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Pulsed femtosecond lasers can generate acoustic pulses propagating in solids while displaying either diffraction, attenuation, nonlinearity and/or dispersion. When acoustic attenuation and diffraction are negligible, shock waves or solitons can form during propagation. Both wave types are phonon wavepackets with characteristic length scales as short as a few nanometer. Hence, they are well suited for acoustic characterization and manipulation of materials on both ultrafast and ultrashort scales. This work presents an overview of nonlinear ultrasonics since its first experimental demonstration at the beginning of this century to the more recent developments. We start by reviewing the main properties of nonlinear ultrafast acoustic propagation based on the underlying equations. Then we show various results obtained by different groups around the world with an emphasis on recent work. Current issues and directions of future research are discussed.
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The deuteron-emission channel in the beta decay of the halo nucleus (11)Li was measured at the Isotope Separator and Accelerator facility at TRIUMF by implanting postaccelerated (11)Li ions into a segmented silicon detector. The events of interest were identified by correlating the decays of (11)Li with those of the daughter nuclei. This method allowed the energy spectrum of the emitted deuterons to be extracted, free from contributions from other channels, and a precise value for the branching ratio B(d)=1.30(13)x10(-4) to be deduced for E(c.m.)>200 keV. The results provide the first unambiguous experimental evidence that the decay takes place essentially in the halo of (11)Li and that it proceeds mainly to the (9)Li+d continuum, opening up a new means to study the halo wave function of (11)Li.
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Acoustic solitons formed during the propagation of a picosecond strain pulse in a GaAs crystal with a ZnSe/ZnMgSSe quantum well on top lead to exciton resonance energy shifts of up to 10 meV, and ultrafast frequency modulation, i.e., chirping, of the exciton transition. The effects are well described by a theoretical analysis based on the Korteweg-de Vries equation and accounting for the properties of the excitons in the quantum well.
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The dynamical eikonal approximation unifies the semiclassical time-dependent and eikonal methods. It allows calculating differential cross sections for elastic scattering and breakup in a quantal way by taking into account interference effects. Good agreement is obtained with experiment for 11Be breakup on 208Pb. Dynamical effects are weak for elastic scattering.
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La presente investigación constituye un estudio cualitativo a través de un diseño de estudio de casos múltiples, que aborda la generación del embarazo en la adolescencia desde la perspectiva que tienen en torno a ello adolescentes de sexo femenino entre 13 y 19 años de edad, cursando su primera gestación en control prenatal en los consultorios municipales de la comuna de Temuco. Para la recolección de datos se utilizó la Entrevista Grupal Formal en su modalidad de Grupo de Discusión. La información fue clasificada, categorizada y codificada de un modo inductivo mediante la identificación de contenidos emergentes siguiendo la premisa de construcción de teoría desde la base. Los resultados obtenidos dan cuenta de las características asociadas al embarazo en esta etapa, configurándose tres núcleos de contenidos. El de mayor relevancia se relacionan con factores individuales, involucrando elementos a nivel emocional, de pensamiento y de acción. Otros ámbitos que influyen son la familia, especialmente a nivel de dinámica y estructura, y lo social que alude a las relaciones interpersonales que establecen las jóvenes y a la percepción que tienen del contexto inmediato en el que se desenvuelven. La discusión se centra en el análisis de los resultados donde se obtiene una comprensión fenomenológica al tema en estudio.
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Humanos , Feminino , Gravidez , Adolescente , Cuidado Pré-Natal/estatística & dados numéricos , Cuidado Pré-Natal , Gravidez na Adolescência/estatística & dados numéricos , Gravidez na Adolescência/etnologia , Gravidez na Adolescência/prevenção & controle , Pesquisa Qualitativa , Análise Multivariada , Chile , Epidemiologia Descritiva , Taxa de Gravidez , Gravidez não DesejadaRESUMO
The biota-sediment accumulation factor (BSAF) model has been suggested as a simple tool to predict bioaccumulation of hydrophobic organic compounds (HOCs) in fish and other aquatic biota from measured concentrations in sediment based on equilibrium partitioning between the sediment organic carbon and biotic lipid pools. Currently, evaluation of this model as a predictive tool has been limited to laboratory studies and small-scale field studies, using a limited number of biotic species. This study evaluates the model, from field data, for a suite of organochlorine HOCs from paired fluvial sediment and biota (fish and bivalves) samples throughout the United States and over a large range of biotic species. These data represent a real-world, worst-case scenario of the model because environmental variables are not controlled. Median BSAF values for fish (3.3) and bivalves (2.8) were not statistically different but are higher than theoretically predicted values (1-2). BSAF values varied significantly in a few species. Differences in chemical-specific BSAF values were not observed in bivalves but were statistically significant in fish. The HOCs with differing BSAF values were those known to be biotransformed. Sediment organic carbon content and biota lipid content had no effect on BSAF values in fish and only a weak effect in bivalves. This study suggests that the BSAF model could be useful under in situ riverine conditions as a first-level screening tool for predicting bioaccumulation; however, variability in BSAF values may impose limits on its utility.
