33 results on '"Garton T"'
Search Results
2. On the Considerations of Using Near Real Time Data for Space Weather Hazard Forecasting
- Author
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Smith, A. W., primary, Forsyth, C., additional, Rae, I. J., additional, Garton, T. M., additional, Jackman, C. M., additional, Bakrania, M., additional, Shore, R. M., additional, Richardson, G. S., additional, Beggan, C. D., additional, Heyns, M. J., additional, Eastwood, J. P., additional, Thomson, A. W. P., additional, and Johnson, J. M., additional
- Published
- 2022
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3. Forecasting the Probability of Large Rates of Change of the Geomagnetic Field in the UK: Timescales, Horizons, and Thresholds
- Author
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Smith, A. W., primary, Forsyth, C., additional, Rae, I. J., additional, Garton, T. M., additional, Bloch, T., additional, Jackman, C. M., additional, and Bakrania, M., additional
- Published
- 2021
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4. Kronian Magnetospheric Reconnection Statistics Across Cassini’s Lifetime
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Garton, T. M., primary, Jackman, C. M., additional, and Smith, A. W., additional
- Published
- 2021
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5. The observational uncertainty of coronal hole boundaries in automated detection schemes
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Reiss, M. A. (Martin A.), Muglach, K. (Karin), Möstl, C. (Christian), Arge, C. N. (Charles N.), Bailey, R. (Rachel), Delouille, V. (Véronique), Garton, T. M. (Tadhg M.), Hamada, A. (Amr), Hofmeister, S. (Stefan), Illarionov, E. (Egor), Jarolim, R. (Robert), Kirk, M. S. (Michael S. F.), Kosovichev, A. (Alexander), Krista, L. (Larisza), Lee, S. (Sangwoo), Lowder, C. (Chris), MacNeice, P. J. (Peter J.), Veronig, A. (Astrid), C. I. (COSPAR ISWAT Coronal Hole Boundary Working Team), Reiss, M. A. (Martin A.), Muglach, K. (Karin), Möstl, C. (Christian), Arge, C. N. (Charles N.), Bailey, R. (Rachel), Delouille, V. (Véronique), Garton, T. M. (Tadhg M.), Hamada, A. (Amr), Hofmeister, S. (Stefan), Illarionov, E. (Egor), Jarolim, R. (Robert), Kirk, M. S. (Michael S. F.), Kosovichev, A. (Alexander), Krista, L. (Larisza), Lee, S. (Sangwoo), Lowder, C. (Chris), MacNeice, P. J. (Peter J.), Veronig, A. (Astrid), and C. I. (COSPAR ISWAT Coronal Hole Boundary Working Team)
- Abstract
Coronal holes are the observational manifestation of the solar magnetic field open to the heliosphere and are of pivotal importance for our understanding of the origin and acceleration of the solar wind. Observations from space missions such as the Solar Dynamics Observatory now allow us to study coronal holes in unprecedented detail. Instrumental effects and other factors, however, pose a challenge to automatically detect coronal holes in solar imagery. The science community addresses these challenges with different detection schemes. Until now, little attention has been paid to assessing the disagreement between these schemes. In this COSPAR ISWAT initiative, we present a comparison of nine automated detection schemes widely applied in solar and space science. We study, specifically, a prevailing coronal hole observed by the Atmospheric Imaging Assembly instrument on 2018 May 30. Our results indicate that the choice of detection scheme has a significant effect on the location of the coronal hole boundary. Physical properties in coronal holes such as the area, mean intensity, and mean magnetic field strength vary by a factor of up to 4.5 between the maximum and minimum values. We conclude that our findings are relevant for coronal hole research from the past decade, and are therefore of interest to the solar and space research community.
- Published
- 2021
6. Early Romanesque Sculpture in Apulia
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Garton, T. E. H.
- Subjects
708 - Published
- 1975
7. Long-term efficacy and safety of once-daily fosamprenavir 1400 mg boosted by ritonavir 100 mg: the BOLD100 study
- Author
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Blick, G, primary, Greiger-Zanlungo, P, additional, Gretz, S, additional, Han, J, additional, Dupree, D, additional, Garton, T, additional, Yau, L H, additional, Wine, B C, additional, and Pakes, G E, additional
- Published
- 2012
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8. Successful Use of Cidofovir in Treating AIDS-Related Cytomegalovirus Retinitis, Encephalitis, and Esophagitis
- Author
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LaGravinese L, Blick G, Hopkins U, and Garton T
- Subjects
business.industry ,Immunology ,medicine.disease ,Virology ,chemistry.chemical_compound ,Acquired immunodeficiency syndrome (AIDS) ,chemistry ,medicine ,Immunology and Allergy ,Cytomegalovirus retinitis ,business ,Esophagitis ,Encephalitis ,Cidofovir - Published
- 1997
9. Emotional stress and heart rate variability measures associated with cardiovascular risk in relocated katrina survivors.
