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)

Levels of biopterin derivatives in urine, serum, milk, cerebrospinal fluid, brain, and liver have been measured with the Crithidia fasciculata assay. Normal levels in serum and urine have been given and compared with those in a number of benign and malignant proliferative disorders, phenylketonuria, kidney disease, Parkinson's disease, schizophrenia, controlled epilepsy, rheumatoid arthritis, and pernicious anaemia. The active component of Crithidia factor in serum was 7,8-dihydrobiopterin. Tissue, urine, and some serum samples contained two active materials, the principal one being 7,8-dihydrobiopterin; a minor constituent was probably tetrahydrobiopterin. Serum biopterin levels following methotrexate administration were raised and subsequent administration of folic acid and 5-formyltetrahydrofolic acid further increased serum levels of biopterin derivatives; this was in contrast to the total absence of response to oral folates without prior methotrexate and to 5-methyltetrahydrofolic acid either with or without methotrexate being given.
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PMID:Biopterin derivatives in human body fluids and tissues. 93 31

Fluctuations of mood and psychic activation were assessed in relation to "mobile" and "immobile" periods in 18 patients with Parkinson's disease presenting typical "end-of-dose deterioration". Twelve subjects with chronic but active rheumatoid arthritis presenting increased physical disability due to severe morning joint stiffness with a repetitive pattern of mobile and immobile periods acted as controls. The overall degree of disability and its fluctuations were close enough in the two groups for fair comparison of changes in affective behaviour. Temporary immobility was accompanied by adverse changes of mood and activation, which were significantly more marked in the Parkinson's disease group than in the controls, though to a lesser extent in those Parkinson's disease patients rated depressed even in their mobile periods. The possible correlation between mood changes and fluctuations of central dopaminergic function in the Parkinson's disease patients is discussed.
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PMID:Mood changes associated with "end-of-dose deterioration" in Parkinson's disease: a controlled study. 378 80

Artificial insemination donor selection requires predicting which men are likely to beget the healthiest offspring. Methods are developed for calculating the "offspring excess recurrence risk", delta R, for an anomaly in the offspring of an afflicted father. Mainly from published family survey and population data delta R is computed for 38 disorders. From a small survey a value for the with-treatment "affliction burden", Bt, is assigned to each anomaly. For each disorder the "offspring excess burden expectation" is delta RBt. Defects such as cataract, hereditary Parkinson disease, psoriasis, seropositive rheumatoid arthritis, and schizophrenia have such a high delta RBt that they are individually sufficient cause for rejecting a donor candidate. A candidate may be rejected because of a combination of lesser defects with sigma delta RBt exceeding an acceptable limit. A limit should also be placed on Bt, because the affliction burden for Tay-Sachs disease or cystic fibrosis is intolerable, however infrequent. Most of the important hereditary defects are late onset, and for the older donor the opportunity to select more directly against late-onset disorders offsets the added risk of newly-arising gene mutations. The most careful donor selection cannot completely eliminate the risk of a child inheriting some disorder, but selection can reduce the average total burden by as much as 17%.
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PMID:Selection against genetic defects in semen donors. 646 72

Despite a realisation that antioxidants will not delay ageing in healthy older people, there is increasing scientific interest in the role of free radical oxidants in a number of diseases associated with older age. For most of these diseases there is suggestive theoretical and laboratory evidence but not confirmatory clinical evidence. Free radical damage seems likely to be significant in the pathophysiology of atherosclerosis, ischaemia-reperfusion injury, Parkinson's disease, cataract, some cancers and rheumatoid arthritis. Evidence to suggest a protective effect from antioxidant vitamins exists for ischaemic heart disease, cataract and some cancers. Attempts to influence the outcome of other diseases such as ischaemia-reperfusion injury, Parkinson's disease and rheumatoid arthritis have so far failed to achieve positive results. Research interest in the field is increasing although hampered by methodological difficulties and the limited financial return for drug companies. In the meantime there seems no reason to discourage older people who wish to ingest extra vitamin E and vitamin C. A diet with adequate vegetables and fruits should provide sufficient beta carotene.
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PMID:Free radicals, antioxidants and preventive geriatrics. 806 Feb 75

We conducted an exploratory study of young-onset Parkinson's disease (YOPD) to examine occupational and environmental factors associated with disease risk. This case-control study included 63 YOPD patients (diagnosis on or before age 50); controls (n = 68) were diagnosed with rheumatoid arthritis. Crude odds ratios (ORs) were computed to identify exposure variables for logistic regression analyses. After controlling for the variables of race, educational level, sex, age, age at diagnosis, and family history of Parkinson's disease (PD), PD was positively associated with insecticide exposure (OR = 5.75, p < 0.001), past residency in a fumigated house (OR = 5.25, p = 0.046), herbicide exposure (OR = 3.22, p = 0.033), rural residency at time of diagnosis (OR = 2.72, p = 0.027), and nuts and seed eating 10 years before diagnosis (OR = 1.49, p = 0.021). PD was inversely associated with cigarette smoking at 5 years (OR = 0.50, p = 0.027), 10 years (OR = 0.43, p = 0.012), and 15 years (OR = 0.37, p = 0.005) before diagnosis, farm residency (OR = 0.38, p = 0.018), and exposure to dimethyl sulfoxide (OR = 0.10, p < 0.001). These findings are consistent with hypotheses linking PD to exposure to pesticide agents.
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PMID:Environmental antecedents of young-onset Parkinson's disease. 817 May 60

