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Norman haughey

Michael S Piepenbrink, Memorie Samuel, Bo Zheng, Brittany Carter, Christopher Fucile, Catherine Bunce, Michelle Kiebala, Atif A Khan, Juilee Thakar, Sanjay B Maggirwar, Diane Morse, Alexander F Rosenberg, Norman J Haughey, William Valenti, Michael C Keefer, James J Kobie
BACKGROUND: Injection drug use is a growing major public health concern. Injection drug users (IDUs) have a higher incidence of co-morbidities including HIV, Hepatitis, and other infections. An effective humoral response is critical for optimal homeostasis and protection from infection; however, the impact of injection heroin use on humoral immunity is poorly understood. We hypothesized that IDUs have altered B cell and antibody profiles. METHODS AND FINDINGS: A comprehensive systems biology-based cross-sectional assessment of 130 peripheral blood B cell flow cytometry- and plasma- based features was performed on HIV-/Hepatitis C-, active heroin IDUs who participated in a syringe exchange program (n = 19) and healthy control subjects (n = 19)...
2016: PloS One
Christopher E Gonzalez, Vijay K Venkatraman, Yang An, Bennett A Landman, Christos Davatzikos, Veera Venkata Ratnam Bandaru, Norman J Haughey, Luigi Ferrucci, Michelle M Mielke, Susan M Resnick
Sphingolipids serve important structural and functional roles in cellular membranes and myelin sheaths. Plasma sphingolipids have been shown to predict cognitive decline and Alzheimer's disease. However, the association between plasma sphingolipid levels and brain white matter (WM) microstructure has not been examined. We investigated whether plasma sphingolipids (ceramides and sphingomyelins) were associated with magnetic resonance imaging-based diffusion measures, fractional anisotropy (FA), and mean diffusivity, 10...
July 2016: Neurobiology of Aging
Elisa Fabbri, An Yang, Eleanor M Simonsick, Chee W Chia, Marco Zoli, Norman J Haughey, Michelle M Mielke, Luigi Ferrucci, Paul M Coen
Cardiorespiratory fitness (VO2 peak) declines with age and is an independent risk factor for morbidity and mortality in older adults. Identifying biomarkers of low fitness may provide insight for why some individuals experience an accelerated decline of aerobic capacity and may serve as clinically valuable prognostic indicators of cardiovascular health. We investigated the relationship between circulating ceramides and VO2 peak in 443 men and women (mean age of 69) enrolled in the Baltimore Longitudinal Study of Aging (BLSA)...
October 2016: Aging Cell
Akshata A Almad, Arpitha Doreswamy, Sarah K Gross, Jean-Philippe Richard, Yuqing Huo, Norman Haughey, Nicholas J Maragakis
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons in the CNS. Astrocytes play a critical role in disease progression of ALS. Astrocytes are interconnected through a family of gap junction proteins known as connexins (Cx). Cx43 is a major astrocyte connexin conducting crucial homeostatic functions in the CNS. Under pathological conditions, connexin expression and functions are altered. Here we report that an abnormal increase in Cx43 expression serves as one of the mechanisms for astrocyte-mediated toxicity in ALS...
July 2016: Glia
Deanna Saylor, Alex M Dickens, Ned Sacktor, Norman Haughey, Barbara Slusher, Mikhail Pletnikov, Joseph L Mankowski, Amanda Brown, David J Volsky, Justin C McArthur
No abstract text is available yet for this article.
May 2016: Nature Reviews. Neurology
Deanna Saylor, Alex M Dickens, Ned Sacktor, Norman Haughey, Barbara Slusher, Mikhail Pletnikov, Joseph L Mankowski, Amanda Brown, David J Volsky, Justin C McArthur
In the past two decades, several advancements have improved the care of HIV-infected individuals. Most importantly, the development and deployment of combination antiretroviral therapy (CART) has resulted in a dramatic decline in the rate of deaths from AIDS, so that people living with HIV today have nearly normal life expectancies if treated with CART. The term HIV-associated neurocognitive disorder (HAND) has been used to describe the spectrum of neurocognitive dysfunction associated with HIV infection. HIV can enter the CNS during early stages of infection, and persistent CNS HIV infection and inflammation probably contribute to the development of HAND...
April 2016: Nature Reviews. Neurology
Joseph P Steiner, Muznabanu Bachani, Brett Wolfson-Stofko, Myoung-Hwa Lee, Tongguang Wang, Guanhan Li, Wenxue Li, David Strayer, Norman J Haughey, Avindra Nath
No abstract text is available yet for this article.
