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1.
Data Brief ; 24: 103921, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31061862

RESUMEN

The data presented here is complementary to the publication entitled "High temperature, low neutron cross-section high-entropy alloys in the Nb-Ti-V-Zr system" [1]. A homogenization methodology with slower cooling rate (∼2 °C/min) was performed. X-ray diffraction and scanning electron microscopy (backscattered electron and energy dispersive spectroscopy) data pertaining to annealed high-entropy alloy composition NbTiVZr is presented.

2.
Neuroimage Clin ; 23: 101844, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31075554

RESUMEN

Paediatric traumatic brain injury (pTBI) is a leading cause of disability for children and young adults. Children are a uniquely vulnerable group with the disease process that occurs following a pTBI interacting with the trajectory of normal brain development. Quantitative MRI post-injury has suggested a long-term, neurodegenerative effect of TBI on the morphometry of the brain, in both adult and childhood TBI. Changes to the brain beyond that of anticipated, age-dependant differences may allow us to estimate the state of the brain post-injury and produce clinically relevant predictions for long-term outcome. The current review synthesises the existing literature to assess whether, following pTBI, the morphology of the brain exhibits either i) longitudinal change and/or ii) differences compared to healthy controls and outcomes. The current literature suggests that morphometric differences from controls are apparent cross-sectionally at both acute and late-chronic timepoints post-injury, thus suggesting a non-transient effect of injury. Developmental trajectories of morphometry are altered in TBI groups compared to patients, and it is unlikely that typical maturation overcomes damage post-injury, or even 'catches up' with that of typically-developing peers. However, there is limited evidence for diverted developmental trajectories being associated with cognitive impairment post-injury. The current review also highlights the apparent challenges to the existing literature and potential methods by which these can be addressed.


Asunto(s)
Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/tendencias , Encéfalo/fisiopatología , Lesiones Traumáticas del Encéfalo/fisiopatología , Niño , Estudios Transversales , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética/métodos
3.
Rev Sci Tech ; 35(1): 175-89, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27217177

RESUMEN

Foot and mouth disease virus (FMDV) is an animal pathogen of global economic significance. Identifying the sources of outbreaks plays an important role in disease control; however, this can be confounded by the ease with which FMDV can spread via movement of infected livestock and animal products, aerosols or fomites, e.g. contaminated persons and objects. As sequencing technologies have advanced, this review highlights the uses of viral genomic data in helping to understand the global distribution and transboundary movements of FMDV, and the role that these approaches have played in control and surveillance programmes. The recent application of next-generation sequencing platforms to address important epidemiological and evolutionary challenges is discussed with particular reference to the advent of 'omics' technologies.


Le virus de la fièvre aphteuse est un agent pathogène affectant les animaux d'élevage, avec des conséquences économiques considérables à l'échelle mondiale. La détection des sources des foyers est un aspect important de la lutte contre cette maladie ; l'efficacité de cette stratégie est toutefois compromise par la facilité avec laquelle le virus de la fièvre aphteuse se propage à la faveur des mouvements d'animaux ou de produits d'origine animale infectés, d'aérosols ou de personnes ou matières contaminées. Les auteurs décrivent, au fur et à mesure des avancées des technologies du séquençage, les données de la génomique virale qui ont permis de mieux comprendre la distribution mondiale et la propagation transfrontalière du virus de la fièvre aphteuse et le rôle que ces approches ont commencé à jouer dans les programmes de contrôle et de surveillance. Les auteurs examinent également les applications récentes des plates-formes de séquençage de nouvelle génération pour résoudre des problèmes épidémiologiques et évolutifs importants, en se référant particulièrement à l'avènement des technologies dites «­omiques ¼.


El virus de la fiebre aftosa es un patógeno animal que reviste importancia planetaria. A la hora de combatir la enfermedad es útil poder determinar el origen de los brotes, tarea que sin embargo puede verse frustrada por la facilidad con que el virus es capaz de diseminarse siguiendo los desplazamientos de animales o derivados animales infectados o por aerosoles o fómites (por ejemplo personas u objetos contaminados). Los autores hacen hincapié en la utilización de datos de genómica vírica para ayudar a aprehender la distribución mundial y los movimientos transfronterizos del virus de la fiebre aftosa, lo cual es posible gracias a los avances que han conocido las técnicas de secuenciación, así como en la función que pueden cumplir estos métodos dentro de los programas de control y vigilancia. También examinan la reciente aplicación de dispositivos de secuenciación de próxima generación para abordar importantes problemas epidemiológicos y evolutivos, refiriéndose especialmente al advenimiento de las técnicas «ómicas¼.