- Author
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Tucker P, Pfefferbaum B, Jeon-Slaughter H, Khan Q, and Garton T
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- 2012
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10. The probable source of both the primary multidrug-resistant (MDR) HIV-1 strain found in a patient with rapid progression to AIDS and a second recombinant MDR strain found in a chronically HIV-1-infected patient.
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Blick G, Kagan RM, Coakley E, Petropoulos C, Maroldo L, Greiger-Zanlungo P, Gretz S, and Garton T
- Abstract
Background. Rapid progression to AIDS after acute infection with a multidrug-resistant (MDR), dual-tropic strain of human immunodeficiency virus type 1 (HIV-1) was reported in a New York City man (hereafter referred to as 'NYC') who has sex with men. The probable source of this HIV-1 (hereafter referred to as 'CT01') and the development of a recombinant MDR HIV-1 in the source's partner (hereafter referred to as 'CT02') are described.Methods. After identification of the epidemiological link of CT01 and CT02 to NYC, viral sequences and phenotypic analyses were compared. Confirmatory genotypic and phenotypic analyses, replicative capacity, and viral coreceptor use were assessed. Viral recombination was assessed using a sliding window technique and phylogenetic tree analysis.Results. NYC and CT01 were linked historically and epidemiologically and were genetically confirmed from CT01's samples acquired 2 days before and subsequent to the transmission event. Genotypic, recombination, and phylogenetic analyses suggest CT02 became superinfected by CT01 with subsequent production of a recombinant panresistant HIV-1.Conclusion. The probable source of a dual-tropic, MDR HIV-1 that was associated with rapid progression to AIDS is illustrated, suggesting progression was not explained by the HIV-1 variant alone. A probable second finding of a chronically infected host becoming superinfected with MDR HIV-1 with subsequent formation of a panresistant recombinant HIV-1 is described. This case illustrates the public health implications of unsafe sex between serodiscordant and seroconcordant partners. Copyright © 2007 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]
- Published
- 2007
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11. The growth of managed care: tracking the impact on audiology practices.
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Garton T
- Published
- 1999
12. Automated coronal hole identification via multi-thermal intensity segmentation
- Author
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Garton Tadhg M., Gallagher Peter T., and Murray Sophie A.
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Sun ,coronal holes ,algorithm ,corona ,solar wind ,Meteorology. Climatology ,QC851-999 - Abstract
Coronal holes (CH) are regions of open magnetic fields that appear as dark areas in the solar corona due to their low density and temperature compared to the surrounding quiet corona. To date, accurate identification and segmentation of CHs has been a difficult task due to their comparable intensity to local quiet Sun regions. Current segmentation methods typically rely on the use of single Extreme Ultra-Violet passband and magnetogram images to extract CH information. Here, the coronal hole identification via multi-thermal emission recognition algorithm (CHIMERA) is described, which analyses multi-thermal images from the atmospheric image assembly (AIA) onboard the solar dynamics observatory (SDO) to segment coronal hole boundaries by their intensity ratio across three passbands (171 Å, 193 Å, and 211 Å). The algorithm allows accurate extraction of CH boundaries and many of their properties, such as area, position, latitudinal and longitudinal width, and magnetic polarity of segmented CHs. From these properties, a clear linear relationship was identified between the duration of geomagnetic storms and coronal hole areas. CHIMERA can therefore form the basis of more accurate forecasting of the start and duration of geomagnetic storms.
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- 2018
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13. A Romanesque Doorway at Killaloe
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Garton, T., primary
- Published
- 1981
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14. Ependymal cells undergo astrocyte-like reactivity in response to neuroinflammation.
