RESUMEN
BACKGROUND: Cognitive deficits, a core feature contributing to disability in schizophrenia, are present in milder form in individuals at clinical high risk (CHR) for psychosis. This study investigated the feasibility of Cognition for Learning and Understanding Everyday Social Situations (CLUES), an integrated neurocognitive and social cognitive treatment for youth at CHR. METHOD: This was an open, pilot feasibility trial. Seventeen individuals meeting CHR criteria were assessed prior to and following participation in CLUES for changes in symptoms, social and role functioning, and cognition. Participant attitudes towards CLUES were also examined. RESULTS: Participants significantly improved in social functioning [t(16)â¯=â¯-4.20, pâ¯=â¯.001, dâ¯=â¯1.02], and trended for improvement in reaction time [t(15)â¯=â¯2.09, pâ¯=â¯.054, dâ¯=â¯0.52] from baseline to end of treatment. No other measures significantly changed. No participants transitioned to full psychosis during the treatment and follow up period. Participants reported they generally liked CLUES and found it helpful. CONCLUSION: While limited by the small sample size and the open label design, our preliminary results indicate that CLUES is feasible and shows promise in improving social functioning. However, further investigation is warranted in order to determine its efficacy. Future directions should include conducting a randomized controlled trial in order to compare the efficacy of CLUES to another intervention.
Asunto(s)
Disfunción Cognitiva/rehabilitación , Remediación Cognitiva/métodos , Trastornos Psicóticos/rehabilitación , Percepción Social , Habilidades Sociales , Adolescente , Adulto , Disfunción Cognitiva/etiología , Comprensión/fisiología , Estudios de Factibilidad , Femenino , Humanos , Aprendizaje/fisiología , Masculino , Proyectos Piloto , Trastornos Psicóticos/complicaciones , Riesgo , Adulto JovenRESUMEN
A 21-year-old woman presented with acute-onset spastic paraparesis. The MRI spinal scan revealed a contrast-enhanced T2 hyperintensity between C5-T2. The most common neurotropic pathogens were excluded by first level tests. Under suspicion of an acute immune-mediated myelitis, a corticosteroid therapy was administered. However, a seropositivity for both human immunodeficiency virus (HIV) type 1 and human T-lymphotropic virus (HTLV) subsequently emerged. An antiretroviral therapy was started while steroids discontinued. Patient's clinical conditions remained unchanged. HIV-HTLV-1 co-infection should be included in the differential diagnosis of any acute myelitis, even in patients with a preserved immune status and no risk factors.
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Infecciones por VIH/diagnóstico , VIH/patogenicidad , Infecciones por HTLV-I/diagnóstico , Virus Linfotrópico T Tipo 1 Humano/patogenicidad , Paraparesia Espástica Tropical/diagnóstico , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/líquido cefalorraquídeo , Antivirales/uso terapéutico , Coinfección , Diagnóstico Diferencial , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/patología , Infecciones por VIH/virología , Infecciones por HTLV-I/tratamiento farmacológico , Infecciones por HTLV-I/patología , Infecciones por HTLV-I/virología , Humanos , Imagen por Resonancia Magnética , Paraparesia Espástica Tropical/tratamiento farmacológico , Paraparesia Espástica Tropical/patología , Paraparesia Espástica Tropical/virología , Adulto JovenAsunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Fructosa/análogos & derivados , Cefalea/tratamiento farmacológico , Indometacina/uso terapéutico , Adulto , Quimioterapia Combinada , Epilepsia/complicaciones , Fructosa/uso terapéutico , Cefalea/complicaciones , Humanos , Masculino , Estimulación Luminosa/efectos adversos , TopiramatoRESUMEN
Failure to respond to commercial limited antigen diets can occur in dogs kept on a dietary trial for the diagnosis of adverse food reaction (AFR). The aim of this study was to assess twelve canine dry limited antigen diets (eleven novel protein diets and one hydrolysed diet) for potential contamination by ingredients of animal origin not mentioned on the label. The validity of the two methods adopted for the detection of such food antigens was also evaluated. Each dietary product was analysed by microscopy analysis using the official method described in Commission Regulation EC 152/2009 with the aim of identifying bone fragments of different zoological classes (mammalian, avian and fish) and by polymerase chain reaction (PCR) for the identification of DNA of animal origin. Discrepancies between the results obtained by PCR and/or microscopy analysis and the ingredients listed on pet food packages were found. Only in two pet foods did the results of both analyses match the ingredients listed on the label. In the remaining ten samples, microscopy detected bone fragments from one or two unpredicted zoological classes, revealing avian fragments in six of ten samples followed by those of fish in five of ten and mammalian fragments in four of ten. In two samples, microscopy analysis identified a contamination that would have otherwise passed unobserved if only PCR had been used. However, PCR confirmed the presence of all the zoological classes detected by microscopy and also identified the DNA of an additional unexpected zoological class in two samples. Dogs might fail to respond to commercial limited antigen diets because such diets are contaminated with potential allergens. Both PCR and microscopy analysis are required to guarantee the absence of undeclared animal sources in pet foods. Before ruling out AFR, a novel protein home-made diet should be considered if the dog is unresponsive to a commercial regimen.