Asunto(s)
Brotes de Enfermedades/veterinaria , Virus de la Fiebre Aftosa/genética , Fiebre Aftosa/virología , Genómica , Animales , Fiebre Aftosa/prevención & control , Epidemiología Molecular
4.
Artículo en Inglés | MEDLINE | ID: mdl-22365109

RESUMEN

The n-3 and n-6 fatty acids are transferred across the placenta with consistently higher 22:6n-3 and lower 18:2n-6 in fetal than maternal plasma. This study sought to determine whether maternal and fetal cord blood red blood cell (RBC) phospholipid fatty acids show similar saturation with 22:6n-3, and also addressed the relationship between 18:2n-6 and Δ6 desaturase product/precursor ratios for 97 mothers and newborns. Despite higher fetal than maternal plasma phospholipid 22:6n-3, the maternal and fetal RBC phospholipid 22:6n-3 showed similar curvilinear relationships to the plasma phospholipid 22:6n-3. Risk of failure to achieve high RBC phospholipid 22:6n-3 increased sharply below a plasma phospholipid 22:6n-3 of 6.5g/100g fatty acids. Higher maternal and fetal 18:2n-6 was associated with lower RBC phospholipid 22:6n-3/22:5n-3, 22:5n-6/22:4n-6 and 18:3n-6/18:2n-6. These findings suggest low placental transfer of 18:2n-6 may be a specific mechanism to prevent inhibition of fetal Δ6 desaturase and facilitate fetal cellular phospholipid 22:6n-3 accretion.


Asunto(s)
Ácidos Docosahexaenoicos/sangre , Ácido Graso Desaturasas/metabolismo , Feto/metabolismo , Ácido Linoleico/sangre , Placenta/metabolismo , Adulto , Ácidos Docosahexaenoicos/metabolismo , Ácidos Grasos Omega-6/sangre , Ácidos Grasos Omega-6/metabolismo , Femenino , Desarrollo Fetal , Humanos , Embarazo
5.
Avian Dis ; 52(2): 260-8, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18646455

RESUMEN

The potency of inactivated Newcastle disease virus (NDV) vaccines in the United States is currently determined using vaccination and challenge of experimental animals against a velogenic strain of NDV. Because velogenic strains of NDV are now classified as select agents in the United States, all vaccine potency testing must be performed in live animals under biosafety level 3 agriculture conditions. If the minimum amount of inactivated viral antigen required for clinical protection can be determined using other methods, vaccines meeting these criteria might be considered of adequate potency. The linearity of correlation between the hemagglutination (HA) assay measurement and the 50% embryo infectious dose titer ofNDV Hitchner B1 vaccine virus was determined. Correlation between hemagglutinin units (HAU) per vaccine dose, clinical protection, and antibody response was then determined using a vaccinate-and-challenge model similar to Chapter 9 of the U.S. code of federal regulations approved method for vaccine potency testing. The dose providing 50% protection of an in-house water-in-oil emulsion vaccine formulated with inactivated NDV B1 was determined to be between 400 and 600 HAU from two separate trials. A positive correlation (R2 = 0.97) was observed between antibody response and HAU per vaccine dose. Serum antibody responses from vaccinated birds indicate HA inhibition titers >2(5) log2 would provide 100% protection from morbidity and mortality and require a minimum protective dose of 1000 HAU per bird. These are the first studies to examine establishing both a minimum protective HAU content for inactivated ND vaccines and a minimum serologic response necessary to ensure potency.


Asunto(s)
Hemaglutininas Virales/administración & dosificación , Enfermedad de Newcastle/prevención & control , Virus de la Enfermedad de Newcastle/inmunología , Vacunas Virales/inmunología , Animales , Embrión de Pollo , Pollos , Relación Dosis-Respuesta Inmunológica , Pruebas de Inhibición de Hemaglutinación/veterinaria , Hemaglutininas Virales/análisis , Enfermedad de Newcastle/inmunología , Enfermedad de Newcastle/virología , Virus de la Enfermedad de Newcastle/aislamiento & purificación , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/análisis , Vacunas de Productos Inactivados/inmunología , Vacunas Virales/administración & dosificación , Vacunas Virales/análisis
6.
Vet Pathol ; 43(6): 925-33, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17099149

