FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Hutt, M
Goldstein, W
Nazarian, J
Price, A
Lim, KJ
Warren, K
Chang, H
Eberhart, CG
Raabe, EH
AF Hutt, Marianne
Goldstein, Wendy
Nazarian, Javad
Price, Antoinette
Lim, Kah Jing
Warren, Katherine
Chang, Howard
Eberhart, Charles G.
Raabe, Eric H.
TI TARGETING THE NOTCH AND MTOR PATHWAYS IN DIFFUSE INTRINSIC PONTINE
GLIOMA
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 17th Annual Scientific Meeting and Education Day of the
Society-for-Neuro-Oncology (SNO)
CY NOV 15-18, 2012
CL Washington, DC
SP Soc Neuro Oncol (SNO)
C1 [Hutt, Marianne; Goldstein, Wendy; Price, Antoinette; Lim, Kah Jing; Eberhart, Charles G.; Raabe, Eric H.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Nazarian, Javad] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Warren, Katherine] NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Chang, Howard] Michigan State Univ, Coll Med, E Lansing, MI 48824 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD OCT
PY 2012
VL 14
SU 6
BP 118
EP 118
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 035TH
UT WOS:000310971300467
ER
PT J
AU Asthagiri, A
Vasquez, R
Butman, J
Wu, TX
Morgan, K
Brewer, C
King, K
Zalewski, C
Kim, HJ
Lonser, R
AF Asthagiri, Ashok
Vasquez, Raul
Butman, John
Wu, Tianxia
Morgan, Keaton
Brewer, Carmen
King, Kelly
Zalewski, Chris
Kim, H. Jeffrey
Lonser, Russell
TI MECHANISMS OF HEARING LOSS IN NEUROFIBROMATOSIS TYPE 2
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 17th Annual Scientific Meeting and Education Day of the
Society-for-Neuro-Oncology (SNO)
CY NOV 15-18, 2012
CL Washington, DC
SP Soc Neuro Oncol (SNO)
C1 [Asthagiri, Ashok; Vasquez, Raul; Butman, John; Wu, Tianxia; Morgan, Keaton; Brewer, Carmen; King, Kelly; Zalewski, Chris; Kim, H. Jeffrey; Lonser, Russell] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD OCT
PY 2012
VL 14
SU 6
BP 124
EP 124
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 035TH
UT WOS:000310971300490
ER
PT J
AU Gutova, M
Frank, JA
Annala, AJ
Barish, ME
Moats, RA
Aboody, KS
AF Gutova, Margarita
Frank, Joseph A.
Annala, Alexander J.
Barish, Michael E.
Moats, Rex A.
Aboody, Karen S.
TI MRI TRACKING OF FERUMOXYTOL-LABELED HUMAN STEM CELLS IN VIVO: STUDIES
LEADING TO CLINICAL USE
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 17th Annual Scientific Meeting and Education Day of the
Society-for-Neuro-Oncology (SNO)
CY NOV 15-18, 2012
CL Washington, DC
SP Soc Neuro Oncol (SNO)
C1 [Gutova, Margarita; Annala, Alexander J.; Barish, Michael E.; Aboody, Karen S.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA USA.
[Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, Natl Inst, Bethesda, MD USA.
[Moats, Rex A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
RI Moats, Rex/F-5995-2015
NR 0
TC 0
Z9 0
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD OCT
PY 2012
VL 14
SU 6
BP 151
EP 152
PG 2
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 035TH
UT WOS:000310971300604
ER
PT J
AU Lee, MH
Amlin-Van Schaick, J
Broman, K
Reilly, K
AF Lee, Min-Hyung
Amlin-Van Schaick, Jessica
Broman, Karl
Reilly, Karlyne
TI THE POTENTIAL MALE-SPECIFIC ONCOGENIC FUNCTION OF CDCA7L IN ASTROCYTOMA
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 17th Annual Scientific Meeting and Education Day of the
Society-for-Neuro-Oncology (SNO)
CY NOV 15-18, 2012
CL Washington, DC
SP Soc Neuro Oncol (SNO)
C1 [Lee, Min-Hyung; Amlin-Van Schaick, Jessica; Reilly, Karlyne] NIH, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Broman, Karl] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD OCT
PY 2012
VL 14
SU 6
BP 162
EP 162
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 035TH
UT WOS:000310971300641
ER
PT J
AU Bradberry, TJ
Metman, LV
Contreras-Vidal, JL
van den Munckhof, P
Hosey, LA
Thompson, JLW
Schulz, GM
Lenz, F
Pahwa, R
Lyons, KE
Braun, AR
AF Bradberry, Trent J.
