45 results on '"Knight AG"'
Search Results
2. Recurrent intravascular papillary endothelial hyperplasia developing from a pyogenic granuloma
- Author
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Inaloz, HS, primary, Patel, G, additional, and Knight, AG, additional
- Published
- 2001
- Full Text
- View/download PDF
3. Malignant atrophic papulosis (Degos’ disease): clinicopathological correlations
- Author
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Chave, TA, primary, Varma, S, additional, Patel, GK, additional, and Knight, AG, additional
- Published
- 2001
- Full Text
- View/download PDF
4. Polypoid clear cell acanthoma: case report
- Author
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Inaloz, Hs, primary, Patel, G, additional, and Knight, Ag, additional
- Published
- 2000
- Full Text
- View/download PDF
5. Grenz ray treatment of recurrent herpes simplex
- Author
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Knight Ag
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,business.industry ,MEDLINE ,Follow up studies ,Herpes Simplex ,Radiotherapy Dosage ,Dermatology ,Text mining ,Chronic disease ,Recurrent herpes simplex ,Recurrence ,Chronic Disease ,Medicine ,Humans ,Female ,business ,Child ,Follow-Up Studies - Published
- 1972
6. Distinguishing Mechanisms for Reactive Uptake at Liquid Surfaces via Angular Distributions of Inelastically Scattered Molecules.
- Author
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Roman MJ, Knight AG, Moon DR, Lane PD, Costen ML, and McKendrick KG
- Abstract
Angular distributions of OH inelastically scattered from the surfaces of the reactive hydrocarbon liquids squalane (fully saturated) and squalene (partially unsaturated) have been measured. A pulsed, rotationally cold molecular beam ( E
i = 35 kJ mol-1 ) of OH was scattered from refreshed liquid surfaces in a vacuum. Spatially and temporally resolved OH number densities were measured by pulsed, planar laser-induced fluorescence. Results are compared with those for the inert liquid perfluoropolyether. The clearly asymmetric distributions for 45° incidence add to the weight of evidence for predominantly impulsive scattering from all three liquids. However, we propose that significant differences in their shapes may be diagnostic of contrasting reaction mechanisms. Direct, near-specular trajectories survive preferentially on squalene, consistent with an addition mechanism removing those at more backward angles. This trend is reversed for squalane, as expected for direct abstraction. The results reinforce the need to consider the effects of composition-dependent contributions from different reaction mechanisms in the modeling of OH-aging of atmospheric aerosol particles.- Published
- 2024
- Full Text
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7. Quantifying the dynamical information content of pulsed, planar laser-induced fluorescence measurements.
- Author
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Knight AG, Olivares CS, Roman MJ, Moon DR, Lane PD, Costen ML, and McKendrick KG
- Abstract
We have analyzed the effects of the spreads in experimental parameters on the reliability of speeds and angular distributions extracted from a generic surface-scattering experiment based on planar laser-induced fluorescence detection. The numerical model assumes a pulsed beam of projectile molecules is directed at a surface. The spatial distribution of the scattered products is detected by imaging the laser-induced fluorescence excited by a thin, pulsed sheet of laser light. Monte Carlo sampling is used to select from realistic distributions of the experimental parameters. The key parameter is found to be the molecular-beam diameter, expressed as a ratio to the measurement distance from the point of impact. Measured angular distributions are negligibly distorted when this ratio is <∼10%. Measured most-probable speeds are more tolerant, being undistorted when it is <∼20%. In contrast, the spread of speeds or of corresponding arrival times in the incident molecular beam has only very minor systematic effects. The thickness of the laser sheet is also unimportant within realistic practical limits. These conclusions are broadly applicable to experiments of this general type. In addition, we have analyzed the specific set of parameters designed to match the experiments on OH scattering from a liquid perfluoropolyether (PFPE) surface in the Paper I [Roman et al., J. Chem. Phys. 158, 244704 (2023)]. This reveals that the detailed form of the molecular-beam profile is important, particularly on apparent angular distributions, for geometric reasons that we explain. Empirical factors have been derived to correct for these effects., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)
- Published
- 2023
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8. Inelastic scattering of OH from a liquid PFPE surface: Resolution of correlated speed and angular distributions.
- Author
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Roman MJ, Knight AG, Moon DR, Lane PD, Greaves SJ, Costen ML, and McKendrick KG
- Abstract
Inelastic collisions of OH with an inert liquid perfluoropolyether (PFPE) surface have been studied experimentally. A pulsed molecular beam of OH with a kinetic energy distribution peaking at 35 kJ mol-1 was directed at a continually refreshed PFPE surface. OH molecules were detected state-selectively with spatial and temporal resolution by pulsed, planar laser-induced fluorescence. The scattered speed distributions were confirmed to be strongly superthermal, regardless of the incidence angle (0° or 45°). Angular scattering distributions were measured for the first time; their reliability was confirmed through extensive Monte Carlo simulations of experimental averaging effects, described in Paper II [A. G. Knight et al., J. Chem. Phys. 158, 244705 (2023)]. The distributions depend markedly on the incidence angle and are correlated with scattered OH speed, consistent with predominantly impulsive scattering. For 45° incidence, the angular distributions are distinctly asymmetric to the specular side but peak at sub-specular angles. This, along with the breadth of the distributions, is incompatible with scattering from a surface that is flat on a molecular scale. New molecular dynamics simulations corroborate the roughness of the PFPE surface. A subtle but unexpected systematic dependence of the angular distribution on the OH rotational state was found, which may be dynamical in origin. The OH angular distributions are similar to those for kinematically similar Ne scattering from PFPE and hence not strongly perturbed by OH being a linear rotor. The results here are broadly compatible with prior predictions from independent quasiclassical trajectory simulations of OH scattering from a model-fluorinated self-assembled monolayer surface., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)
- Published
- 2023
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9. Affect enhances object-background associations: evidence from behaviour and mathematical modelling.
