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1.
Animal ; 14(2): 409-417, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31354111

ABSTRACT

Lameness is an important economic problem in the dairy sector, resulting in production loss and reduced welfare of dairy cows. Given the modern-day expansion of dairy herds, a tool to automatically detect lameness in real-time can therefore create added value for the farmer. The challenge in developing camera-based tools is that one system has to work for all the animals on the farm despite each animal having its own individual lameness response. Individualising these systems based on animal-level historical data is a way to achieve accurate monitoring on farm scale. The goal of this study is to optimise a lameness monitoring algorithm based on back posture values derived from a camera for individual cows by tuning the deviation thresholds and the quantity of the historical data being used. Back posture values from a sample of 209 Holstein Friesian cows in a large herd of over 2000 cows were collected during 15 months on a commercial dairy farm in Sweden. A historical data set of back posture values was generated for each cow to calculate an individual healthy reference per cow. For a gold standard reference, manual scoring of lameness based on the Sprecher scale was carried out weekly by a single skilled observer during the final 6 weeks of data collection. Using an individual threshold, deviations from the healthy reference were identified with a specificity of 82.3%, a sensitivity of 79%, an accuracy of 82%, and a precision of 36.1% when the length of the healthy reference window was not limited. When the length of the healthy reference window was varied between 30 and 250 days, it was observed that algorithm performance was maximised with a reference window of 200 days. This paper presents a high-performing lameness detection system and demonstrates the importance of the historical window length for healthy reference calculation in order to ensure the use of meaningful historical data in deviation detection algorithms.


Subject(s)
Algorithms , Cattle Diseases/diagnosis , Dairying/methods , Lameness, Animal/diagnosis , Animals , Cattle , Farms , Female , Gait , Posture , Sensitivity and Specificity , Sweden
2.
Animal ; 13(12): 3009-3017, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31516101

ABSTRACT

Economic pressures continue to mount on modern-day livestock farmers, forcing them to increase herds sizes in order to be commercially viable. The natural consequence of this is to drive the farmer and the animal further apart. However, closer attention to the animal not only positively impacts animal welfare and health but can also increase the capacity of the farmer to achieve a more sustainable production. State-of-the-art precision livestock farming (PLF) technology is one such means of bringing the animals closer to the farmer in the facing of expanding systems. Contrary to some current opinions, it can offer an alternative philosophy to 'farming by numbers'. This review addresses the key technology-oriented approaches to monitor animals and demonstrates how image and sound analyses can be used to build 'digital representations' of animals by giving an overview of some of the core concepts of PLF tool development and value discovery during PLF implementation. The key to developing such a representation is by measuring important behaviours and events in the livestock buildings. The application of image and sound can realise more advanced applications and has enormous potential in the industry. In the end, the importance lies in the accuracy of the developed PLF applications in the commercial farming system as this will also make the farmer embrace the technological development and ensure progress within the PLF field in favour of the livestock animals and their well-being.


Subject(s)
Animal Husbandry/methods , Farmers , Farms/economics , Livestock , Animal Husbandry/economics , Animal Welfare/standards , Animals , Farms/organization & administration , Humans
3.
Atmos Meas Tech ; 12(11): 6079-6089, 2019 Nov.
Article in English | MEDLINE | ID: mdl-32514321

ABSTRACT

In this work, a new commercially available, laser-based, and ultra-portable formaldehyde (HCHO) gas sensor is characterized, and its usefulness for monitoring HCHO mixing ratios in both indoor and outdoor environments is assessed. Stepped calibrations and intercomparison with well-established laser-induced fluorescence (LIF) instrumentation allow a performance evaluation of the absorption-based, mid-infrared HCHO sensor from Aeris Technologies, Inc. The Aeris sensor displays linear behavior (R2 > 0.940) when compared with LIF instruments from Harvard and NASA Goddard. A non-linear least-squares fitting algorithm developed independently of the sensor's manufacturer to fit the sensor's raw absorption data during post-processing further improves instrument performance. The 3σ limit of detection (LOD) for 2, 15, and 60 min integration times are 2190, 690, and 420 pptv HCHO, respectively, for mixing ratios reported in real-time, though the LOD improves to 1800, 570, and 300 pptv HCHO, respectively, during post-processing. Moreover, the accuracy of the sensor was found to be ±(10% + 0.3) ppbv when compared against LIF instrumentation sampling ambient air. This sub-ppbv precision and level of accuracy are sufficient for most HCHO levels measured in indoor and outdoor environments. While the compact Aeris sensor is currently not a replacement for the most sensitive research-grade instrumentation available, its usefulness for monitoring HCHO is clearly demonstrated.

