Arts and Humanities Commons^™

Development Of Antigen-Specific Memory Cd8+ T Cells Following Live-Attenuated Chimeric West Nile Virus Vaccination, Heidi Smith, Thomas Monath, Pamela Pazoles, Alan Rothman, Diane Casey, Masanori Terajima, Francis Ennis, Farshad Guirakhoo, Sharone Green

Alan Rothman

ChimeriVax-WN02 is a novel live-attenuated West Nile virus (WNV) vaccine containing modified WNV premembrane (prM) and envelope (E) sequences inserted into the yellow fever 17D vaccine genome. We investigated the induction and evolution of CD8(+) T cell responses to a WNV envelope epitope, which is a dominant target in naturally infected HLA-A*02-positive individuals. WNV epitope-specific CD8(+) T cells were detected by HLA tetramer staining in 22 of 23 donors tested, with peak frequencies occurring between days 14 and 28. WNV epitope-specific T cells evolved from an effector phenotype to a long-lived memory phenotype. In the majority of donors, CD8(+) T …

Intracellular Cytokine Production By Dengue Virus-Specific T Cells Correlates With Subclinical Secondary Infection, Steven Hatch, Timothy Endy, Stephen Thomas, Anuja Mathew, James Potts, Pamela Pazoles, Daniel Libraty, Robert Gibbons, Alan Rothman

Alan Rothman

The pathophysiology of dengue virus infection remains poorly understood, although secondary infection is strongly associated with more severe disease. In the present study, we performed a nested, case-control study comparing the responses of pre-illness peripheral blood mononuclear cells between children who would subsequently develop either subclinical or symptomatic secondary infection 6-11 months after the baseline blood samples were obtained and frozen. We analyzed intracellular cytokine production by CD4(+) and CD8(+) cells in response to stimulation with dengue antigen. We found higher frequencies of dengue virus-specific TNFalpha, IFNgamma-, and IL-2-producing T cells among schoolchildren who subsequently developed subclinical infection, compared with …

Determinants Of Inapparent And Symptomatic Dengue Infection In A Prospective Study Of Primary School Children In Kamphaeng Phet, Thailand, Timothy Endy, Kathryn Anderson, Ananda Nisalak, In-Kyu Yoon, Sharone Green, Alan Rothman, Stephen Thomas, Richard Jarman, Daniel Libraty, Robert Gibbons

Alan Rothman

BACKGROUND: Dengue viruses are a major cause of morbidity in tropical and subtropical regions of the world. Inapparent dengue is an important component of the overall burden of dengue infection. It provides a source of infection for mosquito transmission during the course of an epidemic, yet by definition is undetected by health care providers. Previous studies of inapparent or subclinical infection have reported varying ratios of symptomatic to inapparent dengue infection.

METHODOLOGY/PRINCIPAL FINDINGS: In a prospective study of school children in Northern Thailand, we describe the spatial and temporal variation of the symptomatic to inapparent (S:I) dengue illness ratio. Our …

B-Cell Responses During Primary And Secondary Dengue Virus Infections In Humans, Anuja Mathew, Kim West, Siripen Kalayanarooj, Robert Gibbons, Anon Srikiatkhachorn, Sharone Green, Daniel Libraty, Smita Jaiswal, Alan Rothman

Alan Rothman

Low-avidity serotype-cross-reactive antibodies are hypothesized to play a key role in triggering severe disease in patients with secondary dengue virus (DENV) infection. However, there is little systematic information about the frequency, avidity, and cross-reactivity of DENV-specific B cells in individuals experiencing primary instead of secondary infection. We compared DENV-specific B-cell responses in a cohort of Thai children with primary or secondary DENV infection. B cells specific for DENV precursor membrane protein, envelope (E) protein, and nonstructural protein 1 were detectable in immune peripheral blood mononuclear cells with the highest frequencies of DENV E-specific B cells detected in patients experiencing primary …

Development Of Antigen-Specific Memory Cd8+ T Cells Following Live-Attenuated Chimeric West Nile Virus Vaccination, Heidi Smith, Thomas Monath, Pamela Pazoles, Alan Rothman, Diane Casey, Masanori Terajima, Francis Ennis, Farshad Guirakhoo, Sharone Green

Sharone Green

ChimeriVax-WN02 is a novel live-attenuated West Nile virus (WNV) vaccine containing modified WNV premembrane (prM) and envelope (E) sequences inserted into the yellow fever 17D vaccine genome. We investigated the induction and evolution of CD8(+) T cell responses to a WNV envelope epitope, which is a dominant target in naturally infected HLA-A*02-positive individuals. WNV epitope-specific CD8(+) T cells were detected by HLA tetramer staining in 22 of 23 donors tested, with peak frequencies occurring between days 14 and 28. WNV epitope-specific T cells evolved from an effector phenotype to a long-lived memory phenotype. In the majority of donors, CD8(+) T …

Determinants Of Inapparent And Symptomatic Dengue Infection In A Prospective Study Of Primary School Children In Kamphaeng Phet, Thailand, Timothy P. Endy, Kathryn B. Anderson, Ananda Nisalak, In-Kyu Yoon, Sharone Green, Alan L. Rothman, Stephen J. Thomas, Richard G. Jarman, Daniel H. Libraty, Robert V. Gibbons