- Author
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Madan CR, Knight AG, Kensinger EA, and Mickley Steinmetz KR
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- Adult, Cues, Emotions, Female, Humans, Male, Memory, Affect physiology, Mental Recall physiology, Models, Psychological, Models, Theoretical, Recognition, Psychology physiology
- Abstract
In recognition memory paradigms, emotional details are often recognised better than neutral ones, but at the cost of memory for peripheral details. We previously provided evidence that, when peripheral details must be recalled using central details as cues, peripheral details from emotional scenes are at least as likely to be recalled as those from neutral scenes. Here we replicated and explicated this result by implementing a mathematical modelling approach to disambiguate the influence of target type, scene emotionality, scene valence, and their interactions. After incidentally encoding scenes that included neutral backgrounds with a positive, negative, or neutral foreground objects, participants showed equal or better cued recall of components from emotional scenes compared to neutral scenes. There was no evidence of emotion-based impairment in cued recall in either of two experiments, including one in which we replicated the emotion-induced memory trade-off in recognition. Mathematical model fits indicated that the emotionality of the encoded scene was the primary driver of improved cued-recall performance. Thus, even when emotion impairs recognition of peripheral components of scenes, it can preserve the ability to recall which scene components were studied together.
- Published
- 2020
- Full Text
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10. Assessment of progressively delayed prompts on guided skill learning in rats.
- Author
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Reid AK, Futch SE, Ball KM, Knight AG, and Tucker M
- Subjects
- Animals, Rats, Learning, Reinforcement, Psychology
- Abstract
We examined the controlling factors that allow a prompted skill to become autonomous in a discrete-trials implementation of Touchette's (1971) progressively delayed prompting procedure, but our subjects were rats rather than children with disabilities. Our prompted skill was a left-right lever-press sequence guided by two panel lights. We manipulated (a) the effectiveness of the guiding lights prompt and (b) the presence or absence of a progressively delayed prompt in four groups of rats. The less effective prompt yielded greater autonomy than the more effective prompt. The ability of the progressively delayed prompt procedure to produce behavioral autonomy depended upon characteristics of the obtained delay (trial duration) rather than on the pending prompt. Sequence accuracy was reliably higher in unprompted trials than in prompted trials, and this difference was maintained in the 2 groups that received no prompts but yielded equivalent trial durations. Overall sequence accuracy decreased systematically as trial duration increased. Shorter trials and their greater accuracy were correlated with higher overall reinforcement rates for faster responding. Waiting for delayed prompts (even if no actual prompt was provided) was associated with lower overall reinforcement rate by decreasing accuracy and by lengthening trials. These findings extend results from previous studies regarding the controlling factors in delayed prompting procedures applied to children with disabilities.
- Published
- 2017
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11. Neutral details associated with emotional events are encoded: evidence from a cued recall paradigm.
- Author
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Mickley Steinmetz KR, Knight AG, and Kensinger EA
- Subjects
- Adolescent, Cues, Female, Humans, Male, Photic Stimulation, Young Adult, Emotions, Memory, Mental Recall
- Abstract
Enhanced emotional memory often comes at the cost of memory for surrounding background information. Narrowed-encoding theories suggest that this is due to narrowed attention for emotional information at encoding, leading to impaired encoding of background information. Recent work has suggested that an encoding-based theory may be insufficient. Here, we examined whether cued recall-instead of previously used recognition memory tasks-would reveal evidence that non-emotional information associated with emotional information was effectively encoded. Participants encoded positive, negative, or neutral objects on neutral backgrounds. At retrieval, they were given either the item or the background as a memory cue and were asked to recall the associated scene element. Counter to narrowed-encoding theories, emotional items were more likely than neutral items to trigger recall of the associated background. This finding suggests that there is a memory trace of this contextual information and that emotional cues may facilitate retrieval of this information.
- Published
- 2016
- Full Text
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12. Brain injury caused by HIV protease inhibitors: role of lipodystrophy and insulin resistance.
- Author
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Gupta S, Knight AG, Losso BY, Ingram DK, Keller JN, and Bruce-Keller AJ
- Subjects
- Animals, Cerebral Cortex drug effects, Cerebral Cortex pathology, HIV Protease Inhibitors administration & dosage, Hippocampus drug effects, Hippocampus pathology, Hyperlipidemias chemically induced, Lopinavir administration & dosage, Lopinavir adverse effects, Male, Mice, Mice, Inbred C57BL, Ritonavir administration & dosage, Ritonavir adverse effects, Brain Injuries chemically induced, HIV Protease Inhibitors adverse effects, Insulin Resistance, Lipodystrophy chemically induced
- Abstract
HIV-associated neurocognitive disorders (HAND) remain prevalent even with widespread use of combination antiretroviral therapy (ART), suggesting a potential role for co-morbidities in neurologic decline. Indeed, it is well established that ART drugs, particularly HIV protease inhibitors, can induce hyperlipidemia, lipodystrophy, and insulin resistance; all of which are associated with neurologic impairment. This study was designed to determine how metabolic dysfunction might contribute to cognitive impairment and to reveal specific metabolic co-morbidities that could be targeted to preserve brain function. Adult male C57BL/6 mice were thus treated with clinically relevant doses of lopinavir/ritonavir for 4 weeks, and subjected to thorough metabolic, neurobehavioral, and biochemical analyses. Data show that lopinavir/ritonavir resulted in manifestations of lipodystrophy, insulin resistance, and hyperlipidemia. Evaluation of neurologic function revealed cognitive impairment and increased learned helplessness, but not motor impairment following treatment with lopinavir/ritonavir. Further analyses revealed a significant linear relationship between cognitive performance and specific markers of lipodystrophy and insulin resistance. Finally, analysis of brain injury indicated that lopinavir/ritonavir treatment resulted in cerebrovascular injury associated with decreased synaptic markers and increased inflammation, and that the cerebral cortex was more vulnerable than the cerebellum or hippocampus. Collectively, these data reveal an intimate link between metabolic co-morbidities and cognitive impairment, and suggest that remediation of selective aspects of metabolic syndrome could potentially reduce the prevalence or severity HIV-associated neurocognitive disorders., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2012
- Full Text
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13. Saturated long-chain fatty acids activate inflammatory signaling in astrocytes.
