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)

The cognitive performance of a group of 82 newly diagnosed patients with Parkinson's disease who had never been treated was reassessed approximately 4 mths after randomization to one of three monotherapies (levodopa, bromocriptine or anticholinergic drugs). Dopaminergic and anticholinergic treatments both led to improvement in motor control but their effects upon cognitive performance dissociated. Anticholinergic drugs produced impairment in processes underlying the immediate registration of information whilst dopaminergic therapy produced improvement on a task dependent on working memory and cognitive sequencing. Other cognitive measures showed no change on treatment. The deficits that were affected by cholinergic and dopaminergic modulation are those that were most compromised in the early, untreated state in Parkinson's disease. The data support the notion that cognitive impairment in Parkinson's disease is multifactorial in origin: short-term memory processes are served by both dopaminergic and cholinergic subcortico-frontal systems but much of the cognitive impairment of Parkinson's disease is independent of this subcortical neurochemical pathology and may be due to early neuronal dysfunction within the cerebral cortex.
Brain 1992 Dec
PMID:Different effects of dopaminergic and anticholinergic therapies on cognitive and motor function in Parkinson's disease. A follow-up study of untreated patients. 148 57

Groups of patients with idiopathic Parkinson's disease, either medicated or unmedicated, were compared with matched groups of normal controls on a computerized battery previously shown to be sensitive to frontal lobe dysfunction, including tests of planning, spatial working memory and attentional set-shifting. In a series of problems based on the 'Tower of London' test, medicated patients with Parkinson's disease were shown to be impaired in the amount of time spent thinking about (planning) the solution to each problem. Additionally, an impairment in terms of the accuracy of the solution produced on this test was only evident in those patients with more severe clinical symptoms and was accompanied by deficits in an associated test of spatial short-term memory. Medicated patients with both mild and severe clinical symptoms were also impaired on a related test of spatial working memory. In contrast, a group of patients who were unmedicated and 'early in the course' of the disease were unimpaired in all three of these tests. However, all three Parkinson's disease groups were impaired in the test of attentional set-shifting ability, although unimpaired in a test of pattern recognition which is insensitive to frontal lobe damage. These data are compared with those previously published from a group of young neurosurgical patients with localized excisions of the frontal lobes and are discussed in terms of the specific nature of the cognitive deficit at different stages of Parkinson's disease.
Brain 1992 Dec
PMID:Fronto-striatal cognitive deficits at different stages of Parkinson's disease. 148 58

The cutaneous reflexes of upper limb muscles were studied in five patients with Parkinson's disease and 10 patients with stimulus-sensitive myoclonus associated with akinetic-rigid syndromes. The middle finger was stimulated with ring electrodes and rectified electromyographs were averaged from seven upper limb muscles and orbicularis oculi. Responses from subjects with Parkinson's disease without stimulus-sensitive myoclonus were similar to those of normal subjects. The responses from patients with stimulus-sensitive myoclonus associated with Parkinson's disease or multiple system atrophy had the normal pattern except that a long latency facilitation, which is present in normal subjects and known as E2, was greatly exaggerated. Patients with stimulus-sensitive myoclonus associated with cortical-basal ganglionic degeneration had a completely different pattern of responses. There was synchronous activation of all recorded upper limb muscles with latencies substantially shorter than those of the long latency facilitation (E2) in normal subjects. Cutaneous reflex testing may therefore be useful in the differentiation of akinetic-rigid syndromes.
Brain 1992 Dec
PMID:Stimulus-sensitive myoclonus in akinetic-rigid syndromes. 148 65

