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排序方式: 共有208条查询结果,搜索用时 15 毫秒
1.
Jerzy Slowinski Jake Dominik Ryan J. Uitti Zeshan Ahmed Dennis D. Dickson Zbigniew K. Wszolek 《Neuropathology》2007,27(1):73-80
We present a case of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) harboring the N279K mutation in the MAPT gene from the family known as pallido‐ponto‐nigral degeneration (PPND). This 49‐year‐old man was followed for 17 years. He presented at age 41 years with left leg stiffness and en‐bloc turning. During the course of his illness he developed a constellation of symptoms including parkinsonism, pyramidal signs, vertical gaze palsy, dysphagia, dystonia, personality and cognitive dysfunction, weight loss and mutism. Gross neuropathological examination showed mild atrophy of the cerebral cortex, hippocampal formation, amygdala, thalamus, subthalamic nucleus and depigmentation of the substantia nigra. Microscopy revealed neuronal loss and gliosis in the same regions. Tau immunohistochemistry showed pretangles, numerous threads, grain‐like structures and oligodendroglial tau‐positive inclusions (“coiled bodies”). In the spinal cord the tau pathology was more abundant in gray than white matter. Pretangles and threads were present in the anterior and, to a lesser extent, in the posterior horns. FTDP‐17 should be suspected in patients with a history of familial parkinsonism combined with behavioral and cognitive changes, onset before age 65 years and an aggressive clinical course. 相似文献
2.
S Calne B Schoenberg W Martin R J Uitti P Spencer D B Calne 《The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques》1987,14(3):303-305
We report here six families with Parkinson's disease in whom the onset of symptoms tended to occur at approximately the same time irrespective of the age of the patient. The mean difference in the time of onset in different generations was 4.6 years while the mean difference in age of onset in children and parents was 25.2 years. We construe this pattern of age separation within families as suggestive of an environmental rather than genetic cause. Support for this view derives from the lack of correlation between occurrence of the disease and the degree of consanguinity. We conclude that our findings are in accord with the hypothesis which attributes the cause of some cases of Parkinson's disease to early, subclinical environmental damage followed by age-related attrition of neurons within the central nervous system. 相似文献
3.
Alex Rajput Jay P Ross Cecily Q Bernales Sruti Rayaprolu Alexandra I Soto-Ortolaza Owen A Ross Jay van Gerpen Ryan J Uitti Zbigniew K Wszolek Ali H Rajput Carles Vilari?o-Güell 《European journal of human genetics : EJHG》2015,23(6):887-888
Exome-sequencing analyses have identified vacuolar protein sorting 35 homolog (VPS35) and DnaJ (Hsp40) homolog, subfamily C, member 13 (DNAJC13) harboring disease-causing variants for Parkinson disease (PD). Owing to the suggested clinical, pathological and genetic overlap between PD and essential tremor (ET) we assessed the presence of two VPS35 and DNAJC13 disease-causing variants in ET patients. TaqMan probes were used to genotype VPS35 c.1858G>A (p.(D620N)) (rs188286943) and DNAJC13 c.2564A>G (p.(N855S)) (rs387907571) in 571 ET patients of European descent, and microsatellite markers were used to define the disease haplotype in variant carriers. Genotyping of DNAJC13 identified two ET patients harboring the c.2564A>G (p.(N855S)) variant previously identified in PD patients. Both patients appear to share the disease haplotype previously reported. ET patients with the VPS35 c.1858G>A (p.(D620N)) variants were not observed. Although a genetic link between PD and ET has been suggested, DNAJC13 c.2564A>G (p.(N855S)) represents the first disease-causing variant identified in both, and suggests the regulation of clathrin dynamics and endosomal trafficking in the pathophysiology of a subset of ET patients. 相似文献
4.
K Saarinen A Karjalainen R Martikainen J Uitti L Tammilehto T Klaukka K Kurppa 《The European respiratory journal》2003,22(2):305-309
This population-based cross-sectional survey assessed the prevalence of work-aggravated asthma symptoms and the effect of the work environment on the aggravation of symptoms of established asthma. A questionnaire was sent to 2,613 persons (aged 20-65 yrs) with asthma. The analyses were restricted to the 969 respondents who were currently employed. The effect of occupational exposure on the aggravation of asthma symptoms at work was assessed according to both self-reported and expert-evaluated exposure. Approximately 21% of the respondents reported work-aggravated asthma symptoms at least weekly during the past month. The prevalence of those with work-aggravated symptoms increased by age, self-reported occupational exposure to dusts, abnormal temperatures or poor indoor air quality, physically strenuous work, and chemicals, and expert-evaluated probability of daily occupational exposure to airborne dusts, gases or fumes. Aggravation of asthma symptoms at work is common among employed adults with asthma. Both self-reported and expert-evaluated exposure to dusts, abnormal temperatures or poor indoor air quality, physically strenuous work, and chemicals explained the significant worsening of symptoms. The findings suggest a marked role of the work environment in the aggravation of symptoms of established asthma. 相似文献
5.