- Author
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Gupta S, Knight AG, Gupta S, Keller JN, and Bruce-Keller AJ
- Subjects
- Animals, Animals, Newborn, Brain cytology, Cells, Cultured, Dose-Response Relationship, Drug, Drug Interactions, Enzyme Inhibitors pharmacology, Enzyme-Linked Immunosorbent Assay, Fatty Acids metabolism, Female, Gene Expression Regulation drug effects, Male, Oleic Acid pharmacology, Palmitic Acid pharmacology, Rats, Rats, Sprague-Dawley, Toll-Like Receptor 2 metabolism, Toll-Like Receptor 4 metabolism, Astrocytes drug effects, Cytokines metabolism, Fatty Acids pharmacology, Signal Transduction drug effects
- Abstract
This study describes the effects of long-chain fatty acids on inflammatory signaling in cultured astrocytes. Data show that the saturated fatty acid palmitic acid, as well as lauric acid and stearic acid, trigger the release of TNFα and IL-6 from astrocytes. Unsaturated fatty acids were unable to induce cytokine release from cultured astrocytes. Furthermore, the effects of palmitic acid on cytokine release require Toll-like receptor 4 rather than CD36 or Toll-like receptor 2, and do not depend on palmitic acid metabolism to palmitoyl-CoA. Inhibitor studies revealed that pharmacologic inhibition of p38 or p42/44 MAPK pathways prevents the pro-inflammatory effects of palmitic acid, whereas JNK and PI3K inhibition does not affect cytokine release. Depletion of microglia from primary astrocyte cultures using the lysosomotropic agent l-leucine methyl ester revealed that the ability of palmitic acid to trigger cytokine release is not dependent on the presence of microglia. Finally, data show that the essential ω-3 fatty acid docosahexaenoic acid acts in a dose-dependent manner to prevent the actions of palmitic acid on inflammatory signaling in astrocytes. Collectively, these data demonstrate the ability of saturated fatty acids to induce astrocyte inflammation in vitro. These data thus raise the possibility that high levels of circulating saturated fatty acids could cause reactive gliosis and brain inflammation in vivo, and could potentially participate in the reported adverse neurologic consequences of obesity and metabolic syndrome., (© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.)
- Published
- 2012
- Full Text
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14. Cognitive impairment in humanized APP×PS1 mice is linked to Aβ(1-42) and NOX activation.
- Author
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Bruce-Keller AJ, Gupta S, Knight AG, Beckett TL, McMullen JM, Davis PR, Murphy MP, Van Eldik LJ, St Clair D, and Keller JN
- Subjects
- Age Factors, Alzheimer Disease complications, Alzheimer Disease genetics, Amyloid beta-Protein Precursor genetics, Animals, Cognition Disorders etiology, Discs Large Homolog 1 Protein, Disease Models, Animal, Guanylate Kinases metabolism, Humans, Membrane Proteins metabolism, Mice, Mice, Transgenic, Presenilin-1 genetics, Synapsins metabolism, Tubulin metabolism, Amyloid beta-Peptides metabolism, Cognition Disorders genetics, Cognition Disorders metabolism, Gene Expression Regulation genetics, NADPH Oxidases metabolism, Peptide Fragments metabolism
- Abstract
Cognitive impairment in Alzheimer's disease (AD) is strongly associated with both extensive deposition of amyloid β peptides and oxidative stress, but the exact role of these indices in the development of dementia is not clear. This study was designed to determine the relationship between cognitive impairment, activation of the free radical producing enzyme NADPH oxidase (NOX), and progressive changes in Aβ deposition and solubility in humanized APP×PS1 knock-in mice of increasing age. Data show that cognitive performance and expression of key synaptic proteins were progressively decreased in aging APP×PS1 mice. Likewise, NOX activity and expression of the specific NOX subunit NOX4 were significantly increased in APP×PS1 mice in an age-dependent manner, and NOX activity and cognitive impairment shared a significant linear relationship. Data further show that age-dependent increases in Aβ(1-42) had a significant linear relationship with both NOX activity and cognitive performance in APP×PS1 knock-in mice. Collectively, these data show that NOX expression and activity are significantly upregulated with age in this humanized model of Aβ pathogenesis, and suggest that NOX-associated redox pathways are intimately linked to both the loss of cognitive function and the deposition of Aβ(1-42)., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
