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Articles 91 - 120 of 273
Full-Text Articles in Medical Sciences
Fusion, 2017, George Washington University, William H. Beaumont Medical Research Honor Society
Fusion, 2017, George Washington University, William H. Beaumont Medical Research Honor Society
Fusion
No abstract provided.
Human Ipsc-Derived Cerebellar Neurons From A Patient With Ataxia-Telangiectasia Reveal Disrupted Gene Regulatory Networks, Sam Nayler, Joseph Powell, Darya Vanichkina, Othmar Korn, Christine Wells, Ryan J. Taft, +Several Additional Authors
Human Ipsc-Derived Cerebellar Neurons From A Patient With Ataxia-Telangiectasia Reveal Disrupted Gene Regulatory Networks, Sam Nayler, Joseph Powell, Darya Vanichkina, Othmar Korn, Christine Wells, Ryan J. Taft, +Several Additional Authors
Genomics and Precision Medicine Faculty Publications
Ataxia-telangiectasia (A-T) is a rare genetic disorder caused by loss of function of the ataxia-telangiectasia-mutated kinase and is characterized by a predisposition to cancer, pulmonary disease, immune deficiency and progressive degeneration of the cerebellum. As animal models do not faithfully recapitulate the neurological aspects, it remains unclear whether cerebellar degeneration is a neurodevelopmental or neurodegenerative phenotype. To address the necessity for a human model, we first assessed a previously published protocol for the ability to generate cerebellar neuronal cells, finding it gave rise to a population of precursors highly enriched for markers of the early hindbrain such as EN1 and …
Distinct Neural Bases Of Disruptive Behavior And Autism Symptom Severity In Boys With Autism Spectrum Disorder., Y.J. Daniel Yang, Denis G Sukhodolsky, Jiedi Lei, Eran Dayan, Kevin A. Pelphrey, Pamela Ventola
Distinct Neural Bases Of Disruptive Behavior And Autism Symptom Severity In Boys With Autism Spectrum Disorder., Y.J. Daniel Yang, Denis G Sukhodolsky, Jiedi Lei, Eran Dayan, Kevin A. Pelphrey, Pamela Ventola
Pediatrics Faculty Publications
BACKGROUND: Disruptive behavior in autism spectrum disorder (ASD) is an important clinical problem, but its neural basis remains poorly understood. The current research aims to better understand the neural underpinnings of disruptive behavior in ASD, while addressing whether the neural basis is shared with or separable from that of core ASD symptoms.
METHODS: Participants consisted of 48 male children and adolescents: 31 ASD (7 had high disruptive behavior) and 17 typically developing (TD) controls, well-matched on sex, age, and IQ. For ASD participants, autism symptom severity, disruptive behavior, anxiety symptoms, and ADHD symptoms were measured. All participants were scanned while …
Visual Neurons In The Superior Colliculus Innervated By Islet2+ Or Islet2− Retinal Ganglion Cells Display Distinct Tuning Properties, Rachel Kay, Jason W. Triplett
Visual Neurons In The Superior Colliculus Innervated By Islet2+ Or Islet2− Retinal Ganglion Cells Display Distinct Tuning Properties, Rachel Kay, Jason W. Triplett
Pediatrics Faculty Publications
Throughout the visual system, different subtypes of neurons are tuned to distinct aspects of the visual scene, establishing parallel circuits. Defining the mechanisms by which such tuning arises has been a long-standing challenge for neuroscience. To investigate this, we have focused on the retina’s projection to the superior colliculus (SC), where multiple visual neuron subtypes have been described. The SC receives inputs from a variety of retinal ganglion cell (RGC) subtypes; however, which RGCs drive the tuning of different SC neurons remains unclear. Here, we pursued a genetic approach that allowed us to determine the tuning properties of neurons innervated …
The Effect Of Hiv Infection And Hcv Viremia On Inflammatory Mediators And Hepatic Injury-The Women's Interagency Hiv Study., Sheila M Keating, Jennifer L Dodge, Philip J Norris, John Heitman, Stephen J Gange, Audrey L French, Marshall J Glesby, Brian R Edlin, Patricia S Latham, Maria C Villacres, Ruth M Greenblatt, Marion G Peters
The Effect Of Hiv Infection And Hcv Viremia On Inflammatory Mediators And Hepatic Injury-The Women's Interagency Hiv Study., Sheila M Keating, Jennifer L Dodge, Philip J Norris, John Heitman, Stephen J Gange, Audrey L French, Marshall J Glesby, Brian R Edlin, Patricia S Latham, Maria C Villacres, Ruth M Greenblatt, Marion G Peters
Pathology Faculty Publications