RESUMEN

Exotic Newcastle disease virus (NDV) isolated from chickens during the 2002-2003 California outbreak (CA exotic Newcastle disease [END] virus) was inoculated into 4-week-old specific-pathogen-free (SPF) White Leghorn chickens, 3-week-old SPF Beltsville White turkeys, 6-week-old commercial Broad Breasted White turkeys, and 10- to 20-week-old racing pigeons, and the clinicopathologic features of disease were compared. Birds were monitored clinically and euthanized sequentially with collection of tissues. Tissues were examined by histopathology, by immunohistochemistry to detect viral nucleoprotein, and by in situ hybridization to detect viral mRNA. Clinically, infected chickens and SPF turkeys showed severe depression, and all died or were euthanized because of severe clinical signs by day 5 postinoculation. In these birds, histologic lesions were widespread and virus was detected in multiple organs. All infected commercial turkeys showed mild depression, and incoordination was observed in some birds. Histologic lesions were mild, and viral distribution was limited. In pigeons, only 1 bird showed overt clinical disease, and histologic lesions and viral distribution were present in limited organs. Consequently, susceptibility to highly virulent NDV was shown to vary among chickens, SPF turkeys, commercial turkeys, and pigeons. Additionally, we have evidence of CA END virus subclinical infections that suggest pigeons could be subclinical carriers of other virulent NDV.


Asunto(s)
Brotes de Enfermedades/veterinaria , Enfermedad de Newcastle/epidemiología , Enfermedad de Newcastle/virología , Virus de la Enfermedad de Newcastle/patogenicidad , Enfermedades de las Aves de Corral/virología , Animales , California/epidemiología , Pollos , Columbidae , Enfermedad de Newcastle/patología , Enfermedades de las Aves de Corral/epidemiología , Organismos Libres de Patógenos Específicos , Pavos
7.
Vet Pathol ; 43(2): 168-78, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16537934

RESUMEN

The pathogenesis of five different Newcastle disease virus (NDV) isolates representing all pathotypes was examined in commercial and specific pathogen-free (SPF) turkeys. Experimentally-infected birds were monitored clinically and euthanatized, with subsequent tissue collection, for examination by histopathology, by immunohistochemistry for the presence of NDV nucleoprotein, and by in situ hybridization for the presence of replicating virus. Clinically, the lentogenic pathotype did not cause overt clinical signs in either commercial or SPF turkeys. Mesogenic viruses caused depression in some birds. Turkeys infected with velogenic neurotropic and velogenic viscerotropic isolates showed severe depression, and neurologic signs. Histologic appearances for all strains had many similarities to lesions observed in chickens inoculated with the various isolates; that is, lesions were present predominantly in lymphoid, intestinal, and central nervous tissues. However, in general, disease among turkeys was less severe than in chickens, and turkeys could be considered a subclinical carrier for some of the isolates.


Asunto(s)
Enfermedad de Newcastle/patología , Enfermedad de Newcastle/virología , Virus de la Enfermedad de Newcastle/clasificación , Virus de la Enfermedad de Newcastle/patogenicidad , Pavos/virología , Animales , Cerebelo/patología , Inmunohistoquímica , Hibridación in Situ , Miocardio/patología , Páncreas/patología , Organismos Libres de Patógenos Específicos , Bazo/patología , Virulencia
8.
Int J Obstet Anesth ; 15(1): 59-62, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16256331

RESUMEN

Clozapine is an atypical antipsychotic agent with a novel pharmacological profile and multiple clinical properties. Because of its side effects, it is recommended in treatment of severe resistant schizophrenia for which purpose it is remarkably effective. Little is known about the safety profile of clozapine during pregnancy and labour and because it is now used more commonly to manage schizophrenia, it is important that we as anaesthetists are aware of its many interactions and potential side effects. We present a case of a successful emergency caesarean section in a schizophrenic patient on clozapine treatment.