January 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
B Lee Peterlin, Michelle M Mielke, Alex M Dickens, Subroto Chatterjee, Paul Dash, Guillermo Alexander, Rebeca V A Vieira, Veera Venkata Ratnam Bandaru, Joelle M Dorskind, Gretchen E Tietjen, Norman H Haughey
OBJECTIVE: To evaluate interictal, circulating sphingolipids in women migraineurs. METHODS: In the fasting state, serum samples were obtained pain-free from 88 women with episodic migraine (EM; n=52) and from controls (n=36). Sphingolipids were detected and quantified by high-performance liquid chromatography coupled with tandem mass spectrometry using multiple reaction monitoring. Multivariate logistic regression was used to examine the association between serum sphingolipids and EM odds...
October 6, 2015: Neurology
Michelle M Mielke, Veera Venkata Ratnam Bandaru, Dingfen Han, Yang An, Susan M Resnick, Luigi Ferrucci, Norman J Haughey
It has been increasingly recognized at the basic science level that perturbations in ceramide metabolism are associated with the development and progression of many age-related diseases. However, the translation of this work to the clinic has lagged behind. Understanding the factors longitudinally associated with plasma ceramides and dihydroceramides (DHCer) at the population level and how these lipid levels change with age, and by sex, is important for the clinical development of future therapeutics and biomarkers focused on ceramide metabolism...
December 2015: Aging Cell
Mariana Figuera-Losada, Marigo Stathis, Joelle M Dorskind, Ajit G Thomas, Veera Venkata Ratnam Bandaru, Seung-Wan Yoo, Nicholas J Westwood, Graeme W Rogers, Justin C McArthur, Norman J Haughey, Barbara S Slusher, Camilo Rojas
Ceramide is a bioactive lipid that plays an important role in stress responses leading to apoptosis, cell growth arrest and differentiation. Ceramide production is due in part to sphingomyelin hydrolysis by sphingomyelinases. In brain, neutral sphingomyelinase 2 (nSMase2) is expressed in neurons and increases in its activity and expression have been associated with pro-inflammatory conditions observed in Alzheimer's disease, multiple sclerosis and human immunodeficiency virus (HIV-1) patients. Increased nSMase2 activity translates into higher ceramide levels and neuronal cell death, which can be prevented by chemical or genetic inhibition of nSMase2 activity or expression...
2015: PloS One
Alex M Dickens, Daniel C Anthony, Reena Deutsch, Michelle M Mielke, Timothy D W Claridge, Igor Grant, Donald Franklin, Debra Rosario, Thomas Marcotte, Scott Letendre, Justin C McArthur, Norman J Haughey
OBJECTIVES: To identify prognostic surrogate markers for change in cognitive states of HIV-infected patients. DESIGN: Longitudinal cerebrospinal fluid (CSF) samples were collected from 98 HIV-infected patients identified by temporal change in cognitive states classified as normal, stably impaired, improving and worsening. METHODS: The metabolic composition of CSF was analysed using H nuclear magnetic resonance (H NMR) spectroscopy that focused on energy metabolites...
March 13, 2015: AIDS
Joseph W McFadden, Susan Aja, Qun Li, Veera V R Bandaru, Eun-Kyoung Kim, Norman J Haughey, Francis P Kuhajda, Gabriele V Ronnett
Modification of hypothalamic fatty acid (FA) metabolism can improve energy homeostasis and prevent hyperphagia and excessive weight gain in diet-induced obesity (DIO) from a diet high in saturated fatty acids. We have shown previously that C75, a stimulator of carnitine palmitoyl transferase-1 (CPT-1) and fatty acid oxidation (FAOx), exerts at least some of its hypophagic effects via neuronal mechanisms in the hypothalamus. In the present work, we characterized the effects of C75 and another anorexigenic compound, the glycerol-3-phosphate acyltransferase (GPAT) inhibitor FSG67, on FA metabolism, metabolomics profiles, and metabolic stress responses in cultured hypothalamic neurons and hypothalamic neuronal cell lines during lipid excess with palmitate...
2014: PloS One
Veera Venkata Ratnam Bandaru, Norman J Haughey
BACKGROUND: Cholesterol metabolism is important for the maintenance of myelin and neuronal membranes in the central nervous system. Blood concentrations of the brain specific cholesterol metabolite 24S-hydroxysterol to the peripheral metabolite 27-hydroxycholesterol may be useful surrogate markers for neurodegenerative diseases including Alzheimer's disease, Huntington's disease, HIV-Associated Neurocognitive Disorders, and Multiple Sclerosis. However, current methods to isolate hydroxycholesterols are labor intensive, prone to produce variable extraction efficiencies and do not discriminate between free and esterfied forms of hydroxycholesterols...
2014: BMC Neuroscience
Joseph P Steiner, Muznabanu Bachani, Brett Wolfson-Stofko, Myoung-Hwa Lee, Tongguang Wang, Tonguang Wang, Guanhan Li, Wenxue Li, David Strayer, Norman J Haughey, Avindra Nath
There are severe neurological complications that arise from HIV infection, ranging from peripheral sensory neuropathy to cognitive decline and dementia for which no specific treatments are available. The HIV proteins secreted from infected macrophages, gp120 and Tat, are neurotoxic. The goal of this study was to screen, identify and develop neuroprotective compounds relevant to HIV-associated neurocognitive disorders (HAND). We screened more than 2000 compounds that included FDA approved drugs for protective efficacy against oxidative stress-mediated neurodegeneration and identified selective serotonin reuptake inhibitors (SSRIs) as potential neuroprotectants...