15. What other states can learn from Vermont's bold experiment: embracing a single-payer health care financing system.
- Author
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Hsiao WC, Knight AG, Kappel S, and Done N
- Subjects
- Cost Savings, Delivery of Health Care economics, Health Care Reform legislation & jurisprudence, Health Care Surveys, Health Resources economics, Humans, Practice Patterns, Physicians' economics, United States, Universal Health Insurance, Vermont, Health Care Reform economics, Single-Payer System economics, Single-Payer System legislation & jurisprudence, State Health Plans organization & administration
- Abstract
Single-payer health care systems consist of publicly financed insurance that provides basic benefits for all citizens. The design is intended to achieve universal coverage and allow greater cost control. Many states have attempted to reform their systems around single-payer principles, but none succeeded until Vermont enacted a law in May 2011. In this article we describe how our team developed a viable single-payer proposal that served as the foundation of Vermont's law. According to our estimates, after the first full year of operation in 2015, our proposed single-payer system is expected to produce an annual savings of 25.3 percent when compared to current state health spending levels; cut employer and household health care spending by $200 million; create 3,800 jobs; and boost the state's overall economic output by $100 million. We describe how this plan was designed, and we discuss lessons for other states considering health system reform.
- Published
- 2011
- Full Text
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16. Metabolic and neurologic consequences of chronic lopinavir/ritonavir administration to C57BL/6 mice.
- Author
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Pistell PJ, Gupta S, Knight AG, Domingue M, Uranga RM, Ingram DK, Kheterpal I, Ruiz C, Keller JN, and Bruce-Keller AJ
- Subjects
- Animals, Cognition drug effects, Drug Administration Schedule, Drug Combinations, HIV drug effects, HIV Infections drug therapy, Lopinavir, Male, Metabolic Syndrome chemically induced, Metabolic Syndrome metabolism, Mice, Mice, Inbred C57BL, Motor Activity drug effects, Pyrimidinones administration & dosage, Pyrimidinones metabolism, Ritonavir administration & dosage, Ritonavir metabolism, Weight Loss drug effects, HIV Protease Inhibitors adverse effects, HIV Protease Inhibitors metabolism, HIV Protease Inhibitors therapeutic use, Pyrimidinones adverse effects, Ritonavir adverse effects
- Abstract
It is well established that HIV antiretroviral drugs, particularly protease inhibitors, frequently elicit a metabolic syndrome that may include hyperlipidemia, lipodystrophy, and insulin resistance. Metabolic dysfunction in non-HIV-infected subjects has been repeatedly associated with cognitive impairment in epidemiological and experimental studies, but it is not yet understood if antiretroviral therapy-induced metabolic syndrome might contribute to HIV-associated neurologic decline. To determine if protease inhibitor-induced metabolic dysfunction in mice is accompanied by adverse neurologic effects, C57BL/6 mice were given combined lopinavir/ritonavir (50/12.5-200/50 mg/kg) daily for 3 weeks. Data show that lopinavir/ritonavir administration caused significant metabolic derangement, including alterations in body weight and fat mass, as well as dose-dependent patterns of hyperlipidemia, hypoadiponectinemia, hypoleptinemia, and hyperinsulinemia. Evaluation of neurologic function revealed that even the lowest dose of lopinavir/ritonavir caused significant cognitive impairment assessed in multi-unit T-maze, but did not affect motor functions assessed as rotarod performance. Collectively, our results indicate that repeated lopinavir/ritonavir administration produces cognitive as well as metabolic impairments, and suggest that the development of selective aspects of metabolic syndrome in HIV patients could contribute to HIV-associated neurocognitive disorders., (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
17. HIV-Tat elicits microglial glutamate release: role of NAPDH oxidase and the cystine-glutamate antiporter.
- Author
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Gupta S, Knight AG, Gupta S, Knapp PE, Hauser KF, Keller JN, and Bruce-Keller AJ
- Subjects
- Amino Acid Transport System y+ antagonists & inhibitors, Amino Acid Transport System y+ genetics, Animals, Animals, Newborn, Cells, Cultured, Enzyme Inhibitors pharmacology, Inflammation pathology, Microglia drug effects, Mitogen-Activated Protein Kinase 1 antagonists & inhibitors, NADPH Oxidases antagonists & inhibitors, NADPH Oxidases genetics, Rats, Rats, Sprague-Dawley, Recombinant Proteins pharmacology, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction drug effects, p38 Mitogen-Activated Protein Kinases antagonists & inhibitors, Amino Acid Transport System y+ metabolism, Glutamic Acid metabolism, Microglia metabolism, NADPH Oxidases metabolism, tat Gene Products, Human Immunodeficiency Virus pharmacology
- Abstract
Excitotoxicity and/or microglial reactivity might underlie neurologic dysfunction in HIV patients. The HIV regulatory protein Tat is both neurotoxic and pro-inflammatory, suggesting that Tat might participate in the pathogenesis of HIV-associated neurocognitive disorders (HAND). The present study was undertaken to evaluate if Tat can increase extracellular glutamate, and was specifically designed to determine the degree to which, and the mechanisms by which Tat could drive microglial glutamate release. Data show that application of Tat to cultured primary microglia caused dose-dependent increases in extracellular glutamate that were exacerbated by morphine, which is known to worsen Tat cytotoxicity. Tat-induced glutamate release was decreased by inhibitors of p38 and p42/44 MAPK, and by inhibitors of NADPH oxidase and the x(c)(-) cystine-glutamate antiporter. Furthermore, Tat increased expression of the catalytic subunit of x(c)(-) (xCT), but Tat-induced increases in xCT mRNA were not affected by inhibition of NADPH oxidase or x(c)(-) activity. Together, these data describe a specific and biologically significant signaling component of the microglial response to Tat, and suggest that excitotoxic neuropathology associated with HIV infection might originate in part with Tat-induced activation of microglial glutamate release., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2010
- Full Text
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18. NOX activity in brain aging: exacerbation by high fat diet.