Asunto(s)
Anestesia General , Anestesia Obstétrica , Antipsicóticos/uso terapéutico , Clozapina/uso terapéutico , Complicaciones del Embarazo/tratamiento farmacológico , Esquizofrenia/tratamiento farmacológico , Adulto , Antipsicóticos/efectos adversos , Cesárea , Clozapina/efectos adversos , Femenino , Humanos , Recién Nacido , Masculino , Embarazo
9.
J Psychopharmacol ; 18(2): 156-72, 2004 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15260903

RESUMEN

In view of the evidence that cognitive deficits in schizophrenia are critically important for long-term outcome, it is essential to establish the effects that the various antipsychotic compounds have on cognition, particularly second-generation drugs. This parallel group, placebo-controlled study aimed to compare the effects in healthy volunteers (n = 128) of acute doses of the atypical antipsychotics amisulpride (300 mg) and risperidone (3 mg) to those of chlorpromazine (100 mg) on tests thought relevant to the schizophrenic process: auditory and visual latent inhibition, prepulse inhibition of the acoustic startle response, executive function and eye movements. The drugs tested were not found to affect auditory latent inhibition, prepulse inhibition or executive functioning as measured by the Cambridge Neuropsychological Test Battery and the FAS test of verbal fluency. However, risperidone disrupted and amisulpride showed a trend to disrupt visual latent inhibition. Although amisulpride did not affect eye movements, both risperidone and chlorpromazine decreased peak saccadic velocity and increased antisaccade error rates, which, in the risperidone group, correlated with drug-induced akathisia. It was concluded that single doses of these drugs appear to have little effect on cognition, but may affect eye movement parameters in accordance with the amount of sedation and akathisia they produce. The effect risperidone had on latent inhibition is likely to relate to its serotonergic properties. Furthermore, as the trend for disrupted visual latent inhibition following amisulpride was similar in nature to that which would be expected with amphetamine, it was concluded that its behaviour in this model is consistent with its preferential presynaptic dopamine antagonistic activity in low dose and its efficacy in the negative symptoms of schizophrenia.


Asunto(s)
Estimulación Acústica , Clorpromazina/efectos adversos , Movimientos Oculares/efectos de los fármacos , Risperidona/efectos adversos , Sulpirida/análogos & derivados , Sulpirida/efectos adversos , Estimulación Acústica/efectos adversos , Administración Oral , Adulto , Acatisia Inducida por Medicamentos/etiología , Amisulprida , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Clorpromazina/administración & dosificación , Clorpromazina/farmacocinética , Ensayos Clínicos Controlados como Asunto , Demografía , Método Doble Ciego , Movimientos Oculares/fisiología , Humanos , Masculino , Pruebas Neuropsicológicas , Estimulación Luminosa , Solución de Problemas/efectos de los fármacos , Solución de Problemas/fisiología , Tiempo de Reacción/efectos de los fármacos , Reflejo de Sobresalto/efectos de los fármacos , Reflejo de Sobresalto/fisiología , Risperidona/administración & dosificación , Risperidona/farmacocinética , Percepción Espacial/efectos de los fármacos , Percepción Espacial/fisiología , Sulpirida/administración & dosificación , Conducta Verbal/efectos de los fármacos , Conducta Verbal/fisiología
10.
Dev Biol (Basel) ; 119: 165-70, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15742628

RESUMEN

Vaccination for Newcastle disease (ND) is routinely practised in countries where virulent strains of the Newcastle disease virus (NDV) are endemic and in countries where virulent strains do not exist but ill-timed infection by a low virulent field strain may have significant economic consequences for the producer. The types of vaccines and vaccination schedules used vary depending on the potential threat, virulence of the field challenge virus, type of production, and production schedules. A combination of live and inactivated ND vaccine, administered simultaneously, is shown to provide better protection against virulent NDV and has been successfully used in control programmes in areas of intense poultry production. A potential limiting factor in the use of live vaccines to control virulent ND is that live virus can interfere with surveillance and laboratory diagnosis. However, a new assay, the real-time reverse transcriptase-polymerase chain reaction (RRT-PCR), differentiates low virulent from virulent NDV, thus minimizing the disadvantage of live virus vaccines in the face of an outbreak and may facilitate the use of such vaccines to control outbreaks of virulent ND in the future.


Asunto(s)
Enfermedad de Newcastle/prevención & control , Virus de la Enfermedad de Newcastle/inmunología , Vacunación/veterinaria , Animales , Enfermedad de Newcastle/diagnóstico , Virus de la Enfermedad de Newcastle/patogenicidad , Aves de Corral , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Vacunas Atenuadas , Vacunas de Productos Inactivados , Vacunas Virales
11.
Radiat Prot Dosimetry ; 105(1-4): 421-5, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-14527001

