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)

Poly(ADP-ribose) polymerase (PARP) is responsible for post-translational modification of proteins in the response to numerous endogenous and environmental genotoxic agents. PARP and poly(ADP-ribosyl)ation are proposed to be important for the regulation of many cellular processes such as DNA repair, cell death, chromatin functions and genomic stability. Activation of PARP is one of the early DNA damage responses, among other DNA sensing molecules, such as DNA-PK, ATM and p53. The generation and characterization of PARP deficient mouse models have been instrumental in defining the biological role of the molecule and its involvement in the pathogenesis of various diseases including diabetes, stroke, Parkinson disease, general inflammation as well as tumorigenesis, and have, therefore, provided information for the development of pharmaceutical strategies for the treatment of diseases.
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PMID:Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. 1137 91

Mitochondrial dysfunction is a cause, or major contributing factor in the development, of degenerative diseases, aging, cancer, many cases of Alzheimer's and Parkinson's disease and Type II diabetes (D. C. Wallace, Science 283, 1482-1488, 1999). Despite major advances in understanding mtDNA defects at the genetic and biochemical level, there is no satisfactory treatment for the vast majority of patients available. Objective limitations of conventional biochemical treatment for patients with defects of mtDNA warrant the exploration of gene therapeutic approaches. However, mitochondrial gene therapy has been elusive, due to the lack of any mitochondria-specific transfection vector. We review here the current state of the development of mitochondrial DNA delivery systems. In particular, we are summarizing our own efforts in exploring the mitochondriotropic properties of dequalinium, a cationic bolaamphiphile with delocalized charge centers, for the design of a vector suited for the transport of DNA to mitochondria in living cells.
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PMID:Towards mitochondrial gene therapy: DQAsomes as a strategy. 1137 19

Thirty men having Parkinsons disease (PD) and 30 controls were studied prospectively by the use of the International Index of Erectile Function (IIEF) to assess erectile dysfunction (ED). Of the patients with PD (mean age of 59 years), 46.66% referred to the practice of sexual activity. All of the parkinsonians were using antiparkinsonian medication. In the control group (mean age of 63 years), 76.66% referred to the practice of sexual activity, 46.60% to arterial hypertension and 6.66% to diabetes mellitus. The median score for the PD group according to the IIEF was 34, and that for the controls 50. The main differences between the two groups were in the erectile function, orgasmic function and satisfaction with the sexual relationship. The IIEF is a multidimensional scale widely accepted to assess the ED. The data obtained suggest that ED is more frequent among parkinsonians and points out to the role of DP in the genesis of ED.
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PMID:[Assessment of erectile dysfunction in patients with Parkinson's disease]. 1158 35

The use of fetal tissue in transplants for treating illnesses such as Parkinson's disease and juvenile diabetes has raised the hopes of patients, their families, and the biomedical community. But, this practice has created considerable controversy. Concerns arise because tissue is usually obtained from electively aborted fetuses. Despite the controversy, there has been little systematic and sustained examination of the ethical and policy issues posed by the use of fetal tissue in biomedicine. The lack of information and analysis hampers serious discussion. In the Spring of 1988, the Center for Biomedical Ethics began an interdisciplinary research project on the scientific, ethical, and policy issues raised by the use of fetal tissue in biomedicine. Twenty-five scholars, drawn mainly, but not exclusively, from the faculty of the University of Minnesota, met to undertake the study. The members of this research group included experts in neonatology, pediatrics, neurology, neurosurgery, organ transplantation, tissue procurement, cell biology, immunology, epidemiology, law, philosophy, moral theology, and the behavioral sciences. The group met every three weeks over a period of ten months to collect and review information about the use of fetal tissue -- with special attention to transplantation -- the potential sources of fetal tissue, and the relevant laws and guidelines in the U.S. and other nations. Six members of the research group had primary responsibility for writing this report.
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PMID:The use of human fetal tissue: scientific, ethical, and policy concerns (January 1990) 1165