Hepatitis C virus infection induces inflammation and while it is believed that HIV co-infection enhances this response, HIV control may reduce inflammation and liver fibrosis in resolved or viremic HCV infection. Measurement of systemic biomarkers in co-infection could help define the mechanism of inflammation on fibrosis and determine if HIV control reduces liver pathology. A nested case-control study was performed to explore the relationship of systemic biomarkers of inflammation with liver fibrosis in HCV viremic and/or seropositive women with and without HIV infection. Serum cytokines, chemokines, growth factors and cell adhesion molecules were measured in HIV uninfected (HIV-, n = …
A Fashi Lymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signalling In Htlv-1-Associated Neuroinflammation., Soraya Maria Menezes, Fabio E Leal, Tim Dierckx, Ricardo Khouri, Daniele Decanine, Gilvaneia Silva-Santos, +Several Additional Authors
A Fashi Lymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signalling In Htlv-1-Associated Neuroinflammation., Soraya Maria Menezes, Fabio E Leal, Tim Dierckx, Ricardo Khouri, Daniele Decanine, Gilvaneia Silva-Santos, +Several Additional Authors
Microbiology, Immunology, and Tropical Medicine Faculty Publications
Human T-cell lymphotropic virus (HTLV)-1 was the first human retrovirus to be associated to cancer, namely Adult T-cell Leukemia (ATL), but its pathogenesis remains enigmatic, since only a minority of infected individuals develops either ATL or the neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A functional FAS -670 polymorphism in an interferon (IFN)-regulated STAT1-binding site has been associated to both ATL and HAM/TSP susceptibility. Fashi T stem cell memory (Tscm) cells have been identified as the hierarchical apex of ATL, but have not been investigated in HAM/TSP. In addition, both FAS and STAT1 have been identified in an IFN-inducible HAM/TSP …
Uncorrelated Neural Firing In Mouse Visual Cortex During Spontaneous Retinal Waves, Matthew Colonnese, Jing Shen, Yasunobu Murata
Uncorrelated Neural Firing In Mouse Visual Cortex During Spontaneous Retinal Waves, Matthew Colonnese, Jing Shen, Yasunobu Murata
Pharmacology and Physiology Faculty Publications
Synchronous firing among the elements of forming circuits is critical for stabilization of synapses. Understanding the nature of these local network interactions during development can inform models of circuit formation. Within cortex, spontaneous activity changes throughout development. Unlike the adult, early spontaneous activity occurs in discontinuous population bursts separated by long silent periods, suggesting a high degree of local synchrony. However, whether the micro-patterning of activity within early bursts is unique to this early age and specifically tuned for early development is poorly understood, particularly within the column. To study this we used single-shank multi-electrode array recordings of spontaneous activity …
Seeing The Invisible: Revealing Atrial Ablation Lesions Using Hyperspectral Imaging Approach, Narine Muselimyan, Luther Swift, Huda Asfour, Tigran Chahbazian, Ramesh Mazhari, Marco Mercader, Narine Sarvazyan
Seeing The Invisible: Revealing Atrial Ablation Lesions Using Hyperspectral Imaging Approach, Narine Muselimyan, Luther Swift, Huda Asfour, Tigran Chahbazian, Ramesh Mazhari, Marco Mercader, Narine Sarvazyan
Pharmacology and Physiology Faculty Publications
Background
Currently, there are limited means for high-resolution monitoring of tissue injury during radiofrequency ablation procedures.
Objective
To develop the next generation of visualization catheters that can reveal irreversible atrial muscle damage caused by ablation and identify viability gaps between the lesions.
Methods
Radiofrequency lesions were placed on the endocardial surfaces of excised human and bovine atria and left ventricles of blood perfused rat hearts. Tissue was illuminated with 365nm light and a series of images were acquired from individual spectral bands within 420-720nm range. By extracting spectral profiles of individual pixels and spectral unmixing, the relative contribution of ablated …
Development Of Activity In The Mouse Visual Cortex., Jing Shen, Matthew T Colonnese
Development Of Activity In The Mouse Visual Cortex., Jing Shen, Matthew T Colonnese
Pharmacology and Physiology Faculty Publications
No abstract provided.
Severe Mortality Impact Of The 1957 Influenza Pandemic In Chile., Gerardo Chowell, Lone Simonsen, Rodrigo Fuentes, Jose Flores, Mark A Miller, Cécile Viboud
Severe Mortality Impact Of The 1957 Influenza Pandemic In Chile., Gerardo Chowell, Lone Simonsen, Rodrigo Fuentes, Jose Flores, Mark A Miller, Cécile Viboud
Microbiology, Immunology, and Tropical Medicine Faculty Publications
INTRODUCTION: Epidemiological studies of the 1957 influenza pandemic are scarce, particularly from lower-income settings.
