Reduced destabilization of blood pressure with lumiracoxib compared to ibuprofen in osteoarthritis patients with controlled hypertension treated with ACE-inhibitor monotherapy

in Osteoarthritis and Cartilage (2007), 15(C), 149

Reduced expression of cell cycle-associated genes in B lymphocytes purified from the peripheral blood of early-stage B chronic lymphocytic leukaemia (B-CLL) patients - response to di Iasio et al.

in British Journal of Haematology (2009)

A reduced extracellular serotonin level increases the 5-HT1A PET ligand F-18-MPPF binding in the rat hippocampus

in Journal of Nuclear Medicine (2003), 44(9), 1495-1501

4,2'-(Methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-fluorobenzamido]ethylpiperazine (F-18-MPPF) is a radiotracer used in clinical PET studies for the visualization of serotonin-1A (5-HT1A) receptors. In a ... [more ▼]

4,2'-(Methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-fluorobenzamido]ethylpiperazine (F-18-MPPF) is a radiotracer used in clinical PET studies for the visualization of serotonin-1A (5-HT1A) receptors. In a previous study, we demonstrated that a rapid enhancement of extracellular serotonin concentrations influences F-18-MPPF-specific binding. Because endogenous serotonin is significantly decreased in some pathologies, the aim of this study was to determine whether F-18-MPPF is sensitive to depletion of this neurotransmitter. Methods: Using the beta-microprobe, an original beta(+)-sensitive intracerebral probe, and micro-dialysis, the effect of decreased serotonin on the specific binding of F-18-MPPF to 5-HT1A receptors was investigated in the hippocampus of the anesthetized rat. Extracellular serotonin was pharmacologically decreased in the hippocampus after a single injection of p-ethynylphenylalanine ([p-EPA] 5 mg/kg), a new tryptophan hydroxylase inhibitor. Results: Our results showed that the F-18-MPPF-specific binding was significantly enhanced after the decrease of extracellular serotonin. These results were confirmed by the F-18-MPPF distribution in cerebral tissues (hippocampus-to-cerebellum ratio) and by the decrease of the extracellular F-18-MPPF collected in hippocampal dialysates. Conclusion: This study further supports the view that 18F-MPPF binding potential is increased in the hippocampus if the endogenous serotonin is pharmacologically decreased after a p-EPA injection. This phenomenon will be an additional factor in the interpretation of the results from F-18-MPPF clinical PET studies. [less ▲]

Reduced global copperativity is a common feature underlying the amyloidogenicity of pathogenic lysozyme mutations

in Journal of Molecular Biology (2005), 346(3), 773-788

One of the 20 or so human amyloid diseases is associated with the deposition in vital organs of full-length mutational variants of the antibacterial protein lysozyme. Here, we report experimental data ... [more ▼]

One of the 20 or so human amyloid diseases is associated with the deposition in vital organs of full-length mutational variants of the antibacterial protein lysozyme. Here, we report experimental data that permit a detailed comparison to be made of the behaviour of two of these amyloidogenic variants, I56T and D67H, under identical conditions. Hydrogen/deuterium exchange experiments monitored by NMR and mass spectrometry reveal that, despite their different locations and the different effects of the two mutations on the structure of the native state of lysozyme, both mutations cause a cooperative destabilisation of a remarkably similar segment of the structure, comprising in both cases the beta-domain and the adjacent C-helix. As a result, both variant proteins populate transiently a closely similar, partially unstructured intermediate in which the beta-domain and the adjacent C-helix are substantially and simultaneously unfolded, whereas the three remaining a-helices that form the core of the a-domain still have their native-like structure. We show, in addition, that the binding of a camel antibody fragment, cAb-HuL6, which was raised against wild-type lysozyme, restores to both variant proteins the stability and cooperativity characteristic of the wild-type protein; as a consequence, it inhibits the formation of amyloid fibrils by both variants. These results indicate that the reduction in global cooperativity, an associated ability to populate transiently a specific, partly unfolded intermediate state under physiologically relevant conditions, is a common feature underlying the behaviour of these two pathogenic mutations. The formation of intermolecular interactions between lysozyme molecules that are in this partially unfolded state is therefore likely to be the fundamental trigger of the aggregation process that ultimately leads to the formation and deposition in tissue of amyloid fibrils. (C) 2004 Elsevier Ltd. All rights reserved. [less ▲]

Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation (HSCT)

in Belgian Journal of Hematology (2011), 2

Reduced intensity conditioning (RIC) regimens have allowed performing allogeneic haematopoietic stem cell transplantation (HSCT) in patients for whom conventional myeloablative allogeneic HSCT is ... [more ▼]

Reduced intensity conditioning (RIC) regimens have allowed performing allogeneic haematopoietic stem cell transplantation (HSCT) in patients for whom conventional myeloablative allogeneic HSCT is associated with unacceptable risks of non-relapse-mortality. This approac relies mainly on graft-versus-tumour effects for tumour eradication. Retrospective studies have suggested that, in patients aged 40 to 60 years, RIC-HSCT was associated with a higher risk of relapse but a lower incidence of transplant-related mortality than myeloablative allogeneic HSCT, leading to similar progression-free and overall survivals. After reviewing the rationale for RIC-HSCT, this article discusses the results of RIC-HSCT in specific deseases, and proposes what could be current indications for RIC-HSCT in 2011. Finally, the article briefly presents some possible strategies aimed at increasing the anti-tumoral activity of the procedure while reducing the incidence and severity of acute graft-versus-host disease. [less ▲]

A reduced order data assimilation scheme coupled with a two-way nested model. Application to the Ligurian Sea

Conference (2004, April)

A system of nested models is coupled with a data assimilation module. The system is composed by a low resolution model (1/4 ) covering the whole Mediterranean Sea, an intermediate resolution model (1/20 ... [more ▼]

A system of nested models is coupled with a data assimilation module. The system is composed by a low resolution model (1/4 ) covering the whole Mediterranean Sea, an intermediate resolution model (1/20 ) of the Liguro-Provençal basin and a high resolution model (1/60 ) simulating the fine mesoscale structures in the Ligurian Sea. Boundary conditions and the averaged fields (feedback) are exchanged between two successive nesting levels. A reduced order, optimal interpolation data assimilation scheme was implemented. The state vector is composed by temperature, salinity and sea surface elevation. Novel in the present approach is that these variables from the three nested model grids are assembled to one multigrid state vector. This implementation allows to take into account the correlation of the variables across the nested model grids in order to avoid for example artificial gradients after an assimilation cycle. The eigenvectors of the covariance matrix are constructed by an EOF analysis of the free model run. Cross-grid correlations especially in the overlapping domains are thus consistently represented. Horizontal correlations over long distances are suppressed by multiplying each error mode with a set of radial Gaussian functions. This procedure increases considerably the rank of the covariance matrix but ensures the local impact of each observation. Sea surface temperature (SST, from the DLR EOWEB), sea surface height (SSH, from the CLS) and CTD profiles (SIRENA cruise from SACLANT Center and cruises from the MEDAR/Medatlas database) are assimilated into the model. In overlapping model grids the measurements are related to the highest resolution grid. Since the SSH has a resolution of 1/8 , the surface elevation of the Ligurian Sea and the Liguro-Provençal model are filtered in order to be coherent with the space scales present in the observations. Starting from the 1st January 1998 the low and intermediate resolution models are spun up for 18 months. The initial conditions for the Ligurian Sea are interpolated from the intermediate resolution model. The three models are then integrated until August 1999. During this period SST, SSH and the CTD profiles are assimilated. The results are compared with a free model run. In particular the model forecast just before the assimilation step are compared with the observations. The model forecast and the measurements are then independent and the difference is a measure of the model forecast skill and the impact of the previous assimilation cycles. [less ▲]

Reduced organ failure with effective glycemic control

in Intensive Care Medicine (2010), 36(2), 173-173

Reduced proviral loads during primo-infection of sheep by Bovine Leukemia virus attenuated mutants.

in Retrovirology (2004), 1(1),

Reduced Slow-Wave Rebound during Daytime Recovery Sleep in Middle-Aged Subjects

in PLoS ONE (2012), 7(8), 43224

Reduced Sperm Counts In Guppies (Poecilia Reticulata) Following Exposure To Low Levels Of Tributyltin And Bisphenol A

in Proceedings of the Royal Society B-Biological Sciences (2000), 267(1459),