Asunto(s)
Alimentación Animal/análisis , Antígenos/aislamiento & purificación , Huesos/química , Enfermedades de los Perros/diagnóstico , Hipersensibilidad a los Alimentos/veterinaria , Animales , Grasas de la Dieta/análisis , Grasas de la Dieta/inmunología , Proteínas en la Dieta/análisis , Proteínas en la Dieta/inmunología , Enfermedades de los Perros/inmunología , Perros , Contaminación de Alimentos , Hipersensibilidad a los Alimentos/diagnósticoRESUMEN
BACKGROUND: The Cardioversion of Atrial Fibrillation in Emergency (CAFE) study was an observational, retrospective, multicenter study focusing on patients with recent onset atrial fibrillation (AF) seen in six different Emergency Departments (ED) of Rome, Italy. AIM: The aim of this study was to present the baseline characteristics and risk factors of the patients enrolled to the CAFE study. MATERIALS AND METHODS: We retrospectively reviewed 3085 eligible patients diagnosed with recent onset AF in any of the EDs between January 2008 and December 2009. Inclusion criteria required documented ICD-9 primary discharge/admission diagnosis of AF in the ED and stable hemodynamic conditions at presentation (systolic blood pressure > 90 mmHg). Exclusion criteria were permanent AF or an ongoing acute coronary syndrome. RESULTS: Median age was 71 years (interquartile ranges, 62-78 years) and 50.8% were men. Palpitations was the most common symptom at ED presentation and was present in 73.5% of the study subjects. Hypertension was the most prevalent comorbidity, affecting 59.3% of the patients evaluated, and the presence of previous episode(s) of AF was also common (52.3%). Regarding home treatment, the drugs most prescribed were antiplatelets (31.2%) and diuretics (25.2%). A CHADS2 score of 0 was found in 814 patients (26.4%), while a CHADS2 score of 1 was reported in 1114 patients (36.1%). Finally, a CHADS2 score ≥ 2 was reported in 1157 patients (37.5%). CONCLUSIONS: The present study represents an important snapshot of demographics, comorbidities, risk factors and anticoagulation management about patients with recent onset AF. Disparities were noted in anticoagulation management, suggesting that this is still a main problem among patients with AF.
