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)

Dopaminergic neuron controls CNS functions such as meso-limbic, striato-nigral and tubero-infundibular systems. The purpose of the present study is the evaluation of the hypothalamic dopaminergic neuron activity in neuro-degenerative disorders. alpha-melanocyte-stimulating hormone (alpha-MSH) is synthesized in the arcuate nucleus and lateral part of the hypothalamus, and its secretion is under the inhibitory control of the dopaminergic neuron both in the hypothalamus and pituitary. alpha-MSH-like-immunoreactivity (alpha-MSH-LI) in CSF is thought to be representative to the dopaminergic neuron activity in the hypothalamus. We therefore evaluated CSF levels of alpha-MSH-LI in spinocerebellar degenerations and extrapyramidal diseases. The subjects are 11 patients with Parkinson's disease, 16 with Shy-Drager syndrome (SDS), 16 with cerebellar cortical atrophy, 3 with Machado-Joseph disease, 3 with dentato-rubro-pallido-luysian atrophy and 2 with Huntington's disease as well as 24 controls. All patients with Parkinson's disease were administered levodopa and carbidopa. CSF was sampled through lumbar puncture in the morning. After the centrifugation, supernatant of CSF was stored at -40 degrees C until used. alpha-MSH in CSF was extracted by Rainero's method and measured by RIA. alpha-MSH-LI levels in control was 23.9 +/- 2.6 pg/ml (mean +/- SD). The significant elevation was observed in Parkinson's disease (40.3 +/- 7.5, p less than 0.001) and SDS (42.3 +/- 9.4, p less than 0.001). The levels showed not significant correlation with age, duration of illness or severity of autonomic disorder. Most of other diseases demonstrated the levels within normal range.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Abnormality of hypothalamic dopaminergic system in neuro-degenerative diseases--evaluation of alpha-melanocyte-stimulating hormone-like immunoreactivity in cerebrospinal fluid]. 176 56

The gradient of negative slope (Ns') changed in parallel with the velocity of step movement in normal individuals. We can not evaluate the MRCPs without considering this factor among patients and/or subjects. We recorded the MRCPs of thirty nine patients with cerebellar ataxias and sixteen patients with Parkinson disease (PD). Goniometer was attached on the patient's wrist to measure the velocity of the wrist movement. In the patients with spinocerebellar degeneration with denate nucleus lesion (Machado-Joseph disease, DRPLA, MERRF, dyssynergia cerebellaris myoclonica, galactosialidosis), the gradients of Ns' were reduced, although the movements themselves were as fast as normal control. In the patients with spinocerebellar degeneration without this lesion, the MRCPs were able to record as normal control, and their gradients of Ns' became steeper according to the increase of the movement angular velocity. On the contrary, in the patients with Parkinson disease, the gradients of Ns' were steeper in the patients with slow movement than in those with fast movement. The MRCP helps us to investigate the pathophysiology of the movement disorders. It is desirable that physiological data on the MRCP are extensively accumulated.
 ...
PMID:[Movement-related cortical potentials (MRCPs) and voluntary movement--clinical usefulness of MRCPs]. 875 52

To clarify the mechanism of brain impairment in Machado-Joseph disease (MJD), we measured the cerebrospinal fluid (CSF) levels of substance P in 7 patients (mean age 45.7 +/- 12.09 years) with this disease. Four patients had type I and three had type II disease. Findings were compared with those obtained in 14 age-matched controls, 8 patients with Parkinson's disease, 7 patients with multiple system atrophy, and 6 patients with myopathy. The CSF level of substance P was significantly (p = 0.0000) lower in the patients with MJD, being 44.5% of the control value. However, the mean CSF levels of substance P in the patients with Parkinson's disease, multiple system atrophy, or myopathy did not differ significantly from that in the control subjects. The alteration in the CSF level of substance P may be related to the neurological impairment observed in MJD.
 ...
PMID:Decreased cerebrospinal fluid levels of substance P in Machado-Joseph disease. 890 28

Molecular genetic analyses have elucidated a class of inherited neurodegenerative disorders caused by expanded CAG repeats encoding polyglutamines (e.g. Huntington disease and Machado-Joseph disease). Proteins containing expanded polyglutamine repeats appear to precipitate by self-aggregation and, as a result, produce a core disease-related phenotype: neuronal cell death or degeneration. In other neurodegenerative disorders, such as Alzheimer disease, prion disease, Parkinson disease and amyotrophic lateral sclerosis, precipitation of abnormal proteins is also now considered to play a key role. These observations might lead to the elucidation of universal mechanisms for neurodegeneration and to effective treatments for many neurodegenerative disorders.
 ...
PMID:Protein precipitation: a common etiology in neurodegenerative disorders? 982 28

The authors report on clinical features and mortality rates in a group of 149 patients with apparent idiopathic parkinsonism starting before the age of 40 years. Ten had juvenile parkinsonism (JP; onset before age 21 years) and 139 had young-onset Parkinson's disease (YOPD; onset at age 21 to 40 years). Included were 60 patients originally reported 10 years ago. Fifty percent of the JP group had a positive family history of parkinsonism in a first-degree relative, and clinical presentation was heterogeneous. Mortality risk was threefold that of the normal population. In the YOPD group, the mortality risk was double that of the normal population. Poor initial response to L-dopa was a risk factor for early death. In two previously reported patients, the diagnosis had been changed to multiple system atrophy and Machado-Joseph disease. After a median disease duration of 18 years, cognitive impairment was found in only 19% of YOPD patients (13% of those younger than 60 years and 43% of those 60 years or older). Age was the most important factor for development of dementia, but female sex and positive family history of parkinsonism also had more modest predictive value. After a disease duration of 10 years or less, only 5% of patients were experiencing falls and 30% freezing, but all patients had developed L-dopa-related fluctuations and dyskinesias. The authors conclude that the mortality rate in parkinsonism starting before the age of 40 is increased in comparison to the normal population and is similar to the general Parkinson's disease population. Intellectual function and postural reflexes are usually well preserved for many years despite a long history of parkinsonism and the early and frequent occurrence of treatment complications, provided the patients remain biologically and chronologically young.
 ...
PMID:Young-onset Parkinson's disease revisited--clinical features, natural history, and mortality. 982 11