Metman, Leonard Verhagen
Contreras-Vidal, Jose L.
van den Munckhof, Pepijn
Hosey, Lara A.
Thompson, Jennifer L. W.
Schulz, Geralyn M.
Lenz, Fredrick
Pahwa, Rajesh
Lyons, Kelly E.
Braun, Allen R.
TI Common and unique responses to dopamine agonist therapy and deep brain
stimulation in Parkinson's disease: An (H2O)-O-15 PET study
SO BRAIN STIMULATION
LA English
DT Article
DE Parkinson's disease; deep brain stimulation; apomorphine; positron
emission tomography
ID SUBTHALAMIC NUCLEUS STIMULATION; BASAL GANGLIA; FDG-PET; NETWORK
MODULATION; MOTOR CORTEX; CEREBELLUM; LEVODOPA; FLUENCY; TREMOR;
APOMORPHINE
AB Background
Dopamine agonist therapy and deep brain stimulation (DBS) of the subthalamic nucleus (STN) are antiparkinsonian treatments that act on a different part of the basal ganglia-thalamocortical motor circuitry, yet produce similar symptomatic improvements.
Objective/Hypothesis
The purpose of this study was to identify common and unique brain network features of these standard treatments.
Methods
We analyzed images produced by (H2O)-O-15 positron emission tomography (PET) of patients with Parkinson's disease (PD) at rest. Nine patients were scanned before and after injection of apomorphine, and 11 patients were scanned while bilateral stimulators were off and while they were on.
Results
Both treatments produced common deactivations of the neocortical sensorimotor areas, including the supplementary motor area, precentral gyrus, and postcentral gyms, and in subcortical structures, including the putamen and cerebellum. We observed concomitant activations of the superior parietal lobule and the midbrain in the region of the substantia nigra/STN. We also detected unique, treatment-specific changes with possible motor-related consequences in the basal ganglia, thalamus, neocortical sensorimotor cortex, and posterolateral cerebellum. Unique changes in nonmotor regions may reflect treatment-specific effects on verbal fluency and limbic functions.
Conclusions
Many of the common effects of these treatments are consistent with the standard pathophysiologic model of PD. However, the common effects in the cerebellum are not readily explained by the model. Consistent deactivation of the cerebellum is interesting in light of recent reports of synaptic pathways directly connecting the cerebellum and basal ganglia, and may warrant further consideration for incorporation into the model. Published by Elsevier Inc.
C1 [Bradberry, Trent J.; Hosey, Lara A.; Thompson, Jennifer L. W.; Braun, Allen R.] NIDCD, Language Sect, Voice Speech & Language Branch, NIH, Bethesda, MD 20892 USA.
[Bradberry, Trent J.; Contreras-Vidal, Jose L.] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA.
[Metman, Leonard Verhagen] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.
[Contreras-Vidal, Jose L.] Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA.
[Contreras-Vidal, Jose L.] Univ Maryland, Grad Program Neurosci & Cognit Sci, College Pk, MD 20742 USA.
[van den Munckhof, Pepijn] Univ Amsterdam, Dept Neurosurg, Amsterdam, Netherlands.
[Schulz, Geralyn M.] George Washington Univ, Dept Speech & Hearing Sci, Washington, DC USA.
[Lenz, Fredrick] Johns Hopkins Univ, Dept Neurol & Neurosurg, Baltimore, MD USA.
[Pahwa, Rajesh; Lyons, Kelly E.] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA.
RP Braun, AR (reprint author), NIDCD, Language Sect, Voice Speech & Language Branch, NIH, Bldg 10,Room 8S235A, Bethesda, MD 20892 USA.
EM brauna@nidcd.nih.gov
FU Division of Intramural Research at the National Institute on Deafness
and other Communication Disorders
FX This study was financially supported by the Division of Intramural
Research at the National Institute on Deafness and other Communication
Disorders.