RESUMEN

In 1997, a collaboration between British Nuclear Fuels plc (BNFL), Westlakes Research Institute and NRPB started, with the aim of producing IMBA (Integrated Modules for Bioassay Analysis), a suite of software modules that implement the new ICRP models for estimation of intakes and doses. This was partly in response to new UK regulations, and partly due to the requirement for a unified approach in estimating intakes and doses from bioassay measurements within the UK. Over the past 5 years, the IMBA modules have been developed further, have gone through extensive quality assurance, and are now used for routine dose assessment by approved dosimetry services throughout the UK. More recently, interest in the IMBA methodology has been shown by the United States Department of Energy (USDOE), and in 2001 an ambitious project to develop a software package (IMBA Expert USDOE Edition) which would meet the requirements of all of the major USDOE sites began. Interest in IMBA Expert is now being expressed in many other countries. The aim of this paper is to outline the origin and evolution of the IMBA modules (the past); to describe the full capabilities of the current IMBA Expert system (the present) and to indicate possible future directions in terms of capabilities and availability (the future).


Asunto(s)
Modelos Biológicos , Modelos Estadísticos , Protección Radiológica/métodos , Radioisótopos/análisis , Radioisótopos/farmacocinética , Radiometría/métodos , Programas Informáticos , Simulación por Computador , Humanos , Dosis de Radiación , Radiometría/normas , Diseño de Software , Reino Unido
12.
Avian Dis ; 47(3 Suppl): 1047-50, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-14575108

RESUMEN

Current vaccines to prevent avian influenza rely upon labor-intensive parenteral injection. A more advantageous vaccine would be capable of administration by mass immunization methods such as spray or water vaccination. A recombinant vaccine (rNDV-AIV-H7) was constructed by using a lentogenic paramyxovirus type 1 vector (Newcastle disease virus [NDV] B1 strain) with insertion of the hemagglutinin (HA) gene from avian influenza virus (AIV) A/chicken/NY/13142-5/94 (H7N2). The recombinant virus had stable insertion and expression of the H7 AIV HA gene as evident by detection of HA expression via immunofluorescence in infected Vero cells. The rNDV-AIV-H7 replicated in 9-10 day embryonating chicken eggs and exhibited hemagglutinating activity from both NDV and AI proteins that was inhibited by antisera against both NDV and AIV H7. Groups of 2-week-old white Leghorn chickens were vaccinated with transfectant NDV vector (tNDV), rNDV-AIV-H7, or sterile allantoic fluid and were challenged 2 weeks later with viscerotropic velogenic NDV (vvNDV) or highly pathogenic (HP) AIV. The sham-vaccinated birds were not protected from vvNDV or HP AIV challenge. The transfectant NDV vaccine provided 70% protection for NDV challenge but did not protect against AIV challenge. The rNDV-AIV-H7 vaccine provided partial protection (40%) from vvNDV and HP AIV challenge. The serologic response was examined in chickens that received one or two immunizations of the rNDV-AIV-H7 vaccine. Based on hemagglutination inhibition and enzyme-linked immunosorbent assay (ELISA) tests, chickens that received a vaccine boost seroconverted to AIV H7, but the serologic response was weak in birds that received only one vaccination. This demonstrates the potential for NDV for use as a vaccine vector in expressing AIV proteins.


Asunto(s)
Virus de la Influenza A/inmunología , Gripe Aviar/inmunología , Enfermedad de Newcastle/inmunología , Virus de la Enfermedad de Newcastle/inmunología , Enfermedades de las Aves de Corral/inmunología , Vacunas Sintéticas/uso terapéutico , Vacunas Virales/uso terapéutico , Animales , Embrión de Pollo/virología , Pollos , Inmunización/métodos , Gripe Aviar/prevención & control , Enfermedad de Newcastle/prevención & control , Enfermedades de las Aves de Corral/prevención & control , Organismos Libres de Patógenos Específicos
13.
J Psychopharmacol ; 16(4): 355-60, 2002 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-12503835

RESUMEN

Most antipsychotic drugs have cardiac effects as a consequence of their pharmacological actions. Recently, thioridazine has been subjected to a restricted indications notice and sertindole had its license withdrawn because of concerns about their potential cardiotoxicity. In the development of new atypical agents, heart-rate corrected QT effects are evaluated but it is unclear how predictive these are of clinically significant cardiotoxicity or sudden death. Heart rate variability (HRV) is a potential index of cardiotoxicity which has been found to be decreased following antidepressants and clozapine. We studied acute HRV changes following antipsychotic agents. Sixteen healthy male volunteers received risperidone (4 mg), olanzapine (10 mg), thioridazine (50 mg) or placebo in a randomized cross-over design. Subjective effects and psychomotor function were assayed at 2 h and both linear (summary statistics) and non-linear (scatterplot) measures of HRV were evaluated by continuous electrocardiogram recording over 10 h. Differential effects of single doses of the three antipsychotic drugs on HRV were found, and these were independent of their sedative effects. Olanzapine increased, and thioridazine decreased HRV, while risperidone had no effect. HRV is sensitive to the acute effects of antipsychotics. It may prove to be a reliable index of their potential for cardiotoxicity. Further studies in both healthy volunteers and patients on antipsychotic medication will be valuable.