Asunto(s)
Fibrilación Atrial/diagnóstico , Servicio de Urgencia en Hospital , Anciano , Antiarrítmicos/uso terapéutico , Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Fibrilación Atrial/fisiopatología , Distribución de Chi-Cuadrado , Comorbilidad , Diuréticos/uso terapéutico , Femenino , Hemodinámica , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Valor Predictivo de las Pruebas , Prevalencia , Recurrencia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Ciudad de Roma/epidemiologíaRESUMEN
The expression of Ki67, BCL-2, and COX-2 was investigated in 53 canine cutaneous mast cell tumors (MCTs) by immunohistochemistry and quantitative real time polymerase chain reaction (qPCR) to evaluate their prognostic significance and the association with the histologic grading and the mitotic index (MI). MCTs were graded according to the Patnaik grading system and the novel 2-tier grading system proposed by Kiupel. The numbers of mitotic figures/10 high-power fields (MI) were counted. Both grading systems were significantly associated with prognosis. The Patnaik grading was of limited prognostic value for grade 2 MCTs, with 23% being associated with mortality. The concordance among pathologists was strongly improved by the application of the 2-tier grading system, and 71% of high-grade MCTs were associated with a high mortality rate. MI and Ki67 protein expression were significantly associated with grading and survival. No significant association between BCL-2 protein expression and either grading system or health status was observed. BCL-2 mRNA expression was significantly higher in grade 2 than in grade 1 MCTs, while no statistically significant differences were detected between low- and high-grade MCTs. The increased BCL-2 mRNA level was significantly associated with increased mortality rate. The COX-2 protein expression was detected in 78% of the MCTs investigated. However, neither association with the tumor grade nor with the health status was observed. COX-2 mRNA was significantly up-regulated in MCTs compared to surgical margins and control skin tissue, but it was neither associated with tumor grade nor with survival.
Asunto(s)
Biomarcadores de Tumor/genética , Enfermedades de los Perros/patología , Sarcoma de Mastocitos/veterinaria , Mastocitosis Cutánea/veterinaria , Neoplasias Cutáneas/veterinaria , Animales , Biomarcadores de Tumor/metabolismo , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Enfermedades de los Perros/metabolismo , Perros , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Inmunohistoquímica/veterinaria , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Mastocitos/metabolismo , Mastocitos/patología , Sarcoma de Mastocitos/metabolismo , Sarcoma de Mastocitos/patología , Mastocitosis Cutánea/metabolismo , Mastocitosis Cutánea/patología , Índice Mitótico , Clasificación del Tumor/veterinaria , Pronóstico , Estudios Prospectivos , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Piel/metabolismo , Piel/patología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patologíaRESUMEN
In humans, the aryl hydrocarbon receptor (AHR) gene battery constitutes a set of contaminant-responsive genes, which have been recently shown to be involved in the regulation of several patho-physiological conditions, including tumorigenesis. As the domestic dog represents a valuable animal model in comparative oncology, mRNA levels of cytochromes P450 1A1, 1A2 and 1B1 (CYP1A1, 1A2 and 1B1), AHR, AHR nuclear translocator (ARNT), AHR repressor (AHRR, whose partial sequence was here obtained) and cyclooxygenase-2 (COX2) were measured in dog control tissues (liver, skin, mammary gland and bone), in 47 mast cell tumors (MCTs), 32 mammary tumors (MTs), 5 osteosarcoma (OSA) and related surgical margins. Target genes were constitutively expressed in the dog, confirming the available human data. Furthermore, their pattern of expression in tumor biopsies was comparable to that already described in a variety of human cancers; in particular, both AHR and COX2 genes were up-regulated and positively correlated, while CYP1A1 and CYP1A2 mRNAs were generally poorly expressed. This work demonstrated for the first time that target mRNAs are expressed in neoplastic tissues of dogs, thereby increasing the knowledge about dog cancer biology and confirming this species as an useful animal model for comparative studies on human oncology.
