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1.
Rev Sci Tech ; 40(2): 395-411, 2021 08.
Article in English | MEDLINE | ID: mdl-34542107

ABSTRACT

Rising per capita consumption, economic growth, and urbanisation, particularly in developing countries, have been driving an increased global demand for food. These changing socio-economic trends, which have greatly influenced changes in dietary patterns globally and, more specifically, have increased consumption of livestock products in developing countries, are expected to endure and to place new pressures on livestock-sector infrastructure and the delivery of veterinary services. This paper summarises current trade in meat and presents plausible projections for the future. It highlights the impact of animal disease on trade and considers the effect of ongoing disease outbreaks, particularly the outbreaks of African swine fever and COVID-19, on current and future trade dynamics. The authors analysed published statistics on the demand for, and international trade in, livestock products at national and regional levels and made projections of the same up to 2050, generated from an integrated model of the global agricultural and food system. The resulting analyses identified patterns of trade consistent with growing populations, increasing incomes and changing diets in developing countries. The analyses also pointed to slow expansion of livestock production, and the impacts of countries' disease status on livestock trade. For most of the livestock products analysed, economic model projections indicate increased consolidation of production and exports among a few countries. Marked increases in the trade in livestock products suggest a changing role for Veterinary Services in facilitating trade and extension in the years to come.


La demande mondiale en denrĆ©es alimentaires connaĆ®t une hausse continue sous l'effet conjuguĆ© de la progression de la consommation par habitant, de la croissance Ć©conomique et de l'urbanisation, en particulier dans les pays en dĆ©veloppement. Ces tendances socio-Ć©conomiques ont modifiĆ© les structures des rĆ©gimes alimentaires dans le monde, plus spĆ©cifiquement dans les pays en dĆ©veloppement oƃĀ¹ la consommation de denrĆ©es alimentaires d'origine animale s'est accrue, et elles vont trĆØs certainement perdurer et exercer de nouvelles pressions sur les infrastructures du secteur de l'Ć©levage comme sur les prestations de services vĆ©tĆ©rinaires. Les auteurs font une synthĆØse de l'Ć©tat actuel des Ć©changes internationaux de viande et prĆ©sentent quelques projections plausibles concernant l'avenir. Ils soulignent l'impact des maladies animales sur les Ć©changes et examinent les rĆ©percussions que les foyers actuels de maladies peuvent avoir sur les dynamiques actuelles et futures des Ć©changes, en citant la peste porcine africaine et l'Ć©pidĆ©mie de COVID-19 Ć  titre d'illustrations. Les auteurs analysent ensuite les statistiques publiĆ©es relatives Ć  la demande en produits issus de l'Ć©levage et aux Ć©changes internationaux de ces produits Ć  l'Ć©chelle nationale et rĆ©gionale, et prĆ©sentent leurs propres projections de ces tendances jusqu'en 2050, Ć©laborĆ©es Ć  partir d'un modĆØle intĆ©grĆ© du systĆØme agricole et alimentaire mondial. Les analyses qui en rĆ©sultent font apparaĆ®tre que les structures des Ć©changes Ć©volueront parallĆØlement Ć  la croissance dĆ©mographique, Ć  l'augmentation des revenus et aux modifications des rĆ©gimes alimentaires dans les pays en dĆ©veloppement. Les analyses relĆØvent Ć©galement une croissance lente de l'Ć©levage, ainsi que les consĆ©quences du statut sanitaire des pays sur les Ć©changes commerciaux. Pour la plupart des produits issus de l'Ć©levage pris en compte dans cette analyse, les projections du modĆØle Ć©conomique prĆ©voient une concentration accrue de la production et des exportations, dans un nombre limitĆ© de pays. Une augmentation marquĆ©e des Ć©changes de produits issus de l'Ć©levage devra s'accompagner d'une Ć©volution du rĆ“le des Services vĆ©tĆ©rinaires afin de faciliter les Ć©changes et de soutenir leur extension dans les annĆ©es Ć  venir.