METHODS: We analyzed the spatial-temporal mortality patterns of the 1957 influenza pandemic in Chile, including detailed age-specific mortality data from a large city, and investigated risk factors for severe mortality impact across regions.
RESULTS: Chile exhibited two waves of excess mortality in winter 1957 and 1959 with a cumulative excess mortality rate of 12 per 10 000, and a ~10-fold mortality difference across provinces. High excess mortality rates were associated with high baseline mortality (R(2) =41.8%; P=.02), but not with latitude (P>.7). Excess mortality rates …
Intranasal Oxytocin Enhances Connectivity In The Neural Circuitry Supporting Social Motivation And Social Perception In Children With Autism., Ilanit Gordon, Allison Jack, Charlotte M Pretzsch, Brent Vander Wyk, James F Leckman, Ruth Feldman, Kevin A. Pelphrey
Intranasal Oxytocin Enhances Connectivity In The Neural Circuitry Supporting Social Motivation And Social Perception In Children With Autism., Ilanit Gordon, Allison Jack, Charlotte M Pretzsch, Brent Vander Wyk, James F Leckman, Ruth Feldman, Kevin A. Pelphrey
Pharmacology and Physiology Faculty Publications
Oxytocin (OT) has become a focus in investigations of autism spectrum disorder (ASD). The social deficits that characterize ASD may relate to reduced connectivity between brain sites on the mesolimbic reward pathway (nucleus accumbens; amygdala) that receive OT projections and contribute to social motivation, and cortical sites involved in social perception. Using functional magnetic resonance imaging and a randomized, double blind, placebo-controlled crossover design, we show that OT administration in ASD increases activity in brain regions important for perceiving social-emotional information. Further, OT enhances connectivity between nodes of the brain's reward and socioemotional processing systems, and does so preferentially for …
Ebola Vp40 In Exosomes Can Cause Immune Cell Dysfunction, Michelle Pleet, Allison Mathiesen, Catherine Demarino, Yao Akpamagbo, Robert Barclay, Sergey N. Iordanskiy, +6 Additional Authors
Ebola Vp40 In Exosomes Can Cause Immune Cell Dysfunction, Michelle Pleet, Allison Mathiesen, Catherine Demarino, Yao Akpamagbo, Robert Barclay, Sergey N. Iordanskiy, +6 Additional Authors
Microbiology, Immunology, and Tropical Medicine Faculty Publications
Ebola virus (EBOV) is an enveloped, ssRNA virus from the family Filoviridae capable of causing severe hemorrhagic fever with up to 80–90% mortality rates. The most recent outbreak of EBOV in West Africa starting in 2014 resulted in over 11,300 deaths; however, long-lasting persistence and recurrence in survivors has been documented, potentially leading to further transmission of the virus. We have previously shown that exosomes from cells infected with HIV-1, HTLV-1 and Rift Valley Fever virus are able to transfer viral proteins and non-coding RNAs to naïve recipient cells, resulting in an altered cellular activity. In the current manuscript, we …
Transcriptomic Analysis Implicates The P53 Signaling Pathway In The Establishment Of Hiv-1 Latency In Central Memory Cd4 T Cells In An In Vitro Model, Cory White, Bastiaan Moesker, Nadejda Beliakova-Bethell, Laura Martins, Celsa Spina, Alberto Bosque, +4 Additional Authors
Transcriptomic Analysis Implicates The P53 Signaling Pathway In The Establishment Of Hiv-1 Latency In Central Memory Cd4 T Cells In An In Vitro Model, Cory White, Bastiaan Moesker, Nadejda Beliakova-Bethell, Laura Martins, Celsa Spina, Alberto Bosque, +4 Additional Authors
Microbiology, Immunology, and Tropical Medicine Faculty Publications
The search for an HIV-1 cure has been greatly hindered by the presence of a viral reservoir that persists despite antiretroviral therapy (ART). Studies of HIV-1 latency in vivo are also complicated by the low proportion of latently infected cells in HIV-1 infected individuals. A number of models of HIV-1 latency have been developed to examine the signaling pathways and viral determinants of latency and reactivation. A primary cell model of HIV-1 latency, which incorporates the generation of primary central memory CD4 T cells (TCM), full-length virus infection (HIVNL4-3) and ART to suppress virus replication, was used to investigate the …
P16ink4a Expression And Immunologic Aging In Chronic Hiv Infection, Susan Ribeiro, Jeffrey Milush, Edecio Cunha-Neto, Esper Kallas, Jorge Kalil, Luiz Felipe D. Passero, Peter W. Hunt, Steven Deeks, Douglas F. Nixon, Devi Sengupta