The paradox of aerobic life, or the 'Oxygen Paradox', is that higher eukaryotic aerobic organisms cannot exist without oxygen, yet oxygen is inherently dangerous to their existence. This 'dark side' of oxygen relates directly to the fact that each oxygen atom has one unpaired electron in its outer valence shell, and molecular oxygen has two unpaired electrons. Thus atomic oxygen is a free radical and molecular oxygen is a (free) bi-radical. Concerted tetravalent reduction of oxygen by the mitochondrial electron-transport chain, to produce water, is considered to be a relatively safe process; however, the univalent reduction of oxygen generates reactive intermediates. The reductive environment of the cellular milieu provides ample opportunities for oxygen to undergo unscheduled univalent reduction. Thus the superoxide anion radical, hydrogen peroxide and the extremely reactive hydroxyl radical are common products of life in an aerobic environment, and these agents appear to be responsible for oxygen toxicity. To survive in such an unfriendly oxygen environment, living organisms generate--or garner from their surroundings--a variety of water- and lipid-soluble antioxidant compounds. Additionally, a series of antioxidant enzymes, whose role is to intercept and inactivate reactive oxygen intermediates, is synthesized by all known aerobic organisms. Although extremely important, the antioxidant enzymes and compounds are not completely effective in preventing oxidative damage. To deal with the damage that does still occur, a series of damage removal/repair enzymes, for proteins, lipids and DNA, is synthesized. Finally, since oxidative stress levels may vary from time to time, organisms are able to adapt to such fluctuating stresses by inducing the synthesis of antioxidant enzymes and damage removal/repair enzymes. In a perfect world the story would end here; unfortunately, biology is seldom so precise. The reality appears to be that, despite the valiant antioxidant and repair mechanisms described above, oxidative damage remains an inescapable outcome of aerobic existence. In recent years oxidative stress has been implicated in a wide variety of degenerative processes, diseases and syndromes, including the following: mutagenesis, cell transformation and cancer; atherosclerosis, arteriosclerosis, heart attacks, strokes and ischaemia/reperfusion injury; chronic inflammatory diseases, such as rheumatoid arthritis, lupus erythematosus and psoriatic arthritis; acute inflammatory problems, such as wound healing; photo-oxidative stresses to the eye, such as cataract; central-nervous-system disorders, such as certain forms of familial amyotrophic lateral sclerosis, certain glutathione peroxidase-linked adolescent seizures, Parkinson's disease and Alzheimer's dementia; and a wide variety of age-related disorders, perhaps even including factors underlying the aging process itself. Some of these oxidation-linked diseases or disorders can be exacerbated, perhaps even initiated, by numerous environmental pro-oxidants and/or pro-oxidant drugs and foods. Alternatively, compounds found in certain foods may be able to significantly bolster biological resistance against oxidants. Currently, great interest centres on the possible protective value of a wide variety of plant-derived antioxidant compounds, particularly those from fruits and vegetables.
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PMID:Oxidative stress: the paradox of aerobic life. 866 Mar 87

Proper bodily response to environmental toxicants presumably requires proper function of the xenobiotic (foreign chemical) detoxification pathways. Links between phenotypic variations in xenobiotic metabolism and adverse environmental response have long been sought. Metabolism of the drug S-carboxymethyl-L-cysteine (SCMC) is polymorphous in the population, having a bimodal distribution of metabolites, 2.5% of the general population are thought to be nonmetabolizers. The researchers developing this data feel this implies a polymorphism in sulfoxidation of the amino acid cysteine to sulfate. While this interpretation is somewhat controversial, these metabolic differences reflected may have significant effects. Additionally, a significant number of individuals with environmental intolerance or chronic disease have impaired sulfation of phenolic xenobiotics. This impairment is demonstrated with the probe drug acetaminophen and is presumably due to starvation of the sulfotransferases for sulfate substrate. Reduced metabolism of SCMC has been found with increased frequency in individuals with several degenerative neurological and immunological conditions and drug intolerances, including Alzheimer's disease, Parkinson's disease, motor neuron disease, rheumatoid arthritis, and delayed food sensitivity. Impaired sulfation has been found in many of these conditions, and preliminary data suggests that it may be important in multiple chemical sensitivities and diet responsive autism. In addition, impaired sulfation may be relevant to intolerance of phenol, tyramine, and phenylic food constituents, and it may be a factor in the success of the Feingold diet. These studies indicate the need for the development of genetic and functional tests of xenobiotic metabolism as tools for further research in epidemiology and risk assessment.
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PMID:Phenotypic variation in xenobiotic metabolism and adverse environmental response: focus on sulfur-dependent detoxification pathways. 871 48

