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排序方式: 共有4105条查询结果,搜索用时 15 毫秒
41.
Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease. 总被引:14,自引:1,他引:13
E R Martin W K Scott M A Nance R L Watts J P Hubble W C Koller K Lyons R Pahwa M B Stern A Colcher B C Hiner J Jankovic W G Ondo F H Allen C G Goetz G W Small D Masterman F Mastaglia N G Laing J M Stajich R C Ribble M W Booze A Rogala M A Hauser F Zhang R A Gibson L T Middleton A D Roses J L Haines B L Scott M A Pericak-Vance J M Vance 《JAMA》2001,286(18):2245-2250
CONTEXT: The human tau gene, which promotes assembly of neuronal microtubules, has been associated with several rare neurologic diseases that clinically include parkinsonian features. We recently observed linkage in idiopathic Parkinson disease (PD) to a region on chromosome 17q21 that contains the tau gene. These factors make tau a good candidate for investigation as a susceptibility gene for idiopathic PD, the most common form of the disease. OBJECTIVE: To investigate whether the tau gene is involved in idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Among a sample of 1056 individuals from 235 families selected from 13 clinical centers in the United States and Australia and from a family ascertainment core center, we tested 5 single-nucleotide polymorphisms (SNPs) within the tau gene for association with PD, using family-based tests of association. Both affected (n = 426) and unaffected (n = 579) family members were included; 51 individuals had unclear PD status. Analyses were conducted to test individual SNPs and SNP haplotypes within the tau gene. MAIN OUTCOME MEASURE: Family-based tests of association, calculated using asymptotic distributions. RESULTS: Analysis of association between the SNPs and PD yielded significant evidence of association for 3 of the 5 SNPs tested: SNP 3, P =.03; SNP 9i, P =.04; and SNP 11, P =.04. The 2 other SNPs did not show evidence of significant association (SNP 9ii, P =.11, and SNP 9iii, P =.87). Strong evidence of association was found with haplotype analysis, with a positive association with one haplotype (P =.009) and a negative association with another haplotype (P =.007). Substantial linkage disequilibrium (P<.001) was detected between 4 of the 5 SNPs (SNPs 3, 9i, 9ii, and 11). CONCLUSIONS: This integrated approach of genetic linkage and positional association analyses implicates tau as a susceptibility gene for idiopathic PD. 相似文献
42.
A low molecular weight allergen of white birch (Betula verrucosa) is highly homologous to human profilin 总被引:1,自引:0,他引:1
R Valenta M Duchêne M Breitenbach K Pettenburger L Koller H Rumpold O Scheiner D Kraft 《International archives of allergy and applied immunology》1991,94(1-4):368-370
Cloning of allergens has contributed substantially to the understanding of mechanisms in allergic diseases by providing information about the sequence and hence biological functions of allergens. The major birch pollen allergen, Bet v I [Breiteneder H, et al: EMBO J 1989;8:1935-1938] and the white-faced hornet venom allergen (antigen 5) [Si Yun Fang K, et al: Proc. Natl. Acad. Sc. USA 1988;85:895-899] were shown to be highly homologous to pathogenesis-related proteins of plants. In the case of the major allergen of house dust mite, Der p I, homology to proteases was demonstrated. Therefore, the proposed biological function of these IgE-binding proteins might be related to their allergenic potential. In this paper we tentatively identify a ubiquitous family of low molecular weight allergens as profilins. The identification is based on a sequence homology, (b) binding to poly(L-proline), and (c) immunological cross-reactivity. Recombinant birch profilin was purified to homogeneity and showed the same properties as natural profilins. 相似文献
43.
N Mutz M Neumann C H?rmann W Koller C Putensen G Putz H Benzer 《Der Anaesthesist》1990,39(10):535-539
In patients with multiple injuries, the development of permeability edema can be assumed. However, no uniform shape of this fluid accumulation can be found even in the presence of severe injuries. Based on the first clinical observations, our aim was to search for correlations between the development of extravascular lung water (EVLW) and the individual injury pattern in severely traumatized ICU patients. PATIENTS and METHODS. Our investigations were performed in 48 artificially ventilated ICU patients. According to the prevailing injury pattern patients were divided into three groups: group A: 18 patients (mean age: 32 years, mean Injury Severity Score (ISS) = 29) with isolated thoracic trauma; group B: 10 patients (mean age: 27 years, mean ISS = 42) with severe multiple trauma but without any thoracic injury; group C: 20 patients (mean age: 33 years, mean ISS = 43) with severe multiple trauma and concomitant thoracic trauma. In all patients (group A, B, C), EVLW was determined by means of a double indicator method on a daily basis from the patient's admission to the ICU (day of trauma) until day 10. Additionally, the hemodynamic parameters (heart rate, mean arterial pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure and cardiac index) were determined at the same time. RESULTS. As shown in Fig 1, EVLW was slightly elevated on day 1. However, on day 2 EVLW decreased within normal values and remained in that range until the end of the observation period. On day 3 a slight and fleeting increase of EVLW, but within normal range, can be seen. In group B (Fig.2), EVLW can be observed within normal range within a period of 4 days. Starting from day 5 until day 7 a marked increase (p greater than 0.01) in EVLW can be seen. From that maximum point EVLW development reverses slightly until day 10--however, without returning to the normal range. In group C, a marked biphasic pattern can be seen due to EVLW maximum values on post-traumatic days 3 and 7. However, in this group the EVLW was in the pathological range during the whole observation period. No statistically significant differences could be seen, when looking at hemodynamic variables. CONCLUSION. Isolated thoracic trauma will not lead to a marked pathological elevation of EVLW within the lungs. Moreover, EVLW decreases rapidly within a short time period. Based on our results, it seems that severe extrathoracic injuries will intensify microvascular injury in the initial period, as shown in our patients in group C. Increase of EVLW at a later time (day 7), as observed in groups B and C, is possibly the expression of a mediator and activator-induced "septiformal" injury of the microvascular endothelium. This may be caused by the underlying massive peripheral soft-tissue trauma. Specific elevations of EVLW subsequent to the individual injury pattern can indicate that that process has begun and is responsible for the origin of the microvascular injuries. 相似文献
44.
