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)

The general concept of gene therapy is now well established and accepted by the medical, scientific and public policy communities, and is rapidly being implemented in human experimental studies. In addition to the initial models of single gene defects, target diseases have now come to include multigenic and multifactorial diseases such as human cancer, neurodegenerative diseases such as Parkinson's disease and firms of cardiovascular disease. While many conceptual and technical obstacles must still be overcome before therapy for disorders such as coronary artery disease and diabetes mellitus will easily be approached at the genetic level, the early results with several multigenic disease models gives some cause for optimism that gene therapies for even those complicated disorders will eventually become available.
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PMID:Approaches to gene therapy of complex multigenic diseases: cancer as a model and implications for cardiovascular disease and diabetes. 141 28

This article examines depression in 6 medical conditions: coronary artery disease (CAD), cancer, human immunodeficiency virus (HIV) infection, Parkinson's disease, pain, and the sex hormone changes of aging. Research is beginning to define specific biological and psychological mechanisms underlying the adverse interactions between depression and these medical conditions. Antidepressant medications, psychosocial therapies, and hormonal manipulations are effective in reducing depressive symptoms. Specific psychosocial interventions may increase longevity in CAD and cancer and may enhance quality of life in HIV infection. Newer antidepressants appear to be safer and better tolerated than older agents for medically ill patients, but do not appear to be as effective for neuropathic pain. Dopamine agonists may benefit depression associated with Parkinson's disease. Hormone replacement therapy may improve subsyndromal depressive symptoms in postmenopausal women and may enhance antidepressant response for older women with major depression.
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PMID:Depression in the medical setting: biopsychological interactions and treatment considerations. 1008 82

Cabergoline is one of several ergoline dopamine agonist medications used in the treatment of Parkinson's disease (PD). We diagnosed constrictive pericarditis (CP) in a patient with PD receiving cabergoline therapy (10 mg daily), who had symptoms and signs of congestive heart failure (CHF). In the absence of previous reported cases of this condition linked to ergoline drugs, cabergoline was not initially identified as the cause. Shortly thereafter, however, the patient developed of a severe pleuropulmonary inflammatory-fibrotic syndrome, a recognized complication of ergoline medications, thus suggesting a common pathogenesis due to cabergoline therapy. To our knowledge, this is the first case in the English literature, although we speculate that CP may be more common than reported among patients with PD who are treated with an ergoline drug (cabergoline, bromocriptine, pergolide, or lisuride). The diagnosis of CP is difficult and requires a high level of suspicion; symptoms may masquerade as CHF due to common mechanisms such as coronary artery disease. In patients with PD who are taking not only cabergoline but also one of the other ergoline drugs, CP should be suspected if symptoms of CHF develop.
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PMID:Constrictive pericarditis and pleuropulmonary disease linked to ergot dopamine agonist therapy (cabergoline) for Parkinson's disease. 1022 67

Human serum paraoxonase (PON1) is associated with high density lipoprotein (HDL) particles. This enzyme is involved in the metabolism of oxidized lipids and also plays a major role in the metabolism and detoxication of insecticides processed through the cytochrome P450/PON1 pathway. An Arg/Gln (R/Q) substitution at position 192 determines a substrate dependent activity polymorphism. In addition to the effect of the amino acid substitution on rates of hydrolysis of different substrates, there is a large interindividual variability in the amount of PON1 protein in sera that is stable over time. Recently, a number of reports based solely on PON1 genotyping have suggested that in some populations, the PON(R192) allele may be a risk factor for coronary artery disease. Another report notes an increased risk of the PON(R192) allele for Parkinson's disease. We report here the development of a two-dimensional, microtitre plate reader-based enzyme analysis that provides a high-throughput assessment of PON1 status. Population distribution plots of diazoxonase versus paraoxonase activities provides PON1 phenotype and an accurate inference of PON1 genotype. Both are important parameters for determining an individual's PON1 status. The analysis also provides PON1 allele frequencies for specific populations.
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PMID:Determination of paraoxonase (PON1) status requires more than genotyping. 1063 37