El aumento del consumo per cĆ”pita, el crecimiento econĆ³mico y los procesos de urbanizaciĆ³n, especialmente en los paĆ­ses en desarrollo, han venido induciendo una mayor demanda mundial de alimentos. Estas tendencias socioeconĆ³micas han influido sobremanera en la evoluciĆ³n de los regĆ­menes alimentarios en todo el mundo y, mĆ”s concretamente, han llevado a un mayor consumo de productos ganaderos en los paĆ­ses en desarrollo. SegĆŗn apuntan las previsiones, esta evoluciĆ³n se prolongarĆ” en el tiempo y ejercerĆ” nuevas presiones sobre la infraestructura del sector pecuario y la prestaciĆ³n de servicios veterinarios. Los autores resumen la situaciĆ³n actual del comercio de productos cĆ”rnicos y presentan proyecciones plausibles de lo que puede deparar el futuro. Tras destacar el peso que tienen las enfermedades animales en el comercio, examinan los efectos de brotes infecciosos hoy en curso, en particular de peste porcina africana y COVID-19, sobre la dinĆ”mica actual y futura del comercio. Los autores analizaron las estadĆ­sticas publicadas sobre la demanda y el comercio internacional de productos procedentes de la ganaderĆ­a, por paĆ­ses y regiones, tras lo cual hicieron proyecciones del curso de estas tendencias hasta 2050, generadas a partir de un modelo integrado del sistema agrĆ­cola y alimentario mundial. Los anĆ”lisis resultantes depararon una configuraciĆ³n del comercio coherente con poblaciones cada vez mĆ”s numerosas, un creciente nivel de ingresos y cambios en el rĆ©gimen alimentario en los paĆ­ses en desarrollo. Los anĆ”lisis tambiĆ©n apuntaban a una lenta expansiĆ³n de la producciĆ³n pecuaria y ponĆ­an de relieve la influencia de la situaciĆ³n sanitaria de los paĆ­ses en el comercio de ganado. Para la mayorĆ­a de los productos ganaderos analizados, las proyecciones de los modelos econĆ³micos apuntaban a una mayor concentraciĆ³n en unos pocos paĆ­ses de la actividad de producciĆ³n y exportaciĆ³n. La marcada intensificaciĆ³n del comercio de productos ganaderos lleva a pensar en una evoluciĆ³n del papel de los Servicios Veterinarios para facilitar el comercio y su extensiĆ³n en los prĆ³ximos aƃĀ±os.


Subject(s)
African Swine Fever , COVID-19 , Swine Diseases , Animals , COVID-19/veterinary , Commerce , Developing Countries , Internationality , Livestock , SARS-CoV-2 , Swine
2.
World Dev ; 148: 105678, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34866757

ABSTRACT

The need for food systems to generate sustainable and equitable benefits for all is a global imperative. However, whilst ample evidence exists linking smallholder farmer coordination and aggregation (i.e. the collective transport and marketing of produce on behalf of multiple farmers) to improved market participation and farmer incomes, the extent to which interventions that aim to improve farmer market engagement may co-develop equitable consumer benefits remains uncertain. This challenge is pertinent to the horticultural systems of South Asia, where the increasing purchasing power of urban consumers, lengthening urban catchments, underdeveloped rural infrastructures and inadequate local demands combine to undermine the delivery of fresh fruits and vegetables to smaller, often rural or semi-rural markets serving nutritionally insecure populations. To this end, we investigate the potential for aggregation to be developed to increase fruit and vegetable delivery to these neglected smaller markets, whilst simultaneously improving farmer returns. Using an innovative system dynamics modelling approach based on an aggregation scheme in Bihar, India, we identify potential trade-offs between outcomes relating to farmers and consumers in smaller local markets. We find that changes to aggregation alone (i.e. scaling-up participation; subsidising small market transportation; mandating quotas for smaller markets) are unable to achieve significant improvements in smaller market delivery without risking reduced farmer participation in aggregation. Contrastingly, combining aggregation with the introduction of market-based cold storage and measures that boost demand improves fruit and vegetable availability significantly in smaller markets, whilst avoiding farmer-facing trade-offs. Critically, our study emphasises the benefits that may be attained from combining multiple nutrition-sensitive market interventions, and stresses the need for policies that narrow the fruit and vegetable cold storage deficits that exist away from more lucrative markets in developing countries. The future pathways and policy options discovered work towards making win-win futures for farmers and disadvantaged consumers a reality.

3.
Food Microbiol ; 75: 103-113, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30056954

ABSTRACT

Economic impact assessments are increasingly important in the context of animal health and food safety, although much of the existing literature does not address the broader systems context in which disease transmission takes place. In this paper, we discuss the role of system dynamics modeling in addressing the value chain impacts associated with animal health and food safety issues. System dynamics methods hold promise as a means of capturing the complex feedbacks that exist between the biology, economics, and behavioral aspects of food safety and animal health systems. We provide a proof-of-concept of this approach in the context of food safety and animal health in the smallholder pig sector of Viet Nam. Results highlight the important tradeoffs that exist between policy objectives and the costs required to achieve them.