4.
J Anim Sci ; 95(4): 1512-1520, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28464112

ABSTRACT

Footpad dermatitis and lameness are a major welfare concern in broiler chicken farming. In general, footpad lesions are linked to poor environmental conditions. Ulcers that arise from advanced lesions can negatively affect the gait of the birds, with effects on the animal welfare, including, in the worst cases, inability to reach the feed or water. In this study, the degree of footpad dermatitis and lameness was manually scored on 4 broiler farms across Europe, as part of an EU-wide welfare assessment program. The welfare of the chickens was assessed 3 times per production cycle (at wk 3, 4, and 5), scoring footpad dermatitis, lameness, and litter quality. In the same broiler farms, variables such as air temperature and relative humidity were automatically measured over the same period. These variables were combined into a widely accepted thermal comfort index and associated to upper and lower thresholds, which made it possible to quantify the percentage of time the birds spent out of the thermal comfort zone (POOC). The data was analyzed by combining data from the welfare assessments with environmental data collected by the automated monitoring systems. Considering the comparison between POOC classes, the highest probabilities of footpad dermatitis and lameness were obtained when POOC values exceeded the 70% threshold. Therefore, the analysis showed that footpad dermatitis and lameness were more frequent when the flock was exposed to poor environmental conditions for prolonged periods ( < 0.001). Since environmental conditions can be continuously measured, and the risk factor for footpad dermatitis and lameness increases with poor environmental conditions, there is the possibility to develop a detection and control system of severe lesions.


Subject(s)
Dermatitis/veterinary , Lameness, Animal/epidemiology , Poultry Diseases/epidemiology , Animal Husbandry , Animal Welfare , Animals , Causality , Chickens , Dermatitis/epidemiology , Environment , Europe , Humidity , Risk Factors , Temperature
5.
Public Health ; 140: 235-243, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27233353

ABSTRACT

OBJECTIVES: There have been increasing calls for more research on interventions to successfully translate evidence-based knowledge into improved health policy and practices. This paper reports on an exploratory study of knowledge translation interventions conducted with participants of global health meetings held in Bangladesh in 2012 and in South Africa in 2013. We measured stakeholders' uptake of evidence-based knowledge in terms of their translation of this knowledge into actions around public health policy and practice. The research sought to determine whether participants shared and used knowledge from the meetings to improve health policy and practices in their settings and the factors influencing sharing and use. STUDY DESIGN: An exploratory study employed quantitative and qualitative methods of online surveys and in-depth interviews to collect data from all meeting participants. METHODS: All participants in the Bangladesh and South Africa meetings were invited to complete an online survey during the meetings and over the following six weeks. Of 411 participants in the 2012 Bangladesh meeting, 148 participants from 22 countries completed the survey. Eleven of these respondents (from eight countries) were interviewed. Of the 436 participants in the 2013 South Africa meeting, 126 respondents from 33 countries completed an online survey; none of these respondents were interviewed. RESULTS: The analysis revealed that most respondents used new knowledge to advocate for policy change (2012: 65.5%; 2013: 67.5%) or improve service quality (2012: 60.1%; 2013: 70.6%). The type of knowledge that respondents most commonly shared was clinical or scientific information (2012: 79.1%; 2013: 66.7%) and country-specific information (2012: 73.0%; 2013: 71.4%). Most 2012 respondents shared knowledge because they thought it would be useful to a co-worker or colleague (79.7%). DISCUSSION: Findings on knowledge use and sharing suggest that most respondents saw themselves as knowledge brokers or intermediaries in a position to influence the translation of knowledge into action in health policy and practices in their countries. Results suggest that supporting knowledge brokers working in a local and regional context to spur change, as described in the paper, has the potential to improve health outcomes. Further research is needed to isolate specific interventions and their knowledge translation outcomes.