Immunohistochemical localization of the injury specific apolipoprotein, acute phase serum amyloid A (A-apoSAA), was compared in brains of patients with neuropathologically confirmed Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD); Pick's disease (Pick's), dementia with Lewy bodies (DLB), coronary artery disease (CAD), and schizophrenia. Affected regions of both AD and MS brains showed intense staining for A-apoSAA in comparison to an unaffected region and non-AD/MS brains. The major site of A-apoSAA staining in both diseases was the myelin sheaths of axons in layers V and VI of affected cortex. A-apoSAA contains a cholesterol binding site near its amino terminus and is likely to have a high affinity for cholesterol-rich myelin. These findings, along with our recent evidence that A-apoSAA can inhibit lipid synthesis in vascular smooth muscle cells suggest that A-apoSAA plays a role in the neuronal loss and white matter damage occurring in AD and MS.
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PMID:Serum amyloid A in Alzheimer's disease brain is predominantly localized to myelin sheaths and axonal membrane. 1084 12

The prevalence and severity of coronary atherosclerosis increase dramatically with age, so that more than half of all deaths in persons aged over 65 are due to coronary arterial disease (CAD) and about three fourths of all deaths from CAD occur in the elderly. The aims of our study were, first, to detect myocardial ischemia development in elderly versus younger patients undergoing treatment for known CAD through the use of both conventional treadmill testing and 201T1 scintigraphy, and second, to determine the relationship between the above non-invasive tests and angiographically confirmed important coronary artery disease (iCAD). A database of 606 patients (355 men and 251 women) who had undergone coronary angiography, exercise ECG testing (ETT) using the treadmill Bruce protocol, and 201T1 scintigraphy, was reviewed retrospectively. All patients had displayed clinical expression of CAD with or without the existence of an old myocardial infarction (MI). The patients were from both sexes (440 men and 252 women) and divided into two groups, according to age. Group A was composed of 265 patients aged over 65 (170 men, 95 women, mean age = 70.3 +/- 5.3 years). Group B was composed of 341 patients aged under 65 (185 men, 156 women, mean age 54.4 +/- 9.1 years). Patients with uncontrolled arterial hypertension, hypertrophic cardiomyopathy, severe valve diseases, severe chronic obstructive lung diseases, severe anemia, peripheral atherosclerosis, orthopedic problems, or Parkinson's disease were excluded from the study. The term "important coronary artery disease" (iCAD) covers the following patterns of coronary anatomy: (a) left main stem stenosis > or = 50% with or without disease elsewhere, (b) proximal three-vessel disease, (c) three-vessel disease including the proximal left anterior descending artery (LAD), (d) proximal two-vessel disease including LAD, and (e) two-vessel disease including the proximal LAD. Biostatistical characteristics such as sensitivity, specificity, and predictive values of ETT-201T1 were estimated. Analyzing our results we concluded that: the biostatistical parameters in predicting important CAD in elderly and younger patients by means of exercise test and thallium scintigraphy need to be redefined through more closely scheduled and prospective studies; in elderly coronary patients, the appearance of positive results in both parameters of ETT-201T1 indicates a significant possibility of iCAD existence; in coronary patients younger than 65 years, the appearance of negative results in both parameters of ETT-201T1 almost excludes iCAD, in contrast to elderly patients, who display a significant proportion of iCAD; in elderly coronary patients, the appearance of equivocal results in both tests indicates a significant possibility of the existence of iCAD, in contrast to younger patients.
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PMID:Detection of myocardial ischemia in the elderly versus the young by stress thallium-201 scintigraphy and its relation to important coronary artery disease. 1222 83

