Introduction: Although the diagnosis of brain death (BD) is usually based on clinical criteria, in sedated patients, ancillary techniques are needed. This study was designed to assess the accuracy of cerebral multislice computed tomographic angiography (CTA) and CT perfusion (CTP) in diagnosing BD.
Methods: Prospective observational study in 27 BD patients.
Background: Monocyte deactivation, defined as the decrease of surface expression of class II molecules of the main histocompatibility complex (MHC) on circulating monocytes, can occur after severe injuries, like trauma, sepsis, or major surgery. We hypothesized that mechanical ventilation could also be a cause.
Methods: Prospective experimental study.
BD was diagnosed by clinical examination, electroencephalogram (EEG), Transcranial Doppler (TCD) and multislice CT of 64 detectors. Initially, a brain perfusion study was performed. This was followed by supra-aortic trunk and brain artery angiography with acquisition of images using 0.
View Article and Find Full Text PDFCCL1 is the predominant chemokine secreted from IgE-activated human and mouse mast cells in vitro, colocalizes to mast cells in lung biopsies, and is elevated in asthmatic airways. CCR8, the receptor for CCL1, is expressed by approximately 70% of CD4(+) T lymphocytes recruited to the asthmatic airways, and the number of CCR8-expressing cells is increased 3-fold in the airways of asthmatic subjects compared with normal volunteers. In vivo, CCL1 expression in the lung is reduced in mast cell-deficient mice after aeroallergen provocation.
View Article and Find Full Text PDFThe identification, optimization, and structure-activity relationship (SAR) of small-molecule CCR4 antagonists is described. An initial screening hit with micromolar potency was identified that was optimized to sub-micromolar binding potency by enantiomer resolution, halogenation of the naphthalene ring, and extension of the alkyl chain linker between the central piperidine ring and the terminal aryl group. An antagonist was identified that showed good cross-reactivity against the mouse receptor and inhibited CCR4-based cell recruitment in dose-dependent fashion.
View Article and Find Full Text PDFObjective: To evaluate the Bispectral Index Scale (BIS) monitor as a method of brain death (BD) detection.
Patients And Methods: We performed an observational prospective study in an intensive care unit (ICU) of a university hospital of 19 patients hospitalized nonconsecutively in the ICU with serious neurologic pathology and evolution toward BD. A BIS monitor, XP model, and the sensor "BIS Quatro" were used to continuously record values: suppression ratio (SR), quality of the signal index, and electromyographic (EMG) activity.
Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), a G protein-coupled receptor activated by prostaglandin D(2) (PGD(2)), has been identified as a receptor expressed on cell types critical to the pathogenesis of asthma. The cDNA encoding guinea pig CRTH2 was cloned and mRNA expression examined in selected tissues. Transcript profiling of guinea pig CRTH2 indicated relatively high levels of expression in bone marrow, intermediate levels in brain and relatively low levels in lung, spleen, thymus, lymph node, etc.
View Article and Find Full Text PDFThe bone marrow is the primary site for neutrophil production and release into the circulation. Because the CXC chemokine receptor-4/stromal derived factor-1 (CXCR4/SDF-1) axis plays a central role in the interactions of hematopoietic stem cells, lymphocytes, and developing neutrophils in the marrow, we investigated whether reciprocal CXCR4-dependent mechanisms might be involved in neutrophil release and subsequent return to the marrow following circulation. Neutralizing antibody to CXCR4 reduced marrow retention of infused neutrophils (45.
View Article and Find Full Text PDFDendritic cells (DCs) are the professional APCs of the immune system, enabling T cells to perceive and respond appropriately to potentially dangerous microbes, while also being able to maintain T cell tolerance toward self. In part, such tolerance can be determined by IL-10 released from certain types of regulatory T cells. IL-10 has previously been shown to render DCs unable to activate T cells and it has been assumed that this process represents a general block in maturation.
View Article and Find Full Text PDFChemokine-induced T lymphocyte recruitment to the lung is critical for allergic inflammation, but chemokine signaling pathways are incompletely understood. Regulator of G protein signaling (RGS)16, a GTPase accelerator (GTPase-activating protein) for Galpha subunits, attenuates signaling by chemokine receptors in T lymphocytes, suggesting a role in the regulation of lymphocyte trafficking. To explore the role of RGS16 in T lymphocyte-dependent immune responses in a whole-organism model, we generated transgenic (Tg) mice expressing RGS16 in CD4(+) and CD8(+) cells.
View Article and Find Full Text PDFInteraction of chemokines with their specific receptors results in tight control of leukocyte migration and positioning. CCR8 is a chemokine receptor expressed mainly in CD4(+) single-positive thymocytes and Th2 cells. We generated CCR8-deficient mice (CCR8(-/-)) to study the in vivo role of this receptor, and describe in this study the CCR8(-/-) mouse response in OVA-induced allergic airway disease using several models, including an adoptive transfer model and receptor-blocking experiments.
View Article and Find Full Text PDFPhys Rev E Stat Nonlin Soft Matter Phys
May 2002
The equivalence between canonical and grand canonical constraints near a random fixed point in a critical disordered system is confirmed by means of Monte Carlo simulations. The slow approach to the asymptotic distribution for canonical averaging given by the L((alpha/nu)(random)) term is overcome by simulating long range correlated diluted Ising systems with (alpha/nu)(random)=(a-d) for the particular values a=2 (linear defects) and d=3 (three dimensional systems).