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Groh AMR, Caporicci-Dinucci N, Afanasiev E, Bigotte M, Lu B, Gertsvolf J, Smith MD, Garton T, Callahan-Martin L, Allot A, Hatrock DJ, Mamane V, Drake S, Tai H, Ding J, Fournier AE, Larochelle C, Calabresi PA, and Stratton JA
- Subjects
- Animals, Mice, Female, Neuroinflammatory Diseases pathology, Transcriptome, Astrocytes metabolism, Astrocytes pathology, Ependyma metabolism, Ependyma pathology, Mice, Inbred C57BL, Encephalomyelitis, Autoimmune, Experimental pathology, Encephalomyelitis, Autoimmune, Experimental metabolism, Encephalomyelitis, Autoimmune, Experimental immunology
- Abstract
Ependymal cells form a specialized brain-cerebrospinal fluid (CSF) interface and regulate local CSF microcirculation. It is becoming increasingly recognized that ependymal cells assume a reactive state in response to aging and disease, including conditions involving hypoxia, hydrocephalus, neurodegeneration, and neuroinflammation. Yet what transcriptional signatures govern these reactive states and whether this reactivity shares any similarities with classical descriptions of glial reactivity (i.e., in astrocytes) remain largely unexplored. Using single-cell transcriptomics, we interrogated this phenomenon by directly comparing the reactive ependymal cell transcriptome to the reactive astrocyte transcriptome using a well-established model of autoimmune-mediated neuroinflammation (MOG
35-55 EAE). In doing so, we unveiled core glial reactivity-associated genes that defined the reactive ependymal cell and astrocyte response to MOG35-55 EAE. Interestingly, known reactive astrocyte genes from other CNS injury/disease contexts were also up-regulated by MOG35-55 EAE ependymal cells, suggesting that this state may be conserved in response to a variety of pathologies. We were also able to recapitulate features of the reactive ependymal cell state acutely using a classic neuroinflammatory cocktail (IFNγ/LPS) both in vitro and in vivo. Taken together, by comparing reactive ependymal cells and astrocytes, we identified a conserved signature underlying glial reactivity that was present in several neuroinflammatory contexts. Future work will explore the mechanisms driving ependymal reactivity and assess downstream functional consequences., (© 2024 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)- Published
- 2024
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15. Neurodegeneration and demyelination in multiple sclerosis.
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Garton T, Gadani SP, Gill AJ, and Calabresi PA
- Abstract
Progressive multiple sclerosis (PMS) is an immune-initiated neurodegenerative condition that lacks effective therapies. Although peripheral immune infiltration is a hallmark of relapsing-remitting MS (RRMS), PMS is associated with chronic, tissue-restricted inflammation and disease-associated reactive glial states. The effector functions of disease-associated microglia, astrocytes, and oligodendrocyte lineage cells are beginning to be defined, and recent studies have made significant progress in uncovering their pathologic implications. In this review, we discuss the immune-glia interactions that underlie demyelination, failed remyelination, and neurodegeneration with a focus on PMS. We highlight the common and divergent immune mechanisms by which glial cells acquire disease-associated phenotypes. Finally, we discuss recent advances that have revealed promising novel therapeutic targets for the treatment of PMS and other neurodegenerative diseases., Competing Interests: Declaration of interests P.A.C. has received consulting fees from Eli Lilly and Novartis and is a PI on a grant to Johns Hopkins University from Genentech., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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16. The Effects of NLY01, a Novel Glucagon-Like Peptide-1 Receptor Agonist, on Cuprizone-Induced Demyelination and Remyelination: Challenges and Future Perspectives.
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Gharagozloo M, Galleguillos D, Jank L, Sotirchos ES, Smith MD, Garton T, Kumar S, Hussein O, Potluri S, Taylor M, Siu C, Mace JW, Dawson T, Dawson VL, Lee S, and Calabresi PA
- Subjects
- Mice, Animals, Cuprizone toxicity, Glucagon-Like Peptide-1 Receptor metabolism, Myelin Sheath, Disease Models, Animal, Mice, Inbred C57BL, Demyelinating Diseases chemically induced, Demyelinating Diseases drug therapy, Remyelination, Multiple Sclerosis metabolism
- Abstract
Recent evidence suggests that the glucagon-like peptide-1 receptor (GLP-1R) agonists have neuroprotective activities in the CNS in animal models of Parkinson's disease, Alzheimer's disease, and multiple sclerosis (MS). This study aimed to investigate whether a novel long-acting GLP-1R agonist, NLY01, could limit demyelination or improve remyelination as occurs in MS using the cuprizone (CPZ) mouse model. Herein, we assessed the expression of GLP-1R on oligodendrocytes in vitro and found that mature oligodendrocytes (Olig2
+ PDGFRa- ) express GLP-1R. We further confirmed this observation in the brain by immunohistochemistry and found that Olig2+ CC1+ cells express GLP-1R. We next administered NLY01 twice per week to C57B6 mice while on CPZ chow diet and found that NLY01 significantly reduced demyelination with greater weight loss than vehicle-treated controls. Because GLP-1R agonists are known to have anorexigenic effect, we then administered CPZ by oral gavage and treated the mice with NLY01 or vehicle to ensure the dose consistency of CPZ ingestion among mice. Using this modified approach, NLY01 was no longer effective in reducing demyelination of the corpus callosum (CC). We next sought to examine the effects of NLY01 treatment on remyelination after CPZ intoxication and during the recovery period using an adoptive transfer-CPZ (AT-CPZ) model. We found no significant differences between the NLY01 and vehicle groups in the amount of myelin or the number of mature oligodendrocytes in the CC. In summary, despite the promising anti-inflammatory and neuroprotective effects of GLP-1R agonists that have been previously described, our experiments provided no evidence to support a beneficial effect of NLY01 on limiting demyelination or enhancing remyelination. This information may be useful in selecting proper outcome measures in clinical trials of this promising class of drugs in MS., (© 2023. The American Society for Experimental Neurotherapeutics, Inc.)- Published
- 2023
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17. Distinct mechanisms of oligodendrocyte injury inform therapeutic interventions in multiple sclerosis.