Bilateral electrical stimulation of the subthalamic nucleus is being used with increasing frequency as a treatment for severe Parkinson disease (PD). Implantable cardiac defibrillators improve survival in certain high-risk patients with coronary artery disease and ventricular arrhythmias. Because of concern about possible interaction between these devices, deep brain stimulation (DBS) systems are routinely disconnected before defibrillators are implanted in patients with PD and arrhythmia. The authors report on a patient with bilateral subthalamic stimulators who underwent successful placement of an implantable defibrillator. Testing of the devices over a wide range of settings revealed no interaction. The patient subsequently underwent multiple episodes of cardioversion when the ventricular lead became dislodged. There was no evidence of adverse neurological effects, and interrogation of the DBS devices after cardioversion revealed no changes in stimulus parameters. The outcome in this case indicates that DBS systems may be safely retained in selected patients who require implantable cardiac defibrillators.
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PMID:Simultaneous use of bilateral subthalamic nucleus stimulators and an implantable cardiac defibrillator. Case report. 1285 61

Stem cell populations are found in most adult tissues and, in general, their differentiation potential may reflect the local cell population. Hematopoietic, epidermal, mesenchymal, neural and hepatic stem cells have been described. It may be that, in the adult, these cells are the reservoirs of reparative cells that are mobilized following injury and migrate to the wound site where, in cooperation with local cells, they participate in the repair response. Mesenchymal stem cells, isolated from the bone marrow, have the capacity to differentiate into cells of connective tissues. Some striking examples of the therapeutic use of MSCs have been reported recently in applications such as coronary artery disease, spinal cord injury, Parkinson's Disease, and liver regeneration. In orthopaedic medicine, MSC therapy has been applied in bone and cartilage repair and in the treatment of osteoarthritis. The question of the host response to implanted MSCs is critical as these cells are being evaluated in clinical applications. There are several aspects to the implanted cell-host interaction that need to be addressed as we attempt to understand the mechanisms underlying stem cell therapies. These are (1) the host immune response to implanted cells, (2) the homing mechanisms that guide delivered cells to a site of injury, and (3) differentiation of implanted cells under the influence of local signals.
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PMID:Biology and clinical applications of mesenchymal stem cells. 1467 78

The human neurofilament medium (hNFM) subunit is one of the 3 neurofilament (NF) polypeptides, which are the most abundant intermediate filament (IF) proteins in post-mitotic neurons. The formation of neurofilamentous aggregates is a pathological hallmark of many neurodegenerative diseases, including the Lewy bodies found in Parkinson disease (PD). A Gly336Ser (G336S) variant in the rod domain of hNFM has recently been described in a patient with early-onset autosomal-dominant PD. In this study, we have generated a mammalian expression vector encoding the variant hNFM cDNA and characterized its effects on the formation of heteropolymeric IFs in heterologous cell lines. We have also investigated the distribution of the (G336S) hNFM variant protein in neuronal CAD cells, as well as the effects of the variant on the distribution of other cellular organelles and proteins. Our results demonstrate that the G336S variant does not affect the formation of IF networks nor the distribution of the variant hNFM protein. Our data suggest that if the G336S variant is involved in the development of PD, it does not appear to be due to defects in the assembly and distribution of NFs.
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PMID:The G336S variant in the human neurofilament-M gene does not affect its assembly or distribution: importance of the functional analysis of neurofilament variants. 1529 Sep 1

Epidemiologic evidence has linked elevation of serum homocysteine to an increased risk of coronary artery disease, stroke, and dementia. An increase in homocysteine levels in Parkinson disease (PD) recently has been discovered. Although B vitamin status and genetic factors are important modifying influences determining the degree of this elevation, the main cause appears to be therapy with L-dopa. It has been suggested that breakdown of L-dopa by catechol-O-methyltransferase results in increased homocysteine formation. Therefore, there are reasons to suggest that management of PD may render patients at increased risk of stroke, heart disease, dementia, and even accelerated nigral degeneration. At present, no controlled prospective studies have evaluated this phenomenon, although they are ongoing.
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PMID:Homocysteine and levodopa: should Parkinson disease patients receive preventative therapy? 1536 41


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