Subject(s)
Congresses as Topic , Global Health , Information Dissemination , Professional Role , Translational Research, Biomedical , Female , Health Policy , Humans , Infant Health , Infant, Newborn , Interprofessional Relations , Maternal Health , Maternal-Child Health Services , Pregnancy , Quality Improvement , Surveys and Questionnaires
6.
Gene Ther ; 22(3): 227-36, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25567537

ABSTRACT

Eradication of human immunodeficiency virus-1 (HIV-1) from an infected individual requires a means of inducing production of virus from latently infected cells and stimulating an immune response against the infected cells. We report the development of lentiviral vectors that transduce dendritic cells (DCs) to both induce production of virus from latently infected cells and stimulate antigen-specific cytotoxic T lymphocytes (CTLs). The vectors package Vpx, a lentiviral accessory protein that counteracts the SAMHD1-mediated block to DC transduction, allowing for long-term expression of vector-encoded proteins. The vectors encode influenza or HIV-1-derived epitopes fused via a self-cleaving peptide to CD40L that releases the peptide into the endoplasmic reticulum for entry into the antigen presentation pathway. Expression of CD40L caused transduced DCs to mature and produce Th1-skewing cytokines. The DCs presented antigen to CD8 T cells, enhancing antigen-specific CTLs. Coculture of the transduced DCs with latently infected cells induced high-level virus production, an effect that was mediated by tumor necrosis factor alpha. The ability of a DC vaccine to reactivate latent HIV-1 and stimulate an adaptive immune response provide a means to reduce the size of the latent reservoir in patients. This strategy can also be applied to develop DC vaccines for other diseases.


Subject(s)
AIDS Vaccines/immunology , HIV Infections/metabolism , HIV-1/physiology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Cytotoxic/immunology , AIDS Vaccines/genetics , CD40 Antigens/metabolism , Cells, Cultured , Dendritic Cells/immunology , Dendritic Cells/metabolism , Genetic Vectors/metabolism , Humans , Lentivirus/genetics , Viral Regulatory and Accessory Proteins/genetics , Viral Regulatory and Accessory Proteins/metabolism , Virus Latency
7.
Calcif Tissue Int ; 93(3): 241-8, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23756612

ABSTRACT

Bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) presents with necrotic bone in the mouth in the setting of BP exposure. It has been studied in cancer patients taking high-dose BP, but BRONJ has also been noted in patients taking lower-dose BP for osteoporosis. The purpose of this study was to characterize the phenotypes and outcomes in a large series of patients with osteoporosis and BRONJ in the setting of BP exposure. We conducted a retrospective case series. The sample was composed of subjects with BRONJ and osteoporosis. Subjects with a history of BP treatment for myeloma or metastatic cancer to the bones were excluded. Descriptive statistics were computed for the study variables. Ninety-one cases of BRONJ met the inclusion criteria. Subjects had a median age of 71 years and were predominantly female (94.5 %). The median time of BP exposure was 60 months (range 2-120). Most subjects were treated with alendronate (82.4 %). The mandible was involved more frequently (58.2 %) than the maxilla (37.3 %). Subjects commonly (65.9 %), but not universally, reported pain. For subjects with treatment outcome data (n = 0), most reported improvement (80.0 %). Although BRONJ is an uncommon condition, the absolute number of cases is fairly large due to the very large number of patients taking BPs for osteoporosis. The findings of this study confirm that BRONJ primarily affects the mandible, a substantial minority present without pain, and patients typically improve with treatment.


Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw/diagnosis , Diphosphonates/adverse effects , Osteoporosis/complications , Osteoporosis/drug therapy , Aged , Aged, 80 and over , Bisphosphonate-Associated Osteonecrosis of the Jaw/epidemiology , Cohort Studies , Female , Humans , Male , Mandible/drug effects , Middle Aged , Necrosis , Phenotype , Retrospective Studies , Risk Factors , Treatment Outcome
8.
Theriogenology ; 70(6): 871-9, 2008 Oct 01.
Article in English | MEDLINE | ID: mdl-18440627

ABSTRACT

This project examined reproductive characteristics of female and male Jackson's hartebeest (Alcelaphus buselaphus jacksoni), a subspecies that originates in Africa and is currently a model for studies of endangered hartebeest subspecies. Progestagen concentrations were measured in fecal samples collected thrice weekly for 1 year from three non-pregnant, adult females, in the Northern Hemisphere (31 degrees 37'N, 81 degrees 09'W). When their ovaries were active, the females exhibited regular luteal cycles with an overall mean (+/-S.D.) cycle length of 21.4+/-4.1 days (n=31 luteal phases). Peak luteal progestagen concentration was 1.73+/-0.63 microg/g, with a nadir concentration of 0.79+/-0.24 microg/g. Cyclic activity ceased from 6 April to 28 June, 7 April to 8 July, and from 18 February to 20 August, for the three females, respectively. During this acyclic period, mean progestagen concentration was 0.90+/-0.23 microg/g. Ejaculates were collected by electroejaculation from seven males throughout all seasons, with mean (+/-S.D.) 40+/-18% motility, 4.1+/-0.19 progressive motility (scale, 0-5), 1373+/-826x10(6) sperm/mL, and 42+/-28% morphologically normal sperm. These data characterized basic reproductive traits for Jackson's hartebeest and established the females as spontaneously ovulating and seasonally polyestrous when housed in the Northern Hemisphere, whereas males produced apparently viable sperm throughout the year.


Subject(s)
Antelopes/physiology , Reproduction/physiology , Seasons , Animals , Antelopes/blood , Estrous Cycle/blood , Female , Male , Progestins/analysis , Progestins/blood , Semen Analysis , Sexual Behavior, Animal/physiology
9.
Control Clin Trials ; 22(5): 573-92, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11578789

ABSTRACT

The Correction of Myopia Evaluation Trial (COMET) is a multicenter, randomized, double-masked, controlled clinical trial evaluating whether there is a difference in the progression of myopia between children wearing progressive addition lenses (PALs) versus conventional single vision lenses (SVLs), as measured by cycloplegic autorefraction. Axial length, measured by A-scan ultrasonography, is an additional outcome measure. To meet the recruitment goal of 450 participants, eligible children ages 6-11 years (inclusive) with myopia in both eyes (spherical equivalent between -1.25 diopters (D) and -4.50 D, astigmatism < or = 1.50 D, and anisometropia < 1.00 D) were recruited at four clinical centers between September 1997 and September 1998. Children who participated were assigned to receive PALs (Varilux Comfort with a +2.00 D addition) or SVLs. Measures include standardized cycloplegic autorefraction (Nidek ARK700A autorefractor), axial length (Sonomed A2500 ultrasound), subjective refraction (Marco TRS system), visual acuity (modified Early Treatment Diabetic Retinopathy Study protocol), accommodation (Canon R-1), and phoria (cover test and Maddox rod). Outcome measures are collected annually; adherence is assessed and prescriptions updated semiannually. Participants are being followed for at least 3 years. COMET enrolled 469 children. Their mean age is 9.3 years (range 6-11 years); 52% are female. COMET children are ethnically diverse, according to a self-report with 46% White, 26% African American, 14% Hispanic, and 8% Asian. Best-corrected visual acuity is better than 20/32 in both eyes. Baseline mean (+/-SD) cycloplegic refractive correction is -2.38 D (+/-0.81) in the right eye and -2.40 D (+/-0.82) in the left eye; mean (+/-SD) axial length is 24.1 mm (+/-0.7) in both eyes. Follow-up of these children will provide a first step in answering the important question of whether there are effective means to slow myopia progression. Study results should be applicable to a large proportion of children with myopia. The study will also provide useful information on myopia progression in children wearing conventional single vision lenses.