View Article and Find Full Text PDFPhys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics
August 1999
Self-averaging of singular thermodynamic quantities at criticality for randomly and thermally diluted three-dimensional Ising systems has been studied by the Monte Carlo approach. Substantially improved self-averaging is obtained for critically clustered (critically thermally diluted) vacancy distributions in comparison with the observed self-averaging for purely random diluted distributions. Critically thermal dilution, leading to maximum relative self-averaging, corresponds to the case when the characteristic vacancy ordering temperature (theta) is made equal to the magnetic critical temperature for the pure three-dimensional (3D) Ising systems (T(3D)(c)).
View Article and Find Full Text PDFWe examined the requirement for and cooperation between CD28 and inducible costimulator (ICOS) in effective T helper (TH) cell responses in vivo. We found that both CD28 and ICOS were critical in determining the outcome of an immune response; cytolytic T lymphocyte-associated antigen 4-immunoglobulin (CTLA-4-Ig), ICOS-Ig and/or a neutralizing ICOS monoclonal antibody attenuated T cell expansion, TH2 cytokine production and eosinophilic inflammation. CD28-dependent signaling was essential during priming, whereas ICOS-B7RP-1 regulated TH effector responses, and the up-regulation of chemokine receptors that determine T cell migration.
View Article and Find Full Text PDFPhys Rev E Stat Nonlin Soft Matter Phys
May 2001
Activated scaling is confirmed to hold in transverse field-induced phase transitions of randomly diluted Ising systems. Quantum Monte Carlo calculations have been made not just at the percolation threshold (pc) but also well below and above it. We follow the evolution of the activated scaling at zero temperature in the phase transition from ferromagnetic to quantum Griffiths phase (p>pc) at the phase boundary (p=pc) and for transitions inside the nonferromagnetic quantum Griffiths phase (p
We have used two models of murine pulmonary inflammation to investigate the signals responsible for the resolution of bronchial hyperresponsiveness (BHR). Both protocols involved two sensitizations with OVA followed by serial aerosolized challenge with OVA. We determined that administration of the second sensitization by aerosol (model A) was associated with a transient response, whereas administration by the i.
View Article and Find Full Text PDFThe understanding of the relative contribution of particular chemokines to the selective accumulation of leukocyte subsets to an organ site during an inflammatory response is made difficult by the simultaneous presence of multiple chemokines with partially overlapping functions at the inflammatory site. The study of several chemokine pathways (expression and function) during the development of a mouse model of allergic airway disease (AAD) has revealed differential expression regulation with distinct cellular sources for individual chemokines with functional bias for the recruitment/localization of regulatory and/or effector leukocyte subsets. In the present review, we propose that distinct functional groups of chemokines co-operate to generate the complete inflammatory response in the lung during AAD.
View Article and Find Full Text PDFOptimal T cell activation requires engagement of CD28 with its counterligands B7-1 and B7-2. Inducible costimulator (ICOS) is the third member of the CD28/CTLA4 family that binds a B7-like protein, B7RP-1. Administration of ICOS-Ig attenuates T cell expansion following superantigen (SAg) administration, but fails to regulate either peripheral deletion or anergy induction.
View Article and Find Full Text PDFPhys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics
July 2000
The universality class of thermally diluted Ising systems, in which the realization of the disposition of magnetic atoms and vacancies is taken from the local distribution of spins in the pure original Ising model at criticality, is investigated by finite size scaling techniques using the Monte Carlo method. We find that the critical temperature, the critical exponents, and therefore the universality class of these thermally diluted Ising systems depart markedly from the ones of short-range correlated disordered systems. Our results agree fairly well with theoretical predictions previously made by Weinrib and Halperin for systems with long-range correlated disorder.
View Article and Find Full Text PDFWhile CD28 is critical for expansion of naive T cells, recent evidence suggests that the activation of effector T cells is largely independent of CD28/B7. We suggest that ICOS, the third member of the CD28/CTLA-4 family, plays an important role in production of IL-2, IL-4, IL-5, and IFNgamma from recently activated T cells and contributes to T cell-dependent B help in vivo. Inhibition of ICOS attenuates lung mucosal inflammation induced by Th2 but not Th1 effector populations.
View Article and Find Full Text PDFStromal cell-derived factor-1alpha/beta (SDF-1alpha/beta) is phylogenetically a primitive chemokine widely expressed in a variety of tissues and cell types. This expression is detectable in the absence of stimuli provided by bacterial or viral infections and allergic or autoimmune disorders. Based on these and other findings, SDF-1alpha has not been considered an inflammatory chemokine, but, rather, has been believed to be involved in certain homeostatic processes, such as leukocyte recirculation.
View Article and Find Full Text PDFThe cloning, expression, and function of the murine (m) homologue of human (h) monocyte-derived chemokine (MDC) is reported here. Like hMDC, mMDC is able to elicit the chemotactic migration in vitro of activated lymphocytes and monocytes. Among activated lymphocytes, Th2 cells were induced to migrate most efficiently.
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