Neuronal thread protein (NTP) is a recently characterized molecule that is over-expressed in brains with Alzheimer's disease (AD) lesions. The present study encompasses a detailed analysis of NTP expression in AD compared with other neurodegenerative diseases and aged controls. Using a specific monoclonal antibody, NTP immunoreactivity was evaluated in 309 paraffin-embedded sections from 8 different regions of the frontal, parietal, and temporal lobes of 73 brains with AD, AD + Down's syndrome (DN), AD + Parkinson's disease (PD), PD dementia (PDD), aged controls, and disease controls with Huntington's disease, multi-infarct dementia, or schizophrenia. In 250 adjacent blocks of snap-frozen unfixed tissue the concentration of NTP (ng/mg of protein) was measured using a 3-site forward sandwich monoclonal antibody based immunoradiometric assay (M-IRMA). Immunohistochemical studies demonstrated that brains with AD, AD + PD, and AD + DN contained significantly higher densities of NTP immunoreactive neurons and more frequent immunostaining of neuropil and white matter fibers compared with PDD and aged controls (both P < 0.001) which had few or no AD lesions. In addition, the overall mean concentrations of NTP in AD, AD + PD, and AD + DN were significantly higher than in PDD and aged controls (P < 0.005). Greater degrees of NTP immunoreactivity and higher concentrations of the protein in cerebral tissue were significantly correlated with AD diagnosis and abundant neurofibrillary tangles (P < 0.005). The findings suggest that NTP over-expression may serve as a marker for the type of neuronal degeneration that occurs in AD.
J Neurol Sci 1992 Dec
PMID:Neuronal thread protein over-expression in brains with Alzheimer's disease lesions. 148 53

Recent studies have shown that compensatory processes have an important role in counteracting the neurodegenerative changes underlining Alzheimer's disease (AD), much like their well known role in Parkinson's disease (PD). In the light of these reports, we review the findings of the positive correlation existing between the appearance of extra-pyramidal symptoms and an increased rate of progression in AD patients. We propose that this correlated symptomatology arises from the wasting of globally shared compensatory resources, manifested both in an increasing inability to compensate for persisting sub-clinical nigral lesions, and in enhanced AD deterioration rate. Our hypothesis gains support from various clinical reports and by the neural modeling of synaptic changes in AD.
Med Hypotheses 1992 Dec
PMID:Extra-pyramidal symptoms in Alzheimer's disease: a hypothesis. 149 18

Several neurological diseases which affect the corpus striatum are candidates for gene therapy. We have developed a defective Herpes Simplex Virus (HSV-1) vector system to introduce genes into postmitotic cells, such as neurons. The prototype vector, pHSVlac, contains a transcription unit which places the E. coli Lac Z gene under the control of the HSV-1 immediate early (IE) 4/5 promoter, a constitutive promoter. We now demonstrate that a HSV-1 vector can deliver a gene into striatal neurons. Infection of cultured rat striatal neurons with pHSVlac virus resulted in stable expression of beta-galactosidase for at least two weeks, without cell death. The potential to replace the Lac Z gene with other genes of interest, such as the gene responsible for Huntington's Disease, once it is isolated, may lead to insights about the pathogenesis of this genetic neurodegenerative disease, and may provide a method for performing gene therapy on this disease. Similarly, introduction of the tyrosine hydroxylase gene, which encodes the rate-limiting enzyme in the conversion of tyrosine to dopamine, into striatal neurons might provide a novel gene therapy approach towards treating Parkinson's Disease.
Nucleic Acids Res 1991 Dec
PMID:Infection of cultured striatal neurons with a defective HSV-1 vector: implications for gene therapy. 166 13

In the last decade it has become quite clear that oxygen free radicals are involved in a vast amount of diseases such as cataract, atherosclerosis, rheumatism, arthritis, Parkinson's disease, reperfusion injuries and many others. The induction of defence systems against certain stresses (heat shock, inflammation) is also mediated by activated oxygen species. Oxygen-activation and -desactivation has to be regulated and well attenuated in aerobic cells and tissues. The biochemical basis of the biological efficacy of oxidants is thus based on a sophisticated balance between catalysis of production and reactivity of oxygen radicals by certain cofactors and transition metals on the one hand and on a reliable detoxification by antioxidants or metabolic chains on the other hand. In this communication, different oxygen activating principles are compared and the biochemical basis for the induction of repair processes by a synthetic heme oxidant, (Tetrachlorodecaoxide, TCDO) is presented.
Klin Wochenschr 1991 Dec 15
PMID:Oxygen radicals--biochemical basis for their efficacy. 166 86

