Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative damage, including modification of nucleic acids, may contribute to dopaminergic neurodegeneration in the substantia nigra (SN) of patients with Parkinson's disease (PD). To investigate the extent and distribution of nucleic acid oxidative damage in these vulnerable dopaminergic neurons, we immunohistochemically characterized a common product of nucleic acid oxidation, 8-hydroxyguanosine (8OHG). In PD patients, cytoplasmic 8OHG immunoreactivity was intense in neurons of the SN, and present to a lesser extent in neurons of the nucleus raphe dorsalis and oculomotor nucleus, and occasionally in glia. The proportion of 8OHG immunoreactive SN neurons was significantly greater in PD patients compared to age-matched controls. Midbrain sections from patients with multiple system atrophy-Parkinsonian type (MSA-P) and dementia with Lewy bodies (DLB) also were examined. These showed increased cytoplasmic 8OHG immunoreactivity in SN neurons in both MSA-P and DLB compared to controls; however, the proportion of positive neurons was significantly less than in PD patients. The regional distribution of 8OHG immunoreactive neurons within the SN corresponded to the distribution of neurodegeneration for these three diseases. Nuclear 8OHG immunoreactivity was not observed in any individual. The type of cytoplasmic nucleic acid responsible for 8OHG immunoreactivity was analyzed by preincubating midbrain sections from PD patients with RNase, DNase, or both enzymes. 8OHG immunoreactivity was substantially diminished by either RNase or DNase, and completely ablated by both enzymes. These results suggest that oxidative damage to cytoplasmic nucleic acid is selectively increased in midbrain, especially the SN, of PD patients and much less so in MSA-P and DLB patients. Moreover, oxidative damage to nucleic acid is largely restricted to cytoplasm with both RNA and mitochondrial DNA as targets.
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PMID:Parkinson's disease is associated with oxidative damage to cytoplasmic DNA and RNA in substantia nigra neurons. 1032 95

We performed in vivo phosphorus magnetic resonance spectroscopy on the occipital lobes of 15 patients with multiple system atrophy (MSA; eight with olivopontocerebellar atrophy [OPCA] and seven with the striatonigral degeneration variant [SND]), 13 patients with idiopathic Parkinson's disease (PD), and 16 age-matched healthy subjects. The MSA group showed significantly reduced phosphocreatine (PCr), increased inorganic phosphate (Pi), and unchanged cytosolic free [Mg2+], and pH. We did not find any significant difference between the OPCA and SND variants. However, patients with PD showed significantly increased content of Pi, decreased cytosolic free [Mg2+], and unchanged [PCr] and pH. Comparing the MSA and PD groups, [PCr] was significantly lower in MSA than in PD, whereas cytosolic free [Mg2+] was significantly lower in PD. Despite a certain degree of overlap of [PCr] and [Mg2+] values between the two groups, by considering both variables at the same time it was possible to classify correctly 93% of cases by discriminant analysis. We conclude that phosphorus magnetic resonance spectroscopy discloses abnormal phosphate metabolite and ion contents in both MSA and PD, respectively, and may provide noninvasive diagnostic help to differentiate MSA from PD.
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PMID:Phosphorus magnetic resonance spectroscopy in multiple system atrophy and Parkinson's disease. 1034 65

We analyzed the clinical and physiological features of autonomic failure with Parkinson's disease (AF-PD) in seven patients and compared them with those of autonomic failure with multiple system atrophy (AF-MSA). In AF-PD, parkinsonism was more gradually progressive than in AF-MSA, and symptoms were responsive to L-dopa. All seven patients with AF-PD had orthostatic hypotension, postprandial hypotension, and constipation, but no urinary retention. Of these, three had hypohidrosis and five had frequent urination; five patients had subnormal plasma norepinephrine (NE) concentrations. Supersensitivity to NE infusion was observed in all patients. Head-up tilting (HUT) test resulted in no increase of plasma NE concentrations in both groups, but a significant increase of the plasma arginine vasopressin (AVP) concentrations in the patients with AF-PD. Urodynamic studies revealed that urinary bladder function was relatively well preserved in AF-PD in contrast to AF-MSA. In conclusion, there exists some clinical and physiological differences in autonomic features between AF-PD and AF-MSA, and postganglionic involvement predominates in AF-PD.
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PMID:Clinical and physiological characteristics of autonomic failure with Parkinson's disease. 1045 60