- Author
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Garton T, Gill AJ, and Calabresi PA
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- Humans, Oligodendroglia physiology, Multiple Sclerosis
- Published
- 2022
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18. Complement component 3 from astrocytes mediates retinal ganglion cell loss during neuroinflammation.
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Gharagozloo M, Smith MD, Jin J, Garton T, Taylor M, Chao A, Meyers K, Kornberg MD, Zack DJ, Ohayon J, Calabresi BA, Reich DS, Eberhart CG, Pardo CA, Kemper C, Whartenby KA, and Calabresi PA
- Subjects
- Animals, Astrocytes immunology, Astrocytes metabolism, Encephalomyelitis, Autoimmune, Experimental immunology, Encephalomyelitis, Autoimmune, Experimental pathology, Humans, Mice, Multiple Sclerosis immunology, Nerve Degeneration immunology, Nerve Degeneration pathology, Neuroinflammatory Diseases immunology, Optic Nerve pathology, Optic Neuritis immunology, Optic Neuritis pathology, Complement C3 metabolism, Multiple Sclerosis pathology, Neuroinflammatory Diseases pathology, Retinal Ganglion Cells pathology
- Abstract
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) characterized by varying degrees of secondary neurodegeneration. Retinal ganglion cells (RGC) are lost in MS in association with optic neuritis but the mechanisms of neuronal injury remain unclear. Complement component C3 has been implicated in retinal and cerebral synaptic pathology that may precede neurodegeneration. Herein, we examined post-mortem MS retinas, and then used a mouse model, experimental autoimmune encephalomyelitis (EAE), to examine the role of C3 in the pathogenesis of RGC loss associated with optic neuritis. First, we show extensive C3 expression in astrocytes (C3
+ /GFAP+ cells) and significant RGC loss (RBPMS+ cells) in post-mortem retinas from people with MS compared to retinas from non-MS individuals. A patient with progressive MS with a remote history of optic neuritis showed marked reactive astrogliosis with C3 expression in the inner retina extending into deeper layers in the affected eye more than the unaffected eye. To study whether C3 mediates retinal degeneration, we utilized global C3-/- EAE mice and found that they had less RGC loss and partially preserved neurites in the retina compared with C3+/+ EAE mice. C3-/- EAE mice had fewer axonal swellings in the optic nerve, reflecting reduced axonal injury, but had no changes in demyelination or T cell infiltration into the CNS. Using a C3-tdTomato reporter mouse line, we show definitive evidence of C3 expression in astrocytes in the retina and optic nerves of EAE mice. Conditional deletion of C3 in astrocytes showed RGC protection replicating the effects seen in the global knockouts. These data implicate astrocyte C3 expression as a critical mediator of retinal neuronal pathology in EAE and MS, and are consistent with recent studies showing C3 gene variants are associated with faster rates of retinal neurodegeneration in human disease., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2021
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19. A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis.
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Absinta M, Maric D, Gharagozloo M, Garton T, Smith MD, Jin J, Fitzgerald KC, Song A, Liu P, Lin JP, Wu T, Johnson KR, McGavern DB, Schafer DP, Calabresi PA, and Reich DS
- Subjects
- Animals, Brain pathology, Complement C1q antagonists & inhibitors, Complement C1q metabolism, Encephalomyelitis, Autoimmune, Experimental pathology, Female, Humans, Inflammation pathology, Magnetic Resonance Imaging, Male, Mice, Mice, Inbred C57BL, Middle Aged, Multiple Sclerosis diagnostic imaging, RNA-Seq, Transcriptome, White Matter pathology, Astrocytes pathology, Lymphocytes pathology, Microglia pathology, Multiple Sclerosis pathology
- Abstract
Multiple sclerosis (MS) lesions that do not resolve in the months after they form harbour ongoing demyelination and axon degeneration, and are identifiable in vivo by their paramagnetic rims on MRI scans
1-3 . Here, to define mechanisms underlying this disabling, progressive neurodegenerative state4-6 and foster development of new therapeutic agents, we used MRI-informed single-nucleus RNA sequencing to profile the edge of demyelinated white matter lesions at various stages of inflammation. We uncovered notable glial and immune cell diversity, especially at the chronically inflamed lesion edge. We define 'microglia inflamed in MS' (MIMS) and 'astrocytes inflamed in MS', glial phenotypes that demonstrate neurodegenerative programming. The MIMS transcriptional profile overlaps with that of microglia in other neurodegenerative diseases, suggesting that primary and secondary neurodegeneration share common mechanisms and could benefit from similar therapeutic approaches. We identify complement component 1q (C1q) as a critical mediator of MIMS activation, validated immunohistochemically in MS tissue, genetically by microglia-specific C1q ablation in mice with experimental autoimmune encephalomyelitis, and therapeutically by treating chronic experimental autoimmune encephalomyelitis with C1q blockade. C1q inhibition is a potential therapeutic avenue to address chronic white matter inflammation, which could be monitored by longitudinal assessment of its dynamic biomarker, paramagnetic rim lesions, using advanced MRI methods., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)- Published
- 2021
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20. Therapeutic Potential of a Novel Glucagon-like Peptide-1 Receptor Agonist, NLY01, in Experimental Autoimmune Encephalomyelitis.