Deprenyl slows the progression of disabling symptoms in Parkinson's disease (PD) by an unknown mechanism. It can block the action of MPTP on substantia nigra compacta (SNc) neurons by inhibiting monoamine oxidase B necessary to mediate the conversion of MPTP to MPP+, its active metabolite, in astroglia. Mice were pretreated with saline or the PD-producing toxin, MPTP (30 mg/kg) daily for 5 days and then after a further 3 days (to allow for the metabolism and excretion of the MPTP) were treated with deprenyl (0.25 or 10 mg/kg) or saline 3 times weekly for 20 days. In three series of mice treated with MPTP alone or MPTP-saline, serial sections through the SNc showed that averages of 37-42% of tyrosine hydroxylase (TH) immunoreactive neurons were lost gradually over 20 days. Joint counts of the numbers of TH-immunoreactive and Nissl-stained SNc somata from immediately adjacent sections established that the reductions in the numbers of TH-immunoreactive somata at 20 days after MPTP treatment represented neuronal death. Deprenyl treatment reduced the loss of TH-immunoreactive SNc neurons to averages of 14-16% for the 10-mg/kg and 0.25-mg/kg doses, respectively, and joint Nissl/TH counts for adjacent sections showed that reduction in the loss of TH-immunoreactive soma represented the rescue of SNc neurons that would have died by 20 days. The gradual loss of SNc neurons over the 20 days following MPTP exposure may reflect the toxin's axotomy-like effects on SNc neurons or the prolonged action of sequestered MPP+.(ABSTRACT TRUNCATED AT 250 WORDS)
J Neurosci Res 1991 Dec
PMID:Rescue of dying neurons: a new action for deprenyl in MPTP parkinsonism. 168 84

The neurotransmitter deficits of dementias, including Alzheimer's dementia, Lewy body dementia and Parkinson's disease are discussed in relation to cognitive and behavioural impairments together with neuropathological changes and available data on the status of receptor transmembrane signalling. Potential therapeutic strategies for dementia are outlined based on the following systems: excitatory amino acids, gamma-amino butyric acid, acetylcholine (muscarinic and nicotinic), noradrenaline, serotonin and peptides. These include the attenuation of transmitter deficits by agonists and agents inhibiting transmitter breakdown and support for surviving neurons by suppression of inhibitory inputs, trophic factors and neural implantation.
Pharmacol Ther 1991 Dec
PMID:Dementia: the neurochemical basis of putative transmitter orientated therapy. 168 28

Thirty healthy and 35 volunteers affected by Parkinson's disease (PD) were examined. Long latency responses (LLRs) and short latency somatosensory evoked potentials (SEPs) after median nerve stimulation were respectively recorded from forearm flexor muscles, and from 19 scalp electrodes, during relaxation (condition 1), light and maximal muscle contraction (conditions 2 and 3). Linear interpolation of SEPs was performed to produce isopotential colour maps. Latencies and amplitudes of the V1-V2 component in LLR, as well as of parietal, central and frontal scalp SEPs were analysed in the 3 experimental conditions. Highly significant inverse correlation matched the frontal SEP to the LLR V2 component amplitudes, both in healthy and in PD subjects. However, the V2 component--which in the former group was reliably identifiable only in condition 3--was presented in conditions 1 and 2 in a high percentage of PD subjects who also showed an abnormally reduced frontal SEP during complete relaxation. Excitability changes of brain motor areas induced by a sensory input were tested as follows: the motor cortex was transcranially stimulated (TCS) by magnetic pulses with an intensity 10% below (A) or above (B) the threshold for twitch elicitation during complete relaxation of forearm muscles; TCS was randomly preceded (range 14-32 msec) by a shock to the median or ulnar nerve at the elbow with identical characteristics as for LLR elicitation. An initial epoch of 'inhibition' followed by a peak of 'facilitation' of the amplitude of motor responses to TCS was observed when conditioning stimuli to the median nerve preceded TCS by 14-20 and by 24-32 msec, respectively. Contrary to normals, conditioning stimulation of the median nerve did not significantly influence the excitability threshold to TCS in those parkinsonians with depressed frontal N30.
Electroencephalogr Clin Neurophysiol 1991 Dec
PMID:Brain excitability and long latency muscular arm responses: non-invasive evaluation in healthy and parkinsonian subjects. 172 87


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>