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1.
Data Brief ; 24: 103921, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31061862

ABSTRACT

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.
Article in English | MEDLINE | ID: mdl-31075554

ABSTRACT

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.


Subject(s)
Brain Injuries, Traumatic/diagnostic imaging , Brain/diagnostic imaging , Magnetic Resonance Imaging/trends , Brain/physiopathology , Brain Injuries, Traumatic/physiopathology , Child , Cross-Sectional Studies , Humans , Longitudinal Studies , Magnetic Resonance Imaging/methods
3.
Rev Sci Tech ; 35(1): 175-89, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27217177

ABSTRACT

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.


Subject(s)
Disease Outbreaks/veterinary , Foot-and-Mouth Disease Virus/genetics , Foot-and-Mouth Disease/virology , Genomics , Animals , Foot-and-Mouth Disease/prevention & control , Molecular Epidemiology
4.
Article in English | MEDLINE | ID: mdl-22365109

ABSTRACT

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.


Subject(s)
Docosahexaenoic Acids/blood , Fatty Acid Desaturases/metabolism , Fetus/metabolism , Linoleic Acid/blood , Placenta/metabolism , Adult , Docosahexaenoic Acids/metabolism , Fatty Acids, Omega-6/blood , Fatty Acids, Omega-6/metabolism , Female , Fetal Development , Humans , Pregnancy
5.
Avian Dis ; 52(2): 260-8, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18646455

ABSTRACT

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.


Subject(s)
Hemagglutinins, Viral/administration & dosage , Newcastle Disease/prevention & control , Newcastle disease virus/immunology , Viral Vaccines/immunology , Animals , Chick Embryo , Chickens , Dose-Response Relationship, Immunologic , Hemagglutination Inhibition Tests/veterinary , Hemagglutinins, Viral/analysis , Newcastle Disease/immunology , Newcastle Disease/virology , Newcastle disease virus/isolation & purification , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/analysis , Vaccines, Inactivated/immunology , Viral Vaccines/administration & dosage , Viral Vaccines/analysis
6.
Vet Pathol ; 43(6): 925-33, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17099149

ABSTRACT

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.


Subject(s)
Disease Outbreaks/veterinary , Newcastle Disease/epidemiology , Newcastle Disease/virology , Newcastle disease virus/pathogenicity , Poultry Diseases/virology , Animals , California/epidemiology , Chickens , Columbidae , Newcastle Disease/pathology , Poultry Diseases/epidemiology , Specific Pathogen-Free Organisms , Turkeys
7.
Vet Pathol ; 43(2): 168-78, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16537934

ABSTRACT

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.


Subject(s)
Newcastle Disease/pathology , Newcastle Disease/virology , Newcastle disease virus/classification , Newcastle disease virus/pathogenicity , Turkeys/virology , Animals , Cerebellum/pathology , Immunohistochemistry , In Situ Hybridization , Myocardium/pathology , Pancreas/pathology , Specific Pathogen-Free Organisms , Spleen/pathology , Virulence
8.
Int J Obstet Anesth ; 15(1): 59-62, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16256331

ABSTRACT

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.


Subject(s)
Anesthesia, General , Anesthesia, Obstetrical , Antipsychotic Agents/therapeutic use , Clozapine/therapeutic use , Pregnancy Complications/drug therapy , Schizophrenia/drug therapy , Adult , Antipsychotic Agents/adverse effects , Cesarean Section , Clozapine/adverse effects , Female , Humans , Infant, Newborn , Male , Pregnancy
9.
J Psychopharmacol ; 18(2): 156-72, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15260903

ABSTRACT

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.


Subject(s)
Acoustic Stimulation , Chlorpromazine/adverse effects , Eye Movements/drug effects , Risperidone/adverse effects , Sulpiride/analogs & derivatives , Sulpiride/adverse effects , Acoustic Stimulation/adverse effects , Administration, Oral , Adult , Akathisia, Drug-Induced/etiology , Amisulpride , Blood Pressure/drug effects , Blood Pressure/physiology , Chlorpromazine/administration & dosage , Chlorpromazine/pharmacokinetics , Controlled Clinical Trials as Topic , Demography , Double-Blind Method , Eye Movements/physiology , Humans , Male , Neuropsychological Tests , Photic Stimulation , Problem Solving/drug effects , Problem Solving/physiology , Reaction Time/drug effects , Reflex, Startle/drug effects , Reflex, Startle/physiology , Risperidone/administration & dosage , Risperidone/pharmacokinetics , Space Perception/drug effects , Space Perception/physiology , Sulpiride/administration & dosage , Verbal Behavior/drug effects , Verbal Behavior/physiology
10.
Dev Biol (Basel) ; 119: 165-70, 2004.
Article in English | MEDLINE | ID: mdl-15742628

ABSTRACT

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.


Subject(s)
Newcastle Disease/prevention & control , Newcastle disease virus/immunology , Vaccination/veterinary , Animals , Newcastle Disease/diagnosis , Newcastle disease virus/pathogenicity , Poultry , Reverse Transcriptase Polymerase Chain Reaction/veterinary , Vaccines, Attenuated , Vaccines, Inactivated , Viral Vaccines
11.
Radiat Prot Dosimetry ; 105(1-4): 421-5, 2003.
Article in English | MEDLINE | ID: mdl-14527001

ABSTRACT

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).