January 2015: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Ned Sacktor, Sachiko Miyahara, Scott Evans, Giovanni Schifitto, Bruce Cohen, Norman Haughey, Julia L Drewes, David Graham, M Christine Zink, Caroline Anderson, Avindra Nath, Carlos A Pardo, Sean McCarthy, Lara Hosey, David Clifford
Elevated cerebrospinal fluid (CSF) levels of markers of oxidative stress, neuronal injury, and inflammation and decreased neurotransmitter levels have been reported in HIV-associated neurocognitive disorders (HAND). Minocycline may have a neuroprotective effect by inhibiting inducible nitric oxide synthase, which produces nitric oxide, a compound that induces oxygen free radical production. In A5235, "Phase II, Randomized, Placebo-Controlled, Double-Blind Study of Minocycline in the Treatment of HIV-Associated Cognitive Impairment," minocycline was not associated with cognitive improvement, but the effect on the above CSF measures was not examined previously...
December 2014: Journal of Neurovirology
Michelle M Mielke, Veera Venkata Ratnam Bandaru, Dingfen Han, Yang An, Susan M Resnick, Luigi Ferrucci, Norman J Haughey
Sphingomyelin metabolism has been linked to several diseases and to longevity. However, few epidemiological studies have quantified individual plasma sphingomyelin species (identified by acyl-chain length and saturation) or their relationship between demographic factors and disease processes. In this study, we determined plasma concentrations of distinct sphingomyelin species in 992 individuals, aged 55 and older, enrolled in the Baltimore Longitudinal Study of Aging. Participants were followed, with serial measures, up to 6 visits and 38 years (3972 total samples)...
February 2015: Aging Cell
Mihyun Bae, Neha Patel, Haoxing Xu, Mingwaoh Lee, Kumiko Tominaga-Yamanaka, Avindra Nath, Jonathan Geiger, Myriam Gorospe, Mark P Mattson, Norman J Haughey
Antiretroviral therapy extends the lifespan of human immunodeficiency virus (HIV)-infected patients, but many survivors develop premature impairments in cognition. These residual cognitive impairments may involve aberrant deposition of amyloid β-peptides (Aβ). By unknown mechanisms, Aβ accumulates in the lysosomal and autophagic compartments of neurons in the HIV-infected brain. Here we identify the molecular events evoked by the HIV coat protein gp120 that facilitate the intraneuronal accumulation of Aβ...
August 20, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Mihyun Bae, Veera Venkata Ratnam Bandaru, Neha Patel, Norman J Haughey
Binge drinking is a common form of alcohol abuse that involves repeated rounds of intoxication followed by withdrawal. The episodic effects of binge drinking and withdrawal on brain resident cells are thought to contribute to neural remodeling and neurological damage. However, the molecular mechanisms for these neurodegenerative effects are not understood. Ethanol (EtOH) regulates the metabolism of ceramide, a highly bioactive lipid that is enriched in brain. We used a mouse model of binge drinking to determine the effects of EtOH intoxication and withdrawal on brain ceramide metabolism...
December 2014: Journal of Neurochemistry
Adriana Bora, Ceereena Ubaida Mohien, Raghothama Chaerkady, Linda Chang, Richard Moxley, Ned Sacktor, Norman Haughey, Justin C McArthur, Robert Cotter, Avindra Nath, David R Graham
We identified and measured proteins in the cerebral spinal fluid (CSF) involved in HIV-associated neurological disorders. Protein levels were determined by mass spectrometry (MS) in pooled CSF taken from three patient groups (human immunodeficiency virus (HIV)-1-infected patients that developed HIV-associated neurocognitive disorders (HANDs), HIV-1-infected patients without HAND, and healthy controls). Pools were generated from 10 patients each per group. CSF from individual patient groups were digested with trypsin and separately labeled using with isobaric tags for relative and absolute quantitation (iTRAQ)...
October 2014: Journal of Neurovirology
Andrew D Sauerbeck, J Lukas Laws, Veera V R Bandaru, Phillip G Popovich, Norman J Haughey, Dana M McTigue
Traumatic spinal cord injury (SCI) causes major disruption to peripheral organ innervation and regulation. Relatively little work has investigated these post-SCI systemic changes, however, despite considerable evidence that multiple organ system dysfunction contributes to chronic impairments in health. Because metabolic dysfunction is common after SCI and the liver is a pivotal site for metabolic homeostasis, we sought to determine if liver pathology occurs as a result of SCI in a rat spinal contusion model...
February 1, 2015: Journal of Neurotrauma
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