Subject(s)
Eyeglasses , Myopia/therapy , Child , Double-Blind Method , Female , Humans , Male , Quality Assurance, Health Care , Visual Acuity
10.
Eur J Immunol ; 31(6): 1876-82, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11433384

ABSTRACT

T cell development is characterized by the induction of apoptosis in most immature thymocytes and the rescue from apoptosis of a small proportion of cells by the process of positive selection.Up-regulation of the anti-apoptotic molecule Bcl-2 is associated with thymocytes undergoing positive selection and a bcl-2 transgene promotes the generation of mature T cells. In contrast,mice transgenic for the pro-apoptotic molecule Bax show impaired T cell maturation. We have used fetal thymic organ culture to determine the action of Bcl-2 and Bax on positive selection of thymocytes. Our data show that Bcl-2 and Bax do not alter the number of thymocytes positively selected by a defined peptide ligand. This implies that Bcl-2 and Bax alter the production of mature T cells in vivo by influencing thymocyte viability rather than by direct action on positive selection. It also presents a solution to the 'chicken-and-egg' scenario relating to Bcl-2 up-regulation and positive selection. The data suggest that the up-regulation of Bcl-2 associated with T cell maturation is a consequence of positive selection rather than a cause of it.


Subject(s)
Proto-Oncogene Proteins c-bcl-2/physiology , Proto-Oncogene Proteins/physiology , T-Lymphocytes/cytology , Animals , Cell Differentiation , Mice , Mice, Knockout , Mice, Transgenic , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-bcl-2/genetics , Time Factors , bcl-2-Associated X Protein
11.
Invest Ophthalmol Vis Sci ; 42(6): 1153-9, 2001 May.
Article in English | MEDLINE | ID: mdl-11328721

ABSTRACT

PURPOSE: In tree shrews, visual form deprivation induces myopia and tissue remodeling in the sclera, characterized by decreased levels of collagen and glycosaminoglycans (GAGs) and increased levels of matrix metalloproteinases (MMPs). Removal of the visual deprivation allows recovery. This study investigated whether these changes are accompanied by changes in steady state mRNA levels in the sclera. METHODS: Quantitative competitive reverse transcription-polymerase chain reaction (RT-PCR) was used to measure steady state levels of mRNA for collagen (alpha1(I) chain), decorin (core protein), gelatinase-A (MMP-2), stromelysin-1 (MMP-3), and a tissue inhibitor of metalloproteinase (TIMP-1) in the scleras of tree shrews that received either 11 days of monocular form deprivation (MD) or 11 days of MD followed by 4 days of recovery. A group of age-matched normal animals was also measured. RESULTS: After 11 days of MD, alpha1(I) collagen mRNA levels were 34% lower, and MMP-2 mRNA levels were 66% higher in the deprived eyes than in the control eyes. After 4 days of recovery, collagen mRNA levels were 33% higher, MMP-2 levels were 20% lower, and TIMP-1 levels were 43% higher in the recovering eyes than in the control eyes. Decorin and MMP-3 mRNA levels were not significantly different between the treated and control eyes after MD or after recovery. CONCLUSIONS: The tissue remodeling in mammalian sclera induced by altering the visual environment is accompanied by modulation of mRNA levels in the sclera. The levels of collagen and MMP-2 mRNA were modulated in a pattern generally consistent with observed changes in protein levels, suggesting that visual regulation of the levels of these scleral proteins may involve modulation of gene expression at the transcriptional level.