On the basis of current literature, clinical and neuropathologic features of idiopathic autonomic neuropathy is presented. Idiopathic autonomic neuropathy is a disease characterized by acute or subacute onset, monophasic course over a period of several years, it is often preceded by an infection. The spectrum of autonomic changes ranges from cholinergic or adrenergic dysfunction to pandysautonomia, leading to heterogeneity of its clinical features. Possible sympathetic system abnormalities found in autonomic neuropathy are: poor pupillary response to light in darkness, orthostatic hypotension leading to syncope, hypotension without compensatory tachycardia, ejaculation disturbances and vasomotor instability. Possible parasympathetic dysfunctions are: salivation and lacrimation disturbances, absent pupillary constriction to light and near gaze, gastrointestinal tract immobility and impairment of gastrointestinal function, atonic bladder with large residual volume, erectile impotence. Pandysautonomia is thought to result from an immune mediated mechanism and responds well to plasmaferesis and intravenous immunoglobin therapy leading to gradual, sometimes not full, recovery. Moreover in this article we pay attention to the clinical value of many tests like cardiovascular or pharmacological studies in the diagnosis of pandysautonomia and in differentiation of pre- and postganglionic changes. In order to diagnose idiopathic autonomic neuropathy one has to rule out a large number of diseases with autonomic dysfunction e.g.: diabetes, malignant neoplasms, acute intermittent porphyria, Shy-Drager syndrome, Riley-Day's dysautonomia, Parkinson's disease, amyloidosis and others.
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PMID:[Idiopathic autonomic neuropathy (pandysautonomia)]. 1173 67

Four outcomes that evidence suggests are candidates for "environmental causation" were chosen for analysis: diabetes, Parkinson's disease (PD), neurodevelopmental effects and hypothyroidism, and deficits in intelligence quotient (IQ). These are an enormous burden in the United States, Canada, and other industrial countries. We review findings on actual social and economic costs, construct estimates of some of the costs from pertinent sources, and provide several hypothetical examples consistent with published evidence. Many detailed costs are estimated, but these are fragmented and missing in coverage and jurisdiction. Nonetheless, the cumulative costs identified are very large, totaling $568 billion to $793 billion per year for Canada and the United States combined. Partial Canadian costs alone are $46 billion to $52 billion per year. Specifics include diabetes (United States and Canada), $128 billion per year; PD in the United States, $13 billion to $28.5 billion per year; neurodevelopmental deficits and hypothryoidism are endemic and, including estimates of costs of childhood disorders that evidence suggests are linked, amount to $81.5 billion to $167 billion per year for the United States and $2 billion per year in Ontario; loss of 5 IQ points cost $30 billion per year in Canada and $275 billion to $326 billion per year in the United States; and hypothetical dynamic economic impacts cost another $19 billion to $92 billion per year for the United States and Canada combined. Reasoned arguments based on the weight of evidence can support the hypothesis that at least 10%, up to 50% of these costs are environmentally induced--between $57 billion and $397 billion per year.
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PMID:Societal costs of exposure to toxic substances: economic and health costs of four case studies that are candidates for environmental causation. 1174 7

Cell transplantation therapy for diabetes and Parkinson's disease offers hope for long-term alleviation of symptoms. However, successful protocols remain elusive due to obstacles, including rejection and lack of tropic support for the graft. To enhance engraftment, testis-derived postmitotic Sertoli cells have been cotransplanted with islets in the diabetic rat (Db) and neurons in the Parkinsonian rat (PD). Sertoli cell tropic, regulatory, and nutritive factors that nourish and stimulate germ cells also support isolated neurons and islets in vitro. Likewise, immunosuppressive properties of Sertoli cells, extant in the testis, are expressed by extratesticular Sertoli cells evidenced by allo- and xenograft immunoprotection of grafts in both the CNS (in the PD model) and the periphery (in the Db model). On this basis, we have created Sertoli islet cell aggregates (SICA) and Sertoli neuron aggregated cells (SNAC) using simulated microgravity culture technology developed by NASA. Isolated rat and pig Sertoli cells were cocultured with neonatal pig islets (SICA) and with immortalized N-Terra-2 (NT2) neurons (SNAC) in the HARV biochamber. Formed aggregates were assayed for desirable functional and structural characteristics. Cell viability in SICA and SNAC exceeded 90% and FasL immunopositive Sertoli cells were present in both. Sertoli cells did not interfere with insulin secretion by SICA and promoted differentiation of NT2 cells to the dopaminergic hNT cell type in SNAC. Addition of Matrigel resulted in structural reorganization of the aggregates and enhanced insulin secretion. We conclude that SICA, SNAC, and Matrigel-induced islet- and neuron-filled "Sertoli cell biochambers" are suitable for long-term transplantation treatment of Db and PD.
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PMID:Formation of Sertoli cell-enriched tissue constructs utilizing simulated microgravity technology. 1179 90