To investigate the mechanism of the vocal cord abductor paralysis (VCAP) in the neurodegenerative diseases, the intrinsic laryngeal muscles (the crycothyroid, the interarytenoid, and the posterior crycoarytenoid muscles) from 41 autopsied cases were histologically examined: 10 cases of amyotrophic lateral sclerosis (ALS), 10 of Parkinson's disease (PD), 9 of multiple system atrophy (MSA), 4 of Machado-Joseph disease (MJD), 4 of progressive supranuclear palsy (PSP), 1 of familial amyloidotic polyneuropathy (FAP), and 3 of cerebrovascular diseases as a control. According to the distribution of the neurogenic changes among above-described three intrinsic laryngeal muscles, three forms were raised: 1. The totally paralytic form showing that all the three muscles developed neurogenic atrophy. This form includes ALS, MJD, and FAP. 2. The posterior muscle-paralytic form showing that only the posterior crycoarytenoid muscle was selectively involved. This form includes MSA. 3. The nonparalytic form showing no morphological abnormalities in any of the intrinsic laryngeal muscles. This type includes PD and PSP. In this nonparalytic form, supranuclear mechanism such as pyramidal or extrapyramidal tract involvement may cause VCAP through the increased laryngeal muscles tone. Considering that VCAP can be seen in any of the above-described forms, our results indicate that the mechanism of VCAP is different among the neurological disorders.
 ...
PMID:[Myopathology of the intrinsic laryngeal muscles in neurodegenerative diseases, with reference to the mechanism of vocal cord paralysis]. 991 15

At present, 8 inherited neurodegenerative disorders (e.g. Huntington disease, Machado-Joseph disease, etc.) are identified to be caused by the polyglutamine-coding CAG triplet expansions in the responsible genes. These disorders commonly demonstrate dominant inheritance, if autosomal, and late onset of their manifestations. Interestingly, the longer expansions result in earlier onset and more severe clinical manifestations. Proteins containing expanded polyglutamine repeats appear to precipitate by self-aggregation, and as a result produce a core disease-related phenotype: neuronal cell death or degeneration. Given that polyglutamine aggregation might be central in neurodegeneration, the parameters that determine the feasibility of the polyglutamines to aggregate would determine the age of onset and the clinical severity. These parameters are postulated to be the concentration and the length of polyglutamines, which is supported by clinical and experimental observations. The stronger neuronal degenerations are always accompanied by the longer polyglutamine stretches and by the higher concentration of the expanded polyglutamines. In other neurodegenerative disorders, such as Alzheimer disease, prion disease, Parkinson disease and amyotrophic lateral sclerosis, precipitation of abnormal proteins is also now considered to play a key role. These observations might lead to the elucidation of universal mechanisms for neurodegeneration and to treatments effective for many neurodegenerative disorders.
 ...
PMID:[Recent progress in the research field on triplet repeat diseases]. 1034 35

We describe several families of African origin with SCA3/Machado-Joseph disease gene expansions. In these cases, the phenotype ranges from ataxia with parkinsonian signs to a syndrome clinically almost indistinguishable from idiopathic, L-dopa-responsive Parkinson's disease. In contrast, these parkinsonian phenotypes are rare in those of European descent. Haplotype analysis shows that these African families do not share a common founder, thus a cis-acting element in the promoter is unlikely to be responsible these unusual presentations. We suggest that trans-acting factors are responsible for the variable phenotype and discuss the implications of diseases showing racially different expressivities.
 ...
PMID:Ethnic differences in the expression of neurodegenerative disease: Machado-Joseph disease in Africans and Caucasians. 1236 May 61

We report on a patient with genetically proven Machado-Joseph Disease (MJD) presenting with signs indistinguishable from Parkinson's disease (PD), including levodopa response and typical levodopa-induced motor fluctuations. Only after 10 years of prolonged benefit from levodopa and different dopamine agonists (DA), the patient developed cerebellar ataxia and pyramidal signs. Preferential D3-receptor-stimulating dopamine agonists especially showed a benefit at the time, when D2 receptor binding was reduced in IBZM SPECT. This is the first report of a meaningful response to DA in MJD.
 ...
PMID:Dopaminergic response in Parkinsonian phenotype of Machado-Joseph disease. 1253 20

In this study no one of our 85 patients of Serbian origin with young-onset (</= 45 years) dopa-responsive parkinsonism (YOP), previously proved negative for PARK1 and PARK2 mutations, had either spinocerebellar ataxia type 2 (SCA2) or SCA3 mutation. These data do not prove the significance of these two mutations in either sporadic or familial YOP suggestive of Parkinson's disease.
 ...
PMID:SCA2 and SCA3 mutations in young-onset dopa-responsive parkinsonism. 1294 Aug 46


1 2 3 4 5 6 Next >>