Subject(s)
Eye Proteins/genetics , Myopia/metabolism , RNA, Messenger/metabolism , Sclera/metabolism , Animals , Collagen/genetics , Collagen/metabolism , DNA Primers/chemistry , Decorin , Extracellular Matrix Proteins , Eye Proteins/metabolism , Light , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 3/genetics , Matrix Metalloproteinase 3/metabolism , Models, Animal , Myopia/etiology , Myopia/physiopathology , Proteoglycans/genetics , Proteoglycans/metabolism , RNA/isolation & purification , Reverse Transcriptase Polymerase Chain Reaction , Sensory Deprivation , Tissue Inhibitor of Metalloproteinase-1/genetics , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tupaiidae
12.
Biologist (London) ; 48(2): 87-90, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11313542

ABSTRACT

We live in an age of increasing emphasis of do-it-yourself, as a mere glance at the TV schedule will prove. Why not apply this same principle to your research? By becoming the guinea pig of your own experimentation you will be following a noble precedent--though maybe not a sane one!


Subject(s)
Human Experimentation/history , Animals , England , History, 20th Century , Humans , Patient Selection , Research Design , Science/history
13.
Syst Parasitol ; 48(1): 47-53, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11213203

ABSTRACT

A new species of isosporan (Apicomplexa: Eimeriidae) is reported from the Bali mynah Leucopsar rothschildi (Passeriformes: Sturnidae). Oöcysts of Isospora rothschildi n. sp. are spherical to subspherical, 22.3 x 21.6 (20-26 x 19-23) microm, with a shape index (length/width) of 1.03 (1.00-1.15). A micropyle and oöcyst residuum are absent, but one to many polar granules are present. Sporocysts are ovoidal, 15.9 x 10.6 (15-18 x 9.5-11) microm, with Stieda and substieda bodies and a shape index of 1.50 (1.39-1.65). Each sporocyst contains an ellipsoidal sporocyst residuum, 8.0 x 5.8 (6-11 x 5-8), and each sporozoite contains two refractile bodies. No correlation was found between the presence of coccidian oöcysts in the faeces of some of the birds and Atoxoplasma in blood smears.


Subject(s)
Animals, Zoo/parasitology , Birds/parasitology , Isospora/classification , Animals , Feces/parasitology , Isospora/isolation & purification , Species Specificity
14.
Clin Lab ; 46(9-10): 469-76, 2000.
Article in English | MEDLINE | ID: mdl-11034532

ABSTRACT

Thirty long-term, stable hemodialysis patients were followed 24 months to identify any predictable relationship between elevated serum cTnT values and the diagnosis of coronary artery disease and/or the occurrence of a cardiac death. Patients with a baseline cTnT value of >0.1 microg/L were at high risk for life-threatening cardiac events during the 2 years follow-up. With regard to predicting a cardiac event, cTnT has a specificity of 93.75% and sensitivity of 81.8% compared to cTnI whose specificity was 87.5% but sensitivity of between 9.1 and 18.2%. CK-MB was the most specific at 100% but had a low sensitivity of 9.1%. The hemodialysis process, while causing an increase in the serum levels of all the markers studied except CK, the increase only proved significant for cTnT. The only markers whose stratification remained consistent over the 2 years where cTnT and CK-MB, for all others a gain or lose was registered. Baseline stratification using cTnT with a cut-off value of >0.1 microg/L offers opportunities to select at risk hemodialysis patients for corrective cardiovascular intervention.


Subject(s)
Coronary Disease/diagnosis , Renal Dialysis/adverse effects , Troponin T/blood , Adult , Aged , Biomarkers/blood , Chronic Disease , Coronary Disease/etiology , Creatine Kinase/blood , Creatine Kinase, MB Form , Death , Female , Follow-Up Studies , Humans , Isoenzymes/blood , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , Middle Aged , Predictive Value of Tests , Regression Analysis , Risk Factors , Sensitivity and Specificity
15.
J Immunol ; 165(5): 2596-602, 2000 Sep 01.
Article in English | MEDLINE | ID: mdl-10946287

ABSTRACT

Complement receptor type 3 (CR3) present on macrophages is used by Mycobacterium tuberculosis as one of its major phagocytic receptors. In this study, we examined the in vivo significance of CR3-mediated phagocytosis on the pathogenesis of disease caused by M. tuberculosis. The outcome of tuberculous infection in mice deficient in the CD11b subunit of CR3 (CR3-/-) on a mixed 129SV and C57BL background and control wild-type counterparts was comparable with respect to survival, bacterial burden, granulomatous lesion development, and cytokine expression in the spleen and lungs. M. tuberculosis infection was also examined in CR3-/- mice on C57BL/6 and BALB/c backgrounds and was found to be similar. In conclusion, our results suggest that in the absence of CR3, M. tuberculosis is able to gain entry into host cells via alternative phagocytic receptors and establish infection. The data also indicate that absence of CR3 does not alter disease course in either the relatively resistant C57BL/6 or the relatively susceptible BALB/c strains of mice.