- Author
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Gharagozloo M, Smith MD, Sotirchos ES, Jin J, Meyers K, Taylor M, Garton T, Bannon R, Lord HN, Dawson TM, Dawson VL, Lee S, and Calabresi PA
- Subjects
- Animals, Encephalomyelitis, Autoimmune, Experimental metabolism, Female, Glucagon-Like Peptide-1 Receptor metabolism, Mice, Mice, Inbred C57BL, Neuroprotective Agents pharmacology, T-Lymphocytes drug effects, T-Lymphocytes immunology, T-Lymphocytes metabolism, Encephalomyelitis, Autoimmune, Experimental drug therapy, Encephalomyelitis, Autoimmune, Experimental immunology, Glucagon-Like Peptide-1 Receptor agonists, Glucagon-Like Peptide-1 Receptor immunology, Neuroprotective Agents therapeutic use
- Abstract
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), characterized by demyelination, gliosis, and neurodegeneration. While the currently available disease-modifying therapies effectively suppress the immune attack on the CNS, there are no therapies to date that directly mitigate neurodegeneration. Glucagon-like peptide-1 (GLP-1) is a small peptide hormone that maintains glucose homeostasis. A novel GLP-1 receptor (GLP-1R) agonist, NLY01, was recently shown to have neuroprotective effects in the animal models of Parkinson's disease and is now in a phase 2 clinical trial. In this study, we investigated the therapeutic potential of NLY01 in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Our data show that NLY01 delays the onset and attenuates the severity of EAE in a prevention paradigm, when given before disease onset. NLY01 inhibits the activation of immune cells in the spleen and reduces their trafficking into the CNS. In addition, we show that NLY01 suppresses the production of chemokines that are involved in leukocyte recruitment to the site of inflammation. The anti-inflammatory effect of NLY01 at the early stage of EAE may block the expression of the genes associated with neurotoxic astrocytes in the optic nerves, thereby preventing retinal ganglion cell (RGC) loss in the progressive stage of EAE. In the therapeutic paradigm, NLY01 significantly decreases the clinical score and second attack in a model of relapsing-remitting EAE. GLP-1R agonists may have dual efficacy in MS by suppressing peripheral and CNS inflammation, thereby limiting neuronal loss., (© 2021. The American Society for Experimental NeuroTherapeutics, Inc.)
- Published
- 2021
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21. Challenges for intraventricular hemorrhage research and emerging therapeutic targets.
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Garton T, Hua Y, Xiang J, Xi G, and Keep RF
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- Adult, Animals, Cerebral Hemorrhage complications, Cerebral Hemorrhage physiopathology, Deferoxamine therapeutic use, Humans, Infant, Infant, Premature, Cerebral Hemorrhage therapy, Iron Chelating Agents therapeutic use, Molecular Targeted Therapy
- Abstract
Introduction: Intraventricular hemorrhage (IVH) affects both premature infants and adults. In both demographics, it has high mortality and morbidity. There is no FDA approved therapy that improves neurological outcome in either population highlighting the need for additional focus on therapeutic targets and treatments emerging from preclinical studies. Areas covered: IVH induces both initial injury linked to the physical effects of the blood (mass effect) and secondary injury linked to the brain response to the hemorrhage. Preclinical studies have identified multiple secondary injury mechanisms following IVH, and particularly the role of blood components (e.g. hemoglobin, iron, thrombin). This review, with an emphasis on pre-clinical IVH research, highlights therapeutic targets and treatments that may be of use in prevention, acute care, or repair of damage. Expert opinion: An IVH is a potentially devastating event. Progress has been made in elucidating injury mechanisms, but this has still to translate to the clinic. Some pathways involved in injury also have beneficial effects (coagulation cascade/inflammation). A greater understanding of the downstream pathways involved in those pathways may allow therapeutic development. Iron chelation (deferoxamine) is in clinical trial for intracerebral hemorrhage and preclinical data suggest it may be a potential treatment for IVH.
