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Genetic contributions to Parkinson's disease 总被引:8,自引:0,他引:8
Sporadic Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by the loss of midbrain dopamine neurons and Lewy body inclusions. It is thought to result from a complex interaction between multiple predisposing genes and environmental influences, although these interactions are still poorly understood. Several causative genes have been identified in different families. Mutations in two genes [α-synuclein and nuclear receptor-related 1 (Nurr1)] cause the same pathology, and a third locus on chromosome 2 also causes this pathology. Other familial PD mutations have identified genes involved in the ubiquitin–proteasome system [parkin and ubiquitin C-terminal hydroxylase L1 (UCHL1)], although such cases do not produce Lewy bodies. These studies highlight critical cellular proteins and mechanisms for dopamine neuron survival as disrupted in Parkinson's disease. Understanding the genetic variations impacting on dopamine neurons may illuminate other molecular mechanisms involved. Additional candidate genes involved in dopamine cell survival, dopamine synthesis, metabolism and function, energy supply, oxidative stress, and cellular detoxification have been indicated by transgenic animal models and/or screened in human populations with differing results. Genetic variation in genes known to produce different patterns and types of neurodegeneration that may impact on the function of dopamine neurons are also reviewed. These studies suggest that environment and genetic background are likely to have a significant influence on susceptibility to Parkinson's disease. The identification of multiple genes predisposing to Parkinson's disease will assist in determining the cellular pathway/s leading to the neurodegeneration observed in this disease. 相似文献
54.
ERP evidence of impaired central nervous system function in virally suppressed HIV patients on antiretroviral therapy. 总被引:2,自引:0,他引:2
Linda L Chao Joselyn A Lindgren Derek L Flenniken Michael W Weiner 《Clinical neurophysiology》2004,115(7):1583-1591
OBJECTIVE: To examine the effects of human immunodeficiency virus (HIV) on central nervous system (CNS) function in patients receiving antiretroviral therapy (ART) who have suppressed viral loads. METHODS: Event-related brain potentials (ERPs) were recorded from 15 virally suppressed HIV patients and 15 age-, sex-, and education-matched controls while they performed a 3-stimulus auditory oddball task. The amplitude and latency of the P3a, P3b, and early auditory components were examined in HIV patients and controls. RESULTS: Virally suppressed HIV patients on ART were more depressed than controls, as determined by the Beck Depression Inventory (BDI). After controlling for the effects of depression, HIV patients had smaller P2, P3a, and P3b amplitudes and longer P3a and P3b latency than control subjects. BDI scores correlated positively with N1 latency in HIV patients and negatively with P3b amplitude in all subjects. CONCLUSIONS: These electrophysiological results suggest that, even in the absence of detectable levels of HIV in the peripheral blood, viral replication persists in the CNS and continues to cause disease in HIV patients on ART. 相似文献
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M S Hussain R T Coutts G B Baker R G Micetich M Daneshtalab 《Progress in neuro-psychopharmacology & biological psychiatry》1991,15(2):285-289
1. Studies on the metabolism of the tricyclic antidepressant trimipramine (TMP) in the rat are described. 2. Twenty metabolites of TMP were isolated from rat urine after enzymatic hydrolysis and their structures were determined by a gas chromatographic-mass spectrometric (GC-MS) method. 3. Twelve TMP metabolites were the result of alicyclic (C10 or C11) oxidation in addition to the other metabolic pathways. 相似文献
56.
Anucha Apisarnthanarak Pattarachai Kiratisin Kanokporn Thongphubeth Chananart Yuakyen Linda M Mundy 《Infection control and hospital epidemiology》2007,28(5):637-639
We describe a pseudo-outbreak of Acinetobacter lwoffii infection that was recognized early. The pseudo-outbreak involved 16 patients and occurred 3.5 months after the GNS-506 Vitek automated system was introduced in the microbiology laboratory. Prompt confirmation of incomplete use of the automated system's algorithm as the point source of the misidentified A. lwoffii clinical isolates averted a full outbreak investigation and excess use of infection control resources. 相似文献
57.
HYPOTHESIS: Irrigation of the mastoid with a quinolone antibiotic-steroid solution may mitigate hearing loss caused by iatrogenic semicircular canal injury in the presence of Pseudomonas aeruginosa (PA) otitis media (OM). BACKGROUND: Studies have shown the cochlea to be more vulnerable to semicircular canal transection (SCT)-related hearing loss in the presence of PA OM. Prophylactic systemic antibiotics and steroids may decrease this hearing loss, but SCT is usually not planned. The aim of this study was to determine if irrigation with ciprofloxacin-dexamethasone (cipro-dex) could improve hearing outcomes following SCT in PA OM. METHODS: PA OM was induced in 28 animals. After three to five days, unilateral SCT was performed in each animal, with sham SCT on the contralateral ear. At surgery, half of the animals (n = 14) underwent irrigation of the both mastoid bullae with cipro-dex; the second group of animals (n = 14) underwent irrigation of the bullae with sterile saline. Auditory thresholds were obtained immediately prior to SCT and 7-10 days after SCT. RESULTS: SCT ears treated with cipro-dex showed a mean click threshold improvement of 4.6 dB from pre-transection to 7-10 days post-transection, whereas thresholds in the SCT ears treated with saline worsened by 7.5 dB (p = 0.15). CONCLUSION: Irrigation of the guinea pig bulla with cipro-dex following SCT in the setting of PA OM appears safe and may yield beneficial effects on hearing. 相似文献
58.
L D Stegink L J Filer G L Baker E F Bell 《The American journal of clinical nutrition》1986,43(4):510-515
Plasma glutamate concentrations in human subjects are markedly lower when monosodium L-glutamate (MSG) is ingested in consomme with starch than when ingested in consomme alone. This study investigated whether sucrose had a similar effect. Six normal adult subjects (three male, three female) ingested two servings of beef consomme each providing 50 mg MSG/kg body weight in a randomized crossover design. One serving of consomme contained no added carbohydrate; the other provided 0.5 g sucrose/kg body weight. Ingestion of the consomme without sucrose significantly (p less than 0.05) increased the mean plasma glutamate concentration from baseline (4.44 +/- 0.97 mumol/dl) to a peak value of 18.1 +/- 6.99 mumol/dl 30 min after dosing. The area under the plasma glutamate concentration-time curve was 553 +/- 238 mumol/dl X min. When the consomme contained 0.5 g sucrose/kg body weight, both the mean peak plasma glutamate concentration (5.48 +/- 2.19 mumol/dl) and the area under the curve (105 +/- 46 mumol/dl X min) were significantly lower. These data confirm that metabolizable carbohydrate has a significant effect on plasma glutamate concentration response after MSG loading. 相似文献
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