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Ecossistema , Sedimentos Geológicos/análise , Modelos Biológicos , Animais , Carbono/análise , Peixes/metabolismo , Lipídeos/análise , Moluscos/metabolismo , Compostos Orgânicos/análiseRESUMO
Field runoff is an important transport mechanism by which agricultural pesticides, including atrazine, move into the hydrologic environment. Atrazine is chosen because it is widely used, is transported in runoff relatively easily, is widely observed in surface waters, and has relatively little loss in the stream network. Data on runoff of atrazine from experimental plot and field studies is combined with annual estimates of load in numerous streams and rivers, resulting in a data set with 408 observations that span 14 orders of magnitude in area. The load as a percent of use (LAPU) on an annual basis is the parameter that is compared among the studies. There is no difference in the mean or range of LAPU values for areas from the size of experimental field plots (> or = 0.000023 ha) and small watersheds (< 100,000 ha). The relatively invariant LAPU value observed across a large range of watershed areas implies that the characteristics of atrazine itself (application method and chemical properties) are important in determining the extent of runoff. The variable influences on the extent of runoff from individual watershed characteristics and weather events are superimposed on the relatively invariant LAPU value observed across the range of watershed areas. The results from this study establish the direct relevance for agricultural field plot studies to watershed studies across the full range of scale.
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Atrazina/análise , Herbicidas/análise , Poluentes Químicos da Água/análise , Agricultura , Chuva , Movimentos da ÁguaRESUMO
Herbicides transported to surface waters by agricultural runoff are partitioned between solution and solid phases. Conservation tillage that reduces upland erosion will also reduce transport of herbicides associated with the solid phase. However, transport of many herbicides occurs predominantly in solution. Conservation tillage practices may or may not reduce transport of solution-phase herbicides, as this depends on the runoff volume. Reducing herbicide application rate is another approach to minimize off-site transport. Herbicide banding can reduce herbicide application rates and costs by one-half or more. Our objective was to compare herbicide losses in runoff from different tillage practices and with band- or broadcast-applied herbicides. The herbicides alachlor [2-chloro-2',6'-diethyl-N-(methoxymethyl)acetanilide] and cyanazine [2-[[4-chloro-6-(ethylamino)-1,3,5-triazin-2-yl]amino]-2-methylpropionitrile] were broadcast- or band-applied to plots managed in a moldboard plow, chisel plow, or ridge till system. Herbicide concentration in runoff was largest for the first runoff event occurring after application and then decreased in subsequent events proportional to the cumulative rain since the herbicide application. When herbicides were broadcast-applied, losses of alachlor and cyanazine in runoff followed the order: moldboard plow > chisel plow > ridge till. Conservation tillage systems reduced runoff loss of herbicides by reducing runoff volume and not the herbicide concentration in runoff. Herbicide banding reduced the concentration and loss of herbicides in runoff compared with the broadcast application. Herbicide losses in the water phase averaged 88 and 97% of the total loss for alachlor and cyanazine, respectively. Cyanazine was more persistent than alachlor in the soil.