- Published
- 2017
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22. CD163, a Hemoglobin/Haptoglobin Scavenger Receptor, After Intracerebral Hemorrhage: Functions in Microglia/Macrophages Versus Neurons.
- Author
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Garton T, Keep RF, Hua Y, and Xi G
- Subjects
- Humans, Antigens, CD metabolism, Antigens, Differentiation, Myelomonocytic metabolism, Cerebral Hemorrhage metabolism, Haptoglobins metabolism, Hemoglobins metabolism, Macrophages metabolism, Microglia metabolism, Neurons metabolism, Receptors, Cell Surface metabolism
- Published
- 2017
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23. Brain iron overload following intracranial haemorrhage.
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Garton T, Keep RF, Hua Y, and Xi G
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- Animals, Brain drug effects, Brain pathology, Homeostasis, Humans, Intracranial Hemorrhages metabolism, Intracranial Hemorrhages pathology, Intracranial Hemorrhages therapy, Iron Chelating Agents therapeutic use, Iron Overload drug therapy, Iron Overload metabolism, Iron Overload pathology, Prognosis, Brain metabolism, Intracranial Hemorrhages complications, Iron metabolism, Iron Overload etiology
- Abstract
Intracranial haemorrhages, including intracerebral haemorrhage (ICH), intraventricular haemorrhage (IVH) and subarachnoid haemorrhage (SAH), are leading causes of morbidity and mortality worldwide. In addition, haemorrhage contributes to tissue damage in traumatic brain injury (TBI). To date, efforts to treat the long-term consequences of cerebral haemorrhage have been unsatisfactory. Incident rates and mortality have not showed significant improvement in recent years. In terms of secondary damage following haemorrhage, it is becoming increasingly apparent that blood components are of integral importance, with haemoglobin-derived iron playing a major role. However, the damage caused by iron is complex and varied, and therefore, increased investigation into the mechanisms by which iron causes brain injury is required. As ICH, IVH, SAH and TBI are related, this review will discuss the role of iron in each, so that similarities in injury pathologies can be more easily identified. It summarises important components of normal brain iron homeostasis and analyses the existing evidence on iron-related brain injury mechanisms. It further discusses treatment options of particular promise., Competing Interests: Competing interests: None declared.
- Published
- 2016
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24. Intraventricular Hemorrhage: the Role of Blood Components in Secondary Injury and Hydrocephalus.
- Author
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Garton T, Keep RF, Wilkinson DA, Strahle JM, Hua Y, Garton HJ, and Xi G
- Subjects
- Humans, Hydrocephalus, Cerebral Hemorrhage
- Published
- 2016
- Full Text
- View/download PDF
25. Microglia/Macrophage Polarization After Experimental Intracerebral Hemorrhage.
- Author
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Zhao H, Garton T, Keep RF, Hua Y, and Xi G
- Subjects
- Animals, Humans, Cell Polarity, Cerebral Hemorrhage physiopathology, Macrophages physiology, Microglia physiology
- Published
- 2015
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26. Role of hemoglobin and iron in hydrocephalus after neonatal intraventricular hemorrhage.
