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)

Monoamine oxidase-B (MAO-B) activity of platelets of an age- and sex-matched group of controls was compared with several groups of inpatients having non-familial dementia of Alzheimer type (DAT), Parkinson's disease (PD), multi-infarct dementia (MID), mixed types of these 3 diseases and a group of other central nervous system (CNS) organic disorders. All patients were subjected to several psychometric tests, including the Sandoz Clinical Assessment--Geriatric Scale, Hamilton Rating Scale for Depression, Mini-Mental State Examination and the Organic mental Disorder Scale (OMDS). A statistically significant enhancement of MAO-B activity could be observed in DAT patients and in PD patients, whereas the MID group showed a mean activity similar to that of the control group and the group with other organic CNS disorders. In DAT patients the degree of dementia in the OMDS test and the enhancement of MAO activity were positively correlated, but PD did not show such a correlation. It is concluded that the increase of MAO activity in PD and in DAT might be due to a disease-related enhanced affinity to oxygen and to such oxygen-derived radicals as superoxide or hydroxyl radicals. However, a possible drug-induced enhancement of MAO activity in PD cannot be excluded. Furthermore, the MAO-B activity values in platelets of individual patients or controls are not indicative of diagnosis or prognosis of any of these diseases and are of no disease-related specificity.
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PMID:Platelet MAO-B activity and the psychopathology of Parkinson's disease, senile dementia and multi-infarct dementia. 322 31

Axial motor impairments are a common cause of disability in patients with Parkinson's disease, become more prominent with longer disease duration, and have been said to be less responsive to levodopa replacement therapy. The ability to turn in bed while lying supine before and after dopaminergic stimulation was studied in a group of 36 patients with Parkinson's disease; 23 were in Hoehn and Yahr stages 3-5 when "off", and 13 were in stages 1-2. Turning was also compared with postural stability and gait before ("off") and after ("on") dopaminergic stimulation. Failure to turn in bed was noted in 19 of the 36 patients in the "off" state, with significant associations between disturbances of gait, postural stability, rising from a chair, whole body bradykinesia, and axial rigidity. Gait, postural stability, rising from a chair, whole body bradykinesia, and axial rigidity were significantly correlated in the "off" state. Disorder of axial movement, gait, and postural stability were not dependent on age at onset of Parkinson's disease, but did relate to duration of disease. After a levodopa challenge, turning in bed returned to normal in all but one patient, and gait, postural stability, rising from a chair, whole body bradykinesia, and axial rigidity also improved in nearly all. It is concluded that in the later stages of Parkinson's disease at least some aspects of axial motor control can remain dopamine responsive.
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PMID:Disordered axial movement in Parkinson's disease. 897 Nov 18