Subject(s)
Food Chain , Meat/analysis , Swine/physiology , Animal Husbandry , Animals , Food Contamination/prevention & control , Food Safety , Health , Humans , Swine/growth & development , Vietnam
4.
Food Microbiol ; 75: 114-118, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30056955

ABSTRACT

This paper summarizes the gaps and challenges related to animal production, health, and food safety as discussed by a panel at the 1st International Symposium of Food Safety (ISFS) in Santiago, Chile, in December 2016. Participating representatives of academia, industry, and government and statements from the audience confirmed that food safety is essential for increasing food security. First, panelists identified the need for a science-based regulatory framework to implement effective regulations. Second, they highlighted the importance of a risk analysis framework to quantify the risk of the potential for antimicrobial resistance associated with the use of antimicrobials, and the need of studies to evaluate foodborne prevention/control strategies. Third, the challenges of filling the gaps between industry and academia were addressed, including examples of successful collaboration, opportunities, and weakness identified by industry. Finally, challenges in animal food production included issues related to changing consumer preferences, animal welfare, the use of antimicrobials, and sustainable animal production. The symposium provided a regional platform to share experiences from the implementation of methods and approaches for food safety. The roundtable successfully explored the future science and technology challenges that are of strategic importance for Chile and the region in animal health and food safety.


Subject(s)
Animal Husbandry/standards , Food Safety , Livestock/growth & development , Animal Feed/analysis , Animal Husbandry/legislation & jurisprudence , Animal Husbandry/methods , Animals , Consumer Product Safety/legislation & jurisprudence , Food Industry/legislation & jurisprudence , Food Industry/standards , Health , Humans , Livestock/physiology
5.
Rev Sci Tech ; 36(1): 115-124, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28926022

ABSTRACT

Animal disease outbreaks generate a range of economic and non-economic impacts. While a significant number of research studies have estimated the effects of various diseases in a variety of contexts, examining the differential impacts and implications associated with the introduction of a novel disease into a developing country, as opposed to a developed one, is a rich area for further research. In this paper, the authors highlight some of the key dimensions and implications associated with the impacts of new diseases, how they differ in different contexts, and their implications for public policy.


La survenue de foyers de maladies animales entraĆ®ne des effets divers, de nature Ć©conomique et non Ć©conomique. Si l'estimation de l'impact de nombreuses maladies dans diffĆ©rents contextes a fait l'objet de trĆØs nombreuses Ć©tudes, l'Ć©valuation diffĆ©rentielle de l'impact de l'introduction d'une maladie nouvelle dans un pays en dĆ©veloppement et de ses consĆ©quences, par opposition Ć  ce qu'ils seraient dans un pays dĆ©veloppĆ©, constitue un domaine de recherche au riche potentiel largement inexplorĆ©. Les auteurs mettent en avant les dimensions et consĆ©quences majeures de l'impact des maladies nouvelles et en soulignent les spĆ©cificitĆ©s selon les contextes ainsi que leurs consĆ©quences en termes de politiques publiques.


Los brotes de enfermedades animales traen consigo una serie de consecuencias de orden econĆ³mico y no econĆ³mico. Si bien ha habido numerosas investigaciones destinadas a evaluar los efectos de varias enfermedades en distintos contextos, el estudio del impacto y las repercusiones diferenciales que se siguen de la introducciĆ³n de una nueva enfermedad en un paĆ­s en desarrollo, por oposiciĆ³n a un paĆ­s desarrollado, constituye un prometedor Ć”mbito de investigaciĆ³n para el futuro. Los autores destacan algunas de las principales dimensiones y repercusiones ligadas a las consecuencias de nuevas enfermedades y examinan cĆ³mo difieren en funciĆ³n del contexto y cĆ³mo repercuten en las polĆ­ticas pĆŗblicas.


Subject(s)
Animal Diseases/economics , Developed Countries/economics , Developing Countries/economics , Animal Diseases/classification , Animals
6.
Rev Sci Tech ; 34(3): 923-38, 2015 Dec.
Article in English | MEDLINE | ID: mdl-27044162

ABSTRACT

In this paper, the authors review the impacts of diseases facing salmon aquaculture, drawing lessons from terrestrial animal diseases. They discuss the implementation of current control strategies, taking into account transmission patterns (vertical versus horizontal), disease reservoirs, and interactions with wild fish. In addition, the decision-making context of aquatic disease control and the institutional organisation of control strategies are considered, with particular emphasis on the roles and responsibilities of regulatory authorities and the private sector. Case studies on the emergence and control of infectious salmon anaemia worldwide and pancreas disease in Norway are used to examine some of the controversies that may influence decision making and provide lessons for the future.