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Acetamidas/análise , Herbicidas/análise , Modelos Teóricos , Chuva , Poluentes do Solo/análise , Triazinas/análise , Agricultura , Monitoramento Ambiental , Cinética , Solubilidade , Movimentos da ÁguaRESUMO
OBJECTIVE: To determine the nature of and to compare the inflammatory responses induced by (1) endovascular and (2) conventional abdominal aortic aneurysm (AAA) repair. MATERIAL AND METHODS: Twelve consecutive patients undergoing elective infrarenal AAA repair were prospectively studied. Seven patients were selected for endovascular procedures (the EAAA group); five patients underwent open surgery (the OAAA group). Three control patients undergoing carotid thromboendarterectomy were also included. Serial peripheral venous blood samples were collected preoperatively, immediately after declamping or placement of the endograft, and at hours 1, 3, 6, 12, 24, 48, and 72. Acute phase response expression of peripheral T lymphocyte and monocyte activation markers and adhesion molecules (flow cytometry), soluble levels of cell adhesion molecules (enzyme-linked immunosorbent assay), cytokine (tumor necrosis factor alpha, interleukin-6, and interleukin-8) release (enzyme-linked immunosorbent assay), and liberation of complement products (nephelometry) were measured. RESULTS: Regarding acute phase response, the EAAA and OAAA groups showed significant increases in C-reactive protein (P <.001 and P =.001), body temperature (P =.035 and P =.048), and leukocyte count (P <.001 and P <.001). Similar time course patterns were observed with respect to body temperature (P =.372). Statistically significant different patterns were demonstrated for C-reactive protein (P =.032) and leukocyte count (P =.002). Regarding leukocyte activation, a significant upregulation of peripheral T lymphocyte CD38 expression was observed in the OAAA group only (P =.001). Analysis of markers such as CD69, CD40L, CD25, and CD54 revealed no perioperative fluctuations in any group. Regarding circulating cell adhesion molecules, the EAAA and OAAA groups displayed significant increases in soluble intercellular adhesion molecule-1 (P =.003 and P =.001); there was no intergroup difference (P =.193). All groups demonstrated high soluble von Willebrand factor levels (P =.018, P =. 007, and P =.027), there being no differences in the patterns (P =. 772). Otherwise, soluble vascular cell adhesion molecule-1, soluble E-selectin, and soluble P-selectin did not appear to vary in any group. Regarding cytokine release, although a tendency toward high tumor necrosis factor alpha and interleukin-8 levels was noticed in the EAAA group, global time course effects failed to reach statistical significance (P =.543 and P =.080). In contrast, interleukin-6 showed elevations in all groups (P =.058, P <.001, and P =.004). Time course patterns did not differ between the EAAA and OAAA groups (P =.840). Regarding complement activation, the C3d/C3 ratio disclosed significant postoperative elevations in the EAAA and OAAA groups (P =.013 and P =.009). This complement product release was reduced in the EAAA group (P <.001). CONCLUSIONS: The current study indicated that both endovascular and coventional AAA repair induced significant inflammatory responses. Our findings showed that there were no large differences between the procedures with respect to circulating cell adhesion molecule and cytokine release. Moreover, the endoluminal approach produced a limited response in terms of acute phase reaction, T lymphocyte activation, and complement product liberation. This might support the concept that endovascular AAA repair represents an attractive alternative to open surgery. Given the relatively small sample size, further larger studies are required for confirmation of our observations.
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Aneurisma da Aorta Abdominal/imunologia , Aneurisma da Aorta Abdominal/cirurgia , Idoso , Moléculas de Adesão Celular/sangue , Proteínas do Sistema Complemento/análise , Procedimentos Cirúrgicos Eletivos , Humanos , Inflamação , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Linfócitos T/imunologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/análise , Procedimentos Cirúrgicos Vasculares/métodosRESUMO
OBJECTIVE: To assess the ability of clinical or biochemical parameters to predict outcome (survival or non-survival; severe or moderate/no complication) using multiple regression analyses. DESIGN: Prospective, descriptive cohort study with no interventions SETTING: 12 surgical intensive care units of university hospitals and large community hospitals; four medical school research laboratories in eight European countries PATIENTS: 128 surgical patients with major intra-abdominal surgery admitted for at least two days to an intensive care unit MAIN OUTCOME MEASURES: Prediction of complications or survival based on analysis of clinical (Multiple Organ Dysfunction Score, Multi-Organ-Failure Score, Acute Physiology and Chronic Health Evaluation II scores) and immunological (plasma levels of endotoxin, endotoxin neutralizing capacity, IL-6, IL-8, cell associated IL-8, Fc-receptor polymorphism, soluble CD-14) parameters, with comparison of predicted and actual outcomes. RESULTS: APACHE II, MODS score, MOF score, platelets, IL-6, IL-8, ENC, cell ass. IL-8 were significantly different between survivors and non-survivors and patients with/without severe complications by univariate analysis. By multivariate analysis only MOF, MODS score, IL-6, platelets, comorbidity predicted complications with a sensitivity of 82% and a specificity of 87%. Multivariate analysis demonstrated that only APACHE II score, plasma IL-8 and complications predicted death (sensitivity 84%; specificity 90%). CONCLUSION: Immunological surrogate parameters may predict complications and death of surgical ICU patients. The use of several parameters may add to increase sensitivity and specificity in a prognostic model.