We have come to understand apoptosis as not merely a single form of cell death, but as a fundamental theme in cell biology that has far-reaching implications in the fields of physiology and pathology. At the present time, however, the mechanism of apoptosis is not clearly understood, as research into apoptosis is still at the initial stages. Nevertheless, the links between apoptosis and a variety of pathological conditions are gradually becoming clearer. In this article, we will provide a simple explanation of apoptosis and its mechanism as a novel concept of cell death and discuss the way in which apoptosis has been linked to a variety of pathological conditions. WHAT IS APOPTOSIS?: In normal tissue, cells that are no longer needed are rapidly eliminated without affecting the overall function of the tissue. In this process cells undergo an active and spontaneous suicide called programmed cell death. In fact, the majority of physiological cell deaths take the form of apoptosis. The word apoptosis is used, in contrast to necrosis, to describe the situation in which a cell actively pursues a course toward death upon receiving certain stimuli [1]. The morphological changes of apoptosis found in most cell types first involve contraction in cell volume and condensation of the nucleus. When this happens the intracellular organelles such as the mitochondria retain their normal morphology. As apoptosis proceeds, blebbing of the plasma membrane occurs, and the nucleus becomes fragmented. Finally, the cell itself fragments to form apoptotic bodies that are engulfed by nearby phagocytes. With respect to biochemical changes, it is known that the chromosomes become fragmented into nucleosome units, and DNA forms characteristic ladder patterns when subjected to agarose gel electrophoresis. MECHANISM OF APOPTOSIS: It has been reported that apoptosis is induced in various cells by many kinds of irritations, but the precise mechanism is still unclear. Cell injuries that induce apoptosis include those that cause DNA damage such as radiation and anticancer drugs, those that are mediated by the TNF receptor and Fas receptor (the so-called "death signal receptors"), and the deprivation of cytokines that supply survival signals such as IL-3 and erythropoietin. The tumor suppressor gene p53 plays a very important role in apoptosis induced by damage to DNA. This has been demonstrated by studying resistance to apoptosis of cells derived from p53 knockout mice [2]. Other than the irritations that induce apoptosis, molecules that have been strongly implicated as major players in the drama of apoptosis include the Bcl-2 family proteins and the IL-1 converting enzyme (ICE) and its homolog proteases (caspase family). Both groups of proteins show homology with proteins that affect cell death in nematodes. It is believed that molecules that contribute to cell death have been well conserved in multicellular organisms all the way from the relatively primitive nematodes to mammals including humans. It was discovered that Bcl-2 suppressed apoptosis induced in IL-3 dependent cells by deprivation of IL-3 [3]. It has since become the gene around which apoptosis research revolves. Recently, it has become clear that cell death involving the Bcl-2 protein is under the control of similar proteins from the same family [4]. It is interesting that the phenomenon of cell death may be regulated by the balance of the molecules involved in it. APOPTOSIS ABNORMALITIES AND DISEASE: Physiological cell death plays a major role in the growth and permanent maintenance of the human body [5]. In the process of forming the nervous system, neurons that do not form proper connections die. Physiological cell death also accompanies the removal of virus-infected cells by cytotoxic T cells, the elimination of autoreactive immune cells, the formation of the gut, the reconstitution of cartilage and bone, etc. When physiological cell death that normally should occur is inhibited, inappropriate physiological cell death may occur that is harmful to the body and forms the basis of disease. For example, in patients with neural degenerative disorders such as Alzheimer's disease and Parkinson's disease, we can find premature cell death in a particular subset of neurons. The death of T cells in AIDS patients is also a form of physiological cell death. Inhibition of cell death in the immune system enables the survival of autoreactive B cells and T cells, and is therefore a cause of autoimmune disorders. Apoptosis has been particularly linked to cancer. Normal cells are programmed for death if they are subjected to many types of non-physiological stress such as anticancer drugs or radiation, if they become isolated from surrounding cells and are unable to receive their tissue-specific survival signals [6], or if oncogenes are expressed haphazardly [7]. On the other hand, it is believed that the ability to survive is enhanced in transformed cancer cells because they are more resistant to apoptosis, they exhibit resistance to anticancer drugs, they are no longer dependent on survival signals, and they can metastasize. Therefore, the cancer progresses as the cancer cells maintain the proliferative superiority they acquire from their oncogenes. In other words, when cancer cells become resistant to apoptosis, they become resistant to treatment, metastasize, and proliferate destructively. The concept that the malignancy of cancer is due to its resistance to apoptosis is a relatively new one and is worthy of further study.
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PMID:Physician Education: Apoptosis. 1038 21

Postural instability (PI) is common in idiopathic Parkinson's disease (IPD). We measured sensory and motor contributions to PI in 50 patients with advanced IPD, off and on medication and in a subset pre- and 3, 6 and 12 months post-unilateral pallidotomy, using computerized dynamic posturography [specifically, the Sensory Organization Test (SOT) and the Unified Parkinson's Disease Rating Scale (UPDRS) subscale PIGD (Postural Instability and Gait Disorder)]. Off medication, all patients had abnormal PIGD scores. The group could be separated into those with normal SOT equilibrium scores (SOTN) and those, the majority, with abnormal postural control when sensory feedback was limited (SOTABN). Medication improved the PIGD scores but worsened the SOT scores in the majority of patients. Increases in spontaneous sway in some patients contributed to the negative effect of medication on SOT scores. However, this could not explain the detrimental effect of medication on SOT scores in at least 40% of patients. On the other hand, pallidotomy improved both PIGD and SOT scores in both groups. A predictor of good outcome from pallidotomy concerning PI was the degree of worsening of the effect that medication had on SOT5 scores. PI in IPD appears to be multifactorial. We propose that the PIGD score reflects sensory and motor aspects of postural control, with normal sensory feedback, while the SOT equilibrium scores measure the sensory organizational process of postural control in the presence of altered sensory inputs. There is a dissociation between the effects of medication and pallidotomy on motor and sensory components of postural control, which may reflect the underlying pathophysiological mechanism responsible for these different components of PI. We suggest that patients with advanced IPD and PI on medication should consider adjuvant surgical treatment for better postural control.
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PMID:Postural instability in idiopathic Parkinson's disease: the role of medication and unilateral pallidotomy. 1218 55