Subject(s)
Macrophage-1 Antigen/genetics , Mycobacterium tuberculosis/immunology , Tuberculosis/genetics , Tuberculosis/immunology , Animals , Cytokines/biosynthesis , Genetic Predisposition to Disease , Immunity, Innate , Immunologic Deficiency Syndromes/genetics , Immunologic Deficiency Syndromes/microbiology , Immunologic Deficiency Syndromes/mortality , Macrophages/immunology , Macrophages/metabolism , Macrophages/microbiology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Mycobacterium tuberculosis/pathogenicity , Phagocytosis/genetics , Phagocytosis/immunology , Species Specificity , Survival Analysis , Tuberculosis/microbiology , Tuberculosis/mortality , Virulence
16.
J Immunol ; 165(3): 1236-42, 2000 Aug 01.
Article in English | MEDLINE | ID: mdl-10903721

ABSTRACT

In this paper we show that the effects of transgenic coreceptor expression on thymocyte development depend on the onset of transgene expression. Thus, a CD8 transgene expressed on CD44+CD25+ (DN2) and CD44-CD25+ (DN3) cells causes a partial block at the stage when TCRbeta selection takes place and diminishes expansion at the subsequent developmental stages, resulting in increased DN3 and markedly reduced double-positive (DP) thymocyte numbers. This effect is evident on a polyclonal TCR repertoire as well as in TCR-transgenic mice (F5). By contrast, a CD8 transgene that leads to the same degree of overexpression on DP thymocytes, but is not expressed on double-negative subsets, has no effect on thymus size or composition. Therefore, the reduction of DP thymocyte numbers in CD8 TCRtg mice can be attributed to interferences at early developmental stages rather than to increased negative selection of DP cells.


Subject(s)
CD8 Antigens/biosynthesis , CD8 Antigens/genetics , Gene Expression Regulation/immunology , Receptors, Antigen, T-Cell, alpha-beta/antagonists & inhibitors , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Thymus Gland/immunology , Thymus Gland/metabolism , Transgenes/immunology , Animals , Cell Differentiation/genetics , Cell Differentiation/immunology , Cell Division/genetics , Cell Division/immunology , Crosses, Genetic , Flow Cytometry , Gene Rearrangement, beta-Chain T-Cell Antigen Receptor/immunology , Humans , Lymphocyte Count , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Mice, Knockout , Mice, Transgenic , Receptors, Antigen, T-Cell, alpha-beta/genetics , Receptors, Interleukin-2/biosynthesis , T-Lymphocyte Subsets/cytology , Thymus Gland/cytology
17.
Immunity ; 12(5): 537-46, 2000 May.
Article in English | MEDLINE | ID: mdl-10843386

ABSTRACT

The T lymphocyte-specific protein tyrosine kinase p56lck (Lck) is an essential component of the TCR-mediated signal transduction complex. Lck knockout mice have reduced numbers of double-positive thymocytes and very few mature single-positive cells, particularly of the CD4 lineage. Here we demonstrate the ability of a tetracycline-based tissue-specific inducible Lck transgene to restore expansion of early thymocytes and maturation of single-positive cells in Lckneg mice upon induction with doxycycline. Restoration of Lck expression is particularly important for positive selection to the CD4+ lineage but has a lesser impact on selection to the CD8+ lineage, suggesting activation of Lck is an important component of the signals involved in lineage choice during thymic differentiation.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Cell Lineage/immunology , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/immunology , Animals , CD4 Antigens , Cell Differentiation/immunology , Gene Expression Regulation/immunology , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/genetics , Mice , Mice, Knockout , Mice, Transgenic
18.
Eur J Immunol ; 30(2): 709-13, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10671231