Asunto(s)
Antipsicóticos/efectos adversos , Cardiopatías/inducido químicamente , Frecuencia Cardíaca/efectos de los fármacos , Pirenzepina/análogos & derivados , Adulto , Antipsicóticos/farmacología , Benzodiazepinas , Sedación Consciente , Método Doble Ciego , Humanos , Masculino , Pruebas Neuropsicológicas , Olanzapina , Pirenzepina/efectos adversos , Pirenzepina/farmacología , Valor Predictivo de las Pruebas , Desempeño Psicomotor/efectos de los fármacos , Tiempo de Reacción/efectos de los fármacos , Medición de Riesgo , Risperidona/efectos adversos , Risperidona/farmacología , Tioridazina/efectos adversos , Tioridazina/farmacología
14.
Br J Cancer ; 86(9): 1401-10, 2002 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-11986771

RESUMEN

Antibody engineering has made it possible to design antibodies with optimal characteristics for delivery of radionuclides for tumour imaging and therapy. A humanised divalent-Fab' cross-linked with a bis-maleimide linker referred to as humanised divalent-Fab' maleimide was produced as a result of this design process. It is a humanised divalent antibody with no Fc, which can be produced in bacteria and has enhanced stability compared with F(ab')(2). Here we describe a clinical study in patients with colorectal cancer using humanised divalent-Fab' maleimide generated from the anti-carcinoembryonic antigen antibody A5B7 radiolabelled with iodine-131. Ten patients received an i.v. injection of iodine-131-labelled A5B7 humanised divalent-Fab' maleimide, and positive tumour images were obtained by gamma camera imaging in eight patients with known lesions, and one previously undetected lesion was identified. True negative results were obtained in two patients without tumour. Area under the curve analysis of serial blood gamma counting and gamma camera images showed a higher tumour to blood ratio compared to A5B7 mF(ab')(2) used previously in the clinic, implying this new molecule may be superior for radioimmunotherapy. MIRD dose calculations showed a relatively high radiation dose to the kidney, which may limit the amount of activity that could be administered in radioimmunotherapy. However the reduction in immunogenicity was also a major advantage for A5B7 humanised divalent-Fab' maleimide over murine versions of this antibody suggesting that humanised divalent-Fab' maleimide should be a useful vehicle for repeated therapies.


Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Fragmentos Fab de Inmunoglobulinas/administración & dosificación , Maleimidas/farmacocinética , Área Bajo la Curva , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/patología , Semivida , Humanos , Maleimidas/administración & dosificación , Radioinmunoterapia/métodos , Cintigrafía
15.
Vet Pathol ; 39(3): 353-62, 2002 May.
Artículo en Inglés | MEDLINE | ID: mdl-12014499

RESUMEN

The pathogenesis of six pigeon-origin isolates of Newcastle disease virus (NDV) was investigated in chickens. Four isolates were previously defined as the variant pigeon paramyxovirus 1 (PPMV-1), and two isolates were classified as avian paramyxovirus 1 (APMV-1). Birds inoculated with PPMV-1 isolates were euthanatized, and tissue samples were collected at 2, 5, and 10 days postinoculation (DPI). Birds inoculated with APMV-1 isolates died or were euthanatized, and tissue samples were collected at 2, 4, and 5 DPI. Tissues were examined by histopathology, immunohistochemistry (IHC) for the presence of NDV nucleoprotein, and in situ hybridization (ISH) for the presence of viral mRNA for the matrix gene. Spleen sections were stained by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay and by IHC using an anti-active caspase-3 antibody (IHC-Casp) to detect apoptotic cells. Brain sections of PPMV-1-infected birds were examined by IHC to detect T and B lymphocytes and glial fibrillary acidic protein (GFAP). Histologically, birds inoculated with PPMV-1 isolates had marked lesions in the heart and brain. Presence of viral nucleoprotein and viral mRNA in the affected tissues was confirmed by IHC and ISH, respectively. Numerous reactive astrocytes were observed in brain sections stained for GFAP Among all the isolates, the IHC-Casp demonstrated that apoptosis was very prominent in the ellipsoid-associated cells of the spleen at 2 DPI. Results of the TUNEL assay indicated that apoptotic cells were prominent at 5 DPI and were more randomly distributed. The clinical signs and gross and histopathologic changes observed in the APMV-1-infected birds were characteristic of an extensive infection with highly virulent NDV evident by IHC.