P16ink4a Expression And Immunologic Aging In Chronic Hiv Infection, Susan Ribeiro, Jeffrey Milush, Edecio Cunha-Neto, Esper Kallas, Jorge Kalil, Luiz Felipe D. Passero, Peter W. Hunt, Steven Deeks, Douglas F. Nixon, Devi Sengupta
Microbiology, Immunology, and Tropical Medicine Faculty Publications
Chronic HIV infection is characterized by increased immune activation and immunosenescence. p16 INK4a (p16) is a member of the cyclin-dependent kinase antagonist family that inhibits cellular proliferation, and its protein expression increases during normal chronological aging. However, some infectious diseases can increase the expression of this anti-proliferative protein, potentially accelerating immunological aging and dysfunction. In order to investigate the immunological aging in HIV patients, p16 protein expression was evaluated by flow cytometry, in T cell subsets in a cohort of chronically HIV-infected patients on and off ART as well as age-matched healthy controls. Results showed that untreated HIV-infected subjects exhibited …
Antiviral Cd8(+) T Cells Restricted By Human Leukocyte Antigen Class Ii Exist During Natural Hiv Infection And Exhibit Clonal Expansion., Srinika Ranasinghe, Pedro A Lamothe, Damien Z Soghoian, Samuel W Kazer, Michael B Cole, Alex K Shalek, Nir Yosef, R. Brad Jones, Faith Donaghey, Chioma Nwonu, Priya Jani, Gina M Clayton, Frances Crawford, Janice White, Alana Montoya, Karen Power, Todd M Allen, Hendrik Streeck, Daniel E Kaufmann, Louis J Picker, John W Kappler, Bruce D Walker
Antiviral Cd8(+) T Cells Restricted By Human Leukocyte Antigen Class Ii Exist During Natural Hiv Infection And Exhibit Clonal Expansion., Srinika Ranasinghe, Pedro A Lamothe, Damien Z Soghoian, Samuel W Kazer, Michael B Cole, Alex K Shalek, Nir Yosef, R. Brad Jones, Faith Donaghey, Chioma Nwonu, Priya Jani, Gina M Clayton, Frances Crawford, Janice White, Alana Montoya, Karen Power, Todd M Allen, Hendrik Streeck, Daniel E Kaufmann, Louis J Picker, John W Kappler, Bruce D Walker
Microbiology, Immunology, and Tropical Medicine Faculty Publications
CD8(+) T cell recognition of virus-infected cells is characteristically restricted by major histocompatibility complex (MHC) class I, although rare examples of MHC class II restriction have been reported in Cd4-deficient mice and a macaque SIV vaccine trial using a recombinant cytomegalovirus vector. Here, we demonstrate the presence of human leukocyte antigen (HLA) class II-restricted CD8(+) T cell responses with antiviral properties in a small subset of HIV-infected individuals. In these individuals, T cell receptor β (TCRβ) analysis revealed that class II-restricted CD8(+) T cells underwent clonal expansion and mediated killing of HIV-infected cells. In one case, these cells comprised 12% …
An Excitatory Cortical Feedback Loop Gates Retinal Wave Transmission In Rodent Thalamus, Yasunobu Murata, Matthew T. Colonnese
An Excitatory Cortical Feedback Loop Gates Retinal Wave Transmission In Rodent Thalamus, Yasunobu Murata, Matthew T. Colonnese
Pharmacology and Physiology Faculty Publications
Spontaneous retinal waves are critical for the development of receptive fields in visual thalamus (LGN) and cortex (VC). Despite a detailed understanding of the circuit specializations in retina that generate waves, whether central circuit specializations also exist to control their propagation through visual pathways of the brain is unknown. Here we identify a developmentally transient, corticothalamic amplification of retinal drive to thalamus as a mechanism for retinal wave transmission in the infant rat brain. During the period of retinal waves, corticothalamic connections excite LGN, rather than driving feedforward inhibition as observed in the adult. This creates an excitatory feedback loop …
Hiv-1 Integrates Widely Throughout The Genome Of The Human Blood Fluke Schistosoma Mansoni., Sutas Suttiprapa, Gabriel Rinaldi, Isheng J Tsai, Victoria H. Mann, Larisa Dubrovsky, Hong-Bin Yan, Nancy Holroyd, Thomas Huckvale, Caroline Durrant, Anna V Protasio, Tatiana Pushkarsky, Sergey Iordanskiy, Matthew Berriman, Michael I. Bukrinsky, Paul J. Brindley
Hiv-1 Integrates Widely Throughout The Genome Of The Human Blood Fluke Schistosoma Mansoni., Sutas Suttiprapa, Gabriel Rinaldi, Isheng J Tsai, Victoria H. Mann, Larisa Dubrovsky, Hong-Bin Yan, Nancy Holroyd, Thomas Huckvale, Caroline Durrant, Anna V Protasio, Tatiana Pushkarsky, Sergey Iordanskiy, Matthew Berriman, Michael I. Bukrinsky, Paul J. Brindley
Microbiology, Immunology, and Tropical Medicine Faculty Publications