In the 3 y since its initial approval, sildenafil has become the most widely used treatment for erectile dysfunction (ED) and has been prescribed to more than 13 million patients worldwide. Significant improvements in erectile function have been demonstrated in double-blind, placebo-controlled studies in diverse patient populations. A significant treatment effect has been shown with sildenafil in men with ED and a history of diabetes, cardiovascular disease, minor depression, spinal cord injury and multiple sclerosis. In addition, promising results have been shown in patients with treated prostate cancer, end-stage renal disease, Parkinson's disease and spina bifida and in multiple-organ transplant recipients. Postmarketing data of the use of sildenafil in clinical practice confirm the efficacy and safety found in clinical trials and high satisfaction with treatment. Public awareness of the common occurrence of ED and the high likelihood of a potentially favorable response to an oral treatment increased dramatically with the introduction of sildenafil. Physicians, however, are still not comfortable with ED management, which negatively affects pharmacotherapy response rates and patients' compliance to treatment. Continuing medical education seems mandatory to overcome existing problems in ED management.
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PMID:Sildenafil citrate: lessons learned from 3 years of clinical experience. 1185 Jul 35

The extent to which concomitant Alzheimer's disease (AD) is etiologically related to the development of dementia in Parkinson's disease (PD) remains controversial. We explored the association of four risk factors associated with AD, including head injury, smoking, hypertension, and diabetes mellitus, with incident dementia in PD. A cohort of 180 nondemented PD patients from the Washington Heights community in northern Manhattan, New York, completed a risk factor questionnaire at baseline and was followed annually with neurological and neuropsychological evaluations. The association of baseline variables with incident dementia was analyzed by using Cox proportional hazards models. All analyses controlled for age at baseline, gender, years of education, duration of PD, and total Unified Parkinson's Disease Rating Scale (UPDRS) motor score at baseline. Of 180 patients (mean age, 71.0 +/- 10.3 years), 52 (29%) became demented during a mean follow-up period of 3.6 +/- 2.2 years. Head injury risk ratio ([RR] 0.9; 95% confidence interval [CI], 0.4-2.2; P = 0.9), hypertension (RR, 0.7; 95% CI, 0.4-1.4, P = 0.3), and diabetes mellitus (RR, 0.8; 95% CI, 0.3-2.3; P = 0.7) were not significantly associated with incident dementia in the Cox models. Patients who reported having ever smoked were at increased risk for the development of dementia compared with nonsmokers (RR, 2.0; 95% CI, 1.0-3.9; P = 0.05). Current smoking was significantly associated with incident dementia (RR, 4.5; 95% CI, 1.2-16.4; P = 0.02), whereas past smoking approached significance (RR, 1.9; 95% CI, 0.9-3.7; P = 0.07). Although an inverse association between smoking and PD has been reported in several studies, our study showed a positive association between smoking and dementia in the setting of PD. The association of smoking with incident dementia in PD deserves further study.
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PMID:Do risk factors for Alzheimer's disease predict dementia in Parkinson's disease? An exploratory study. 1192 Nov 9

Free radicals damage both lipids and proteins and evidence has accumulated for the presence of both oxidised lipids and proteins in aged tissue samples as well as those from a variety of pathologies including atherosclerosis, diabetes, and Parkinson's disease. Oxidation of the protein and lipid moieties of low-density lipoprotein is of particular interest due to its potential role in the unregulated uptake of lipids and cholesterol by macrophages; this may contribute to the initial stage of foam cell formation in atherosclerosis. In the study reported here, we examined the comparative time-courses of lipid and protein oxidation during copper-ion-mediated oxidation of low-density lipoprotein. We show that there is an early, lipid-mediated loss of 40-50% of the Trp residues of the apoB100 protein. There is no comparable loss over an identical period during the copper-ion-mediated oxidation of lipid-free BSA. Concomitant with Trp loss, the antioxidant alpha-tocopherol is consumed with subsequent extensive lipid peroxidation. Further changes to the protein, including the copper-ion-dependent 3.5-fold increase in 3,4-dihydroxyphenylalanine and the copper-ion-independent 3-5-fold increase in o-tyrosine, oxidation products of Tyr and Phe, respectively, only occur after maximal lipid peroxidation. Long incubation periods result in depletion of 3,4-dihydroxyphenylalanine, presumably reflecting further oxidative changes. Overall, copper-ion-mediated oxidation of LDL appears to proceed initially by lipid radical-dependent processes, even though some of the earliest detectable changes occur on the apoB100 protein. This is followed by extensive lipid peroxidation and subsequent additional oxidation of aromatic residues on apoB100, though it is not yet clear whether this late protein oxidation is lipid-dependent or occurs as a result of direct radical attack.
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PMID:Comparative time-courses of copper-ion-mediated protein and lipid oxidation in low-density lipoprotein. 1205 33


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