Subject(s)
Aquaculture , Communicable Diseases, Emerging/veterinary , Fish Diseases/prevention & control , Animals , Communicable Diseases, Emerging/prevention & control , Global Health , Isavirus , Norway/epidemiology , Orthomyxoviridae Infections/epidemiology , Orthomyxoviridae Infections/veterinary , Orthomyxoviridae Infections/virology , Pancreatic Diseases/epidemiology , Pancreatic Diseases/veterinary , Salmon , Time Factors
7.
bioRxiv ; 2023 Oct 29.
Article in English | MEDLINE | ID: mdl-37961580

ABSTRACT

The neuromuscular junction (NMJ) is the linchpin of nerve-evoked muscle contraction. Broadly considered, the function of the NMJ is to transduce a nerve action potential into a muscle fiber action potential (MFAP). Efficient information transfer requires both cholinergic signaling, responsible for the generation of endplate potentials (EPPs), and excitation, the activation of postsynaptic voltage-gated sodium channels (Nav1.4) to trigger MFAPs. In contrast to the cholinergic apparatus, the signaling pathways that organize Nav1.4 and muscle fiber excitability are poorly characterized. Muscle-specific kinase (MuSK), in addition to its Ig1 domain-dependent role as an agrin-LRP4 receptor, is also a BMP co-receptor that binds BMPs via its Ig3 domain and shapes BMP-induced signaling and transcriptional output. Here we probed the function of the MuSK-BMP pathway at the NMJ using mice lacking the MuSK Ig3 domain ('ΔIg3-MuSK'). Synapses formed normally in ΔIg3-MuSK animals, but the postsynaptic apparatus was fragmented from the first weeks of life. Anatomical denervation was not observed at any age examined. Moreover, spontaneous and nerve-evoked acetylcholine release, AChR density, and endplate currents were comparable to WT. However, trains of nerve-evoked MFAPs in ΔIg3-MuSK muscle were abnormal as revealed by increased jitter and blocking in single fiber electromyography. Further, nerve-evoked compound muscle action potentials (CMAPs), as well as twitch and tetanic muscle torque force production, were also diminished. Finally, Nav1.4 levels were reduced at ΔIg3-MuSK synapses but not at the extrajunctional sarcolemma, indicating that the observed excitability defects are the result of impaired localization of this voltage-gated ion channel at the NMJ. We propose that MuSK plays two distinct roles at the NMJ: as an agrin-LRP4 receptor necessary for establishing and maintaining cholinergic signaling, and as a BMP co-receptor required for maintaining proper Nav1.4 density, nerve-evoked muscle excitability and force production. The MuSK-BMP pathway thus emerges as a target for modulating excitability and functional innervation, which are defective in conditions such as congenital myasthenic syndromes and aging.

8.
Science ; 248(4961): 1419-21, 1990 Jun 15.
Article in English | MEDLINE | ID: mdl-2356470

ABSTRACT

Systemically administered flunarizine enhanced neuronal survival in lumbar sensory ganglia in newborn rats after axotomy. Flunarizine-treated rats lost 71 percent fewer neurons than the untreated control rats at the end of 1 week. In cell culture, flunarizine at 30 to 40 microM also prevented neuronal death in nerve growth factor-dependent embryonic sensory and sympathetic neurons after the abrupt withdrawal of neurotrophic support. The drug may cause this effect by acting at an intracellular site, one distinct from its blockade of voltage-dependent calcium channels.


Subject(s)
Flunarizine/pharmacology , Nerve Growth Factors/pharmacology , Neurons/cytology , Animals , Animals, Newborn , Cell Survival/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Flunarizine/administration & dosage , Ganglia, Spinal/cytology , Ganglia, Spinal/embryology , Ganglia, Sympathetic/cytology , Ganglia, Sympathetic/embryology , Microscopy, Electron, Scanning , Nerve Crush , Nerve Growth Factors/administration & dosage , Neurons/drug effects , Rats , Sciatic Nerve/physiology , Sciatic Nerve/surgery
9.
Science ; 249(4976): 1574-7, 1990 Sep 28.
Article in English | MEDLINE | ID: mdl-2120774

ABSTRACT

The segment of the malarial circumsporozoite (CS) protein designated Region II is highly conserved among different malarial species. A similar sequence is also present in several other proteins, including thrombospondin, properdin, and a blood-stage antigen of Plasmodium falciparum. By means of peptides synthesized from sequences of the Plasmodium vivax CS protein in the vicinity of Region II, it was found that two overlapping 18- to 20-amino acid peptides promoted the adhesion of a variety of human hematopoietic cell lines. The amino acid sequence valine-threonine-cysteineglycine (VTCG), contained within this common motif, was shown to be the critical sequence for the observed cell-adhesive properties.


