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Verbeek XA Auricchio A Yu Y Ding J Pochet T Vernooy K Kramer A Spinelli J Prinzen FW 《American journal of physiology. Heart and circulatory physiology》2006,290(3):H968-H977
This study explores the use of interventricular asynchrony (interVA) for optimizing cardiac resynchronization therapy (CRT), an idea emerging from a simple pathway model of conduction in the ventricles. Measurements were performed in six dogs with chronic left bundle branch block (LBBB) and in 29 patients of the Pacing Therapies for Congestive Heart Failure (PATH-CHF)-I study. In the dogs, intraventricular asynchrony (intraVA) was determined using left ventricular (LV) endocardial activation maps. In dogs and patients, the maximum rate of rise of LV pressure (LV dP/dt(max)) and the pulse pressure (PP) and interVA [time delay between upslope of LV and right ventricular (RV) pressure curves] were measured during LV, RV, and biventricular (BiV) pacing with various atrioventricular (AV) delays. Measurements in the canine hearts supported the pathway model in that optimal resynchronization occurred at approximately 50% reduction of intraVA and at an interVA value halfway that during LBBB and LV pacing. In patients with significant hemodynamic response during pacing (n = 22), intrinsic interVA and interVA at peak improvement (interVA(p)) varied widely between patients (from -83 to -15 ms and from -42 to +31 ms, respectively). However, the model predicted individual interVA(p) accurately (SD of +/-6 ms and +/-12 ms for LV dP/dt(max) and PP, respectively). At equal interVA, LV and BiV pacing produced equal hemodynamic response, but in 11 of 22 responders, BiV pacing reduced interVA insufficiently to reach the maximum hemodynamic response. LV pacing at short AV delay proved to result in better hemodynamics than predicted by the model, indicating that additional factors determine hemodynamics during LV preexcitation. Guided by a simple pathway model, interVA measurements accurately predict optimal hemodynamic performance in individual CRT patients. 相似文献
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Richard H. M. Eertman Bart A. Kornman Ed Stikvoort Harm Verbeek 《Restoration Ecology》2002,10(3):438-449
Because of land reclamation, reinforcement of dikes, and the deepening of shipping channels, large areas of tidal marshes have been removed or eroded from the Scheldt estuary during the last two centuries. Tidal wetland restoration contributes toward compensating this loss of habitat. Not all restoration projects are meticulously planned, however; some are forced by nature. During a severe storm in 1990, a dike was breached in the brackish part of the Scheldt estuary and returned tidal influence to the Sieperda polder. In the 10 years since the dike breach, the former polder has changed into a brackish tidal marsh. Here we report on the geomorphologic and ecological developments that have taken place in the marsh. Tidal intrusion into the former polder turned crop fields into mudflats and changed pastures into salty marsh vegetation. The digging of a new creek improved marsh hydrology and enhanced tidal intrusion further into the marsh. Macrofauna typical of estuarine mudflats established rapidly in the developing marsh. Vegetation succession took place rapidly. Within 5 years, large areas of mudflats became covered with marsh vegetation. Birds characteristic of salt marshes were observed breeding or seen foraging in the marsh. The number of wading birds declined as areas of mudflat became overgrown. It is demonstrated that tidal flow is the engine to tidal marsh restoration. Tidal influence caused geomorphologic changes, which directed ecological developments in the former polder. 相似文献
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Complement facilitates early prion pathogenesis 总被引:16,自引:0,他引:16
Klein MA Kaeser PS Schwarz P Weyd H Xenarios I Zinkernagel RM Carroll MC Verbeek JS Botto M Walport MJ Molina H Kalinke U Acha-Orbea H Aguzzi A 《Nature medicine》2001,7(4):488-492
New-variant Creutzfeldt-Jakob disease and scrapie are typically initiated by extracerebral exposure to the causative agent, and exhibit early prion replication in lymphoid organs. In mouse scrapie, depletion of B-lymphocytes prevents neuropathogenesis after intraperitoneal inoculation, probably due to impaired lymphotoxin-dependent maturation of follicular dendritic cells (FDCs), which are a major extracerebral prion reservoir. FDCs trap immune complexes with Fc-gamma receptors and C3d/C4b-opsonized antigens with CD21/CD35 complement receptors. We examined whether these mechanisms participate in peripheral prion pathogenesis. Depletion of circulating immunoglobulins or of individual Fc-gamma receptors had no effect on scrapie pathogenesis if B-cell maturation was unaffected. However, mice deficient in C3, C1q, Bf/C2, combinations thereof or complement receptors were partially or fully protected against spongiform encephalopathy upon intraperitoneal exposure to limiting amounts of prions. Splenic accumulation of prion infectivity and PrPSc was delayed, indicating that activation of specific complement components is involved in the initial trapping of prions in lymphoreticular organs early after infection. 相似文献