We measured total glutathione concentrations in the cerebrospinal fluid (CSF) of non-demented Parkinson's disease patients (PD; n=71), demented PD patients (PDD; n=13), multiple system atrophy patients (MSA; n=10), Alzheimer's disease patients (AD; n=17) and age-matched controls (n=21). No statistically significant differences in the mean total CSF glutathione concentrations were found between groups and dopaminomimetic treatment was not found to have any effect on total CSF glutathione levels. Our main conclusion is that total glutathione is not useful as a CSF marker for assumed oxidative stress in patients with PD, MSA or AD.
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PMID:Normal cerebrospinal fluid glutathione concentrations in Parkinson's disease, Alzheimer's disease and multiple system atrophy. 1052 92

Auditory brainstem responses (ABRs) were examined in six patients with autonomic failure with Parkinson's disease (AF with PD) and 10 patients with autonomic failure with multiple system atrophy (AF with MSA), all of which showed marked parkinsonian features as a principal sign. We designated the central abnormalities of ABRs as prolongation of latencies (wave III or V) and interpeak latencies (IPLs; I-III, I-V, and III-V IPL) or decreased amplitude ratios of wave III or V to those of wave I (less than 1.0). None of the patients with AF with PD showed abnormalities in ABRs. In contrast, in those with AF with MSA, the peak latencies or IPLs were prolonged in two of the 10 patients, and the amplitude ratios of wave III or V to those of wave I were decreased in other two of these patients. Moreover, both prolongation of latencies and a decreased ratio were observed in other one. Overall, five of the 10 patients with AF with MSA showed central abnormalities in ABRs. It is clinically difficult to differentiate AF with PD from AF with MSA, particularly when no cerebellar signs are apparent in AF with MSA patients. When central abnormalities of ABRs are observed in AF patients, AF with MSA should be suspected rather than AF with PD. In conclusion, ABRs provide useful information for the differential diagnosis of AF with PD and AF with MSA.
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PMID:Auditory brainstem responses in patients with autonomic failure with Parkinson's disease and multiple system atrophy. 1058 Mar 1

We studied cerebral metabolism in 82 patients with nonfamilial parkinsonism, including Parkinson's disease (PD; n = 23), progressive supranuclear palsy (PSP; n = 12), corticobasal degeneration (CBD; n = 19), multiple systemic atrophy (MSA; n = 18) and vascular parkinsonism (VP; n = 10) by using proton magnetic resonance spectroscopy ((1)H-MRS), which allowed noninvasive measurement of signal intensities from N-acetylasparate (NAA), choline-containing compounds (CHO) and creatine plus phosphocreatine (CRE). As compared to normal controls, patients with PSP, CBD, MSA and VP, but not PD, had significant reduction of the NAA/CRE ratio in the frontal cortex, whereas patients with PSP, CBD, MSA and PD, but not VP, had significant reduction of the NAA/CRE ratio in the putamen. Patients with CBD had significant reduction of the NAA/CRE ratio in the frontal cortex and putamen as compared to patients with PD, MSA and VP. Patients with PSP showed a significant reduction of the NAA/CRE ratio in the putamen as compared with patients with PD and MSA. Patients with CBD showed clear asymmetry in the putamen as compared to controls and other patients. The reduction of the NAA/CRE ratio in the putamen correlated well with the severity of parkinsonism. (1)H-MRS may be useful in monitoring patients with various types of parkinsonism.
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PMID:Proton magnetic resonance spectroscopy of patients with parkinsonism. 1097 1