Subject(s)
Antigens, Protozoan/genetics , Cell Adhesion , Plasmodium falciparum/genetics , Plasmodium vivax/genetics , Protozoan Proteins/genetics , Amino Acid Sequence , Animals , Cell Line , Fluorescein-5-isothiocyanate , Fluoresceins , Fluorescent Dyes , Humans , Molecular Sequence Data , Peptides/chemical synthesis , Thiocyanates
10.
Infect Dis Obstet Gynecol ; 2009: 456717, 2009.
Article in English | MEDLINE | ID: mdl-19893751

ABSTRACT

OBJECTIVE: To assess clinical progression and inflammatory markers among women stopping or continuing antiretroviral therapy (ART) after pregnancy. METHODS: ART-naĆÆve women with CD4+ lymphocyte counts >350 cells/uL initiating ART during pregnancy had clinical events and laboratory markers compared over one year postpartum between those stopping (n = 59) or continuing (n = 147) ART. RESULTS: Slopes in CD4 count and HIV RNA did not differ between groups overall and in subsets of ZDV or combination therapy. The hazard ratio (HR) of a new class B event was 2.09 (95% CI 0.79-5.58) among women stopping ART, 1.24 (0.31-4.95) in those stopping ZDV, and 2.93 (0.64-13.36) among those stopping combination therapy. Women stopping ART had increased immune activation. No significant differences were seen in C-reactive protein, lipids, leptin, or interleukin-6. CONCLUSIONS: While changes in CD4 and HIV RNA levels over one year were similar between women stopping or continuing ART postpartum, higher immune activation among women stopping therapy requires further study.


Subject(s)
Anti-Retroviral Agents/administration & dosage , HIV Infections/drug therapy , HIV-1/growth & development , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy Complications, Infectious/drug therapy , Adult , Biomarkers/blood , CD4 Lymphocyte Count , Disease Progression , Female , HIV Infections/blood , HIV Infections/transmission , HIV Infections/virology , Humans , Logistic Models , Pregnancy , Pregnancy Complications, Infectious/virology , Prospective Studies , RNA, Viral/blood , Risk Factors , Viral Load , Zidovudine/administration & dosage
11.
Oncogene ; 26(18): 2563-73, 2007 Apr 19.
Article in English | MEDLINE | ID: mdl-17099729

ABSTRACT

Transglutaminase 2 (TG2, a.k.a. tissue transglutaminase) belongs to a family of transglutaminase enzymes that stabilize proteins by affecting covalent crosslinking via formation of amide bonds. Cell surface TG2 is directly involved as an adhesive receptor in cell-extracellular matrix (ECM) interactions. Here, we show that TG2 activity is elevated in glioblastomas compared with non-neoplastic brain. Immunofluorescent studies showed increased staining of fibronectin colocalized with TG2 in the ECM in glioblastomas. In addition, small clusters of invading human glioblastoma cells present in non-neoplastic brain parenchyma secrete high levels of TG2 and fibronectin that distinguish them from normal brain stroma. Downregulation of TG2 in U87MG glioblastoma cells with RNAi demonstrated decreased assembly of fibronectin in the ECM. Treatment with KCC009 blocked the remodeling of fibronectin in the ECM in glioblastomas in both in vitro and in vivo studies. KCC009 treatment in mice harboring orthotopic glioblastomas (DBT-FG) sensitized the tumors to N,N'-bis(2-chloroethyl)-N-nitrosourea chemotherapy, as measured by reduced bioluminescence, increased apoptosis and prolonged survival. The ability of KCC009 to interfere with the permissive remodeling of fibronectin in the ECM in glioblastomas suggests a novel target to enhance sensitivity to chemotherapy directed not only at the tumor mass, but also invading glioblastoma cells.


Subject(s)
Enzyme Inhibitors/pharmacology , Extracellular Matrix/drug effects , Fibronectins/metabolism , GTP-Binding Proteins/antagonists & inhibitors , Glioblastoma/drug therapy , Isoxazoles/pharmacology , Transglutaminases/antagonists & inhibitors , Animals , Brain/metabolism , Brain Neoplasms/drug therapy , Carmustine/pharmacology , Extracellular Matrix/metabolism , Female , Fluorescent Antibody Technique , GTP-Binding Proteins/metabolism , Humans , Mice , Mice, Inbred BALB C , Protein Glutamine gamma Glutamyltransferase 2 , RNA, Small Interfering/pharmacology , Survival Rate , Transglutaminases/metabolism , Tumor Cells, Cultured
12.
J Clin Invest ; 72(5): 1650-7, 1983 Nov.
Article in English | MEDLINE | ID: mdl-6605368

ABSTRACT

Immunological evaluations (lymphocyte markers, B cell differentiation, T cell function) were performed on peripheral blood mononuclear cells from four individuals with hyper IgM immunodeficiency. Number, proportion, and proliferation of T lymphocytes and T lymphocyte subpopulations were relatively normal in affected individuals. The percentage and number of B cells expressing surface IgM and IgD were either normal or elevated in both blood and lymph nodes. However, surface IgG- and IgA-bearing B lymphocytes were completely absent. In vitro stimulation of blood lymphocytes with both T cell-dependent and T-cell independent polyclonal B cell activators resulted in normal numbers of IgM plasma cells and IgM secretion in cultures, but failed to induce any IgG- or IgA-producing cells. This failure of isotype switching was intrinsic to the B cell population and did not involve aberrant T cell help or suppression. Therefore, individuals with this disorder possess an intrinsic B cell dysfunction that is not related to abnormal T cell regulation.