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Prx1 and Prx2 are upstream regulators of sonic hedgehog and control cell proliferation during mandibular arch morphogenesis 总被引:3,自引:0,他引:3
ten Berge D Brouwer A Korving J Reijnen MJ van Raaij EJ Verbeek F Gaffield W Meijlink F 《Development (Cambridge, England)》2001,128(15):2929-2938
The aristaless-related homeobox genes Prx1 and Prx2 are required for correct skeletogenesis in many structures. Mice that lack both Prx1 and Prx2 functions display reduction or absence of skeletal elements in the skull, face, limbs and vertebral column. A striking phenotype is found in the lower jaw, which shows loss of midline structures, and the presence of a single, medially located incisor. We investigated development of the mandibular arch of Prx1(-/-)Prx2(-/-) mutants to obtain insight into the molecular basis of the lower jaw abnormalities. We observed in mutant embryos a local decrease in proliferation of mandibular arch mesenchyme in a medial area. Interestingly, in the oral epithelium adjacent to this mesenchyme, sonic hedgehog (Shh) expression was strongly reduced, indicative of a function for Prx genes in indirect regulation of SHH: Wild-type embryos that were exposed to the hedgehog-pathway inhibitor, jervine, partially phenocopied the lower jaw defects of Prx1(-/-)Prx2(-/-) mutants. In addition, this treatment led to loss of the mandibular incisors. We present a model that describes how loss of Shh expression in Prx1(-/-)Prx2(-/-) mutants leads to abnormal morphogenesis of the mandibular arch. 相似文献
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Christine van der Leeuw Machteld Marcelis Sanne C. T. Peeters Marcel M. Verbeek Paul P. C. A. Menheere Lieuwe de Haan Jim van Os Nico J. M. van Beveren for Genetic Risk Outcome in Psychosis 《PloS one》2013,8(12)
Background
S100B is a potential marker of neurological and psychiatric illness. In schizophrenia, increased S100B levels, as well as associations with acute positive and persisting negative symptoms, have been reported. It remains unclear whether S100B elevation, which possibly reflects glial dysfunction, is the consequence of disease or compensatory processes, or whether it is an indicator of familial risk.Methods
Serum samples were acquired from two large independent family samples (n = 348 and n = 254) in the Netherlands comprising patients with psychotic disorder (n = 140 and n = 82), non-psychotic siblings of patients with psychotic disorder (n = 125 and n = 94) and controls (n = 83 and n = 78). S100B was analyzed with a Liaison automated chemiluminescence system. Associations between familial risk of psychotic disorder and S100B were examined.Results
Results showed that S100B levels in patients (P) and siblings (S) were not significantly different from controls (C) (dataset 1: P vs. C: B = 0.004, 95% CI −0.005 to 0.013, p = 0.351; S vs. C: B = 0.000, 95% CI −0.009 to 0.008, p = 0.926; and dataset 2: P vs. C: B = 0.008, 95% CI −0.011 to 0.028, p = 0.410; S vs. C: B = 0.002, 95% CI −0.016 to 0.021, p = 0.797). In patients, negative symptoms were positively associated with S100B (B = 0.001, 95% CI 0.000 to 0.002, p = 0.005) in one of the datasets, however with failure of replication in the other. There was no significant association between S100B and positive symptoms or present use or type of antipsychotic medication.Conclusions
S100B is neither an intermediate phenotype, nor a trait marker for psychotic illness. 相似文献59.
E Verbeek JR Waas MH Oliver LM McLeay DM Ferguson LR Matthews 《Hormones and behavior》2012,62(2):162-172
Low food availability often coincides with pregnancy in grazing animals. This study investigated how chronic reductions in food intake affected feeding motivation, and metabolic and endocrine parameters in pregnant sheep, which might be indicative of compromised welfare. Ewes with an initial Body Condition Score of 2.7±0.3 (BCS; 0 indicates emaciation and 5 obesity) were fed to attain low (LBC 2.0±0.0,), medium (MBC 2.9±0.1) or high BCS (HBC 3.7±0.1) in the first trimester of pregnancy. A feeding motivation test in which sheep were required to walk a set distance for a palatable food reward was conducted in the second trimester. LBC and MBC ewes consumed more rewards (P=0.001) and displayed a higher expenditure (P=0.02) than HBC ewes, LBC ewes also tended to consume more rewards than MBC ewes (P=0.09). Plasma leptin and glucose concentrations were inversely correlated to expenditure (both P<0.05) and appear to be associated with hunger in sheep. LBC ewes were in negative energy balance, with lower muscle dimensions, plasma glucose, leptin, insulin, cortisol, and insulin-like growth factor-1 concentrations and higher free fatty acids concentrations compared to HBC ewes; metabolic and endocrine parameters of the MBC ewes were intermediate. The high feeding motivation and negative energy balance of low BCS ewes suggested an increased risk of compromised welfare. Imposing even a small cost on a food reward reduced motivation substantially in high BCS ewes (despite high intake when food was freely available). Assessment of a willingness to work for rewards, combined with measures of key metabolic and endocrine parameters, may provide sensitive barometers of welfare in energetically-taxed animals. 相似文献
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