Asunto(s)
Pollos/virología , Columbidae/virología , Enfermedad de Newcastle/virología , Virus de la Enfermedad de Newcastle/patogenicidad , Animales , Apoptosis , Encéfalo/patología , Encéfalo/virología , Embrión de Pollo , Proteína Ácida Fibrilar de la Glía/metabolismo , Corazón/virología , Inmunohistoquímica/veterinaria , Hibridación in Situ/veterinaria , Etiquetado Corte-Fin in Situ/veterinaria , Enfermedad de Newcastle/patología , Virus de la Enfermedad de Newcastle/clasificación , Virus de la Enfermedad de Newcastle/genética , Proteínas de la Nucleocápside , Nucleoproteínas/metabolismo , ARN Viral/química , ARN Viral/genética , Organismos Libres de Patógenos Específicos , Bazo/patología , Bazo/virología , Proteínas Virales/metabolismo
16.
Acta Crystallogr D Biol Crystallogr ; 58(Pt 2): 233-41, 2002 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11807247

RESUMEN

Mucosal addressin cell-adhesion molecule (MAdCAM-1) is a membrane-bound leukocyte receptor regulating both the passage and retention of leukocytes in mucosal tissues. A crystal structure for the two extracellular amino-terminal domains of human MAdCAM-1 has previously been reported, confirming their expected immunoglobulin superfamily topology. In this study, a second crystal structure of this fragment is described. Although the overall structure is similar to that previously reported, one edge strand in the amino-terminal domain is instead located on the opposite sheet. This alters the arrangement and conformation of amino acids in this region that have previously been shown to be crucial for ligand binding. MAdCAM-1 is also seen to form dimers within the crystal lattice, raising the possibility that oligomerization may influence the biological role of this adhesion molecule.


Asunto(s)
Inmunoglobulinas/química , Inmunoglobulinas/metabolismo , Integrinas/metabolismo , Mucoproteínas/química , Mucoproteínas/metabolismo , Moléculas de Adhesión Celular , Cristalografía por Rayos X , Dimerización , Humanos , Inmunoglobulinas/genética , Modelos Moleculares , Mucoproteínas/genética , Conformación Proteica , Estructura Terciaria de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
17.
Clin Exp Immunol ; 126(2): 280-6, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11703372

RESUMEN

HIV-1 continually replicates in spite of long-term highly active anti-retroviral therapy (HAART) and therefore, it is conceivable that the low level, persistent viral activity could continue to stimulate the hosts immune system despite remaining below the detection limit of the current assays. In this study, we performed a longitudinal analysis of the CD8+ T-cell receptor Vbeta repertoire in HAART-treated and untreated HIV patients. HAART-mediated control of viremia, for up to 18 months, did not prevent similar perturbations within the CD8+ Vbeta repertoire in both study groups as defined by CDR3 spectratyping. Oligoclonal Vbeta expansions, with new dominant CDR3 lengths, were observed throughout the study period. Our findings are compatible with antigen-driven CD8+ immune responses to bursts of replication from a continuously changing viral reservoir, regardless of HAART-mediated suppression of HIV-1 viremia.


Asunto(s)
Terapia Antirretroviral Altamente Activa , Linfocitos T CD8-positivos/inmunología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/patología , Estudios de Casos y Controles , Regiones Determinantes de Complementariedad , Infecciones por VIH/patología , VIH-1 , Humanos , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Factores de Tiempo , Viremia/tratamiento farmacológico , Viremia/inmunología , Viremia/patología
18.
Clin Lab Med ; 21(3): 549-91, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11572141

RESUMEN

In the past 100 years, to our knowledge there have been approximately 12 events involving the intentional introduction of microbiologic agents into livestock and animal populations worldwide, of which three were World War I events in the United States. To the best of the authors' knowledge, there has been no recent intentional introduction of microbiologic agents (viruses or bacteria) into livestock and animal populations in the United States. The criminal or terrorist use of chemicals against animals and agriculture products have been more common. With the political, economic, and military new world order, however, the United States must maintain a vigilant posture. The framework for this vigilance must be an intelligence system sensitive to the needs of agriculture and a first-class animal disease diagnostic surveillance and response system.