- Author
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Bruce-Keller AJ, White CL, Gupta S, Knight AG, Pistell PJ, Ingram DK, Morrison CD, and Keller JN
- Subjects
- Age Factors, Animals, Antigens, Differentiation metabolism, Dietary Fats adverse effects, Male, Mice, Mice, Inbred C57BL, Neuroglia drug effects, Neuroglia metabolism, Neuroglia pathology, Oxidation-Reduction drug effects, Protein Carbonylation, Cerebral Cortex physiology, Dietary Fats administration & dosage, NADPH Oxidases metabolism
- Abstract
This study describes how age and high fat diet affect the profile of NADPH oxidase (NOX). Specifically, NOX activity and subunit expression were evaluated in the frontal cerebral cortex of 7-, 16-, and 24-month old mice following a 4-month exposure to either Western diet (WD, 41% calories from fat) or very high fat lard diet (VHFD, 60% calories from fat). Data reveal a significant effect of age in on NOX activity, and show that NOX activity was only increased by VHFD, and only in 24-month old mice. NOX subunit expression was also increased by diet only in older mice. Quantification of protein carbonyls revealed significant age-related increases in protein oxidation, and indicate that only aged mice respond to high fat diet with enhanced protein oxidation. Histological analyses indicate prominent neuronal localization of both NOX subunits and protein carbonylation. Finally, data indicate that changes in reactive microgliosis, but not astrocytosis, mirror the pattern of diet-induced NOX activation and protein oxidation. Collectively, these data show that both age and dietary fat drive NOX activation, and further indicate that aged mice are preferentially sensitive to the effects of high fat diet. These data also suggest that high fat diets might exacerbate age-related oxidative stress in the brain via increased NOX., ((c) 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
- Full Text
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19. NOX activity is increased in mild cognitive impairment.
- Author
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Bruce-Keller AJ, Gupta S, Parrino TE, Knight AG, Ebenezer PJ, Weidner AM, LeVine H 3rd, Keller JN, and Markesbery WR
- Subjects
- Activities of Daily Living, Aged, Aged, 80 and over, Alzheimer Disease etiology, Alzheimer Disease pathology, Amyloid beta-Peptides chemical synthesis, Amyloid beta-Peptides pharmacology, Animals, Cells, Cultured drug effects, Cells, Cultured enzymology, Cerebellum enzymology, Cognition Disorders pathology, Disease Progression, Enzyme Induction, Female, Follow-Up Studies, Humans, Male, Membrane Glycoproteins genetics, Membrane Glycoproteins physiology, Microglia enzymology, NADPH Oxidase 2, NADPH Oxidases genetics, NADPH Oxidases physiology, Nerve Tissue Proteins genetics, Nerve Tissue Proteins physiology, Neurons enzymology, Neurons pathology, Oxidation-Reduction, Oxidative Stress, Peptide Fragments chemical synthesis, Peptide Fragments pharmacology, Rats, Rats, Sprague-Dawley, Severity of Illness Index, Temporal Lobe pathology, Alzheimer Disease enzymology, Cognition Disorders enzymology, Membrane Glycoproteins biosynthesis, NADPH Oxidases biosynthesis, Nerve Tissue Proteins biosynthesis, Temporal Lobe enzymology
- Abstract
This study was undertaken to investigate the profile of NADPH oxidase (NOX) in the clinical progression of Alzheimer's disease (AD). Specifically, NOX activity and expression of the regulatory subunit p47phox and the catalytic subunit gp91phox was evaluated in affected (superior and middle temporal gyri) and unaffected (cerebellum) brain regions from a longitudinally followed group of patients. This group included both control and late-stage AD subjects, and also subjects with preclinical AD and with amnestic mild cognitive impairment (MCI) to evaluate the profile of NOX in the earliest stages of dementia. Data show significant elevations in NOX activity and expression in the temporal gyri of MCI patients as compared with controls, but not in preclinical or late-stage AD samples, and not in the cerebellum. Immunohistochemical evaluations of NOX expression indicate that whereas microglia express high levels of gp91phox, moderate levels of gp91phox also are expressed in neurons. Finally, in vitro experiments showed that NOX inhibition blunted the ability of oligomeric amyloid beta peptides to injure cultured neurons. Collectively, these data show that NOX expression and activity are upregulated specifically in a vulnerable brain region of MCI patients, and suggest that increases in NOX-associated redox pathways in neurons might participate in the early pathogenesis of AD.
- Published
- 2010
- Full Text
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20. Cognitive impairment following high fat diet consumption is associated with brain inflammation.
- Author
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Pistell PJ, Morrison CD, Gupta S, Knight AG, Keller JN, Ingram DK, and Bruce-Keller AJ
- Subjects
- Analysis of Variance, Animals, Behavior, Animal, Body Weight physiology, Brain-Derived Neurotrophic Factor metabolism, Cytokines metabolism, Dietary Fats metabolism, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay methods, Gene Expression Regulation physiology, Glial Fibrillary Acidic Protein metabolism, Maze Learning physiology, Mice, Mice, Inbred C57BL, Neuroglia physiology, Brain metabolism, Cognition Disorders etiology, Cognition Disorders pathology, Dietary Fats adverse effects, Encephalitis etiology, Encephalitis pathology
- Abstract
C57Bl/6 mice were administered a high fat, Western diet (WD, 41% fat) or a very high fat lard diet (HFL, 60% fat), and evaluated for cognitive ability using the Stone T-maze and for biochemical markers of brain inflammation. WD consumption resulted in significantly increased body weight and astrocyte reactivity, but not impaired cognition, microglial reactivity, or heightened cytokine levels. HFL increased body weight, and impaired cognition, increased brain inflammation, and decreased BDNF. Collectively, these data suggest that while different diet formulations can increase body weight, the ability of high fat diets to disrupt cognition is linked to brain inflammation., (Copyright 2009 Elsevier B.V. All rights reserved.)