Asunto(s)
Ciclooxigenasa 2/biosíntesis , Enfermedades de los Perros/metabolismo , Neoplasias/veterinaria , Receptores de Hidrocarburo de Aril/biosíntesis , Animales , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/veterinaria , Enfermedades de los Perros/enzimología , Perros , Femenino , Masculino , Sarcoma de Mastocitos/enzimología , Sarcoma de Mastocitos/metabolismo , Sarcoma de Mastocitos/veterinaria , Neoplasias/enzimología , Neoplasias/metabolismo , Osteosarcoma/enzimología , Osteosarcoma/metabolismo , Osteosarcoma/veterinaria , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinariaRESUMEN
Degradation of the extracellular matrix and angiogenesis are associated with tumour invasion and metastasis in human and canine neoplasia. Matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and vascular endothelial growth factor-A (VEGF-A) are key mediators of these respective processes. Mast cell tumour (MCT) is the most common malignant cutaneous tumour in dogs. MCTs are always considered potentially malignant, but their true metastatic potential is unknown. In the present study, samples from seven grade 1, 22 grade 2 and six grade 3 MCTs were subjected to quantitative real-time polymerase chain reaction and immunohistochemistry (IHC) to evaluate MMP-2, MMP-9, membrane-type 1 MMP (MT1-MMP), TIMP-2 and VEGF-A mRNA and protein expression. Gelatin zymography (GZ) was also performed to evaluate MMP-2 and MMP-9 activity. MMP-9 and VEGF-A mRNA increased with histological grade, while TIMP-2 decreased with increasing grade. Gene expression data obtained for MMP-9, VEGF-A and TIMP-2 were confirmed by IHC for evaluation of the respective proteins. In contrast, MMP-2 and MT1-MMP had variable, but similar, expression for both mRNA and protein. Despite the high variability observed, there was correlation between MMP-2 and MT1-MMP mRNA expression (r=+0.91, P<0.0001). The MMP-2:TIMP-2 and MMP-9:TIMP-1 mRNA ratios showed an imbalance between MMPs and their specific inhibitors in MCTs, which increased with the histological grade. Finally, the activities of both latent and active forms of MMP-2 and MMP-9 were evaluated by GZ and there were significant increases in their activities with increasing histological grade and immunohistochemical expression. This study demonstrates that MMP-9, TIMP-2 and VEGF-A expression is related to histological grade and suggests that these markers are possible indicators of malignancy and targets for therapeutic strategies.
Asunto(s)
Enfermedades de los Perros/genética , Regulación Neoplásica de la Expresión Génica/fisiología , Sarcoma de Mastocitos/veterinaria , Metaloproteinasas de la Matriz/genética , Neoplasias Cutáneas/veterinaria , Inhibidores Tisulares de Metaloproteinasas/genética , Factor A de Crecimiento Endotelial Vascular/genética , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , ADN de Neoplasias/análisis , Enfermedades de los Perros/metabolismo , Enfermedades de los Perros/patología , Perros , Femenino , Inmunohistoquímica , Masculino , Sarcoma de Mastocitos/genética , Sarcoma de Mastocitos/metabolismo , Sarcoma de Mastocitos/patología , Metaloproteinasas de la Matriz/metabolismo , Reacción en Cadena de la Polimerasa/veterinaria , ARN Mensajero/metabolismo , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The quantitative simultaneous description of both variable region gene usage and antigen specificity of immunoglobulin repertoires is a major goal in immunology. Current quantitative assays are labor intensive and depend on extensive gene expression cloning prior to screening for antigen specificity. Here we describe an alternative method based on high efficiency single B cell cultures coupled with RT-PCR that can be used for rapid characterization of immunoglobulin gene segment usage, clonal size and antigen specificity. This simplified approach should facilitate the study of antibody repertoires expressed by defined B cell subpopulations, the analysis of immune responses to self and nonself-antigens, the development and screening of synthetic antibodies and the accelerated study and screening of neutralizing antibodies to pathogenic threats.
Asunto(s)
Linfocitos B/inmunología , Células Clonales/inmunología , Clonación Molecular/métodos , Región Variable de Inmunoglobulina/inmunología , Animales , Linfocitos B/citología , Femenino , Región Variable de Inmunoglobulina/genética , Ratones , Ratones Endogámicos BALB C , ARN/química , ARN/genética , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADNRESUMEN
During June and July of 2009, sudden deaths, tremulous movements and population declines of adult honey bees were reported by the beekeepers in the region of Peloponnesus (Mt. Mainalo), Greece. A preliminary study was carried out to investigate these unexplained phenomena in this region. In total, 37 bee samples, two brood frames containing honey bee brood of various ages, eight sugar samples and four sugar patties were collected from the affected colonies. The samples were tested for a range of pests, pathogens and pesticides. Symptomatic adult honey bees tested positive for Varroa destructor, Nosema ceranae, Chronic bee paralysis virus (CBPV), Acute paralysis virus (ABPV), Deformed wing virus (DWV), Sacbrood virus (SBV) and Black queen cell virus (BQCV), but negative for Acarapis woodi. American Foulbrood was absent from the brood samples. Chemical analysis revealed that amitraz, thiametoxan, clothianidin and acetamiprid were all absent from symptomatic adult bees, sugar and sugar patty samples. However, some bee samples, were contaminated with imidacloprid in concentrations between 14 ng/g and 39 ng/g tissue. We present: the infection of Greek honey bees by multiple viruses; the presence of N. ceranae in Greek honey bees and the first record of imidacloprid (neonicotonoid) residues in Greek honey bee tissues. The presence of multiple pathogens and pesticides made it difficult to associate a single specific cause to the depopulation phenomena observed in Greece, although we believe that viruses and N. ceranae synergistically played the most important role. A follow-up in-depth survey across all Greek regions is required to provide context to these preliminary findings.