NR 49
TC 8
Z9 8
U1 5
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1935-861X
J9 BRAIN STIMUL
JI Brain Stimul.
PD OCT
PY 2012
VL 5
IS 4
BP 605
EP 615
DI 10.1016/j.brs.2011.09.002
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 043GZ
UT WOS:000311532200022
PM 22019080
ER
PT J
AU Maholmes, V
Fluke, JD
Rinehart, RD
Huebner, G
AF Maholmes, Valerie
Fluke, John D.
Rinehart, Richard D.
Huebner, Gillian
TI Protecting children outside of family care in low and middle income
countries: What does the evidence say?
SO CHILD ABUSE & NEGLECT
LA English
DT Editorial Material
C1 [Maholmes, Valerie] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Proc Maltreatment & Violence Progr, NIH, US Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Fluke, John D.] Univ Colorado, Sch Med, Dept Pediat, Kempe Ctr Prevent & Treatment Child Abuse & Negle, Aurora, CO USA.
[Rinehart, Richard D.; Huebner, Gillian] US Agcy Int Dev, Washington, DC 20523 USA.
RP Maholmes, V (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Proc Maltreatment & Violence Progr, NIH, US Dept Hlth & Human Serv, 6100 Execut Blvd,Room 4B05A, Rockville, MD 20852 USA.
NR 7
TC 5
Z9 5
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0145-2134
J9 CHILD ABUSE NEGLECT
JI Child Abuse Negl.
PD OCT
PY 2012
VL 36
IS 10
SI SI
BP 685
EP 688
DI 10.1016/j.chiabu.2012.09.001
PG 4
WC Family Studies; Psychology, Social; Social Work
SC Family Studies; Psychology; Social Work
GA 039TP
UT WOS:000311269700001
PM 23092938
ER
PT J
AU Higgs, ES
Zlidar, VM
Balster, RL
AF Higgs, Elizabeth S.
Zlidar, Vera M.
Balster, Robert L.
TI Evidence acquisition and evaluation for a U.S. Government Evidence
Summit on Protecting Children Outside Family Care
SO CHILD ABUSE & NEGLECT
LA English
DT Article
DE Evidence-based practice; Review; Orphans; Vulnerable children; Evidence
Summit
ID HEALTH-PROMOTION INTERVENTIONS; FRAMEWORK; STATEMENT
AB Recognizing the need for evidence to inform policies, strategies, and programs to care for vulnerable children, the U.S. Government convened an Evidence Summit on Protecting Children Outside of Family Care on December 12-13, 2011, in Washington, DC, USA. This paper summarizes the background and methods for the acquisition and evaluation of the evidence used to achieve the goals of the Summit. A multistep process was undertaken to identify the appropriate evidence for review. It began by identifying crucial focal questions intended to inform low and middle income governments and the U.S. Government about effective systems for protecting children outside family care. This was followed by a systematic attempt to gather relevant peer reviewed and gray literature that would inform these focal questions. The search processes, methods used for screening and quality reviews are described. In addition, members of the Evidence Review Teams were invited to add relevant papers not identified in the initial literature review to complete the bibliographies. These teams were asked to comply with a specific evaluation framework for recommendations on practice and policy based on both expert opinion and the quality of the data. This was the first U.S. Government Evidence Summit originating in the U.S. Agency for International Development Global Health Bureau and valuable lessons were learned on the identification and assessment of evidence informing complex development challenges. Published by Elsevier Ltd.
C1 [Higgs, Elizabeth S.; Balster, Robert L.] US Agcy Int Dev, Global Hlth Bur, Washington, DC 20523 USA.
[Zlidar, Vera M.] Knowledge Management Serv, Washington, DC USA.
[Balster, Robert L.] Virginia Commonwealth Univ, Inst Drug & Alcohol Studies, Richmond, VA USA.
RP Higgs, ES (reprint author), NIAID, Div Clin Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ehiggs@niaid.nih.gov
NR 19
TC 6
Z9 6
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0145-2134
J9 CHILD ABUSE NEGLECT
JI Child Abuse Negl.