- Published
- 2010
- Full Text
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21. A novel mutation (p.Thr198Ser) in the 1A helix of keratin 5 causes the localized variant of epidermolysis bullosa simplex.
- Author
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Bowden PE, Knight AG, and Liovic M
- Subjects
- Exons genetics, Female, Humans, Male, Pedigree, Protein Structure, Tertiary genetics, Epidermolysis Bullosa Simplex genetics, Genetic Predisposition to Disease genetics, Keratin-5 genetics, Mutation, Missense genetics
- Abstract
A novel missense mutation (p.Thr198Ser) in the 1A helix of keratin 5 (K5) has been identified in a four-generation family with a history of the localized variant of epidermolysis bullosa simplex (EBS-loc), a genetic skin fragility disorder caused by K5 or K14 mutations. Genomic DNA was isolated from blood samples of patients and their healthy relatives, and all exons of the genes encoding K5 and K14 (KRT5 and KRT14) were amplified by PCR and directly sequenced. The identified mutation was confirmed by mismatch allele-specific (MM-AS)-PCR and restriction enzyme digestion with RsaI. K5 p.Thr198Ser lies at the C-terminal end of the 1A helical domain and is considered to be outside of the main mutation hotspot region. This is the first reported mutation to affect position 30 of the 1A helix (1A:T30S) in any of the 54 known keratins.
- Published
- 2009
- Full Text
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22. Generalised cutaneous necrosis: a complication of low-molecular-weight heparin.
- Author
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Patel GK and Knight AG
- Subjects
- Aged, Female, Humans, Necrosis chemically induced, Necrosis therapy, Tinzaparin, Fibrinolytic Agents adverse effects, Heparin, Low-Molecular-Weight adverse effects, Skin pathology
- Abstract
Subcutaneous low-molecular-weight heparin (LMWH) injections have a predictable dose-dependent anticoagulant effect and have therefore become popular for the prevention and management of thromboembolic diseases. It was initially hoped that use of the smaller molecule and better dose titration would reduce the incidence of side-effects associated with conventional heparin therapy. However, case reports such as this have demonstrated that LMWHs still have the capacity to cause heparin-induced thrombocytopaenia and heparin-induced thrombocytopaenia with thrombosis, as well as heparin necrosis. To our knowledge, this is the first-ever-reported case of heparin necrosis associated with tinazaparin. Heparin necrosis is characterised by widespread life-threatening cutaneous necrosis and systemic thrombosis, in which fatal progression of disease can only be halted by stopping heparin therapy. As heparin necrosis is an uncommon disorder, in this report we focus on the clinical clues that may help woundcare professionals consider and confirm the diagnosis.
- Published
- 2005
- Full Text
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23. Erythema elevatum diutinum and IgA paraproteinaemia: 'a preclinical iceberg'.
- Author
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Chowdhury MM, Inaloz HS, Motley RJ, and Knight AG
- Subjects
- Erythema pathology, Humans, Male, Middle Aged, Paraproteinemias pathology, Erythema blood, Erythema complications, Immunoglobulin A blood, Paraproteinemias blood, Paraproteinemias complications
- Published
- 2002
24. An aggressive treatment for aggressive digital papillary adenocarcinoma.
- Author
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Inaloz HS, Patel GK, and Knight AG
- Subjects
- Adenocarcinoma, Papillary surgery, Adult, Amputation, Surgical, Biopsy, Carcinoembryonic Antigen analysis, Fingers pathology, Fingers surgery, Humans, Male, S100 Proteins analysis, Sweat Gland Neoplasms surgery, Sweat Glands pathology, Adenocarcinoma, Papillary pathology, Sweat Gland Neoplasms pathology
- Abstract
Aggressive digital papillary adenoma (ADPA) and adenocarcinoma (ADPAca) are adnexal tumors that are not often recognized because of their rarity. We present a rare case of ADPAca involving the left middle finger of a 43-year-old man. Histopathological features of ADPAca are distinct from those of other eccrine sweat gland tumors; however, ADPAca may be misdiagnosed particularly for a metastasis of papillary adenocarcinoma originating in the colon, thyroid, or breast. Clinicopathological correlation is essential to ule out a possible risk of metastatic carcinoma of the skin. Recognition of these tumors is important because of a potential risk of local recurrence nd distant metastases. Aggressive surgical treatment consisting of digit amputation is advocated in the treatment of ADPAca.
- Published
- 2002
25. Familial confluent and reticulated papillomatosis.
- Author
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Inalöz HS, Patel GK, and Knight AG
- Subjects
- Adult, Humans, Immunohistochemistry, Ki-67 Antigen analysis, Male, Papilloma immunology, Papilloma pathology, Skin Neoplasms immunology, Skin Neoplasms pathology, Papilloma genetics, Skin Neoplasms genetics
- Published
- 2002
- Full Text
- View/download PDF
26. Dystrophic calcinosis cutis in venous ulcers: a cause of treatment failure.
- Author
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Chave TA, Varma S, and Knight AG
- Subjects
- Aged, Aged, 80 and over, Bandages, Female, Humans, Treatment Outcome, Varicose Ulcer therapy, Calcinosis complications, Skin Diseases complications, Varicose Ulcer complications