Subject(s)
Models, Biological , Models, Statistical , Radiation Protection/methods , Radioisotopes/analysis , Radioisotopes/pharmacokinetics , Radiometry/methods , Software , Computer Simulation , Humans , Radiation Dosage , Radiometry/standards , Software Design , United Kingdom
12.
Avian Dis ; 47(3 Suppl): 1047-50, 2003.
Article in English | MEDLINE | ID: mdl-14575108

ABSTRACT

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.


Subject(s)
Influenza A virus/immunology , Influenza in Birds/immunology , Newcastle Disease/immunology , Newcastle disease virus/immunology , Poultry Diseases/immunology , Vaccines, Synthetic/therapeutic use , Viral Vaccines/therapeutic use , Animals , Chick Embryo/virology , Chickens , Immunization/methods , Influenza in Birds/prevention & control , Newcastle Disease/prevention & control , Poultry Diseases/prevention & control , Specific Pathogen-Free Organisms
13.
J Psychopharmacol ; 16(4): 355-60, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12503835

ABSTRACT

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.


Subject(s)
Antipsychotic Agents/adverse effects , Heart Diseases/chemically induced , Heart Rate/drug effects , Pirenzepine/analogs & derivatives , Adult , Antipsychotic Agents/pharmacology , Benzodiazepines , Conscious Sedation , Double-Blind Method , Humans , Male , Neuropsychological Tests , Olanzapine , Pirenzepine/adverse effects , Pirenzepine/pharmacology , Predictive Value of Tests , Psychomotor Performance/drug effects , Reaction Time/drug effects , Risk Assessment , Risperidone/adverse effects , Risperidone/pharmacology , Thioridazine/adverse effects , Thioridazine/pharmacology
14.
Br J Cancer ; 86(9): 1401-10, 2002 May 06.
Article in English | MEDLINE | ID: mdl-11986771

ABSTRACT

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.


Subject(s)
Colorectal Neoplasms/drug therapy , Immunoglobulin Fab Fragments/administration & dosage , Maleimides/pharmacokinetics , Area Under Curve , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/pathology , Half-Life , Humans , Maleimides/administration & dosage , Radioimmunotherapy/methods , Radionuclide Imaging
15.
Vet Pathol ; 39(3): 353-62, 2002 May.
Article in English | MEDLINE | ID: mdl-12014499

ABSTRACT

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.


Subject(s)
Chickens/virology , Columbidae/virology , Newcastle Disease/virology , Newcastle disease virus/pathogenicity , Animals , Apoptosis , Brain/pathology , Brain/virology , Chick Embryo , Glial Fibrillary Acidic Protein/metabolism , Heart/virology , Immunohistochemistry/veterinary , In Situ Hybridization/veterinary , In Situ Nick-End Labeling/veterinary , Newcastle Disease/pathology , Newcastle disease virus/classification , Newcastle disease virus/genetics , Nucleocapsid Proteins , Nucleoproteins/metabolism , RNA, Viral/chemistry , RNA, Viral/genetics , Specific Pathogen-Free Organisms , Spleen/pathology , Spleen/virology , Viral Proteins/metabolism
16.
Acta Crystallogr D Biol Crystallogr ; 58(Pt 2): 233-41, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11807247

ABSTRACT

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.


Subject(s)
Immunoglobulins/chemistry , Immunoglobulins/metabolism , Integrins/metabolism , Mucoproteins/chemistry , Mucoproteins/metabolism , Cell Adhesion Molecules , Crystallography, X-Ray , Dimerization , Humans , Immunoglobulins/genetics , Models, Molecular , Mucoproteins/genetics , Protein Conformation , Protein Structure, Tertiary , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism
17.
Clin Exp Immunol ; 126(2): 280-6, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11703372

ABSTRACT

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.


Subject(s)
Antiretroviral Therapy, Highly Active , CD8-Positive T-Lymphocytes/immunology , HIV Infections/drug therapy , HIV Infections/immunology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/pathology , Case-Control Studies , Complementarity Determining Regions , HIV Infections/pathology , HIV-1 , Humans , Receptors, Antigen, T-Cell, alpha-beta/metabolism , Time Factors , Viremia/drug therapy , Viremia/immunology , Viremia/pathology
18.
Clin Lab Med ; 21(3): 549-91, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11572141

ABSTRACT

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.


Subject(s)
Animal Diseases/epidemiology , Animal Diseases/pathology , Bioterrorism , Communicable Diseases/epidemiology , Communicable Diseases/pathology , Agriculture , Animal Diseases/transmission , Animals , Animals, Domestic , Communicable Diseases/transmission , Humans
19.
Clin Exp Immunol ; 125(3): 447-54, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11531953

ABSTRACT

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.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/immunology , T-Lymphocytes/immunology , Adolescent , Child , Child, Preschool , Clinical Trials as Topic , Complementarity Determining Regions , Genes, T-Cell Receptor beta , HIV Infections/transmission , Humans , Infectious Disease Transmission, Vertical , Lymphocyte Count , Pilot Projects , T-Lymphocytes/cytology
20.
J Clin Microbiol ; 39(9): 3171-8, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11526146

ABSTRACT

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.


Subject(s)
Heteroduplex Analysis/methods , Newcastle Disease/diagnosis , Newcastle disease virus/classification , Newcastle disease virus/genetics , Viral Fusion Proteins/chemistry , Amino Acid Sequence , Animals , Birds , Chickens , Molecular Sequence Data , Newcastle Disease/virology , Newcastle disease virus/isolation & purification , Newcastle disease virus/pathogenicity , Phylogeny , Sequence Analysis, DNA , Turkeys , Viral Fusion Proteins/genetics , Virulence
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