Nakamoto, Beau MD PhD

Research Overview

2011-2012 RMATRIX Collaboration Pilot Projects Program Awards

Project Description

Abstract

Neuroimaging Correlates of Monocyte/Macrophage Infiltration in HIV-infected Individuals: A Cross-sectional Pilot Study Using IV Furomoxytol

The primary goal of the proposed study is to determine if a novel monocyte/macrophage-specific MRI contrast agent (ferumoxytol) can be used as a biomarker for HIV-associated cognitive impairment. The study will capitalize on a pre-existing collaboration between a clinician and basic scientist in NeuroAIDS at the University of Hawaii and foster a collaboration with a neuroradiologist at the Oregon Health Science University. Cognitive impairment in Native-Hawaiians infected with HIV remains prevalent and a major source of morbidity and mortality despite widespread availability of effective antiretroviral therapy. One hypothesis to explain the persistence of this cognitive dysfunction is that current medications incompletely eradicate the reservoir of HIV infected monocytes/macrophages in the bloodstream, which allow these infected cells to traffic across the blood-brain barrier and precipitate an inflammatory cascade in the brain leading to neuronal dysfunction and ultimately cognitive dysfunction. Prior studies using gadolininum-enhanced MRI demonstrated that nonspecific inflammation preferentially affects the basal ganglia and subcortical frontal white matter. Ferumoxytol is a novel MRI contrast agent endocytosed by macrophages and is a promising modality to directly assess inflammatory changes associated with monocyte/macrophage infiltration in the brain. We propose a pathogenesis-driven, proof-of-concept pilot study to determine the neuroimaging correlates on Feridexenhanced MRI in HIV-infected individuals with cognitive impairment and high levels of HIV DNA in peripheral blood mononuclear cells (PBMCs). Research Aim: To examine the relationship between PBMC HIV DNA and monocyte/macrophage infiltration in the basal ganglia and subcortical frontal white matter using ferumoxytol contrast-enhanced brain MRI. Hypothesis: Individuals with HIV-associated cognitive impairment and high levels of PBMC HIV DNA will demonstrate ferumoxytol contrast enhancement in the basal ganglia and subcortical frontal white matter supporting monocyte/macrophage-specific infiltration in these regions.

Selected Publications

• Chang DA, Ede RC, Chow DC, Souza RD, Gangcuangco LM, Hanks N, Nakamoto BK, Mitchell B, Masutani AT, Fisk S, Shikuma CM, Dill JE.
  Early Childhood Vision Screening in Hawai'i Utilizing a Hand-Held Screener.
  Hawaii J Med Public Health 2015 [more...]


• Chow D, Nakamoto BK, Sullivan K, Sletten DM, Fujii S, Umekawa S, Kocher M, Kallianpur KJ, Shikuma CM, Low P.
  Symptoms of Autonomic Dysfunction in Human Immunodeficiency Virus.
  Open Forum Infect Dis 2015 [more...]


• Kocher MH, Hetzler RK, Shikuma CM, Kimura IF, Stickley CD, Lindsey RA, Nakamoto BK, Chow DC.
  Autonomic Function is Associated with Fitness Level in HIV-Infected Individuals.
  Jacobs J AIDS HIV 2015 [more...]


• Munger AM, Chow DC, Playford MP, Parikh NI, Gangcuangco LM, Nakamoto BK, Kallianpur KJ, Ndhlovu LC, Shikuma CM, Mehta NN.
  Characterization of lipid composition and high-density lipoprotein function in HIV-infected individuals on stable antiretroviral regimens.
  AIDS Res Hum Retroviruses 2015 [more...]


• Parikh NI, Gerschenson M, Bennett K, Gangcuangco LM, Lopez MS, Mehta NN, Playford MP, Nakamoto BK, Seto TB, Chow DC, Shikuma CM.
  Lipoprotein concentration, particle number, size and cholesterol efflux capacity are associated with mitochondrial oxidative stress and function in an HIV positive cohort.
  Atherosclerosis 2015 [more...]


• Sentell TL, Valcour N, Ahn HJ, Miyamura J, Nakamoto B, Chow D, Masaki K, Seto TB, Chen JJ, Shikuma C.
  High rates of Native Hawaiian and older Japanese adults hospitalized with dementia in Hawai'i.
  J Am Geriatr Soc 2015 [more...]


• Shikuma CM, Bennett K, Ananworanich J, Gerschenson M, Teeratakulpisarn N, Jadwattanakul T, DeGruttola V, McArthur JC, Ebenezer G, Chomchey N, Praihirunkit P, Hongchookiat P, Mathajittiphun P, Nakamoto B, Hauer P, Phanuphak P, Phanuphak N.
  Distal leg epidermal nerve fiber density as a surrogate marker of HIV-associated sensory neuropathy risk: risk factors and change following initial antiretroviral therapy.
  J Neurovirol 2015 [more...]