ABSTRACT

Apoptosis plays a critical role in T cell development and thymic selection. Thymocytes which undergo antigen-induced negative selection have been demonstrated to die by apoptosis. Despite this, relatively little is known about the specific apoptotic pathway involved in negative selection. We have examined the role of cyclin-dependent kinase 2 (Cdk2), a key regulator of thymocyte apoptosis, in this process. Stimulation of thymocytes with cognate antigen leads to a large increase in Cdk2 kinase activity. We also show that pharmacological inhibitors of Cdk2 block thymocyte apoptosis in response to antigen. Our data show that Cdk2 activity is essential for the apoptotic pathway used in negative selection.


Subject(s)
Apoptosis/immunology , CDC2-CDC28 Kinases , Cyclin-Dependent Kinases/immunology , Protein Serine-Threonine Kinases/immunology , T-Lymphocytes/immunology , Thymus Gland/immunology , Animals , Cell Differentiation/immunology , Cyclin-Dependent Kinase 2 , Enzyme Activation/immunology , Lymphocyte Activation , Mice , Signal Transduction/immunology , Thymus Gland/cytology
19.
J Zoo Wildl Med ; 31(4): 570-5, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11428408

ABSTRACT

Six wild-caught, captive canyon tree frogs (Hyla arenicolor) purchased as a group and housed at the North Carolina Zoological Park were diagnosed with intradermal Hannemania mites, the first described infestation of this frog species by this mite. Typical gross lesions were orange-colored skin vesicles approximately 1 mm in diameter, predominantly located on the ventrum and ventral hind limbs. The larval mites had ovoid bodies approximately 44 microm in length and 240 microm in width. Three of the frogs died, and three became free of mites and pathologic changes after approximately 28 wk of treatment with transcutaneous ivermectin and manual mite removal. The frogs remained free of mites at a 1-yr recheck.


Subject(s)
Bufonidae/parasitology , Mite Infestations/veterinary , Trombiculidae , Animal Diseases/drug therapy , Animal Diseases/pathology , Animals , Fatal Outcome , Insecticides/therapeutic use , Ivermectin/therapeutic use , Mite Infestations/drug therapy , Mite Infestations/pathology , North Carolina , Skin/pathology
20.
Nat Genet ; 23(4): 457-61, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10581035

ABSTRACT

Locus control regions (LCRs) are gene regulatory elements in mammals that can overcome the highly repressive effects normally associated with heterochromatic transgene locations (for example the centromere) in mice. Deletion of essential LCR sequences renders the cognate gene susceptible to this form of repression, so a proportion of the cells from transgenic mice that would normally express the transgene are silenced-a phenomenon known as position effect variegation (PEV). We show here that PEV can also occur when the transgene is non-centromeric and that the extent of variegation can be developmentally regulated. Furthermore, by overexpressing a mammalian homologue (M31) of Drosophila melanogaster heterochromatin protein 1 (HP1; refs 7,8) in transgenic mouse lines that exhibit PEV, it is possible to modify the proportion of cells that silence the transgene in a dose-dependent manner. Thus, we show M31 overexpression to have two contrasting effects which are dependent on chromosomal context: (i) it enhanced PEV in those lines with centromeric or pericentromeric transgene locations; and (ii) it suppressed PEV when the transgene was non-centromeric. Our results indicate that components or modifiers of heterochromatin may have a chromosomal-context-dependent role in gene silencing and activation decisions in mammals.


Subject(s)
Chromosomal Proteins, Non-Histone/genetics , Amino Acid Sequence , Animals , CD2 Antigens/genetics , Chromobox Protein Homolog 5 , Drosophila melanogaster/genetics , Female , Gene Expression , Heterochromatin/genetics , Humans , Locus Control Region , Male , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Mice, Transgenic , Molecular Sequence Data , Phenotype , T-Lymphocytes/immunology
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