PD OCT
PY 2012
VL 36
IS 10
SI SI
BP 689
EP 700
DI 10.1016/j.chiabu.2012.09.002
PG 12
WC Family Studies; Psychology, Social; Social Work
SC Family Studies; Psychology; Social Work
GA 039TP
UT WOS:000311269700002
PM 23083899
ER
PT J
AU Boothby, N
Wessells, M
Williamson, J
Huebner, G
Canter, K
Rolland, EG
Kutlesic, V
Bader, F
Diaw, L
Levine, M
Malley, A
Michels, K
Patel, S
Rasa, T
Ssewamala, F
Walker, V
AF Boothby, Neil
Wessells, Mike
Williamson, John
Huebner, Gillian
Canter, Kelly
Rolland, Eduardo Garcia
Kutlesic, Vesna
Bader, Farah
Diaw, Lena
Levine, Maya
Malley, Anita
Michels, Kathleen
Patel, Sonali
Rasa, Tanya
Ssewamala, Fred
Walker, Vicki
TI What are the most effective early response strategies and interventions
to assess and address the immediate needs of children outside of family
care?
SO CHILD ABUSE & NEGLECT
LA English
DT Article
DE Early response; Child protection; Children outside of family care;
Humanitarian response; Emergency; Assessment
ID YOUNG-CHILDREN; FOSTER; RESILIENCE; ORPHANAGE; SETTINGS; PROJECT; HEALTH
AB Objectives: Children outside of family care face increased risk of threats to their well-being, have lower educational achievement, and experience adverse developmental outcomes. While it is generally accepted that early response and intervention is critical to reducing the risk of harm for children who have been separated from their families, it is not always clear what the most effective early response strategies are for assessing and addressing their immediate needs. The purpose of this review was to identify evidence-based early response strategies and interventions for improving the outcomes of children outside of family care, including children of and on the street, institutionalized children, trafficked children, children affected by conflict and disaster, and who are exploited for their labor.
Methods: A multi-phased, systematic evidence review was conducted on peer-reviewed and gray literature, which yielded a total of 101 documents that met the inclusion criteria and were reviewed.
Results: Overall there is a weak evidence base regarding assessment and early response interventions for children living outside of family care. Few studies included careful outcome measures or comparison groups. Although few proven interventions emerged, the review identified several promising early interventions and approaches. In emergency settings, family tracing and reunification is a highly effective response in regard to separated children, whereas placing children in institutional care is problematic, with the possible exception of time-limited placements of formerly recruited children in interim care centers. Livelihood supports are promising in regard to preventing and responding to children living outside family care. Other promising interventions include psychosocial support, including the use of traditional cleansing rituals as appropriate, educational supports such as Child Friendly Spaces, the maintenance of family connectedness for children of or on the streets, the use of community-based approaches that aid social integration, and approaches that enable meaningful child participation. A recurrent theme was that to be effective, all assessments and interventions must fit the context. A strong need exists for strengthening the evidence base regarding the effectiveness of early assessments and responses to children living outside family care and for using the evidence to guide operational policy and practice. Recommendations regarding policy, practices, and research emerged from the review process. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Boothby, Neil; Wessells, Mike; Ssewamala, Fred] Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10032 USA.
[Malley, Anita] US Agcy Int Dev, Off US Foreign Disaster Assistance, Washington, DC 20523 USA.
[Rolland, Eduardo Garcia] Int Rescue Comm, New York, NY USA.
[Levine, Maya] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Bader, Farah; Michels, Kathleen] Fogarty Int Ctr, NIH, Bethesda, MD USA.
[Diaw, Lena] NHLBI, NIH, Bethesda, MD 20892 USA.
[Patel, Sonali] US Dept Hlth & Human Serv, Adm Children & Families, Washington, DC USA.
[Rasa, Tanya] US Dept Labor, Off Child Labor Forced Labor & Human Trafficking, Washington, DC 20210 USA.
[Walker, Vicki] Winrock Int Livestock Res & Training Ctr, Arlington, VA USA.
RP Wessells, M (reprint author), Columbia Univ, Mailman Sch Publ Hlth, 722 W 168th St, New York, NY 10032 USA.
NR 108
TC 10
Z9 10
U1 3
U2 48
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0145-2134
J9 CHILD ABUSE NEGLECT
JI Child Abuse Negl.