Asunto(s)
Enfermedades de los Animales/epidemiología , Enfermedades de los Animales/patología , Bioterrorismo , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/patología , Agricultura , Enfermedades de los Animales/transmisión , Animales , Animales Domésticos , Enfermedades Transmisibles/transmisión , Humanos
19.
Clin Exp Immunol ; 125(3): 447-54, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11531953

RESUMEN

In this pilot study, we address the nature of the re-population of the T-cell compartment in HIV-1+ (Human Immunodeficiency Virus 1), vertically infected children placed on successful regimens of HAART (highly active anti-retroviral therapy) incorporating 2 NRTI and a protease inhibitor. The clonality of the T-cell compartment and the abundance of RTEs (Recent Thymic Emigrants) were determined 2 weeks before and 20 weeks after initiation of HAART in a subgroup of children taking part in the PENTA (Paediatric European Network for the Treatment of AIDS) 5 trial. Analysis of the clonality of the circulating T-cell compartment was assessed using CDR3 spectratyping and analysed using the Kolmogorov-Smirnov two sample test. This revealed that a high degree of T-cell clonal restriction still exists 5 months into therapy, despite the appearance of previously undetectable T-cell clones within the periphery. We detected no increase in RTE abundance in this 5 month period, as determined by PCR detection of TRECs (T-Cell Receptor Excision Circles). We conclude that the observed re-population of T cells within the periphery of treated children is heavily reliant upon the maintenance/expansion of pre-existing cells during the 5 month period immediately following the initiation of therapy.


Asunto(s)
Terapia Antirretroviral Altamente Activa , Infecciones por VIH/inmunología , Linfocitos T/inmunología , Adolescente , Niño , Preescolar , Ensayos Clínicos como Asunto , Regiones Determinantes de Complementariedad , Genes Codificadores de la Cadena beta de los Receptores de Linfocito T , Infecciones por VIH/transmisión , Humanos , Transmisión Vertical de Enfermedad Infecciosa , Recuento de Linfocitos , Proyectos Piloto , Linfocitos T/citología
20.
J Clin Microbiol ; 39(9): 3171-8, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11526146

RESUMEN

Newcastle disease virus (NDV) is an economically important pathogen of poultry that may cause clinical disease that ranges from a mild respiratory syndrome to a virulent form with high mortality, depending on an isolate's pathotype. Infections with virulent NDV strains are required to be reported by member nations to the Office of International Epizootes (OIE). The primary determinant for virulence among NDV isolates is the presence or absence of dibasic amino acids in the fusion (F) protein cleavage activation site. Along with biological virulence determinations as the definitive tests, OIE accepts reporting of the F protein cleavage site sequence of NDV isolates as a virulence criterion. Nucleotide sequence data for many NDV isolates recently isolated from infected chickens and other avian species worldwide have been deposited in GenBank. Consequently, viral genomic information surrounding the F protein cleavage site coding sequence was used to develop a heteroduplex mobility assay (HMA) to aid in further identification of molecular markers as predictors of NDV virulence. Using common vaccine strains as a reference, we were able to distinguish virulent viruses among NDV isolates that correlated with phylogenetic analysis of the nucleotide sequence. This technique was also used to examine NDV isolates not previously characterized. We were able to distinguish vaccine-like viruses from other isolates potentially virulent for chickens. This technique will help improve international harmonization of veterinary biologics as set forth by the OIE and the Veterinary International Cooperation on Harmonization of Technical Requirements of Veterinary Medicinal Products. Ultimately, the HMA could be used for initial screening among a large number of isolates and rapid identification of potentially virulent NDV that continue to threaten commercial poultry worldwide.


Asunto(s)
Análisis Heterodúplex/métodos , Enfermedad de Newcastle/diagnóstico , Virus de la Enfermedad de Newcastle/clasificación , Virus de la Enfermedad de Newcastle/genética , Proteínas Virales de Fusión/química , Secuencia de Aminoácidos , Animales , Aves , Pollos , Datos de Secuencia Molecular , Enfermedad de Newcastle/virología , Virus de la Enfermedad de Newcastle/aislamiento & purificación , Virus de la Enfermedad de Newcastle/patogenicidad , Filogenia , Análisis de Secuencia de ADN , Pavos , Proteínas Virales de Fusión/genética , Virulencia
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