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Modelos Biológicos , Insuficiência de Múltiplos Órgãos/imunologia , APACHE , Antibacterianos/administração & dosagem , Estudos de Coortes , Endotoxinas/sangue , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Receptores de Lipopolissacarídeos/sangue , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Estudos Prospectivos , Receptores Fc/sangue , Receptores Fc/genéticaRESUMO
Numerous chromosome abnormalities have been described in myelodysplastic syndromes, but single karyotypic aberrations are much less frequent. We report the case of a 65-year-old woman who presented a trisomy 21 as the sole karyotypic anomaly for a refractory anemia with ring sideroblasts. The nature of such an anomaly is discussed in regard to pathogenesis and prognosis.
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Anemia Sideroblástica/genética , Síndrome de Down , Idoso , Medula Óssea/patologia , Medula Óssea/fisiologia , Feminino , Humanos , Hibridização in Situ FluorescenteRESUMO
Single-chain variable fragment (scFv) antibodies are genetically engineered molecules comprising the variable regions responsible for specific binding. scFv that recognize certain surface molecules on professional antigen presenting cells could therefore be suitable for targeting Ag to these cells. We have produced an scFv that recognizes murine complement receptors 1 and 2 (CR1/CR2) and genetically fused it with different numbers of influenza hemagglutinin peptides which contain both B and T cell epitopes. The CR1/CR2 specific hybridoma 7G6 was used for RT-PCR to obtain the variable regions, which were then combined to create an scFv fragment. The influenza hemagglutinin intersubunit peptide HA317-41 (IP) was engineered to the N terminus of the scFv in one, two or three copies. The so obtained IP(1-3)7G6scFv still bound the complement receptors; the peptides in the construct were recognized by the peptide specific monoclonal IP2-11-1 on Western blots and ELISAs. The CR1/CR2 positive B lymphomas A20 and 2PK3 presented the peptide to an I-Ed restricted IP specific T cell hybridoma more efficiently when incubated with the IP(1)7G6 constructs as compared to the free peptide. The results suggest that scFv could work as targeting devices in subunit vaccines.
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Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Fragmentos de Imunoglobulinas/imunologia , Vírus da Influenza A/imunologia , Receptores de Complemento 3b/imunologia , Receptores de Complemento 3d/imunologia , Sequência de Aminoácidos , Animais , Epitopos de Linfócito B/genética , Epitopos de Linfócito T/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Fragmentos de Imunoglobulinas/biossíntese , Fragmentos de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Região Variável de Imunoglobulina/imunologia , Camundongos , Dados de Sequência Molecular , Ratos , Receptores de Complemento 3b/genética , Receptores de Complemento 3d/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologiaRESUMO
During an ongoing immune response, immune complexes, composed of Ag, complement factors, and Igs, are formed that can interact with complement receptors (CRs) and IgG Fc receptors (Fc gamma R). The role of CR1/2 and Fc gamma R in the regulation of the immune response was investigated using OVA that was chemically conjugated to whole IgG of the rat anti-mouse CR1/2 mAb 7G6. FACS analysis using the murine B cell lymphoma IIA1.6 confirmed that the 7G6-OVA conjugate recognized CR1/2. Incubating IIA1.6 cells with 7G6-OVA triggered tyrosine phosphorylation and Ag presentation to OVA-specific T cells in vitro. Immunizing mice with 7G6-OVA at a minimal dose of 1 microgram i.p. per mouse markedly enhanced the anti-OVA Ig response, which was primarily of the IgG1 isotype subclass. The 7G6-OVA did not enhance the anti-OVA response in CR1/2-deficient mice. OVA coupled to an isotype control Ab induced a considerably lower anti-OVA response compared with that induced by OVA alone, suggesting inhibition by interaction between the Fc part of the Ab and the inhibitory Fc gamma RIIb on B cells. This findings was supported by the observation that IIA1.6 cells which were incubated with 7G6-OVA lost the ability to present Ag upon transfection with Fc gamma RIIb. In sum, 7G6-conjugated OVA, resembling a natural immune complex, induces an enhanced anti-OVA immune response that involves at least CR1/2-mediated stimulation and that may be partially suppressed by Fc gamma RIIb.