PD OCT
PY 2012
VL 36
IS 10
SI SI
BP 711
EP 721
DI 10.1016/j.chiabu.2012.09.004
PG 11
WC Family Studies; Psychology, Social; Social Work
SC Family Studies; Psychology; Social Work
GA 039TP
UT WOS:000311269700004
PM 23084623
ER
PT J
AU Fluke, JD
Goldman, PS
Shriberg, J
Hillis, SD
Yun, K
Allison, S
Light, E
AF Fluke, John D.
Goldman, Philip S.
Shriberg, Janet
Hillis, Susan D.
Yun, Katherine
Allison, Susannah
Light, Enid
TI Systems, strategies, and interventions for sustainable long-term care
and protection of children with a history of living outside of family
care
SO CHILD ABUSE & NEGLECT
LA English
DT Article
DE Child protection system; Trafficked children; Street children;
Institutionalized children; Conflict; Disaster; Family care; Children
outside of family care
ID MENTAL-HEALTH; FOSTER-CARE; INSTITUTIONAL CARE; ORPHANAGES; ATTACHMENT;
SOLDIERS; RECOVERY; ADOPTION; OUTCOMES; PROJECT
AB Objectives: This article reviews the available evidence regarding the efficacy, effectiveness, ethics, and sustainability of approaches to strengthen systems to care for and protect children living outside family care in low- and middle-income countries.
Method: For trafficked children, children of and on the street, children of conflict/disaster, and institutionalized children, a systems framework approach was used to organize the topic of sustainable approaches in low- and middle-income countries and addresses the following: legislation, policies, and regulations; system structures and functions (formal and informal); and continuum of care and services. The article draws on the findings of a focal group convened by the U.S. Government Evidence Summit: Protecting Children Outside of Family Care (December 12-13,2011, Washington, DC), tasked with reviewing the literature on systems, strategies, and interventions for sustainable long-term care and protection of children with a history of living outside of family care in low- and middle-income country contexts. The specific methodology for the review is described in the commentary paper (Higgs, Zlidar, & Balster, 2012) that accompanies these papers.
Results: For the most part, the evidence base in support of sustainable long-term care for the populations of interest is relatively weak, with some stronger but unreplicated studies. Some populations have been studied more thoroughly than others, and there are many gaps. Most of the existing studies identify population characteristics, needs, and consequences of a lack of systemic services to promote family-like care. There is some evidence of the effectiveness of laws and policies, as well as some evidence of service effectiveness, in improving outcomes for children outside of family care.
Conclusions: Despite the weaknesses and gaps of the existing research, there is a foundation of research for going forward, which should focus on developing and implementing systems for these most vulnerable children. The evidence reviewed indicates that child protection systems should aim for appropriate, permanent family care (including reunification, adoption, kinship care, or kafalah) for children in order to secure the best environment for a child's developmental prospects. Evidence also suggests that the quality and duration of care, including both permanent family care and alternative care, are important regardless of setting. The diversity of political, socioeconomic, historical, regional, community, and cultural contexts in which child protection systems operate need to be taken into account during programming and research design. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Goldman, Philip S.] Maestral Int, Minneapolis, MN USA.
[Shriberg, Janet] USAID, Off HIV AIDS, Washington, DC USA.
[Hillis, Susan D.] Ctr Dis Control & Prevent, US Publ Hlth Serv, Natl Ctr Injury Prevent & Control, Atlanta, GA USA.
[Yun, Katherine] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Allison, Susannah] NIMH, Infant Child & Adolescent Res Program, Div AIDS Res, NIH, Bethesda, MD 20892 USA.
[Light, Enid] NIMH, Div Int Training & Res, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Fluke, John D.] Univ Colorado, Sch Med, Dept Pediat, Kempe Ctr Prevent & Treatment Child Abuse & Negle, Aurora, CO 80045 USA.
RP Fluke, JD (reprint author), Univ Colorado, Sch Med,Dept Pediat, Colorado Sch Med,Gary Pavil Childrens Hosp Colora, Kempe Ctr Prevent & Treatment Child Abuse & Negle, Anschutz Med Campus,13123 E 16th Ave,B390, Aurora, CO 80045 USA.
NR 86
TC 9
Z9 9
U1 2
U2 42
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0145-2134
J9 CHILD ABUSE NEGLECT
JI Child Abuse Negl.