Subject(s)
B-Lymphocytes/immunology , Dysgammaglobulinemia/immunology , Hypergammaglobulinemia/immunology , Immunoglobulin M/immunology , Adolescent , Adult , Child , Child, Preschool , Humans , IgA Deficiency , IgG Deficiency , Lymphocyte Activation , Male , Plasma Cells/immunology , T-Lymphocytes/immunology
13.
J Clin Invest ; 66(2): 389-95, 1980 Aug.
Article in English | MEDLINE | ID: mdl-7400322

ABSTRACT

Transplantation of histocompatible allogeneic peripheral blood leukocytes resulted in successful reconstitution of an adenosine deaminase (ADA)-deficient, severe combined immune-deficient patient. Erythrocyte transfusions before the transplant were associated with a rise of serum immunoglobulin concentration to normal without improvement in T cell function. The patient received 5 x 10(7) peripheral blood mononuclear leukocytes/kg obtained from the histocompatible father by leukopheresis. 3 wk after the transplant the lymphocyte count, proportion of E rosetting lymphocytes, and the ADA content of the patient's mononuclear leukocytes became normal while the phytohemagglutinin-stimulated blastogenic responses improved and became normal 52 d after the transplant. Antibody response to diphtheria immunization and response to naturally acquired herpes simplex infection were normal while isohemagglutinins progressively increased. Immunization with a neoantigen, bacteriophage phiX 174, resulted in a small but definite antibody response but no amplification of the response after secondary immunization. A positive reaction to a skin test for Candida albicans developed. Erythrocyte deoxy ATP (dATP) concentration decreased during the course of erythrocyte transfusions. 9 mo after the transplant, the erythrocyte dATP was elevated to twice pretransfusion levels while mononuclear leukocyte dATP varied from normal to elevated during the first 4 mo of the posttransplant period, but remained normal during the last 8 mo. The improvement in immune function persisted during the 12-mo posttransplant observation period while the mononuclear leukocyte ADA concentration stabilized at approximately 0.25 of normal, which is similar to the enzyme activity of the donor cells. This in vivo study supports the hypothesis that lymphoid precursor cells are present in peripheral blood which may partially reconstitute an immune-deficient recipient.


Subject(s)
Adenosine Deaminase/deficiency , Immunologic Deficiency Syndromes/immunology , Leukocyte Transfusion , Nucleoside Deaminases/deficiency , Deoxyadenine Nucleotides/metabolism , Humans , Immunologic Deficiency Syndromes/therapy , Transplantation, Homologous
14.
Ann N Y Acad Sci ; 1097: 114-45, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17413016

ABSTRACT

It is widely believed that the path to early and effective treatment for Alzheimer's disease (AD) requires the development of early diagnostic markers that are both sensitive and specific. To this aim, using longitudinal study designs, we and others have examined magnetic resonance imaging (MRI), 2-fluoro-2-deoxy-d-glucose-positron emission tomography (FDG/PET), and cerebrospinal fluid (CSF) biomarkers in cognitively normal elderly (NL) subjects and in patients with mild cognitive impairment (MCI). Such investigations have led to the often replicated findings that structural evidence of hippocampal atrophy as determined by MRI, as well as metabolic evidence from FDG-PET scan of hippocampal damage, predicts the conversion from MCI to AD. In this article we present a growing body of evidence of even earlier diagnosis. Brain pathology can be detected in NL subjects and used to predict future transition to MCI. This prediction is enabled by examinations revealing reduced glucose metabolism in the hippocampal formation (hippocampus and entorhinal cortex [EC]) as well as by the rate of medial temporal lobe atrophy as determined by MRI. However, neither regional atrophy nor glucose metabolism reductions are specific for AD. These measures provide secondary not primary evidence for AD. Consequently, we will also summarize recent efforts to improve the diagnostic specificity by combining imaging with CSF biomarkers and most recently by evaluating amyloid imaging using PET. We conclude that the combined use of conventional imaging, that is MRI or FDG-PET, with selected CSF biomarkers incrementally contributes to the early and specific diagnosis of AD. Moreover, selected combinations of imaging and CSF biomarkers measures are of importance in monitoring the course of AD and thus relevant to evaluating clinical trials.