Schistosomiasis is the most important helminthic disease of humanity in terms of morbidity and mortality. Facile manipulation of schistosomes using lentiviruses would enable advances in functional genomics in these and related neglected tropical diseases pathogens including tapeworms, and including their non-dividing cells. Such approaches have hitherto been unavailable. Blood stream forms of the human blood fluke, Schistosoma mansoni, the causative agent of the hepatointestinal schistosomiasis, were infected with the human HIV-1 isolate NL4-3 pseudotyped with vesicular stomatitis virus glycoprotein. The appearance of strong stop and positive strand cDNAs indicated that virions fused to schistosome cells, the nucleocapsid internalized and the …
Method And Phantom To Study Combined Effects Of In-Plane (X,Y) And Z-Axis Resolution For 3d Ct Imaging., David Goodenough, Josh Levy, Smari Kristinsson, Jesper Fredriksson, Hildur Olafsdottir, Austin Healy
Method And Phantom To Study Combined Effects Of In-Plane (X,Y) And Z-Axis Resolution For 3d Ct Imaging., David Goodenough, Josh Levy, Smari Kristinsson, Jesper Fredriksson, Hildur Olafsdottir, Austin Healy
Radiology Faculty Publications
Increasingly, the advent of multislice CT scanners, volume CT scanners, and total body spiral acquisition modes has led to the use of Multi Planar Reconstruction and 3D datasets. In considering 3D resolution properties of a CT system it is important to note that both the in-plane (x,y) and z-axis (slice thickness) influence the visual-ization and detection of objects within the scanned volume. This study investigates ways to consider both the in-plane resolution and the z-axis resolution in a single phantom wherein analytic or visualized analysis can yield information on these combined effects. A new phantom called the "Wave Phantom" is …
Respiratory Rate Variability In Sleeping Adults Without Obstructive Sleep Apnea, Guillermo Gutierrez, Jeffrey Williams, Ghadah Alrehaili, Anna Mclean, Ramin Pirouz, Richard L. Amdur, Vivek Jain, Jalil Ahari, Amandeep Bawa, Shawn Kimbro
Respiratory Rate Variability In Sleeping Adults Without Obstructive Sleep Apnea, Guillermo Gutierrez, Jeffrey Williams, Ghadah Alrehaili, Anna Mclean, Ramin Pirouz, Richard L. Amdur, Vivek Jain, Jalil Ahari, Amandeep Bawa, Shawn Kimbro
Surgery Faculty Publications
Characterizing respiratory rate variability (RRV) in humans during sleep is challenging, since it requires the analysis of respiratory signals over a period of several hours. These signals are easily distorted by movement and volitional inputs. We applied the method of spectral analysis to the nasal pressure transducer signal in 38 adults with no obstructive sleep apnea, defined by an apnea‐hypopnea index <5, who underwent all‐night polysomnography (PSG). Our aim was to detect and quantitate RRV during the various sleep stages, including wakefulness. The nasal pressure transducer signal was acquired at 100 Hz and consecutive frequency spectra were generated for the length of the PSG with the Fast Fourier Transform. For each spectrum, we computed the amplitude ratio of the first harmonic peak to the zero frequency peak (H1/DC), and defined as RRV as (100 − H1/DC) %. RRV was greater during wakefulness compared to any sleep stage, including rapid‐eye‐movement. Furthermore, RRV correlated with the depth of sleep, being lowest during N3. Patients spent most their sleep time supine, but we found no correlation between RRV and body position. There was a correlation between respiratory rate and sleep stage, being greater in wakefulness than in any sleep stage. We conclude that RRV varies according to sleep stage. Moreover, spectral analysis of nasal pressure signal appears to provide a valid measure of RRV during sleep. It remains to be seen if the method can differentiate normal from pathological sleep patterns.
The Global Economic And Health Burden Of Human Hookworm Infection., Sarah M Bartsch, Peter J. Hotez, Lindsey Asti, Kristina M Zapf, Maria Elena Bottazzi, David J. Diemert, Bruce Y Lee
The Global Economic And Health Burden Of Human Hookworm Infection., Sarah M Bartsch, Peter J. Hotez, Lindsey Asti, Kristina M Zapf, Maria Elena Bottazzi, David J. Diemert, Bruce Y Lee
Microbiology, Immunology, and Tropical Medicine Faculty Publications
BACKGROUND: Even though human hookworm infection is highly endemic in many countries throughout the world, its global economic and health impact is not well known. Without a better understanding of hookworm's economic burden worldwide, it is difficult for decision makers such as funders, policy makers, disease control officials, and intervention manufacturers to determine how much time, energy, and resources to invest in hookworm control.