Asunto(s)
Abejas/virología , Colapso de Colonias/inducido químicamente , Colapso de Colonias/microbiología , Imidazoles/efectos adversos , Nitrocompuestos/efectos adversos , Plaguicidas/efectos adversos , Virosis/virología , Animales , Cromatografía Liquida , ADN Viral/análisis , Grecia , Virus de Insectos , Espectrometría de Masas , Neonicotinoides , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The dystrophin defective mdx mouse, acknowledged model of Duchenne Muscular Dystrophy (DMD), bears outstanding alterations of the cortical architecture, that could be responsible for the cognitive impairment often accompanying this pathological condition. Using a retrograde tract tracing technique to label neurons in Golgi-like fashion, we investigated the fine anatomical organization of associative cortico-cortical projections in mdx mice. While the absolute number of associative pyramidal neurons was significantly higher in mdx than in control animals, the ratio between the number of supra- and infragranular cortico-cortical cells was substantially unmodified. Basal dendrites of layer 2/3 pyramidal neurons displayed longer terminal branches in mdx compared to controls. Finally, the density of dendritic spines was significantly lower in mdx animals. The anomalies of associative cortico-cortical projections provide potential groundwork on the neurobiological bases of cognitive involvement in DMD and value the role of cortical microcircuitry alterations as possible source of interference with peripheral motor impairment.
Asunto(s)
Corteza Cerebral/patología , Trastornos del Conocimiento/patología , Distrofina/deficiencia , Distrofia Muscular de Duchenne/patología , Red Nerviosa/patología , Células Piramidales/patología , Animales , Biotina/análogos & derivados , Recuento de Células , Forma de la Célula/fisiología , Corteza Cerebral/metabolismo , Corteza Cerebral/fisiopatología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/metabolismo , Dendritas/metabolismo , Dendritas/patología , Dendritas/ultraestructura , Espinas Dendríticas/metabolismo , Espinas Dendríticas/patología , Espinas Dendríticas/ultraestructura , Dextranos , Modelos Animales de Enfermedad , Distrofina/genética , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos mdx , Corteza Motora/metabolismo , Corteza Motora/patología , Corteza Motora/fisiopatología , Distrofia Muscular de Duchenne/complicaciones , Distrofia Muscular de Duchenne/metabolismo , Red Nerviosa/metabolismo , Red Nerviosa/fisiopatología , Trazadores del Tracto Neuronal , Células Piramidales/metabolismo , Células Piramidales/ultraestructura , Corteza Somatosensorial/metabolismo , Corteza Somatosensorial/patología , Corteza Somatosensorial/fisiopatología , Coloración y EtiquetadoRESUMEN
Lipopolysaccharide (LPS) from gram-negative bacteria activates B cells, enabling them to proliferate and differentiate into plasma cells. This response is critically dependent on the expression of TLR4; but other genes, such as RP105 and MHC class II, have also been shown to contribute to B cell LPS response. Here, we have evaluated the role of genetic control of the B cell response to LPS at the single cell level. We compared the response to LPS of peritoneal cavity (PEC) and splenic B cells on the BALB/c genetic background (LPS-low responder) to those on the C57BL/6J background (LPS-high responder) and their F1 progeny (CB6F1). Both PEC and splenic B cells from B6 exhibited 100% clonal growth in the presence of LPS; whereas, BALB/c PEC and splenic B cells achieved only 50% and 23% clonal growth, respectively. Adding CpG to the LPS stimulus pushed PEC B cell clonal growth in the low responder strain BALB/c up to 90%, showing that the nonresponse to LPS is a specific effect. Surprisingly, PEC B cells on the F1 background behaved as high responders, while splenic B cells behaved as low responders to LPS. The data presented here reveals a previous unsuspected behavior in the genetic control of the B cell response to LPS with an opposing impact in splenic versus peritoneal cavity B cells. These results suggest the existence of an, as yet, unidentified genetic factor exclusively expressed by coelomic B cells that contributes to the control of the LPS signaling pathway in the B lymphocyte.