Subject(s)
Aging/genetics , Aging/pathology , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Brain/growth & development , Brain/pathology , Genomics , Alzheimer Disease/epidemiology , Animals , Apolipoproteins E/genetics , Brain/diagnostic imaging , Cognition Disorders/pathology , Humans , Magnetic Resonance Imaging , Positron-Emission Tomography , Risk Factors
15.
J Neurol ; 254(12): 1666-75, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17994313

ABSTRACT

Very little data exist to evaluate the value of longitudinal CSF biological markers for Alzheimer's disease (AD). Most studies indicate that tau and amyloid beta markers do not reflect disease progression. We now report on a longitudinal, three-time point, CSF Isoprostane (IsoP) and quantitative MRI study that examined 11 normal elderly (NL) volunteers and 6 Mild Cognitive Impairment (MCI) patients. After 4 years, all 6 MCI patients declined to AD and 2 of the NL subjects declined to MCI. At baseline and longitudinally, the MCI patients showed reduced delayed memory, increased IsoP levels, and reduced medial temporal lobe gray matter concentrations as compared to NL. A group comprised of all decliners to AD or to MCI (n = 8) was distinguished at baseline from the stable NL controls (n = 9) by IsoP with 100% accuracy.Moreover, both at baseline and longitudinally, the IsoP measures significantly improved the diagnostic and predictive outcomes of conventional memory testing and quantitative MRI measurements. These data indicate that IsoP is potentially useful for both the early detection of AD-related pathology and for monitoring the course of AD.


Subject(s)
Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/pathology , Isoprostanes/cerebrospinal fluid , Adult , Aged , Aged, 80 and over , Analysis of Variance , Atrophy , Brain Mapping , Cognition Disorders/cerebrospinal fluid , Cognition Disorders/pathology , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Predictive Value of Tests
16.
Vet Rec ; 160(7): 238-41, 2007 Feb 17.
Article in English | MEDLINE | ID: mdl-17308024

ABSTRACT

Foot-and-mouth disease (FMD) remains one of the most important livestock diseases of the world, given its highly infectious nature, its broad economic impacts on animal wellbeing and productivity, and its implications for successful access to domestic and export markets for livestock and products. The impacts of the disease vary markedly between developed and developing countries, and also within many developing countries. These differences in impact shape some markedly heterogeneous incentives for FMD control and eradication, which become of particular importance when setting priorities for poverty reduction in developing countries. Some consider that the benefits from FMD control accrue only to the better off in such societies and, as such, may not be a priority for investments targeted at poverty reduction. But is that view justified? Others see the control of FMD as a major development opportunity in a globalised environment. In this paper, Brian Perry and Karl Rich summarise the differential impacts of FMD and its control, and link these findings with the growing understanding of how the control of this globally important disease may contribute to the processes of pro-poor growth in certain countries of the developing world.


Subject(s)
Animal Husbandry/economics , Animal Husbandry/methods , Foot-and-Mouth Disease/prevention & control , International Cooperation , Poverty , Animal Welfare , Animals , Cattle , Communicable Disease Control/economics , Communicable Disease Control/organization & administration , Cost of Illness , Developing Countries , Foot-and-Mouth Disease/economics , Foot-and-Mouth Disease/epidemiology , Primary Prevention
17.
Neurobiol Aging ; 27(3): 394-401, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16125823

ABSTRACT

The diagnosis of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) is limited because it is based on non-specific behavioral and neuroimaging findings. The lesions of Alzheimer's disease: amyloid beta (Abeta) deposits, tau pathology and cellular oxidative damage, affect the hippocampus in the earlier stages causing memory impairment. In a 2-year longitudinal study of MCI patients and normal controls, we examined the hypothesis that cerebrospinal fluid (CSF) markers for these pathological features improve the diagnostic accuracy over memory and magnetic resonance imaging (MRI)-hippocampal volume evaluations. Relative to control, MCI patients showed decreased memory and hippocampal volumes and elevated CSF levels of hyperphosphorylated tau and isoprostane. These two CSF measures consistently improved the diagnostic accuracy over the memory measures and the isoprostane measure incremented the accuracy of the hippocampal volume achieving overall diagnostic accuracies of about 90%. Among MCI patients, over 2 years, longitudinal hippocampal volume losses were closely associated with increasing hyperphosphorylated tau and decreasing amyloid beta-42 levels. These results demonstrate that CSF biomarkers for AD contribute to the characterization of MCI.