Bradykinetic-rigid syndromes are often accompanied by cognitive impairment. Because prominent motor involvement in these disorders may interfere with neuropsychological testing, we used event-related potentials (ERPs) for the assessment of cognition and attention in 41 patients with various bradykinetic-rigid syndromes of less than 5 years duration: idiopathic Parkinson's disease corticobasal degeneration, Steele-Richardson-Olszewski syndrome (SRO), and multiple system atrophy. Patients were compared with matched normals. ERP abnormalities in the auditory "oddball" paradigm were found only in corticobasal degeneration and SRO. ERP abnormalities in selective attention tasks were present in all patient groups, changes in SRO being the most prevalent. Abnormalities in corticobasal degeneration were present under "less-attention-demanding" conditions and suggested involvement of posterior parts of the brain. Multiple system atrophy and idiopathic Parkinson's disease patient groups had minimal ERP abnormalities. However, reaction times in MSA were longer in all paradigms. The results of the study support the view that bradykinetic-rigid syndromes involve some attentional deficits, but also have distinct reaction time and ERP characteristics, which may be helpful in differential diagnosis.
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PMID:Attention and cognition in bradykinetic-rigid syndromes: an event-related potential study. 1170 61

The mitochondrial 4977-bp common deletion has been reported in some studies to occur exclusively or with increased frequency in the midbrain of patients with Parkinson's disease (PD). Other studies could not confirm these results; rather, it was suggested that the mitochondrial common deletion is associated with aging in the midbrain and not PD. One possible explanation for these conflicting results is the difficulty in quantifying mitochondrial DNA deletions or mutations in the whole midbrain or substantia nigra (SN) while only a subset of midbrain neurons degenerate in PD. In addition, none of the studies has addressed the cell types with the common deletion within the midbrain. In this study we used in situ hybridization to detect the common deletion in sections of midbrain from patients with PD, multiple system atrophy-parkinsonian type (MSA-P), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), age-matched controls, and individuals of different ages. The results demonstrated that the mitochondrial common deletion accumulated primarily in neurons but not glia in both the SN and other midbrain regions. There was no significant difference in the number or distribution of neurons with the common deletion or the average of the mean densities (AMD) of staining with the common deletion in nigral neurons among patients with PD, MSA-P, PSP, DLB, or age-matched controls. In addition, there was no difference in the number or distribution of neurons with the common deletion in nigral neurons between any age group, although there was a tendency for the common deletion to increase in the non-nigral neurons in older patients. These data indicate that accumulation of the 4977-bp common deletion in mitochondrial DNA in midbrain occurred primarily in neurons, and by this cytological approach, it was not associated with nigral neurodegeneration in the common movement disorders or aging.
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PMID:The mitochondrial common deletion in Parkinson's disease and related movement disorders. 1203 26

We investigated histamine concentration in post-mortem brain samples of patients with Parkinson's disease (PD, n = 24), multiple system atrophy (MSA, n = 8) and age-matched controls (n = 27). Histamine concentrations were significantly increased in the putamen (to 159% of the control mean), substantia nigra pars compacta (to 201%), internal globus pallidus (to 234%) and external globus pallidus (to 200%), i.e. in areas which play a crucial role in the motor behaviour and which show typical functional alterations in PD. In MSA no significant differences were seen. Tele-methylhistamine (histamine metabolite) concentrations were unchanged in PD. These results indicate that histamine concentration, but not its metabolism is increased in PD, but not in MSA. This finding may have implications in developing new drug therapies for PD and in differential diagnosis between PD and MSA.
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PMID:Increased brain histamine levels in Parkinson's disease but not in multiple system atrophy. 1206 7

Olfactory loss is a prominent symptom in idiopathic Parkinson's disease (IPD). Experiment 1 re-investigated the diagnostic value of psychophysical testing in the differentiation between idiopathic Parkinson disease (IPD) from non-IPD; 50 consecutive PS patients participated. In Experiment 2 five de-novo patients received 3 olfactory tests spread over a period of approximately one year. Nineteen IPD patients were anosmic, and 18 were hyposmic. All but one patient with MSA and PSP had mild/moderate hyposmia. Normosmia was found in CBD/misdiagnosed PS/psychogenic movement disorder. In Experiment 2, one of the de-novo patients was normosmic, 3 hyposmic, and 1 anosmic. Follow up investigations indicated decreased olfactory function in 3 patients while it improved in one. The normosmic patient retained olfactory abilities. This patient failed to respond to pharmacological treatment. In summary, olfactory tests differentiate IPD from non-IPD. Furthermore, tests of olfactory function may also be of interest in investigations related to treatment of PS.
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PMID:Olfactory function in idiopathic Parkinson's disease (IPD): results from cross-sectional studies in IPD patients and long-term follow-up of de-novo IPD patients. 1211 70


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