Asunto(s)
Linfocitos B/inmunología , Regulación de la Expresión Génica , Lipopolisacáridos/inmunología , Peritoneo/inmunología , Bazo/citología , Animales , Linfocitos B/metabolismo , Cruzamientos Genéticos , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Peritoneo/citología , Bazo/inmunologíaRESUMEN
This work correlates time series of biological and physical variables to the marine viruses across trophic gradients within Arraial do Cabo upwelling system, Southeast of Brazil. The objective is to investigate the major controlling factors of virioplankton dynamics among different water masses. It was used an in situ and ex situ flow cytometry for accessing the plankton community. Viruses were highly correlated to bacteria and phytoplankton, but although the lack of direct correlation with physicals, upwelling turned out to be the main contributing factor to the highest values of viral abundance and virus:bacterial ratio. Our data suggest that the lowest temperature of upwelled South Atlantic Central Waters would help to maintain a high viral abundance and higher temperatures of Coastal and Tropical Waters might be another ecological niche allowing the co-existence.
Asunto(s)
Flora Acuática , Citometría de Flujo , Fitoplancton/genética , Técnicas In Vitro , Plancton/aislamiento & purificación , Virión/genética , Métodos , Métodos , Corrientes de AguaRESUMEN
OBJECTIVES: This study aimed to isolate and characterize stem/progenitor cells, starting from normal airway epithelia, obtained from human adults. MATERIALS AND METHODS: Cultures of multicellular spheroids were obtained from human lung tissue specimens after mechanical and enzymatic digestion. Tissue-specific markers were detected on their cells by immunohistochemical and immunofluorescent techniques. Ultrastructural morphology of the spheroids (termed as bronchospheres) was evaluated by electron microscopy, gene expression analysis was performed by reverse transcription-polymerase chain reaction, and gene down-regulation was analysed by an RNA interference technique. RESULTS: Bronchospheres were found to be composed of cells with high expression of stem cell regulatory genes, which was not or was only weakly detectable in original tissues. Morphological analysis showed that bronchospheres were composed of mixed phenotype cells with type II alveolar and Clara cell features, highlighting their airway resident cell origin. In addition to displaying specific pulmonary and epithelial commitment, bronchospheres showed mesenchymal features. Silencing of the Slug gene, known to play a pivotal role in epithelial-mesenchymal transition processes and which was highly expressed in bronchospheres but not in original tissue, led bronchospheres to gain a differentiated bronchial/alveolar phenotype and to lose the stemness gene expression pattern. CONCLUSIONS: Ours is the first study to describe ex vivo expansion of stem/progenitor cells resident in human lung epithelia, and our results suggest that the epithelial-mesenchymal transition process, still active in a subset of airway cells, may regulate transit of stem/progenitor cells towards epithelial differentiation.
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Separación Celular , Pulmón/citología , Células Madre/citología , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Diferenciación Celular , Femenino , Humanos , Inmunohistoquímica , Masculino , Mesodermo/citología , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Interferencia de ARN , ARN Interferente Pequeño , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
This work correlates time series of biological and physical variables to the marine viruses across trophic gradients within Arraial do Cabo upwelling system, Southeast of Brazil. The objective is to investigate the major controlling factors of virioplankton dynamics among different water masses. It was used an in situ and ex situ flow cytometry for accessing the plankton community. Viruses were highly correlated to bacteria and phytoplankton, but although the lack of direct correlation with physicals, upwelling turned out to be the main contributing factor to the highest values of viral abundance and virus:bacterial ratio. Our data suggest that the lowest temperature of upwelled South Atlantic Central Waters would help to maintain a high viral abundance and higher temperatures of Coastal and Tropical Waters might be another ecological niche allowing the co-existence.