- Published
- 2001
- Full Text
- View/download PDF
27. Thalidomide usage in Wales: the need to follow guidelines.
- Author
-
Chave TA, Finlay AY, and Knight AG
- Subjects
- Dermatologic Agents adverse effects, Dermatology statistics & numerical data, Drug Utilization standards, Humans, Informed Consent, Neural Conduction drug effects, Peripheral Nervous System Diseases chemically induced, Skin Diseases drug therapy, Surveys and Questionnaires, Thalidomide adverse effects, Wales, Dermatologic Agents therapeutic use, Dermatology standards, Drug Utilization statistics & numerical data, Guideline Adherence, Practice Patterns, Physicians' statistics & numerical data, Teratogens, Thalidomide therapeutic use
- Abstract
Background: Thalidomide is a potentially useful drug for several dermatological disorders., Objectives: To assess prescribing and monitoring practices for this drug in Wales., Methods: A questionnaire was completed by 17 of 19 consultant dermatologists concerning thalidomide usage in Wales (population 2.93 million)., Results: Eleven of the 17 respondents had used thalidomide in 40 patients. Only two consultants gave information leaflets and only five obtained written consent. Four obtained baseline nerve conduction studies and nine obtained these during therapy. Of seven women of child-bearing age currently taking thalidomide, none had had baseline pregnancy tests., Conclusions: We describe variability in prescribing practices for thalidomide. Published guidelines are reviewed and suggestions made concerning consent forms, pregnancy testing, nerve conduction studies and patient information.
- Published
- 2001
- Full Text
- View/download PDF
28. Localised facial swelling associated with isotretinoin.
- Author
-
Patel GK, Chowdhury MM, Clark SM, and Knight AG
- Subjects
- Acne Vulgaris drug therapy, Adult, Humans, Male, Middle Aged, Edema chemically induced, Face, Isotretinoin adverse effects
- Published
- 1999
- Full Text
- View/download PDF
29. Cutaneous calcinosis--an unusual complication of intravenous phosphate administration.
- Author
-
Mills CM and Knight AG
- Subjects
- Aged, Aged, 80 and over, Female, Humans, Infusions, Intravenous, Phosphates administration & dosage, Calcinosis chemically induced, Drug Eruptions etiology, Phosphates adverse effects
- Abstract
The case of an 80-year-old woman who developed extensive cutaneous calcification following intravenous phosphate administration is presented. Also the circumstances under which cutaneous calcification may occur are discussed.
- Published
- 1993
- Full Text
- View/download PDF
30. Lichenoid tattoo hypersensitivity.
- Author
-
Taaffe A, Knight AG, and Marks R
- Subjects
- Adult, Dermatitis, Contact immunology, Dermatitis, Contact pathology, Fluorescent Antibody Technique, Humans, Lichen Planus immunology, Lichen Planus pathology, Male, Patch Tests, Dermatitis, Contact etiology, Lichen Planus etiology, Tattooing adverse effects
- Abstract
Four patients are described who developed granulomatous reactions in the red portions of their tattoos. Histopathological and immunofluorescence studies showed features of lichen planus. Mercury was identified in only one patient's lesion, and hypersensitivity to mercury was shown by patch testing in one other patient. Tattooing may provide a localised antigenic challenge resulting in spontaneously occurring lichen planus.
- Published
- 1978
- Full Text
- View/download PDF
31. Hydrallazine-induced necrotising vasculitis.
- Author
-
Finlay AY, Statham B, and Knight AG
- Subjects
- Humans, Male, Middle Aged, Hydralazine adverse effects, Vasculitis, Leukocytoclastic, Cutaneous chemically induced
- Published
- 1981
- Full Text
- View/download PDF
32. The effect of temperature and humidity on the growth of Trichophyton mentagrophytes spores on human stratum corneum in vitro.
- Author
-
Knight AG
- Subjects
- Humans, Humidity, Spores, Fungal growth & development, Temperature, Skin microbiology, Trichophyton growth & development
- Published
- 1976
- Full Text
- View/download PDF
33. Possible histiocytic medullary reticulosis.
- Author
-
Knight AG and Jones EW
- Subjects
- Aged, Brain Neoplasms diagnosis, Female, Heart Neoplasms diagnosis, Humans, Kidney Neoplasms diagnosis, Lymph Nodes, Lymphatic Diseases diagnosis
- Published
- 1976
34. Pityriasis amiantacea: a clinical and histopathological investigation.
- Author
-
Knight AG
- Subjects
- Adolescent, Adult, Alopecia etiology, Child, Child, Preschool, Female, Humans, Male, Pityriasis complications, Scalp pathology, Pityriasis pathology, Scalp Dermatoses pathology
- Published
- 1977
- Full Text
- View/download PDF
35. A clinical double-blind trial of topical miconazole and clotrimazole against superficial fungal infections and erythrasma.
- Author
-
Clayton YM and Knight AG
- Subjects
- Adolescent, Adult, Candidiasis, Cutaneous drug therapy, Child, Child, Preschool, Clinical Trials as Topic, Female, Humans, Male, Middle Aged, Pityriasis drug therapy, Clotrimazole therapeutic use, Corynebacterium Infections drug therapy, Dermatomycoses drug therapy, Erythrasma drug therapy, Imidazoles therapeutic use, Miconazole therapeutic use
- Published
- 1976
- Full Text
- View/download PDF
36. Cutaneous cryptococcosis: treatment with oral fluconazole.
- Author
-
Shuttleworth D, Philpot CM, and Knight AG
- Subjects
- Administration, Oral, Aged, Aged, 80 and over, Antifungal Agents administration & dosage, Fluconazole, Humans, Male, Triazoles administration & dosage, Antifungal Agents therapeutic use, Cryptococcosis drug therapy, Dermatomycoses drug therapy, Triazoles therapeutic use
- Abstract
A case of cutaneous cryptococcosis is described in an immunocompromised patient. The initial lesion developed on the dorsum of the hand following trauma and was initially thought to be neoplastic. Satellite subcutaneous lesions developed in a 'sporotrichoid' pattern along the forearm. Treatment with oral fluconazole resulted in the complete resolution of the lesions. This is the first published report of the use of fluconazole in the treatment of cutaneous cryptococcosis.