METHODOLOGY/PRINCIPLE FINDINGS: We developed a computational simulation model to estimate the economic and health burden of hookworm infection in every country, WHO region, and globally, in 2016 from the societal perspective. Globally, hookworm infection resulted in …
Microfluidic Platform For Electrophysiological Recordings From Host-Stage Hookworm And Ascaris Suum Larvae: A New Tool For Anthelmintic Research, Janis Weeks, William Roberts, Kristin Robinson, Melissa Keaney, Jon Vermiere, Joseph Urban, Shawn Lockery, John M. Hawdon
Microfluidic Platform For Electrophysiological Recordings From Host-Stage Hookworm And Ascaris Suum Larvae: A New Tool For Anthelmintic Research, Janis Weeks, William Roberts, Kristin Robinson, Melissa Keaney, Jon Vermiere, Joseph Urban, Shawn Lockery, John M. Hawdon
Microbiology, Immunology, and Tropical Medicine Faculty Publications
The screening of candidate compounds and natural products for anthelmintic activity is important for discovering new drugs against human and animal parasites. We previously validated in Caenorhabditis elegans a microfluidic device (‘chip’) that records non-invasively the tiny electrophysiological signals generated by rhythmic contraction (pumping) of the worm's pharynx. These electropharyngeograms (EPGs) are recorded simultaneously from multiple worms per chip, providing a medium-throughput readout of muscular and neural activity that is especially useful for compounds targeting neurotransmitter receptors and ion channels. Microfluidic technologies have transformedC. elegans research and the goal of the current study was to validate hookworm andAscaris …
Concurrent Presentation Of Waldenstrom's Macroglobulinemia And Angioimmunoblastic T-Cell Lymphoma, Amar Jariwala, Fadi Alakeel, Elsie Lee, Donald S. Karcher
Concurrent Presentation Of Waldenstrom's Macroglobulinemia And Angioimmunoblastic T-Cell Lymphoma, Amar Jariwala, Fadi Alakeel, Elsie Lee, Donald S. Karcher
Pathology Faculty Publications
A 73-year-old woman presented with generalized lymphadenopathy, atypical peripheral blood lymphocytosis, and Coombs-positive hemolytic anemia. She was diagnosed with Waldenstrom macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL), on the basis of IgM monoclonal gammopathy, significant lymphoplasmacytic infiltrate in bone marrow, circulating plasmacytoid lymphocytes in peripheral blood, monoclonal B lymphocytes with LPL-compatible immunophenotype by flow cytometry in bone marrow and peripheral blood, and clonal immunoglobulin heavy-chain gene rearrangement by polymerase chain reaction in peripheral blood. Molecular study results for MYB deletion and MYD88 mutation were negative. Following brief chemotherapy for WM, the patient's IgM monoclonal gammopathy and hemolytic anemia improved and the number of …
Blimp-1–Mediated Cd4 T Cell Exhaustion Causes Cd8 T Cell Dysfunction During Chronic Toxoplasmosis, Sujin Hwang, Dustin A. Cobb, Rajarshi Bhadra, Ben Youngblood, Imtiaz A. Khan
Blimp-1–Mediated Cd4 T Cell Exhaustion Causes Cd8 T Cell Dysfunction During Chronic Toxoplasmosis, Sujin Hwang, Dustin A. Cobb, Rajarshi Bhadra, Ben Youngblood, Imtiaz A. Khan
Microbiology, Immunology, and Tropical Medicine Faculty Publications
CD8, but not CD4, T cells are considered critical for control of chronic toxoplasmosis. Although CD8 exhaustion has been previously reported inToxoplasma encephalitis (TE)–susceptible model, our current work demonstrates that CD4 not only become exhausted during chronic toxoplasmosis but this dysfunction is more pronounced than CD8 T cells. Exhausted CD4 population expressed elevated levels of multiple inhibitory receptors concomitant with the reduced functionality and up-regulation of Blimp-1, a transcription factor. Our data demonstrates for the first time that Blimp-1 is a critical regulator for CD4 T cell exhaustion especially in the CD4 central memory cell subset. Using a tamoxifen-dependent …
Hepatic Fibrosis And Immune Phenotype Vary By Hcv Viremia In Hcv/Hiv Co-Infected Subjects: A Women's Interagency Hiv Study., Seema N Desai, Jennifer L Dodge, Alan L Landay, Marshall J Glesby, Patricia S. Latham, Maria C Villacres, Audrey L French, Stephen J Gange, Ruth M Greenblatt, Marion G Peters
Hepatic Fibrosis And Immune Phenotype Vary By Hcv Viremia In Hcv/Hiv Co-Infected Subjects: A Women's Interagency Hiv Study., Seema N Desai, Jennifer L Dodge, Alan L Landay, Marshall J Glesby, Patricia S. Latham, Maria C Villacres, Audrey L French, Stephen J Gange, Ruth M Greenblatt, Marion G Peters
Pathology Faculty Publications
HCV and HIV independently lead to immune dysregulation. The mechanisms leading to advanced liver disease progression in HCV/HIV coinfected subjects remain unclear.
