to be suppression of the function of Axokine by the down-regulation of the ciliary neurotrophic factor or its receptor gene. Conversely, when we produced photoreceptor degeneration by constant light damage in the rats, we found partial photoreceptor rescue by transplantation of the growth factor gene introduced RPE. We show here the possibility that growth factor gene introduced cell transplantation may be applied to retinal diseases, if we select appropriate cells and genes.
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PMID:[Regeneration of the retina using pigment epithelial cell transplantation]. 1261 Aug 37

Chronic inflammation is associated with a broad spectrum of neurodegenerative diseases of aging. Included are such disorders as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis, the Parkinson-dementia complex of Guam, all of the tauopathies, and age-related macular degeneration. Also included are such peripheral conditions as osteoarthritis, rheumatoid arthritis, atherosclerosis, and myocardial infarction. Inflammation is a two-edged sword. In acute situations, or at low levels, it deals with the abnormality and promotes healing. When chronically sustained at high levels, it can seriously damage viable host tissue. We describe this latter phenomenon as autotoxicity to distinguish it from autoimmunity. The latter involves a lymphocyte-directed attack against self proteins. Autotoxicity, on the other hand, is determined by the concentration and degree of activation of tissue-based monocytic phagocytes. Microglial cells are the brain representatives of the monocyte phagocytic system. Biochemically, the intensity of their activation is related to a spectrum of inflammatory mediators generated by a variety of local cells. The known spectrum includes, but is not limited to, prostaglandins, pentraxins, complement components, anaphylotoxins, cytokines, chemokines, proteases, protease inhibitors, adhesion molecules, and free radicals. This spectrum offers a huge variety of targets for new anti-inflammatory agents. It has been suggested, largely on the basis of transgenic mouse models, that stimulating inflammation rather than inhibiting it can be beneficial in such diseases as AD. If this were the case, administration of NSAIDs, or other anti-inflammatory drugs, would be expected to exacerbate conditions such as AD, PD, and atherosclerosis. However, epidemiological evidence overwhelmingly demonstrates that the reverse is true. This indicates that, at least in these diseases, the inflammation is harmful. So far, advantage has not been taken of opportunities indicated by these epidemiological studies to treat AD and PD with appropriate anti-inflammatory agents. Based on this evidence, classical NSAIDs are the most logical choice. Dosage, though, must be sufficient to combat the inflammation. Analysis of mRNA levels of inflammatory mediators indicates that the intensity of inflammation is considerably higher in AD hippocampus and in PD substantia nigra than in osteoarthritic joints. Thus, full therapeutic doses of NSAIDs, or combinations of anti-inflammatory agents, are needed to achieve the suggested neurological benefits.
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PMID:Inflammation and the degenerative diseases of aging. 1568 3

For the last century, there has been great physiological interest in brain iron and its role in brain function and disease. It is well known that iron accumulates in the brain for people with Huntington's disease, Parkinson's disease, Alzheimer's disease, multiple sclerosis, chronic hemorrhage, cerebral infarction, anemia, thalassemia, hemochromatosis, Hallervorden-Spatz, Down syndrome, AIDS and in the eye for people with macular degeneration. Measuring the amount of nonheme iron in the body may well lead to not only a better understanding of the disease progression but an ability to predict outcome. As there are many forms of iron in the brain, separating them and quantifying each type have been a major challenge. In this review, we present our understanding of attempts to measure brain iron and the potential of doing so with magnetic resonance imaging. Specifically, we examine the response of the magnetic resonance visible iron in tissue that produces signal changes in both magnitude and phase images. These images seem to correlate with brain iron content, perhaps ferritin specifically, but still have not been successfully exploited to accurately and precisely quantify brain iron. For future quantitative studies of iron content we propose four methods: correlating R2' and phase to iron content; applying a special filter to the phase to obtain a susceptibility map; using complex analysis to extract the product of susceptibility and volume content of the susceptibility source; and using early and late echo information to separately predict susceptibility and volume content.
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PMID:Imaging iron stores in the brain using magnetic resonance imaging. 1573 84