Naomi Kouri Yari Carlomagno Matthew Baker Amanda M. Liesinger Richard J. Caselli Zbigniew K. Wszolek Leonard Petrucelli Bradley F. Boeve Joseph E. Parisi Keith A. Josephs Ryan J. Uitti Owen A. Ross Neill R. Graff-Radford Michael A. DeTure Dennis W. Dickson Rosa Rademakers 《Acta neuropathologica》2014,127(2):271-282
In order to determine the frequency of microtubule-associated protein tau gene (MAPT) mutations and rare variants in CBD, we performed a systematic sequence analysis of MAPT coding and 3′ untranslated region (3′UTR) in a large cohort of autopsy-confirmed CBD patients (N = 109). This identified a novel MAPT mutation in exon 13, p.N410H, in a case that is neuropathologically indistinguishable from sporadic CBD. On immunoblot, the p.N410H mutation carrier had the same insoluble tau profile as seen in CBD. Additionally, tau expression analysis in brain tissue found a significant increase in the 4R/3R tau mRNA ratio (P = 0.04), indicating that p.N410H disrupts tau isoform homeostasis. Biochemically, recombinant tau protein with p.N410H showed a marked increase in tau filament formation compared to wild-type tau (P < 0.001), had a 19.2 % decrease in rate of microtubule assembly (P < 0.05), and a 10.3 % reduction in the extent of total microtubule polymerization (P < 0.01). Sequence analysis of the complete MAPT 3′UTR in autopsy-confirmed CBD cases further identified two rare variants with nominally significant association with CBD. An ATC nucleotide insertion (“MAPTv8”) was found in 4.6 % of CBD patients compared to 1.2 % of controls (P = 0.031, OR = 3.71), and rs186977284 in 4.6 % CBD patients, but only 0.9 % of controls (P = 0.04, OR = 3.58). Rs186977284 was also present in 2.7 % of a large cohort of autopsy-confirmed PSP patients (N = 566) and only 0.9 % of an additional control series (P = 0.034, OR = 3.08), extending the association to PSP. Our findings show that mutations in MAPT can cause CBD and MAPT non-coding variants may increase the risk of complex 4R tauopathies. 相似文献
6.
Catherine Labbé Alexandra I. Soto-Ortolaza Sruti Rayaprolu Andrea M. Harriott Audrey J. Strongosky Ryan J. Uitti Jay A. Van Gerpen Zbigniew K. Wszolek Owen A. Ross 《Parkinsonism & related disorders》2013,19(8):755-757
Essential Tremor is the most common form of movement disorder. Aggregation in families suggests a strong genetic component to disease. Linkage and association studies have identified several risk loci but the specific causal variants are still unknown. A recent study using whole exome sequencing identified a rare nonsense variant in the FUS gene (p.Q290X) that segregated with Essential Tremor in a large French Canadian family. In addition, two other rare FUS variants were identified (p.R216C and p.P431L) in Essential Tremor patients however co-segregation analysis with disease was not possible. In the present study, we sequenced all 15 exons of FUS in 152 familial probands with Essential Tremor and genotyped three reported FUS variants in 112 sporadic Essential Tremor patients and 716 control subjects recruited at Mayo Clinic Florida. Only known synonymous SNPs unlikely to be pathogenic were detected in our sequencing and not any of the recently identified mutations or novel ones. We conclude that the FUS mutations associated with risk of Essential Tremor are probably a rare occurrence. 相似文献
7.
8.