Heiko Kilter Olaf Lenz Karl La Rosée Markus Flesch Robert H. G. Schwinger Martin Mädge Ferdinand Kuhn-Regnier Michael Böhm 《Naunyn-Schmiedeberg's archives of pharmacology》1995,352(3):308-312
Nitric oxide (NO) has been reported to mediate several effects in response to muscarinic cholinergic stimulation in cardiovascular tissues. Recently, an attenuation of guinea pig cardiac myocyte contraction by NO has been described. The aim of the present study was to determine whether the indirect negative inotropic effect of M-cholinoceptor stimulation in human myocardium is in part due to an effect of endogenous NO. Therefore, the effect of carbachol was studied under control conditions and during inhibition of NO-synthase by pretreatment with NG-monomethyl-l-arginine (NMMA). Functional experiments were performed in isolated, electrically driven (1 Hz, 37°C) left ventricular papillary muscle strips of human myocardium. Since cytokines have been reported to be increased in the serum of patients with heart failure and could induce NO-synthase activity in failing myocardium, we compared samples from nonfailing and terminally failing (classified as NYHA IV) hearts. The indirect negative inotropic effect of carbachol (10 mol/l) was studied in the presence of the \-adrenoceptor agonist isoprenaline (0.03 mol/l).After stimulation with isoprenaline, carbachol significantly (P < 0.05) reduced force of contraction. This effect was diminished in failing myocardium compared to nonfailing, probably due to the diminished inotropic response most likely due to the lower cAMP levels in response to \-adrenoceptor stimulation in the former condition. Pretreatment with NMMA (100 mol/l) altered the antiadrenergic effect of carbachol neither in nonfailing nor in failing preparations. Furthermore, inhibition of guanylyl cyclase, the target enzyme of NO, by preincubation with methylene blue (10 mol/l) for 30 min had no effect on the carbachol-induced decrease in force of contraction. Basal force of contraction, as well as the positive inotropic effect of isoprenaline remained unaffected by NMMA or methylene blue.The present study provides evidence that the indirect negative inotropic effect of M-cholinoceptor agonists is not due to an effect of NO in the human myocardium. Furthermore, the well known enhancement of cGMP in response to M-cholinoceptor stimulation appears not to be involved in this antiadrenergic effect. 相似文献
45.
M. Koller H. Kienapfel D. Hinder E. Sabau G. Wingert M. Pfeiffer P. Griss W. Lorenz 《Der Chirurg》1999,70(11):1364-1373
A scale for measuring symptoms related to degenerative diseases of the cervical spine is presented. Twenty typical symptoms are listed, e. g., neck pain, dysesthesia, and reduced mobility. Responses are assessed via a 6-point scaling ("did not have symptom" - "had symptom and suffered very strongly".) The cervical spine scale was tested in three samples: patients having undergone cervical spine surgery (n = 70), patients with other orthopedic diagnoses (n = 104), and healthy students (n = 100). The single items of the scale were aggregated into four scores: total number of symptoms, degree of overall symptom distress, functional disability, and pain/psychological distress. Statistical analyses proved the high reliability (Cronbach's alpha = 0.85 to 0.95) and validity (content, convergent, discriminant) of all scores. The scale differs clearly between cervical spine patients, other orthopedic patients and healthy individuals, and between cervical spine patients with different subjective operative outcomes. For applied clinical purposes the cervical spine scale can be included in a quality of life profile (QL-profile); this allows for a readily understandable graphic depiction of individual patients' QL-status. 相似文献
46.
A phase 1, randomized, placebo-controlled, five-level dose escalation safety and tolerability and pharmacokinetic study of a single IV dose of natalizumab was performed. Doses of 0.03 to 3.0 mg/kg natalizumab or placebo were studied in 28 stable relapsing-remitting or secondary-progressive MS. All doses were safe and well tolerated in MS. Serum concentrations of natalizumab are detectable for 3 to 8 weeks after a single 1- or 3-mg/kg IV dose and justify controlled efficacy studies. 相似文献
47.
48.
Martino K Merrit S Boyakye K Sernas T Koller C Hauser CJ Lavery R Livingston DH 《The Journal of trauma》1999,46(3):369-71; discussion 372-3
49.
Andel H Rab M Felfernig M Andel D Koller R Kamolz LP Zimpfer M 《Burns : journal of the International Society for Burn Injuries》1999,25(8):1081-756
In severely burned patients the approach to the central vein is often difficult due to concomitant edema, but also due to the fact that the skin area, where commonly used approaches are performed, is burned as well, whereas the axillary region is often not involved. In order to perform an axillary approach to the central vein as an alternative to the commonly used approaches in patients, an anatomical dissection in fresh human cadavers was carried out. Considering the anatomical landmarks which were found during dissection of the axillary region, the axillary approach to the central vein was used in 35 patients in our intensive burn care unit with unaffected axillary skin. In three cases the only complication observed was an occasional puncture of the axillary artery without major hematoma. The infection rate of the catheters was similar to the commonly used puncture sites. This approach to the central venous line in severely burned patients can be recommended. 相似文献
50.
Spallek H Spallek G 《Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft》1999,96(11):741-748
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Material und Methode: Die Effektivit?t einer Internet-Recherche h?ngt vom Wissenstand über vorhandene Suchstrategien ab. Es werden Suchsysteme
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