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Anticorpos Monoclonais/farmacologia , Antígenos/imunologia , Antígenos/metabolismo , Imunoglobulina G/biossíntese , Receptores de Complemento 3b/imunologia , Receptores de Complemento 3d/imunologia , Receptores Fc/metabolismo , Animais , Apresentação de Antígeno , Antígenos/administração & dosagem , Sítios de Ligação de Anticorpos , Feminino , Imunoglobulina G/administração & dosagem , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Fosforilação , Receptores de Complemento 3b/metabolismo , Receptores de Complemento 3d/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Células Tumorais Cultivadas , Tirosina/metabolismoRESUMO
A qualitative (Instantia) and a quantitative (VIDAS D-Dimer) D-Dimer test have been evaluated and compared with an ELISA method (Asserachrom D-D) in a population of 74 patients suspected of presenting a deep vein thrombosis. Among the thirty-two patients presenting a deep vein thrombosis on phlebography, there were 16 (50%) proximal vein thrombosis and 16 (50%) distal vein thrombosis. Sensitivity and negative predictive value for proximal thrombosis were 100% in all three tests. For distal vein thrombosis, sensitivity and negative predictive value were respectively 81% and 81% for Asserachrom D-DI 75% and 76% for VIDAS D-Dimer and 63% and 82% for Instantia. In conclusion, this study shows that these D-Di assays are a useful tool to exclude proximal vein thrombosis, at least for patients who are not under anticoagulant therapy.
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Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Kit de Reagentes para Diagnóstico , Trombose Venosa/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaio de Imunoadsorção Enzimática , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Flebografia , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Trombose Venosa/sangue , Trombose Venosa/diagnóstico por imagemRESUMO
The molecular basis of hereditary antithrombin (AT) deficiency has been investigated in ten Belgian and three Dutch unrelated kindreds. Eleven of these families had a quantitative or type I AT deficiency, with a history of major venous thromboembolic events in different affected members. In the other two families a qualitative or type II AT deficiency was occasionally diagnosed. DNA studies of the AT gene were performed, using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis, followed by direct sequencing of the seven exons and intron-exon junction regions. Six novel point mutations were identified: four missense, one nonsense mutation and a single nucleotide deletion near the reactive site, causing a frameshift with premature translation termination. In two kindreds the underlying genetic defect was caused by a whole gene deletion, known as a rare cause of AT deficiency. In these cases, Southern blot and polymorphism analysis of different parts of the AT gene proved useful for diagnosis. In another kindred a partial gene deletion spanning 698 basepairs could precisely be determined to a part of intron 3B and exon 4. In two type I and in both type II AT deficient families a previously reported mutation was identified. In all cases, the affected individuals were heterozygous for the genetic defect.
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Antitrombinas/deficiência , Antitrombinas/genética , Mutação da Fase de Leitura , Mutação Puntual , Adolescente , Adulto , Bélgica , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países BaixosRESUMO
Previously, we have demonstrated that phagocytosis of IgG1-coated particles by macrophages in vitro is impaired by deletion of Fc gamma RIII in mice, suggesting that IgG1 may interact preferentially with Fc gamma RIII. In the present study, the biologic relevance of this observation was addressed by triggering various effector functions of the immune system in Fc gamma RIII(-/-) mice, using panels of mAbs of different IgG subclasses. Both binding and phagocytosis of IgG1-coated sheep or human erythrocytes by Fc gamma RIII(-/-) macrophages in vitro were strongly impaired, indicating that the impaired ingestion of complexed IgG1 by Fc gamma RIII(-/-) macrophages is due to a defect in binding. An in vivo consequence of the defective phagocytosis was observed by resistance of Fc gamma RIII-deficient mice to experimental autoimmune hemolytic anemia, as shown by a lack of IgG1-mediated erythrophagocytosis in vivo by liver macrophages. Furthermore, trapping of soluble IgG1-containing immune complexes by follicular dendritic cells in mesenteric lymph nodes from Fc gamma RIII(-/-) mice was abolished. Whole blood from Fc gamma RIII(-/-) mice was unable to induce lysis of tumor cells in the presence of IgG1 antitumor Abs. Finally, IgG1 mAbs proved unable to mount a passive cutaneous anaphylaxis in Fc gamma RIII(-/-) mice. Together, these results demonstrate that IgG1 complexes, either in particulate or in soluble form, trigger in vitro and in vivo immune effector functions in mice predominantly via Fc gamma RIII.