Uitti RJ Tsuboi Y Pooley RA Putzke JD Turk MF Wszolek ZK Witte RJ Wharen RE 《Neurosurgery》2002,51(6):1423-28; discussion 1428-31
OBJECTIVE: To determine whether cranial magnetic resonance imaging (MRI) is associated with deep brain stimulation (DBS) lead displacement or program interference. METHODS: In vitro and in vivo studies were performed with the Itrel II implantable pulse generator (IPG) (Model 7424; Medtronic, Minneapolis, MN), Medtronic 3387 and 3389 leads, and a 1.5-T GE Horizon LX scanner (General Electric, Milwaukee, WI). In the in vivo study, two MRI volumetric data sets were compared for each of five patients undergoing staged, bilateral, DBS electrode placement in the thalamic or subthalamic nucleus. The data sets were acquired shortly after the initial implantation and during stereotactic planning for the second implantation (1-8 mo between acquisitions). An additional thalamotomy-treated patient was included as a control patient. Volumetric data were analyzed in a blinded manner, using AnalyzeAVW 3.0 software (Biomedical Imaging Resource, Mayo Clinic, Rochester, MN), to determine lead movement. In the in vitro study, the IPG and leads were positioned in the magnetic field in various configurations and were systematically assessed for movement. RESULTS: In vivo, the majority of measured deviations (88%) were within the standard error of measurement (1.4 mm). The maximal measured deviation was 3 mm (2% occurrence). Excellent tremor control with stimulation was demonstrated, which did not change after MRI. In vitro, the DBS leads demonstrated no deflection when introduced into the magnetic field. Similarly, no changes in IPG battery strength, lead impedance, or program settings were observed. CONCLUSION: MRI was not associated with significant DBS electrode movement or changes in clinical responses. Other IPG models and components and MRI scanners should be evaluated, to develop specific guidelines for MRI among individuals with implanted DBS systems. 相似文献
9.
Huvinen M Uitti J Oksa P Palmroos P Laippala P 《Occupational medicine (Oxford, England)》2002,52(4):203-212
The aim of this study was to determine whether occupational exposure to chromite, trivalent chromium (Cr(3+)) or hexavalent chromium (Cr(6+)) causes respiratory diseases, an excess of respiratory symptoms, a decrease in pulmonary function or signs of pneumoconiosis among workers in stainless steel production. Altogether, 203 exposed workers and 81 referents with an average employment of 23 years were investigated for indicators of respiratory health on two occasions, in 1993 and in 1998. Data collection with a self-administered questionnaire, flow volume spirometry, measurement of diffusing capacity, chest radiography and laboratory tests were carried out by a mobile research unit. Exposure to different chromium species and other metals was monitored regularly and studied separately. No adverse respiratory health effects were observed in the group exposed to Cr(6+), either in comparison with the control group in the first cross-sectional study or during the additional 5 year follow-up. Among the Cr (3+) exposed people, the production of phlegm, shortness of breath and breathlessness on exertion were significantly more frequent than in the control group, but the frequency of the symptoms did not increase during the follow-up; no differences were observed in the lung function tests and the radiographic findings did not progress. In the chromite group, the prevalence of breathlessness on exertion was higher than in the control group. However, in the follow-up, the occurrence of symptoms did not differ from 1993 to 1998. In the first study, most parameters of lung function were lower among the smokers in the chromite group than among the smoking controls, but in 1998 the difference was less marked. An average exposure time of 23 years in modern ferrochromium and stainless steel production and low exposure to dusts and fumes containing Cr(6+), Cr(3+), nickel and molybdenum do not lead to respiratory changes detectable by lung function tests or radiography. The workers exposed to Cr(3+) had more respiratory symptoms than those in the control group. The workers in the chromite mine had lower lung function test results than the control group due to earlier exposure to higher dust concentrations. 相似文献
10.
Neuropathology of two members of a German-American kindred (Family C) with late onset parkinsonism 总被引:1,自引:0,他引:1
Wszolek ZK Gwinn-Hardy K Wszolek EK Muenter MD Pfeiffer RF Rodnitzky RL Uitti RJ McComb RD Gasser T Dickson DW 《Acta neuropathologica》2002,103(4):344-350
We present genealogical and longitudinal clinical observations and autopsy findings of a previously reported kindred, Family C (German-American), with late-onset autosomal dominant parkinsonism with evidence for linkage on chromosome 2p13. The clinical phenotype includes the cardinal features of idiopathic Parkinson's disease. In addition, postural tremor and dementia are detected in some individuals. Two members of the kindred, one affected and one unaffected have recently come to autopsy. The unaffected family member was an 82-year-old woman whose brain showed only mild age-related pathology and no evidence of subclinical Lewy body disease. In contrast, the affected family member was an 83-year-old man whose brain had neuronal loss, gliosis and Lewy bodies in the substantia nigra and other monoaminergic brain stem nuclei, as well as the basal forebrain and amygdala. Lewy bodies and Lewy neurites had a distribution typical of cases of idiopathic Parkinson's disease. Thus, the clinical and pathological findings in this family with autosomal dominant parkinsonism are similar to those of sporadic Parkinson's disease. 相似文献