RESUMEN
The interstitialcy theory is used to calculate the kinetics of shear modulus relaxation induced by structural relaxation of metallic glasses. A continuous distribution of activation energies is shown to be a salient feature of the relaxation. High precision in situ contactless electromagnetic acoustic-transformation shear modulus (600- kHz) measurements performed on a Zr-based bulk metallic glass are found to strongly support the approach under consideration. It is revealed that the activation energy spectra derived from isothermal and isochronal shear modulus measurements are in good agreement with each other. It is concluded that the increase of the shear modulus during structural relaxation can be understood as a decrease of the concentration of structural defects similar to dumbbell interstitials in simple crystalline metals.
RESUMEN
The ongoing H5N1 Asian epidemic is currently affecting a number of avian species including ducks. These birds are an important part of the poultry industry in the affected countries, and it is likely that they are acting as a reservoir of infection. Ten Pekin ducks were challenged with 100 microl containing 10(7) 50% egg infective dose of the highly pathogenic avian influenza virus (HPAIV) A/Duck/Vietnam/12/05 (H5N1), administered by an intra-nasal and oral route. Clinical symptoms were recorded twice a day up to 14 days postinfection (dpi). Clinical signs were first noted at 2 dpi, with conjunctivitis and slight depression, and progressed over a period of 1-3 days to severe neurologic signs consisting of torticollis, incoordination, tremors, and seizures. Survival times varied from 3 to 7 dpi. On postmortem examination, hemorrhages were observed in the duodenum, ceca, proventriculus, ventriculus, trachea, pancreas, and brain. Histologic lesions, as well as immunohistochemistry positivity, were recorded in the pancreas and brain. In situ hybridization revealed viral antigen associated with acinar pancreatic cells, bronchial epithelial cells, and with cells of the central nervous system as well as neurons of the submucosal plexus of the duodenum. Our experimental findings agree with those previously observed in ducks naturally infected with HPAIV H5N1 viruses, confirming the acquired viral neurotropism and pancreatotropism, as previously noted in other avian species, as well as in humans.
Asunto(s)
Patos , Subtipo H5N1 del Virus de la Influenza A , Gripe Aviar/patología , Animales , Tronco Encefálico/virología , Corteza Cerebral/patología , Corteza Cerebral/virología , Inmunohistoquímica , Hibridación in Situ , Gripe Aviar/virología , Neuroglía/virología , Neuronas/virología , Páncreas/patología , Páncreas/virología , ARN ViralRESUMEN
Strategically positioned in peripheral tissues, immune sentinel cells sense microbes and/or their shed products through different types of pattern-recognition receptors. Upon secretion, pre-formed pro-inflammatory mediators activate the microvasculature, inducing endothelium/neutrophil adherence and impairing endothelium barrier function. As plasma proteins enter into peripheral tissues, short-lived proinflammatory peptides are rapidly generated by limited proteolysis of complement components and the kininogens (i.e. kinin-precursor proteins). While much emphasis has been placed on the studies of the vascular functions of kinins, their innate effector roles remain virtually unknown. A few years ago, we reported that exogenous bradykinin (BK) potently induces dendritic cell (DC) maturation, driving IL-12-dependent Th1 responses through the activation of G-protein-coupled BK B(2) receptors (B(2)R). The premise that immature DC might sense kinin-releasing pathogens through B(2)R was demonstrated in the subcutaneous mouse model of Trypanosoma cruzi infection. Analysis of the dynamics of parasite-evoked inflammation revealed that activation of TLR2/neutrophils drives the influx of plasma proteins, including kininogens, into peripheral tissues. Once associated to cell surfaces and/or extracellular matrices, the surface-bound kininogens are cleaved by T. cruzi cysteine proteases. Acting as short-lived 'danger' signals, kinins activate DC via B(2)R, converting them into Th1 inducers. Fine tuned control of the extravascular levels of these natural peptide adjuvants is exerted by kinin-degrading metallopeptidases, e.g. Angiotensin converting enzyme (ACE/CD143). In summary, the studies in the subcutaneous model of T. cruzi infection revealed that the peripheral levels of BK, a DC maturation signal, are controlled by TLR2/neutrophils and ACE, respectively characterized as positive and negative modulators of innate/adaptive immunity.