PD OCT
PY 2012
VL 36
IS 10
SI SI
BP 722
EP 731
DI 10.1016/j.chiabu.2012.09.005
PG 10
WC Family Studies; Psychology, Social; Social Work
SC Family Studies; Psychology; Social Work
GA 039TP
UT WOS:000311269700005
PM 23102720
ER
PT J
AU Ager, A
Zimmerman, C
Unlu, K
Rinehart, R
Nyberg, B
Zeanah, C
Hunleth, J
Bastiaens, I
Weldy, A
Bachman, G
Blum, AB
Strottman, K
AF Ager, Alastair
Zimmerman, Cathy
Unlu, Kathy
Rinehart, Richard
Nyberg, Beverly
Zeanah, Charles
Hunleth, Jean
Bastiaens, Ida
Weldy, Andre
Bachman, Gretchen
Blum, Alexander B.
Strottman, Kathleen
TI What strategies are appropriate for monitoring children outside of
family care and evaluating the impact of the programs intended to serve
them?
SO CHILD ABUSE & NEGLECT
LA English
DT Article
DE Child protection; Children outside of family care; Child protection
systems; Monitoring; Evaluation; Longitudinal
ID STREET CHILDREN; YOUNG-CHILDREN; FOSTER-CARE; INSTITUTIONAL CARE;
MENTAL-HEALTH; AIDS ORPHANS; PROTECTION; WOMEN; VULNERABILITY;
PERSPECTIVE
AB Objectives: To strengthen the evidence-base for policy and practice for support of children outside of family care requires effective, efficient and sustainable mechanisms for monitoring and evaluation. Toward that end, two core questions guided a systematic review of evidence: What strategies are appropriate for monitoring the needs and circumstances of children outside of family care? What strategies are suitable for evaluating the impact of the programs intended to serve such children?
Methods: A structured document search and review process was implemented within the context of the U.S. Government Evidence Summit on Protecting Children Outside of Family Care of December 2011. Through successive review phases, initially using structured screening criteria, followed by thematic review by an expert panel, 73 documents were identified for analysis.
Results: Analysis of models and strategies indicates that: (1) tools are available for assessment of children's needs, but require refining to accommodate contextual demands; (2) well-designed evaluations are able to identify the influence of assistance; (3) long-term follow-up is crucial to developing a strong evidence-base on effective strategies; and (4) insights into systems-wide monitoring mechanisms are emerging. In addition to describing key components of monitoring and evaluation strategies, findings draw attention to the evaluation of children's resiliency and protective factors, community based monitoring and the role of caregivers, as well as concerns over the stigmatization of children (through data collection methodologies encouraging the 'labeling' of children) and the importance of children's participation. Fostering a stronger evidence-base to improve protection for vulnerable children requires evaluations that are integrated into program development, use context-appropriate methodologies able to assess intervention scalability and employ more longitudinal designs to explore children's trajectories. Further, future programming will benefit from systems-wide data coordination and international comparisons, research that emphasizes coping and resilience mechanisms, and children's participation in monitoring and evaluation. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Ager, Alastair] Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10032 USA.
[Zimmerman, Cathy] London Sch Hyg & Trop Med, Dept Global Hlth & Dev, London WC1H 9SH, England.
[Unlu, Kathy] US Dept State, Off Childrens Issues, Washington, DC 20520 USA.
[Rinehart, Richard] US Agcy Int Dev, Ctr Excellence Children Adversity, Washington, DC 20523 USA.
[Nyberg, Beverly] Peace Corps, Off Global Hlth & HIV, Washington, DC USA.
[Zeanah, Charles] Tulane Univ, Sch Med, New Orleans, LA 70112 USA.
[Hunleth, Jean] Washington Univ, Div Publ Hlth Sci, Sch Med, St Louis, MO USA.
[Bastiaens, Ida] Univ Pittsburgh, Grad Sch Publ & Int Affairs, Pittsburgh, PA 15260 USA.
[Blum, Alexander B.] NIH, Off Behav & Social Sci Res, Off Director, Bethesda, MD 20892 USA.
[Strottman, Kathleen] Congress Coalit Adopt Inst, Washington, DC USA.
[Weldy, Andre] FHI 360, Washington, DC USA.