- Published
- 1989
- Full Text
- View/download PDF
37. The activity of various topical griseofulvin preparations and the appearance of oral griseofulvin in the stratum corneum.
- Author
-
Knight AG
- Subjects
- Administration, Oral, Administration, Topical, Biological Assay, Culture Techniques, Dermatomycoses prevention & control, Griseofulvin analysis, Humans, Methods, Pharmaceutical Vehicles, Skin analysis, Skin metabolism, Time Factors, Trichophyton drug effects, Griseofulvin administration & dosage, Griseofulvin pharmacology, Skin Absorption
- Published
- 1974
- Full Text
- View/download PDF
38. Immune deficiency and multiple viral warts: a possible variant of the Wiskott-Aldrich syndrome.
- Author
-
Ormerod AD, Finlay AY, Knight AG, Mathews N, Stark JM, and Gough J
- Subjects
- Adult, Antibody Formation, Hand Dermatoses immunology, Humans, Immunity, Cellular, Male, Warts immunology, Wiskott-Aldrich Syndrome immunology, Wiskott-Aldrich Syndrome therapy, Hand Dermatoses etiology, Warts etiology, Wiskott-Aldrich Syndrome complications
- Published
- 1983
- Full Text
- View/download PDF
39. Eosinophilic spongiosis: A clinical histological and immunofluorescent correlation.
- Author
-
Knight AG, Black MM, and Delaney TJ
- Subjects
- Adult, Aged, Antibodies analysis, Biopsy, Dermatitis Herpetiformis pathology, Humans, Male, Middle Aged, Pemphigus pathology, Skin Diseases, Vesiculobullous immunology, Eosinophils pathology, Skin Diseases, Vesiculobullous pathology
- Published
- 1976
- Full Text
- View/download PDF
40. A follow-up of tetracycline-treated rosacea. With special reference to rosacea keratitis.
- Author
-
Knight AG and Vickers CF
- Subjects
- Clinical Trials as Topic, Female, Follow-Up Studies, Humans, Keratitis complications, Keratitis drug therapy, Male, Middle Aged, Recurrence, Rosacea blood, Rosacea complications, Tetracycline blood, Rosacea drug therapy, Tetracycline therapeutic use
- Abstract
Seventy patients with rosacea were treated with systemic tetracycline for 6 months. Sixty-eight of them cleared with treatment. After withdrawal of the drug seventeen relapsed immediately and the overall relapse rate over 4 years was 69%. The serum tetracycline levels were not significantly different in two patients who failed to respond. Six patients had rosacea keratitis and responded dramatically within 1 month. Symptoms recurred as the drug was withdrawn. It is suggested that rosacea patients with keratitis should receive early and prolonged tetracycline medication.
- Published
- 1975
- Full Text
- View/download PDF
41. Candidiasis.
- Author
-
Knight AG
- Subjects
- Antifungal Agents therapeutic use, Candidiasis drug therapy, Candidiasis, Cutaneous diagnosis, Candidiasis, Oral diagnosis, Candidiasis, Vulvovaginal diagnosis, Diagnosis, Differential, Female, Humans, Infant, Inguinal Canal, Male, Paronychia diagnosis, Candidiasis diagnosis
- Published
- 1975
42. A review of experimental human fungus infections.
- Author
-
Knight AG
- Subjects
- Antifungal Agents therapeutic use, Antigens, Fungal, Dermatomycoses immunology, Epidermophyton immunology, Epidermophyton pathogenicity, Griseofulvin therapeutic use, Humans, Humidity, Hydrocortisone, Microsporum immunology, Microsporum pathogenicity, Skin injuries, Skin pathology, Skin Tests, Spores, Fungal pathogenicity, Tinea immunology, Tinea microbiology, Tinea pathology, Tinea Capitis drug therapy, Trichophyton immunology, Trichophyton pathogenicity, Dermatomycoses microbiology
- Published
- 1972
- Full Text
- View/download PDF
43. Attempted suicide with herbicide containing MCPA.
- Author
-
Jones DI, Knight AG, and Smith AJ
- Subjects
- Humans, Male, Herbicides poisoning, Suicide
- Published
- 1967
- Full Text
- View/download PDF
44. Culture of dermatophytes upon stratum corneum.
- Author
-
Knight AG
- Subjects
- Antifungal Agents, Culture Media, Humans, Methods, Spores, Fungal, Trichophyton growth & development, Arthrodermataceae growth & development, Culture Techniques, Skin
- Published
- 1972
- Full Text
- View/download PDF
45. Human models for in vivo and in vitro assessment of topical antifungal compounds.
- Author
-
Knight AG
- Subjects
- Cyclic N-Oxides therapeutic use, Humans, In Vitro Techniques, Phenyl Ethers therapeutic use, Pyridines therapeutic use, Skin microbiology, Sulfhydryl Compounds therapeutic use, Thiabendazole therapeutic use, Time Factors, Tolnaftate therapeutic use, Antifungal Agents therapeutic use, Models, Biological, Tinea drug therapy, Trichophyton drug effects
- Published
- 1973
- Full Text
- View/download PDF
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