Sharone Green

BACKGROUND: Dengue viruses are a major cause of morbidity in tropical and subtropical regions of the world. Inapparent dengue is an important component of the overall burden of dengue infection. It provides a source of infection for mosquito transmission during the course of an epidemic, yet by definition is undetected by health care providers. Previous studies of inapparent or subclinical infection have reported varying ratios of symptomatic to inapparent dengue infection. METHODOLOGY/PRINCIPAL FINDINGS: In a prospective study of school children in Northern Thailand, we describe the spatial and temporal variation of the symptomatic to inapparent (S:I) dengue illness ratio. Our …

B-Cell Responses During Primary And Secondary Dengue Virus Infections In Humans, Anuja Mathew, Kim West, Siripen Kalayanarooj, Robert Gibbons, Anon Srikiatkhachorn, Sharone Green, Daniel Libraty, Smita Jaiswal, Alan Rothman

Sharone Green

Low-avidity serotype-cross-reactive antibodies are hypothesized to play a key role in triggering severe disease in patients with secondary dengue virus (DENV) infection. However, there is little systematic information about the frequency, avidity, and cross-reactivity of DENV-specific B cells in individuals experiencing primary instead of secondary infection. We compared DENV-specific B-cell responses in a cohort of Thai children with primary or secondary DENV infection. B cells specific for DENV precursor membrane protein, envelope (E) protein, and nonstructural protein 1 were detectable in immune peripheral blood mononuclear cells with the highest frequencies of DENV E-specific B cells detected in patients experiencing primary …

Decoupling Of Stretch Reflex And Background Muscle Activity During Anticipatory Postural Adjustments In Humans, Siddharth Vedula, Robert Kearney, Ross Wagner, Paul Stapley

Dr Paul J Stapley

We studied the evolution of stretch reXexes in relation to background electromyographic (EMG) activity in the soleus muscle preceding the onset of voluntary arm raise movements. Our objective was to investigate if changes in reXex EMG and muscle activity occur simultaneously and are similarly scaled in amplitude. Ten human subjects stood with each foot on pedals able to exert short dorsiXexor pulses during stance. Subjects were asked to product consistent voluntary arm raise movements to a target upon a visual cue. In ¼ of trials, no pulse perturbations were given, but in the remaining ¾’s of all trials pulses were …

Independent Control Of Limb Force Underlies Stability During Voluntary Head Movements In Standing Humans, Paul Stapley, Alicia Hilderley, Julia Leonard

Dr Paul J Stapley

Postural stability during voluntary head movements is maintained through the integration of vestibular and neck afferent inputs. These inputs combine to accurately estimate trunk position in space, relative to a turning head. In animals, a loss of vestibular information leads to an active destabilization of balance as neck afferent information is interpreted as a movement of the trunk under a stable head (Stapley et al. 2006).

Postural Adjustments For Online Corrections Of Arm Movements In Standing Humans, Julia Leonard, Valeriya Gritsenko, Ryan Ouckama, Paul Stapley

Dr Paul J Stapley

The aim of this study was to investigate how humans correct ongoing arm movements while standing. Specifically, we sought to understand whether the postural adjustments in the legs required for online corrections of arm movements are predictive or rely on feedback from the moving limb. To answer this question we measured online corrections in arm and leg muscles during pointing movements while standing. Nine health right-handed subjects reached with their dominant arm to a visual target in front of them and aligned with their midline. In some trials, the position of the target would switch from the central target to …

Reflex Changes Associated With Anticipatory Postural Adjustments Preceding Voluntary Arm Movements In Standing Humans, Siddharth Vedula, Paul J. Stapley, Robert E. Kearney

Dr Paul J Stapley

Dynamic changes in human stability, such as those induced by upper body movements, are preceded by anticipatory postural adjustments (APAs) in the rest of the body. We measured the excitability of the stretch reflex of the triceps-surae muscle group during APAs associated with unilateral right arm raises in standing humans. Our results demonstrate that reflex excitability and underlying muscle activity are linked during the APA period, but that they differ in their relative timing. This supports the idea that reflexes are controlled independently of muscle activation.

Factors Related To Declining Luteal Function In Women During The Menopausal Transition, Nanette Santoro, Sybil L. Crawford, Bill Lasley, J. L. Luborsky, Karen A. Matthews, Daniel Mcconnell, John F. Randolph, Ellen B. Gold, Gail A. Greendale, S. G. Korenman, Lynda H. Powell, Mary Fran R. Sowers, Gerson Weiss

Sybil L. Crawford

CONTEXT: Reproductive hormones are incompletely characterized during the menopause transition (MT). Hypothesis: Increased anovulation and decreased progesterone accompany progress through the MT. DESIGN: The Daily Hormone Study (DHS) of the Study of Women's Health Across the Nation (SWAN) included 848 women aged 43-53 yr at baseline who collected daily urine for one cycle or up to 50 d annually for 3 yr. MAIN OUTCOME MEASURES: LH, FSH, estrone conjugates, and pregnanediol glucuronide levels were assessed. Cycles were classified by presumed luteal (ovulatory) status and bleeding. Hormones were related to time in study, age, menopausal status, and selected variables. RESULTS: Ovulatory-appearing …