In this cross-sectional study, we assessed the association of HCV viremia, liver fibrosis, and immune response patterns in well-characterized HIV phenotypes: Elite controllers (Elites), HIV controlled (ARTc), and HIV uncontrolled (ARTuc) matched by age and race. Groups were stratified by HCV RNA status. Regulatory T-cell frequencies, T-cell activation (HLADR+CD38+), apoptosis (Caspase-3+), and intracellular cytokines (interferon-γ, IL-2, IL-17) were assessed using multiparametric flow-cytometry. Liver fibrosis was scored by AST to platelet ratio index (APRI).
We found liver fibrosis (APRI) …
Human Herpesvirus Multiplex Ddpcr Detection In Brain Tissue From Low- And High-Grade Astrocytoma Cases And Controls., Cheng-Te Major Lin, Emily C Leibovitch, M Isabel Almira-Suarez, Steven Jacobson
Human Herpesvirus Multiplex Ddpcr Detection In Brain Tissue From Low- And High-Grade Astrocytoma Cases And Controls., Cheng-Te Major Lin, Emily C Leibovitch, M Isabel Almira-Suarez, Steven Jacobson
Pathology Faculty Publications
BACKGROUND: Glioblastoma (GBM) is a fatal CNS malignancy, representing 50 % of all gliomas with approximately 12-18 months survival time after initial diagnosis. Recently, the human herpesvirus cytomegalovirus (CMV) has been suggested to have an oncogenic role, yet this association remains controversial. In addition, human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) have also been associated with low-grade gliomas, but few studies have examined HHV-6 and EBV in glioblastomas. Droplet digital PCR (ddPCR) is a highly precise diagnostic tool that enables the absolute quantification of target DNA. This study examines the association between multiple human herpesviruses and astrocytomas.
METHODS: This …
Cellular Minichromosome Maintenance Complex Component 5 (Mcm5) Is Incorporated Into Hiv-1 Virions And Modulates Viral Replication In The Newly Infected Cells., Steven Santos, Yuri Obukhov, Sergei Nekhai, Tatiana Pushkarsky, Beda Brichacek, Michael Bukrinsky, Sergey Iordanskiy
Cellular Minichromosome Maintenance Complex Component 5 (Mcm5) Is Incorporated Into Hiv-1 Virions And Modulates Viral Replication In The Newly Infected Cells., Steven Santos, Yuri Obukhov, Sergei Nekhai, Tatiana Pushkarsky, Beda Brichacek, Michael Bukrinsky, Sergey Iordanskiy
Microbiology, Immunology, and Tropical Medicine Faculty Publications
The post-entry events of HIV-1 infection occur within reverse transcription complexes derived from the viral cores entering the target cell. HIV-1 cores contain host proteins incorporated from virus-producing cells. In this report, we show that MCM5, a subunit of the hexameric minichromosome maintenance (MCM) DNA helicase complex, associates with Gag polyprotein and is incorporated into HIV-1 virions. The progeny virions depleted of MCM5 demonstrated reduced reverse transcription in newly infected cells, but integration and subsequent replication steps were not affected. Interestingly, increased packaging of MCM5 into the virions also led to reduced reverse transcription, but here viral replication was impaired. …
Inversion Of The Vδ1 To Vδ2 Γδ T Cell Ratio In Cvid Is Not Restored By Ivig And Is Associated With Immune Activation And Exhaustion., Dominic Paquin-Proulx, Nathália Silveira Barsotti, Bianca A N Santos, Ana Karolina B B Marinho, Cristina M Kokron, Karina I Carvalho, Myrthes T Barros, Jorge Kalil, Douglas F. Nixon, Esper G Kallas
Inversion Of The Vδ1 To Vδ2 Γδ T Cell Ratio In Cvid Is Not Restored By Ivig And Is Associated With Immune Activation And Exhaustion., Dominic Paquin-Proulx, Nathália Silveira Barsotti, Bianca A N Santos, Ana Karolina B B Marinho, Cristina M Kokron, Karina I Carvalho, Myrthes T Barros, Jorge Kalil, Douglas F. Nixon, Esper G Kallas
Microbiology, Immunology, and Tropical Medicine Faculty Publications