Subject(s)
Alzheimer Disease/diagnosis , Amyloid beta-Peptides/cerebrospinal fluid , Cognition Disorders/diagnosis , Hippocampus/pathology , Isoprostanes/cerebrospinal fluid , Magnetic Resonance Imaging/methods , tau Proteins/cerebrospinal fluid , Aged , Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/complications , Biomarkers/cerebrospinal fluid , Cognition Disorders/cerebrospinal fluid , Cognition Disorders/etiology , Female , Humans , Image Enhancement/methods , Longitudinal Studies , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity
18.
J Clin Pathol ; 59(5): 489-91, 2006 May.
Article in English | MEDLINE | ID: mdl-16489175

ABSTRACT

AIMS: To test the hypothesis that artefact caused by postmortem off-gassing is at least partly responsible for the presence of gas within the vascular system and tissues of the cadaver following death associated with compressed air diving. METHODS: Controlled experiment sacrificing sheep after a period of simulated diving in a hyperbaric chamber and carrying out sequential postmortem computed tomography (CT) on the cadavers. RESULTS: All the subject sheep developed significant quantities of gas in the vascular system within 24 hours, as demonstrated by CT and necropsy, while the control animals did not. CONCLUSIONS: The presence of gas in the vascular system of human cadavers following diving associated fatalities is to be expected, and is not necessarily connected with gas embolism following pulmonary barotrauma, as has previously been claimed.


Subject(s)
Brain/diagnostic imaging , Diving/injuries , Embolism, Air/etiology , Intracranial Embolism/etiology , Tomography, X-Ray Computed , Animals , Artifacts , Autopsy , Diagnosis, Differential , Diving/adverse effects , Embolism, Air/diagnostic imaging , Humans , Intracranial Embolism/diagnostic imaging , Models, Animal , Postmortem Changes , Sheep , Time Factors
19.
Cancer Res ; 61(5): 1825-9, 2001 Mar 01.
Article in English | MEDLINE | ID: mdl-11280731

ABSTRACT

Oligodendrogliomas are the second most common type of glial neoplasm with distinct prognostic and therapeutic implications. Although refinements have led to improved clinical stratification, current grading schemes are still limited by subjective histopathological criteria. In this report, we have used oligonucleotide array technology to perform expression profiling in morphologically classic oligodendrogliomas. Expression information from approximately 1100 genes divided tumors into two molecularly distinct groups that corresponded exactly to their previously assigned histological grades. Subsequent gene clustering identified a subset of 196 transcripts showing a common, differential expression pattern between tumor grades. A number of these genes have been associated with the maintenance of cytoarchitecture, cellular differentiation and maturation, immunogenicity, and chemotherapeutic resistance. These results demonstrate the utility of gene expression profiling as an objective, ancillary tool for grading oligodendrogliomas and a potential approach for classifying diffuse gliomas where histological assessment may be difficult or ambiguous.


Subject(s)
Brain Neoplasms/genetics , Brain Neoplasms/pathology , Oligodendroglioma/genetics , Oligodendroglioma/pathology , Adult , Aged , Brain Neoplasms/classification , Cluster Analysis , Female , Gene Expression , Gene Expression Profiling , Humans , Male , Middle Aged , Oligodendroglioma/classification , Oligonucleotide Array Sequence Analysis , World Health Organization
20.
Cancer Res ; 41(11 Pt 1): 4226-36, 1981 Nov.
Article in English | MEDLINE | ID: mdl-6272967

ABSTRACT

Multiple methods, pedigree analysis, clinical evaluation, and Epstein-Barr virus (EBV)-specific serology, EBV DNA hybridization of tissues to probe for viral genome, staining of touch imprints for EBV nuclear-associated antigen, establishment of spontaneous infected B-cell lines from peripheral blood or tissues, examination of peripheral blood smears, and hematopathology studies, were used to study seven patients with the X-linked lymphoproliferative syndrome and seven additional patients with life-threatening EBV-associated diseases. These studies demonstrated EBV in the tissues of all 14 patients and immunodeficient antibody responses to EBV were documented. This virus can produce various life-threatening lymphoproliferative diseases in a variety of immunodeficient patients.


Subject(s)
Antibodies, Viral/analysis , Herpesvirus 4, Human/immunology , Immunologic Deficiency Syndromes/microbiology , Lymphoproliferative Disorders/microbiology , Tumor Virus Infections/microbiology , Adolescent , Animals , Blood Cell Count , Cell Line , Child , Child, Preschool , Female , Herpesvirus 4, Human/genetics , Humans , Immunoglobulin A/analysis , Immunoglobulin G/analysis , Immunoglobulin M/analysis , Lymphoproliferative Disorders/genetics , Lymphoproliferative Disorders/immunology , Male , Phenotype , Photomicrography , Tumor Virus Infections/immunology , Tumor Virus Infections/mortality
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