- Author
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Strahle JM, Garton T, Bazzi AA, Kilaru H, Garton HJ, Maher CO, Muraszko KM, Keep RF, and Xi G
- Subjects
- Animals, Animals, Newborn, Blotting, Western, Cerebral Hemorrhage metabolism, Cerebral Hemorrhage physiopathology, Deferoxamine pharmacology, Disease Models, Animal, Heme Oxygenase-1 analysis, Heme Oxygenase-1 biosynthesis, Hemoglobins administration & dosage, Hydrocephalus metabolism, Hydrocephalus physiopathology, Immunohistochemistry, Injections, Intraventricular, Iron administration & dosage, Lateral Ventricles pathology, Male, Rats, Rats, Sprague-Dawley, Cerebral Hemorrhage complications, Hemoglobins toxicity, Hydrocephalus etiology, Iron toxicity
- Abstract
Background: Neonatal germinal matrix hemorrhage/intraventricular hemorrhage is common and often results in hydrocephalus. The pathogenesis of posthemorrhagic hydrocephalus is not fully understood., Objective: To explore the potential role of hemoglobin and iron released after hemorrhage., Methods: Artificial cerebrospinal fluid (aCSF), hemoglobin, or iron was injected into the right lateral ventricle of postnatal day-7 Sprague Dawley rats. Ventricle size, heme oxygenase-1 (HO-1) expression, and the presence of iron were evaluated 24 and 72 hours after injection. A subset of animals was treated with an iron chelator (deferoxamine) or vehicle for 24 hours after hemoglobin injection, and ventricle size and cell death were evaluated., Results: Intraventricular injection of hemoglobin and iron resulted in ventricular enlargement at 24 hours compared with the injection of aCSF. Protoporphyrin IX, the iron-deficient immediate heme precursor, did not result in ventricular enlargement after injection into the ventricle. HO-1, the enzyme that releases iron from heme, was increased in the hippocampus and cortex of hemoglobin-injected animals at 24 hours compared with aCSF-injected controls. Treatment with an iron chelator, deferoxamine, decreased hemoglobin-induced ventricular enlargement and cell death., Conclusion: Intraventricular injection of hemoglobin and iron can induce hydrocephalus. Treatment with an iron chelator reduced hemoglobin-induced ventricular enlargement. This has implications for the pathogenesis and treatment of posthemorrhagic hydrocephalus., Abbreviations: aCSF, artificial cerebrospinal fluidDAB, 3,3'-diaminobenzidine-4HClGMH-IVH, germinal matrix hemorrhage/intraventricular hemorrhageHO-1, heme oxygenase-1ICH, intracerebral hemorrhagePBS, phosphate-buffered salineSVZ, subventricular zoneTBST, tris-buffered saline with Tween 20.
- Published
- 2014
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27. Implementing a ward accreditation programme to drive improvements in infection prevention.
- Author
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Jones G, Brooks J, Garton T, and Aplin S
- Abstract
University Hospitals Southampton NHS Foundation Trust aspires to be a national leader in the reduction of healthcare associated infections (HCAIs). The need to further improve patient safety requires continual improvements in infection control practice in order to sustain high quality and safe patient care. To help achieve this, an infection prevention ward accreditation scheme was introduced across the trust in 2009. The accreditation scheme was initially based on the results of clinical wards'/areas' infection prevention audits, aiming to motivate wards to achieve success and support areas to identify and address gaps in compliance. The ward accreditation scheme acts as a certification of best practice and policy compliance related to reducing HCAIs. Since its introduction four years ago, the ward accreditation programme has been expanded and developed to incorporate other elements of infection prevention policy and practice and continues to be developed in order to drive the trust forward as leaders in infection prevention. The introduction and ongoing development of the accreditation scheme has encouraged healthy competition, aiding local ownership and driving forward improvements, and with this, the trust has significantly reduced infection rates over the last four years., Competing Interests: Declaration of conflicting interest: The author declares that there is no conflict of interest.
- Published
- 2014
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28. Effect of amusement park rides on programmable shunt valve settings.
- Author
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Strahle J, Collins K, Stetler WR Jr, Smith BW, Garton T, Garton C, Garton HJ, and Maher CO
- Subjects
- Child, Equipment Design, Gravitation, Humans, Risk Assessment, Acceleration adverse effects, Cerebrospinal Fluid Shunts adverse effects, Hydrocephalus surgery, Leisure Activities, Magnetic Fields adverse effects
- Abstract
Background: Magnetically programmable shunt valves are susceptible to environmental factors including magnetic fields and accelerative forces. It is unknown if rollercoasters with or without magnetic brakes or linear induction motors (LIMs) are capable of altering the setting of a programmable shunt valve., Methods: Two different valve types (type A, n = 10; type B, n = 9) were tested at varying resistance settings in 2 trials on 6 different amusement park rides including 2 rides with LIMs, 2 rides with magnetic brakes, and 2 rides without magnetic technology., Results: The performance level of valve type A and the setting of valve type B changed on rollercoasters with magnets (A = 2.5% [2/80]; B = 5.6% [4/72]) and without magnets (A = 7.5% [3/40]; B = 2.8% [1/36]). Neither valve setting changed when exposed to a Ferris wheel or during ambulation throughout the park., Conclusion: Magnetically programmable valves are susceptible to changes in pressure settings when exposed to amusement park rides with elevated vertical gravitational forces, irrespective of the presence of LIMs or magnetic brakes., (© 2013 S. Karger AG, Basel.)