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Complexo Antígeno-Anticorpo/fisiologia , Imunoglobulina G/fisiologia , Receptores de IgG/fisiologia , Animais , Anticorpos Monoclonais/farmacologia , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Complexo Antígeno-Anticorpo/sangue , Complexo Antígeno-Anticorpo/metabolismo , Antígenos de Grupos Sanguíneos/imunologia , Neoplasias da Mama , Células Dendríticas/imunologia , Eritrócitos/imunologia , Eritrócitos/metabolismo , Humanos , Soros Imunes/fisiologia , Imunoglobulina G/sangue , Imunoglobulina G/farmacologia , Fígado/imunologia , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Especificidade de Órgãos/imunologia , Anafilaxia Cutânea Passiva , Fagocitose/imunologia , Formação de Roseta , Células Tumorais CultivadasRESUMO
Several international standards and corresponding interpretation documents for quality management systems have been published. Although these standards are found useful to some extent, they are considered to be insufficient in several areas important for medical laboratories particularly in the pre- and post-examinational phases. The normative document for accreditation of laboratories (ISO/IEC Guide 25) is presently being revised and a document for medical laboratories (ISO/TC 212, CD 15189) is at draft stage. Both aim to include aspects of total quality management. The concept of total quality management is rather vague. Generally, its goal has been defined as "business excellence". This term, however, needs some explanation if applied to medical laboratories. Therefore, a project group of the European Confederation of Laboratory Medicine (ECLM) has developed a model for total quality management, which is based on a comprehensive management concept issued by the European Foundation for Quality Management. In the case of a medical laboratory, the term "business excellence" should be replaced by "good medical laboratory services". The proposed model could serve as a basis for future developments of total quality management standards in laboratory medicine. The goal of the "journey" should be clarified before it starts. To the best of our knowledge, this is the first attempt to develop a model of a good medical laboratory.
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Laboratórios/normas , Modelos Organizacionais , Acreditação , Laboratórios/organização & administração , Objetivos Organizacionais , Gestão da Qualidade TotalRESUMO
The CD40 molecule expressed on endothelial cells has been shown to transduce activation signals resulting in upregulation of adhesion molecules. Herein, we studied the impact of CD40 engagement on the induction of tissue factor (TF)-dependent procoagulant activity (PCA) at the surface of human umbilical vein endothelial cells (HUVECs). First, we found that co-incubation of HUVECs with 3T6 fibroblasts transfected with the CD40L gene (3T6-CD40L) resulted in a clear induction of PCA which was not observed with control untransfected fibroblasts. The specificity of this finding was established by inhibition experiments using monoclonal antibodies (mAbs) blocking CD40 or CD40L. PCA induced by CD40 ligation was TF-related as it was not observed in factor VII-deficient plasma and was associated with the accumulation of TF mRNA. To investigate the role of CD40/CD40L interactions in the induction of endothelial cell PCA by lymphocytes, interferon (IFN)-gamma-stimulated EC were incubated with T cells in the absence or presence of anti-CD40 or anti-CD40L mAb. The 60-70% inhibition of PCA induced by these mAbs but not their isotype-matched control indicated that the CD40 pathway is involved in the induction of PCA resulting from interactions between activated HUVECs and T cells. We conclude that activation signals elicited by CD40 engagement on endothelial cells result in the induction of TF-dependent PCA. The CD40/CD40L pathway might therefore be involved in the development of prothrombic states during diseases associated with endothelial cell and T cell activation.