• Dalrymple K, Saito EK, Diaz N, Morrow J, Nakamoto B, McMurtray AM.
  Past Cigarette Smoking Is More Common among Those with Cholinergic Than Noncholinergic Dementias.
  Neurol Res Int 2014 [more...]


• Ndhlovu LC, Umaki T, Chew GM, Chow DC, Agsalda M, Kallianpur KJ, Paul R, Zhang G, Ho E, Hanks N, Nakamoto B, Shiramizu BT, Shikuma CM.
  Treatment intensification with maraviroc (CCR5 antagonist) leads to declines in CD16-expressing monocytes in cART-suppressed chronic HIV-infected subjects and is associated with improvements in neurocognitive test performance: implications for...
  J Neurovirol 2014 [more...]


• Saito E, Nakamoto BK, Mendez MF, Mehta B, McMurtray A.
  Cost effective community based dementia screening: a markov model simulation.
  Int J Alzheimers Dis 2014 [more...]


• Shikuma CM, Chow DC, Gangcuangco LM, Zhang G, Keating SM, Norris PJ, Seto TB, Parikh N, Kallianpur KJ, Nakamoto BK, Nagamine LS, Ndhlovu LC, Barbour JD.
  Monocytes expand with immune dysregulation and is associated with insulin resistance in older individuals with chronic HIV.
  PLoS One 2014 [more...]


• Shikuma CM, Gangcuangco LM, Killebrew DA, Libutti DE, Chow DC, Nakamoto BK, Liang CY, Milne CI, Ndhlovu LC, Barbour JD, Shiramizu BT, Gerschenson M.
  The role of HIV and monocytes/macrophages in adipose tissue biology.
  J Acquir Immune Defic Syndr 2014 [more...]


• Chow D, Nakamoto B, So E, Parikh N, Souza S, Kallianpur K, Shikuma C.
  Rates of autonomic dysfunction in HIV patients receiving antiretroviral therapy.
  J Neurovirol 2013 [more...]


• Gangcuangco LM, Chow DC, Liang CY, Nakamoto BK, Umaki TM, Kallianpur KJ, Shikuma CM.
  Predictors of 25-hydroxyvitamin D levels in HIV-infected patients in Hawai'i.
  Hawaii J Med Public Health 2013 [more...]


• Jalbert E, Crawford TQ, D'Antoni ML, Keating SM, Norris PJ, Nakamoto BK, Seto T, Parikh NI, Shikuma CM, Ndhlovu LC, Barbour JD.
  IL-1B enriched monocytes mount massive IL-6 responses to common inflammatory triggers among chronically HIV-1 infected adults on stable anti-retroviral therapy at risk for cardiovascular disease.
  PLoS One 2013 [more...]


• Kallianpur KJ, Shikuma C, Kirk GR, Shiramizu B, Valcour V, Chow D, Souza S, Nakamoto B, Sailasuta N.
  Peripheral blood HIV DNA is associated with atrophy of cerebellar and subcortical gray matter.
  Neurology 2013 [more...]


• Lin C, Grandinetti A, Shikuma C, Souza S, Parikh N, Nakamoto B, Kallianpur KJ, Chow D.
  The effects of extended release niacin on lipoprotein sub-particle concentrations in HIV-infected patients.
  Hawaii J Med Public Health 2013 [more...]


• McMurtray AM, Saito EK, Diaz N, Mehta B, Nakamoto B.
  Greater frequency of depression associated with chronic primary headaches than chronic post-traumatic headaches.
  Int J Psychiatry Med 2013 [more...]


• Nakamoto BK, Shikuma CM, Ogata-Arakaki D, Umaki T, Neuwelt EA, Shiramizu BT, Chow DC, Parikh NI, Kallianpur KJ, Hamilton BE.
  Feasibility and potential role of ferumoxytol-enhanced neuroimaging in HIV-associated neurocognitive disorder.
  J Neurovirol 2013 [more...]


• Nakamoto BK, Siu AM, Hashiba KA, Sinclair BT, Baker BJ, Gerber MS, McMurtray AM, Pearce AM, Pearce JW.
  Surfer's myelopathy: a radiologic study of 23 cases.
  AJNR Am J Neuroradiol 2013 [more...]


• Tongma C, Shikuma CM, Nakamoto BK, Kallianpur KJ, Umaki TM, Barbour JD, Ndhlovu L, Parikh NI, Chow DC.
  Albuminuria as a marker of cardiovascular risk in HIV-infected individuals receiving stable antiretroviral therapy.
  Hawaii J Med Public Health 2013 [more...]