Corticotropin-releasing factor (CRF) plays a major role in coordinating the endocrine, autonomic, behavioral and immune responses to stress through actions in the brain and the periphery. CRF receptors identified in brain, pituitary and spleen have comparable kinetic and pharmacological characteristics, guanine nucleotide sensitivity and adenylate cyclase-stimulating activity. Differences were observed in the molecular mass of the CRF receptor complex between the brain (58,000 Da) and the pituitary and spleen (75,000 Da), which appeared to be due to differential glycosylation of the receptor proteins. The recently cloned CRF receptor in the pituitary and the brain (designated as CRF1) encodes a 415 amino acid protein comprising seven putative membrane-spanning domains and is structurally related to the calcitonin/vasoactive intestinal peptide/growth hormone-releasing hormone subfamily of G-protein-coupled receptors. A second member of the CRF receptor family encoding a 411 amino acid rat brain protein with approximately 70% homology to CRF1 has recently been identified (designated as CRF2); there exists an additional splice variant of the CRF2 receptor with a different N-terminal domain encoding a protein of 431 amino acids. In autoradiographic studies, CRF receptors were localized in highest densities in the anterior and intermediate lobes of the pituitary gland, olfactory bulb, cerebral cortex, amygdala, cerebellum and the macrophage-enriched zones and red pulp regions of the spleen. CRF can modulate the number of CRF receptors in a reciprocal manner. For example, stress and adrenalectomy increase hypothalamic CRF secretion which, in turn, down-regulates CRF receptors in the anterior pituitary. CRF receptors in the brain and pituitary are also altered as a consequence of the development and aging processes. In addition to a physiological role for CRF in integrating the responses of the brain, endocrine and immune systems to physiological, psychological and immunological stimuli, recent clinical data implicate CRF in the etiology and pathophysiology of various endocrine, psychiatric, neurologic and inflammatory illnesses. Hypersecretion of CRF in the brain may contribute to the symptomatology seen in neuropsychiatric disorders, such as depression, anxiety-related disorders and anorexia nervosa. Furthermore, overproduction of CRF at peripheral inflammatory sites, such as synovial joints may contribute to autoimmune diseases such as rheumatoid arthritis. In contrast, deficits in brain CRF are apparent in neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, as they relate to dysfunction of CRF neurons in the brain areas affected in the particular disorder. Strategies directed at developing CRF-related agents may hold promise for novel therapies for the treatment of these various disorders.
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PMID:Corticotropin-releasing factor receptors: physiology, pharmacology, biochemistry and role in central nervous system and immune disorders. 883 89

Tachykinins belong to an evolutionarily conserved family of peptide neurotransmitters. The mammalian tachykinins include substance P, neurokinin A and neurokinin B, which exert their effects by binding to specific receptors. These tachykinin receptors are divided into three types, designated NK1, NK2 and NK3, respectively. Tachykinin receptors have been cloned and contain seven segments spanning the cell membrane, indicating their inclusion in the G-protein-linked receptor family. The continued development of selective agonists and antagonists for each receptor has helped elucidate roles for these mediators, ranging from effects in the central nervous system to the perpetuation of the inflammatory response in the periphery. Various selective ligands have shown both inter- and intraspecies differences in binding potencies, indicating distinct binding sites in the tachykinin receptor. The interaction of tachykinin with its receptor activates Gq, which in turn activates phospholipase C to break down phosphatidyl inositol bisphosphate into inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 acts on specific receptors in the sarcoplasmic reticulum to release intracellular stores of Ca2+, while DAG acts via protein kinase C to open L-type calcium channels in the plasma membrane. The rise in intracellular [Ca2+] induces the tissue response. With an array of actions as diverse as that seen with tachykinins, there is scope for numerous therapeutic possibilities. With the development of potent, selective non-peptide antagonists, there could be potential benefits in the treatment of a variety of clinical conditions, including chronic pain, Parkinson's disease, Alzheimer's disease, depression, rheumatoid arthritis, irritable bowel syndrome and asthma.
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PMID:Tachykinins: receptor to effector. 892 4

Neurodegeneration is characterized by a marked accumulation of iron in the affected brain regions. The reason for this is still unknown. In this article we review the available data on the possible involvement of iron and mediated oxidative stress in the aetiology of Parkinson's disease and related disorders. Iron chelators, if they effectively prevent radical formation, have great therapeutic potential against ischaemia/reperfusion, rheumatoid arthritis, and anthracycline toxicity, which are most likely free radical-mediated. The efficacy of the best established chelating drug desferal in neurodegenerative disease is limited due to its high cerebro- and oculotoxicity. New bioactive chelating agents are currently being developed, among them are oxidative stress activatable iron chelators which are most likely less toxic and can flexibly respond to an increase of free radical formation in the cell.
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PMID:The potential role of iron chelators in the treatment of Parkinson's disease and related neurological disorders. 914 Jan 34


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