- Published
- 2013
- Full Text
- View/download PDF
29. Nefazodone and cyp450 3a4 interactions with cyclosporine and tacrolimus1.
- Author
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Garton T
- Subjects
- Alanine Transaminase blood, Aspartate Aminotransferases blood, Cytochrome P-450 CYP3A, Drug Interactions, Hepatitis C surgery, Humans, Liver Transplantation immunology, Liver Transplantation psychology, Male, Piperazines, Substance-Related Disorders complications, Substance-Related Disorders drug therapy, Triazoles pharmacokinetics, Antidepressive Agents, Second-Generation adverse effects, Antidepressive Agents, Second-Generation therapeutic use, Cyclosporine therapeutic use, Cytochrome P-450 Enzyme System metabolism, Liver Transplantation physiology, Mixed Function Oxygenases metabolism, Tacrolimus therapeutic use, Triazoles adverse effects, Triazoles therapeutic use
- Published
- 2002
- Full Text
- View/download PDF
30. Successful resolution of progressive multifocal leukoencephalopathy after combination therapy with cidofovir and cytosine arabinoside.
- Author
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Blick G, Whiteside M, Griegor P, Hopkins U, Garton T, and LaGravinese L
- Subjects
- Adult, Cidofovir, Cytosine administration & dosage, Drug Therapy, Combination, Humans, Male, Antiviral Agents administration & dosage, Cytarabine administration & dosage, Cytosine analogs & derivatives, Leukoencephalopathy, Progressive Multifocal drug therapy, Organophosphonates, Organophosphorus Compounds administration & dosage
- Published
- 1998
- Full Text
- View/download PDF
31. Passive immunotherapy in advanced HIV infection and therapeutic plasmapheresis in asymptomatic HIV-positive individuals: a four-year clinical experience.
- Author
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Blick G, Scott WF, Crook SW, Buchanan S, Garton T, Hopkins U, Vadaboncoeur AM, Doolittle J, Bulcraig IA, Greiger-Zanlungo P, and Karpas A
- Subjects
- AIDS-Related Complex blood, AIDS-Related Complex therapy, Acquired Immunodeficiency Syndrome blood, Acquired Immunodeficiency Syndrome prevention & control, Adolescent, Adult, Blood Donors, Disease Progression, Female, HIV Infections blood, HIV Seropositivity blood, Humans, Male, Middle Aged, HIV Infections therapy, HIV Seropositivity therapy, HIV-1, Immunization, Passive, Plasmapheresis
- Abstract
We have been treating patients with advanced HIV disease using passive immunotherapy (PIT). Earlier studies of PIT which have been published concerned relatively short periods of treatment: our study is by far the longest and reports also on the long-term effects of plasmapheresis on healthy HIV-infected individuals. Fifty-nine patients with an average CD4+ T-cell count of 55 per cu.mm. at baseline were transfused at monthly intervals with 500 ml of hyperimmune plasma. No disease progression or death occurred among the 8 asymptomatic patients under the treatment, which lasted for 36.25 months on average. Seven of the 15 ARC patients progressed to AIDS but none died in an average period of 25.9 months. Seven of the 36 symptomatic AIDS patients with advanced disease died in an average period of 19.6 months. PIT appears to be nontoxic and to have beneficial effects lasting at least four years under continuous treatment. It probably delays disease progression in ARC and AIDS patients, and almost certainly does so in asymptomatic late HIV infection with a very low CD4+ T-cell count. None of the 51 donors suffered adverse effects, nor did any progress to ARC or AIDS in an average period of 30.1 months. Their laboratory parameters indicated a nearly stable condition: in particular, their average CD4+ T-cell count rose from 478 to 498. The study of our plasma donors indicated that repeated and frequent plasma donation by asymptomatic HIV-infected individuals could delay disease progression, although further studies are needed to investigate this.
- Published
- 1998
- Full Text
- View/download PDF
32. Successful use of cidofovir in treating AIDS-related cytomegalovirus retinitis, encephalitis, and esophagitis.
- Author
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Blick G, Garton T, Hopkins U, and LaGravinese L
- Subjects
- Adult, Cidofovir, Cytosine therapeutic use, Humans, Male, AIDS-Related Opportunistic Infections drug therapy, Antiviral Agents therapeutic use, Cytomegalovirus Infections drug therapy, Cytosine analogs & derivatives, Encephalitis, Viral drug therapy, Esophagitis drug therapy, Organophosphonates, Organophosphorus Compounds therapeutic use, Retinitis drug therapy
- Published
- 1997
- Full Text
- View/download PDF
33. Marketing health care: its untapped potential.
- Author
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Garton T
- Subjects
- Community-Institutional Relations, Health Services Needs and Demand economics, Public Opinion, Advertising, Hospital Administration, Public Relations
- Abstract
Hospitals should not equate marketing with Madison Avenue styled promotional campaigns. A neutral instrument, marketing offers a range of highly developed basic techniques of data gathering, data analysis, market segmentation, advertising research, and a host of others, from which hospitals can pick and choose to discover the needs and desires of the communities they serve and to better meet these needs and desires.
- Published
- 1978
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