Common variable immunodeficiency (CVID) is defined by low levels of IgG and IgA, but perturbations in T cells are also commonly found. However, there is limited information on γδ T cells in CVID patients. Newly diagnosed CVID patients (n = 15) were enrolled before and after intravenous IgG (IVIg) replacement therapy. Cryopreserved peripheral blood mononuclear cells were then used to study γδ T cells and CVID patients were compared to healthy controls (n = 22). The frequency and absolute count of Vδ1 γδ T cells was found to be increased in CVID (median 0.60% vs 2.64%, P <0.01 and 7.5 vs 39, P <0.01 respectively), while they were decreased for Vδ2 γδ T cells (median, 2.36% vs 0.74%,P <0.01 and 37.8 vs 13.9, P …0.01>0.01>0.01>
Biliary Microbiota, Gallstone Disease And Infection With Opisthorchis Felineus., Irina V. Saltykova, Vjacheslav A Petrov, Maria D Logacheva, Polina G Ivanova, Nikolay V Merzlikin, Alexey E Sazonov, Ludmila M Ogorodova, Paul J. Brindley
Biliary Microbiota, Gallstone Disease And Infection With Opisthorchis Felineus., Irina V. Saltykova, Vjacheslav A Petrov, Maria D Logacheva, Polina G Ivanova, Nikolay V Merzlikin, Alexey E Sazonov, Ludmila M Ogorodova, Paul J. Brindley
Microbiology, Immunology, and Tropical Medicine Faculty Publications
BACKGROUND: There is increasing interest in the microbiome of the hepatobiliary system. This study investigated the influence of infection with the fish-borne liver fluke, Opisthorchis felineus on the biliary microbiome of residents of the Tomsk region of western Siberia.
METHODOLOGY/PRINCIPAL FINDINGS: Samples of bile were provided by 56 study participants, half of who were infected with O. felineus, and all of who were diagnosed with gallstone disease. The microbiota of the bile was investigated using high throughput, Illumina-based sequencing targeting the prokaryotic 16S rRNA gene. About 2,797, discrete phylotypes of prokaryotes were detected. At the level of phylum, bile from …
Brief Report: Hiv-1 Gp120 T-Cell Responses Correspond To Infection Outcomes In The Global Iprex Chemoprophylaxis Trial., Peter J Kuebler, Brian I Shaw, Kaitlyn S Leadabrand, Megha L Mehrotra, Robert M Grant, Esper G Kallás, Douglas F Nixon
Brief Report: Hiv-1 Gp120 T-Cell Responses Correspond To Infection Outcomes In The Global Iprex Chemoprophylaxis Trial., Peter J Kuebler, Brian I Shaw, Kaitlyn S Leadabrand, Megha L Mehrotra, Robert M Grant, Esper G Kallás, Douglas F Nixon
Microbiology, Immunology, and Tropical Medicine Faculty Publications
Association of HIV-1-specific T-cell responses to infection risk in seronegative individuals is controversial. We quantified and phenotypically characterized gp120-specific T-cell responses in HIV-1 exposed, but uninfected subjects enrolled in the global Pre-exposure Prophylaxis Initiative (iPrEx) chemoprophylaxis trial. IFNγ ELISpot responses were detected in 24% of subjects irrespective of infection outcome. HIV-1 gp120 envelope-specific T-cell responses were more uniformly IFN-γ+TNF-α+Mip-1β+ in persistently seronegative subjects relative to subjects who later seroconverted (median frequency of 76.5% and 66.5%, respectively). IFNγ responses targeted the V2 loop for subjects who remained seronegative. HIV-1 gp120 envelope V2 loop-specific CD8 T-cell responses may help to protect against …
Oligodendrocyte Ablation As A Tool To Study Demyelinating Diseases, Ahdeah Pajoohesh-Ganji, Robert H. Miller
Oligodendrocyte Ablation As A Tool To Study Demyelinating Diseases, Ahdeah Pajoohesh-Ganji, Robert H. Miller
Anatomy and Regenerative Biology Faculty Publications
Multiple sclerosis (MS) is an autoimmune mediated neurodegenerative disease characterized by demyelination and oligodendrocyte (OL) loss in the central nervous system and accompanied by local inflammation and infiltration of peripheral immune cells. Although many risk factors and symptoms have been identified in MS, the pathology is complicated and the cause remains unknown. It is also unclear whether OL apoptosis precedes the inflammation or whether the local inflammation is the cause of OL death and demyelination. This review briefly discusses several models that have been developed to specifically ablate oligodendrocytes in an effort to separate the effects of demyelination from inflammation.