Alterations in dopaminergic system are known to lie in the basis of such diseases as Parkinson's disease, Huntington's disease, Attention Deficit/Hyperactivity Disorder, Tourette syndrome, schizophrenia and drug abuse. This induced broad investigations of dopaminergic system in nearly all the areas of neuroscience. New insights into the pathogenesis of neuropsychiatric diseases have emerged. Research in the field of dopaminergic neurotransmission and memory was awarded Nobel prize in the year 2000. New avenues for the development of more selective drugs have been opened. In their daily practice clinicians are often prescribing medications acting on presynaptic or postsynaptic sites of dopaminergic units. Thus the aim of this review was to renew some knowledge on the architecture of dopaminergic system and also to glance through some of the studies implying its modulating effect on cognitive functions.
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PMID:[Dopaminergic modulation of cerebral activity and cognitive functions]. 1247 82

The authors investigated the prevalence of DIS-ascertained DSM-III psychiatric disorders occurring in 28 patients with dystonia and 28 patients with Parkinson's Disease (PD). In patients with dystonia, lifetime prevalences of major depression (25.0%), bipolar disorder (7.1%), atypical bipolar disorder (7.1%), social phobia (17.9%), and generalized anxiety disorder (25.0%) were significantly more common than in epidemiologic catchment area (ECA) study population controls (p < 0.005). Social phobia and generalized anxiety disorder preceded dystonia (primary), while bipolar disorder developed after dystonia onset (secondary). In PD patients, the lifetime prevalence of simple phobia (35.7%, p < 0.0001) and atypical depression (21.4%) were significantly more common. Parkinson's Disease was associated with primary simple phobia and secondary atypical depression. These findings are considered in light of previous results and in terms of the differences in pallidothalamic physiologies in dystonia and PD. These data suggest distinctive profiles of psychiatric disorders in dystonia and PD.
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PMID:Differential DSM-III psychiatric disorder prevalence profiles in dystonia and Parkinson's disease. 1499 Jul 56

The objective of this study was to examine the chronobiology of visual hallucinations in Parkinson's disease (PD) patients to test whether hallucinations are more severe during darker months (winter) than summer months. We extracted longitudinal data on the UPDRS Thought Disorder (TD) score, taken as part of regular patient management on sequential visits through a 1-year cycle in hallucinating PD patients. To reduce the confounding effects of medication adjustments, analysis was restricted to patients with a baseline evaluation that did not involve a medication change. The primary outcome was the seasonal change in hallucination severity, defined as a change in TD score or neuroleptic use. Using Wilcoxon rank-sum tests, we compared the exacerbation of hallucination by season, focusing on winter (December through February) versus summer (June through August). A total of 51 hallucinating patients met entry criteria, and their longitudinal data were analyzed. There was no difference in hallucination severity with changing season; the level of wintertime exacerbation was no greater than summertime exacerbation (P = 0.42). Although hallucinations frequently develop in dimmed environments and evening hours, the darkness of wintertime does not exacerbate hallucinations in PD subjects on stable medications. Because we found no evidence of seasonal variations, we cannot recommend phototherapy or other strategies affecting chronobiological systems as research priorities to treat PD hallucinations. (c) 2006 Movement Disorder Society.
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PMID:Does seasonal variation affect hallucinations in PD? A longitudinal study. 1653 49

Postural control requires precise integration of sensory inputs and motor output, but clinical assessments of postural control do not differentiate between these. Previously, we found that this differentiation is important in Parkinson's disease (PD) as there was a dissociated effect of medication versus pallidotomy on sensory aspects of postural instability. In this study, we address several questions that emerged from that work in 28 different patients with PD off and on medication, before and after bilateral subthalamic nucleus deep brain stimulation (B-STN DBS): (1) In a different cohort is there still an unusually large percentage of patients with postural instability in sensory-deprived conditions? (2) Are more specific measures of motor aspects of postural control using dynamic posturography (postural movement velocity [MV] and reaction time [RT]) abnormal in PD as seen clinically using the Postural Instability and Gait Disorder score of the Unified Parkinson's Disease Rating Scale? (3) What is the effect of B-STN DBS versus medication on sensory versus motor aspects of postural instability in PD? The results included (1) substantially more patients (39%) versus controls (5%) exhibited postural instability in conditions of limited sensory feedback; (2) postural MV and postural RT were abnormal off medication preoperatively (N(subset) = 23; P < 0.001 for both); (3) B-STN DBS improved abnormal sensory aspects of postural instability (P < 0.05) and postural MV (P = 0.005), whereas medication did not. Neither B-STN DBS nor medication improved postural RT. For the group as a whole, STN DBS plus medication was better therapy than medication preoperatively for sensory aspects of postural control (P = 0.003).
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PMID:Bilateral subthalamic nucleus deep brain stimulation improves certain aspects of postural control in Parkinson's disease, whereas medication does not. 1667 Oct 73