Photobiomodulation by light in the red to near infrared range (630-1000 nm) using low energy lasers or light-emitting diode (LED) arrays has been shown to accelerate wound healing, improve recovery from ischemic injury in the heart and attenuate degeneration in the injured optic nerve. Recent evidence indicates that the therapeutic effects of red to near infrared light result, in part, from intracellular signaling mechanisms triggered by the interaction of NIR light with the mitochondrial photoacceptor molecule cytochrome c oxidase. We have demonstrated that NIR-LED photo-irradiation increases the production of cytochrome oxidase in cultured primary neurons and reverses the reduction of cytochrome oxidase activity produced by metabolic inhibitors. We have also shown that NIR-LED treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients. Photobiomodulation improves wound healing in genetically diabetic mice by upregulating genes important in the promotion of wound healing. More recent studies have provided evidence for the therapeutic benefit of NIR-LED treatment in the survival and functional recovery of the retina and optic nerve in vivo after acute injury by the mitochondrial toxin, formic acid generated in the course of methanol intoxication. Gene discovery studies conducted using microarray technology documented a significant upregulation of gene expression in pathways involved in mitochondrial energy production and antioxidant cellular protection. These findings provide a link between the actions of red to near infrared light on mitochondrial oxidative metabolism in vitro and cell injury in vivo. Based on these findings and the strong evidence that mitochondrial dysfunction is involved in the pathogenesis of numerous diseases processes, we propose that NIR-LED photobiomodulation represents an innovative and non-invasive therapeutic approach for the treatment of tissue injury and disease processes in which mitochondrial dysfunction is postulated to play a role including diabetic retinopathy, age-related macular degeneration, Leber's hereditary optic neuropathy and Parkinson's disease.
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PMID:Mitochondrial signal transduction in accelerated wound and retinal healing by near-infrared light therapy. 1612 Apr 14

Inflammation is characteristic of neurodegenerative diseases of aging. Neuropathological evidence of activated microglia and activated astrocytes in lesioned areas, combined with epidemiological evidence of sparing of Alzheimer's disease (AD), Parkinson's disease (PD) and age-related macular degeneration (AMD) in long-term users of anti-inflammatory agents, indicates that inflammation is autodestructive of neurons. Locally produced autodestructive molecules include the membrane attack complex (MAC) of complement and oxygen-free radicals. Stimulation is provided by a variety of inflammatory cytokines. Agents which reduce the intensity of inflammation should have broad spectrum application in degenerative diseases of aging.
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PMID:Inflammation, the complement system and the diseases of aging. 1619 46

1. Retinal dystrophies (RD) comprise a group of clinically and genetically heterogeneous retinal disorders, which typically result in the degeneration of photoreceptors followed by the impairment or loss of vision. Although age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are among the most common forms of RD, currently, there is no effective treatment for either disorder. 2. Recently, abnormal protein accumulation and aggregation due to protein misfolding and proteasome inhibition have been implicated in the pathogenesis of RD. In this paper we describe effects of several factors on protein aggregation and survival of photoreceptor cells. 3. Expression of rhodopsin carrying P23H mutation causes its accumulation in intracellular inclusion bodies in a perinuclear area of photoreceptor cells. beta- and gamma-synucleins and heat shock protein Hsp-70, but not alpha-synuclein, protect cultured ocular cells from mutant opsin accumulation. This effect might be explained by their chaperonic activity. 4. Knock-out of alpha- and gamma-synucleins does not affect gross retinal morphology, but induces tyrosine hydroxylase in the inner prexiform layer of the retina. Selegiline-a monoamine oxidase inhibitor used for the treatment of Parkinson's disease, reduces apoptosis and increases viability in cultured retinal pigment epithelium cells (APRE-19). 5. These results suggest that chaperones and selegiline may be considered promising candidates for the protection of ocular cells from the accumulation of misfolded and aggregated proteins.
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PMID:Protein aggregation in retinal cells and approaches to cell protection. 1639 36


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