Asunto(s)
Bradiquinina/metabolismo , Diferenciación Celular/inmunología , Células Dendríticas/metabolismo , Inmunidad Activa , Mediadores de Inflamación/fisiología , Quininógenos/fisiología , Péptido Hidrolasas/metabolismo , Animales , Células Dendríticas/enzimología , Células Dendríticas/patología , Humanos , Mediadores de Inflamación/metabolismo , Quininógenos/metabolismo , Transducción de Señal/inmunologíaRESUMEN
BACKGROUND: Reversible ischaemia/reperfusion (I/R) liver injury has been used to induce engraftment and hepatic parenchymal differentiation of exogenous beta2-microglubulin(-)/Thy1(+) bone marrow derived cells. AIM: To test the ability of this method of hepatic parenchymal repopulation, theoretically applicable to clinical practice, to correct the metabolic disorder in a rat model of congenital hyperbilirubinaemia. METHODS AND RESULTS: Analysis by confocal laser microscopy of fluorescence labelled cells and by immunohistochemistry for beta2-microglubulin, 72 hours after intraportal delivery, showed engraftment of infused cells in liver parenchyma of rats with I/R, but not in control animals with non-injured liver. Transplantation of bone marrow derived cells obtained from GFP-transgenic rats into Lewis rats resulted in the presence of up to 20% of GFP positive hepatocytes in I/R liver lobes after one month. The repopulation rate was proportional to the number of transplanted cells. Infusion of GFP negative bone marrow derived cells into GFP positive transgenic rats resulted in the appearance of GFP negative hepatocytes, suggesting that the main mechanism underlying parenchymal repopulation was differentiation rather than cell fusion. Transplantation of wild type bone marrow derived cells into hyperbilirubinaemic Gunn rats with deficient bilirubin conjugation after I/R damage resulted in 30% decrease in serum bilirubin, the appearance of bilirubin conjugates in bile, and the expression of normal UDP-glucuronyltransferase enzyme evaluated by polymerase chain reaction. CONCLUSIONS: I/R injury induced hepatic parenchymal engraftment and differentiation into hepatocyte-like cells of bone marrow derived cells. Transplantation of bone marrow derived cells from non-affected animals resulted in the partial correction of hyperbilirubinaemia in the Gunn rat.
Asunto(s)
Trasplante de Médula Ósea/métodos , Hiperbilirrubinemia Hereditaria/terapia , Regeneración Hepática , Acondicionamiento Pretrasplante/métodos , Animales , Bilirrubina/metabolismo , Diferenciación Celular , Modelos Animales de Enfermedad , Supervivencia de Injerto , Hepatocitos/patología , Hiperbilirrubinemia Hereditaria/metabolismo , Hiperbilirrubinemia Hereditaria/patología , Circulación Hepática , Ratas , Ratas Gunn , Daño por Reperfusión/patología , Resultado del TratamientoRESUMEN
One hundred and one patients suffering from chronic daily headache (CDH) and medication overuse were treated, in an in-patient setting, with abrupt discontinuation of the medication overused, intravenous hydrating, and intravenous administration of benzodiazepines and ademetionine. The mean time to CDH resolution was 8.8 days. The in-patient withdrawal protocol used was effective, safe and well tolerated. There was a trend for a shorter time to CDH resolution in patients who overused triptans (P=0.062). There was no correlation between time to CDH resolution and either the type of initial primary headache or duration of medication abuse, whereas time to CDH resolution was related to daily drug intake (P=0.01). In multiple regression analysis, daily drug intake, age and type of medication overused were independent predictors of time to CDH resolution. At 3-months' follow-up, no patient had relapsed and was again overusing symptomatic medications.