In this study we have explored the nature and range of sleep dysfunction that occurs in untreated Parkinson's disease (PD) comparing data obtained from the use of the Parkinson's disease sleep scale (PDSS) in an untreated PD patient group compared to advanced PD and healthy controls. 25 untreated (drug-naive, DNPD) PD patients (mean age 66.9 years, range 53-80, 18 males) completed the validated Parkinson's disease sleep scale (PDSS), mean duration of PD was 2.1 years (1-10, up to 4 years in all except one patient with tremulous PD reporting tremor duration of 10 years) and mean Hoehn and Yahr score 1.9 (1-3). Data were compared to 34 advanced PD (mean age 70.2 years, range 51-88, 23 male), mean duration of PD 11 years (range 4-22), mean Hoehn and Yahr score 3.4 (3-5) and PDSS data obtained from 131 healthy controls (mean age 66.6 years, range 50-93, 56 males). Total PDSS scores and PDSS sub-items, except PDSS item 2, were highly significantly different (p<0.001) between DNPD, advanced PD and controls. Controls reported higher mean PDSS scores than both groups of patients, and advanced cases reported lower (mean+/-S.D.) PDSS scores (86.95+/-20.78) than drug-naive (105.72+/-21.5) (p<0.001). Logistic regression analysis showed that items PDSS8 (nocturia), PDSS11 (cramps), PDSS12 (dystonia), PDSS13 (tremor), and PDSS15 (daytime somnolence) were significantly impaired in DNPD compared to controls while PDSS7 (nighttime hallucinations) additionally separated advanced PD from DNPD. In a subgroup of 11 advanced PD cases (mean age 62 years, range=49-84 years, mean Hoehn and Yahr score 2.5, range=1-3) with high Epworth Sleepiness Scale (ESS) scores (mean 14.5), low item 15 PDSS score (mean 4.7) and complaints of severe daytime sleepiness, underwent detailed overnight polysomnography (PSG) studies, all showing abnormal sleep patterns. We conclude that nocturia, nighttime cramps, dystonia, tremor and daytime somnolence seem to be the important nocturnal disabilities in DNPD and some of these symptoms may be reminiscent of "off" period related symptoms even though patients are untreated. Furthermore, polysomnography in "sleepy" PD patients may help diagnose unrecognised conditions such as periodic limb movement of sleep (PLMS), obstructive sleep apnoea (OSA) and REM Sleep Behaviour Disorder.
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PMID:The range and nature of sleep dysfunction in untreated Parkinson's disease (PD). A comparative controlled clinical study using the Parkinson's disease sleep scale and selective polysomnography. 1678 Aug 88

Our paper discusses two experimental studies suggesting that Visual Hallucinations (VH) in Parkinson's Disease (PD) may have separate origins. The first is a prospective 8years study evaluating the appearance of VH, visual abnormalities assessed by Visual Evoked Potentials (VEPs) and REM sleep Behaviour Disorder (RBD), in 80 PD patients treated with l-Dopa and Dopaminoagonists (DA). In chronically treated, cognitively unimpaired, PD patients VH were statistically related (p=0.001) to RBD occurrence and high DA doses. Visual abnormalities were significantly reduced by l-Dopa or DA intake, and were statistically unrelated to VH. The second study involved PD patients placed in a Virtual Reality Environment, to decontextualize visual input. When motor symptoms worsened and VEP abnormalities developed patients consistently described hallucinatory dysperceptions of the virtual environment. The two studies therefore show that VH can occur in two seemingly distinct conditions, one is related to chronic treatment and to a sleep disorder frequently observed in PD, the other is probably related to a hypodopaminergic state. Our studies support a recently proposed integrative model of VH, and show that the neural circuits purported to explain VH must include the retinal dopaminergic system and the REM sleep regulatory system.
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PMID:Visual hallucinations in Parkinson's disease: clues to separate origins. 1680 69


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