• Tse GG, Kim BB, McMurtray AM, Nakamoto BK.
  Case of levodopa toxicity from ingestion of Mucuna gigantea.
  Hawaii J Med Public Health 2013 [more...]


• Tse GG, Masuda EM, McMurtray AM, Nakamoto BK.
  Coiled internal carotid arteries associated with bilateral sequential strokes.
  Case Rep Vasc Med 2013 [more...]


• Tse GG, Santos-Ocampo AS, Chow DC, McMurtray AM, Nakamoto BK.
  Diffuse leukoencephalopathy and subacute parkinsonism as an early manifestation of systemic lupus erythematosus.
  Case Rep Neurol Med 2013 [more...]


• Umaki TM, Gangcuangco LM, Chow DC, Nakamoto BK, Marotz L, Kallianpur KJ, Shikuma CM.
  Poorer neuropsychological performance increases risk for social services among HIV-infected individuals.
  Hawaii J Med Public Health 2013 [more...]


• Chow D, Kocher M, Shikuma C, Parikh N, Grandinetti A, Nakamoto B, Seto T, Low P.
  Effects of antiretroviral therapy on autonomic function in early HIV infection: a preliminary report.
  Int J Med Sci 2012 [more...]


• Chow D, Thomas BS, Liang CY, Souza SC, Nakamoto BK, Parikh NI, Shikuma C.
  Role of the veterans aging cohort study index in assessing total atherosclerotic burden.
  Clin Infect Dis 2012 [more...]


• Kallianpur KJ, Kirk GR, Sailasuta N, Valcour V, Shiramizu B, Nakamoto BK, Shikuma C.
  Regional cortical thinning associated with detectable levels of HIV DNA.
  Cereb Cortex 2012 [more...]


• Nakamoto BK, Jahanshad N, McMurtray A, Kallianpur KJ, Chow DC, Valcour VG, Paul RH, Marotz L, Thompson PM, Shikuma CM.
  Cerebrovascular risk factors and brain microstructural abnormalities on diffusion tensor images in HIV-infected individuals.
  J Neurovirol 2012 [more...]


• Shikuma C, Gerschenson M, Ananworanich J, Valcour V, Teeratakulpisarn N, Jadwattanakul T, Degruttola V, Liang CY, McArthur J, Ebenezer G, Chomchey N, Praihirunkit P, Hongchookiath P, Mathajittiphun P, Nakamoto B, Hauer P, Phanuphak P, Phanuphak N.
  Determinants of epidermal nerve fibre density in antiretroviral-na�¯ve HIV-infected individuals.
  HIV Med 2012 [more...]


• Shikuma CM, Nakamoto B, Shiramizu B, Liang CY, DeGruttola V, Bennett K, Paul R, Kallianpur K, Chow D, Gavegnano C, Hurwitz SJ, Schinazi RF, Valcour VG.
  Antiretroviral monocyte efficacy score linked to cognitive impairment in HIV.
  Antivir Ther 2012 [more...]


• Chow DC, Wood R, Choi J, Grandinetti A, Gerschenson M, Sriratanaviriyakul N, Nakamoto B, Shikuma C, Low P.
  Cardiovagal autonomic function in HIV-infected patients with unsuppressed HIV viremia.
  HIV Clin Trials 2011 [more...]


• Nakamoto BK, Valcour VG, Kallianpur K, Liang CY, McMurtray A, Chow D, Kappenburg E, Shikuma CM.
  Impact of cerebrovascular disease on cognitive function in HIV-infected patients.
  J Acquir Immune Defic Syndr 2011 [more...]


• Shimizu SM, Chow DC, Valcour V, Masaki K, Nakamoto B, Kallianpur KJ, Shikuma C.
  The Impact of Depressive Symptoms on Neuropsychological Performance Tests in HIV-Infected Individuals: A Study of the Hawaii Aging with HIV Cohort.
  World J AIDS 2011 [more...]


• Nakamoto BK, McMurtray A, Davis J, Valcour V, Watters MR, Shiramizu B, Chow DC, Kallianpur K, Shikuma CM.
  Incident neuropathy in HIV-infected patients on HAART.
  AIDS Res Hum Retroviruses 2010 [more...]


• Digre KB, Nakamoto BK, Warner JE, Langeberg WJ, Baggaley SK, Katz BJ.
  A comparison of idiopathic intracranial hypertension with and without papilledema.
  Headache 2009 [more...]


• McMurtray A, Saito E, Nakamoto B.
  Language preference and development of dementia among bilingual individuals.
  Hawaii Med J 2009 [more...]


• McMurtray A, Nakamoto B, Shikuma C, Valcour V.
  Cortical atrophy and white matter hyperintensities in HIV: the Hawaii Aging with HIV Cohort Study.
  J Stroke Cerebrovasc Dis 2008 [more...]