RP Ager, A (reprint author), Columbia Univ, Mailman Sch Publ Hlth, 60 Haven Ave, New York, NY 10032 USA.
NR 74
TC 4
Z9 4
U1 2
U2 16
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0145-2134
J9 CHILD ABUSE NEGLECT
JI Child Abuse Negl.
PD OCT
PY 2012
VL 36
IS 10
SI SI
BP 732
EP 742
DI 10.1016/j.chiabu.2012.09.006
PG 11
WC Family Studies; Psychology, Social; Social Work
SC Family Studies; Psychology; Social Work
GA 039TP
UT WOS:000311269700006
PM 23083900
ER
PT J
AU D'Adamo, CR
Miller, RR
Shardell, MD
Orwig, DL
Hochberg, MC
Ferrucci, L
Semba, RD
Yu-Yahiro, JA
Magaziner, J
Hicks, GE
AF D'Adamo, Christopher R.
Miller, Ram R.
Shardell, Michelle D.
Orwig, Denise L.
Hochberg, Marc C.
Ferrucci, Luigi
Semba, Richard D.
Yu-Yahiro, Janet A.
Magaziner, Jay
Hicks, Gregory E.
TI Higher serum concentrations of dietary antioxidants are associated with
lower levels of inflammatory biomarkers during the year after hip
fracture
SO CLINICAL NUTRITION
LA English
DT Article
DE Antioxidants; Inflammation; Vitamin E; Carotenoids; Micronutrients; Hip
fracture
ID NF-KAPPA-B; VITAMIN-E; OXIDATIVE STRESS; PHYSICAL-ACTIVITY;
CONTROLLED-TRIAL; WOMEN; COMMUNITY; PLASMA; ALPHA; SUPPLEMENTATION
AB Background & aims: Chronic inflammation impairs recovery among the 1.6 million people who suffer from hip fracture annually. Vitamin E and the carotenoids are two classes of dietary antioxidants with profound anti-inflammatory effects, and the goal of this study was to assess whether higher post-fracture concentrations of these antioxidants were associated with lower levels of interleukin 6 (IL-6) and the soluble receptor for tumor necrosis factor-alpha (sTNF-alpha R1), two common markers of inflammation.
Methods: Serum concentrations of the dietary antioxidants and inflammatory markers were assessed at baseline and 2, 6, and 12 month follow-up visits among 148 hip fracture patients from The Baltimore Hip Studies. Generalized estimating equations modeled the relationship between baseline and time-varying antioxidant concentrations and inflammatory markers.
Results: Higher post-fracture concentrations of vitamin E and the carotenoids were associated with lower levels of inflammatory markers. Associations were strongest at baseline, particularly between the alpha-tocopherol form of vitamin E and sTNF-alpha R1 (p = 0.05) and total carotenoids and both sTNF-alpha R1(p = 0.01) and IL-6 (p = 0.05). Higher baseline and time-varying alpha-carotene and time-varying lutein concentrations were also associated with lower sTNF-alpha R1 at all post-fracture visits (p <= 0.05).
Conclusions: These findings suggest that a clinical trial increasing post-fracture intake of vitamin E and the carotenoids may be warranted. (C) 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
C1 [D'Adamo, Christopher R.; Miller, Ram R.; Shardell, Michelle D.; Orwig, Denise L.; Magaziner, Jay] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Hochberg, Marc C.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Semba, Richard D.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
[Yu-Yahiro, Janet A.] Union Mem Hosp, Dept Orthoped Res, Baltimore, MD USA.
[Hicks, Gregory E.] Univ Delaware, Dept Phys Therapy, Newark, DE USA.
RP D'Adamo, CR (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, 520 W Lombard St,E Hall, Baltimore, MD 21201 USA.
EM cdadamo@compmed.umm.edu
FU National Institutes of Health [R01 AG018668, R01 AG027012, R37 AG09901,
T32 AG00262, K23 AG027746, P60 AG12583, P30 AG028747]; University of
Maryland School of Medicine
FX This work was supported by the National Institutes of Health (grant
numbers R01 AG018668, R01 AG027012, R37 AG09901, T32 AG00262, K23
AG027746, P60 AG12583, and P30 AG028747) and an intramural grant from
the University of Maryland School of Medicine. Study sponsors had no
involvement in the study design, the collection, analysis, and
interpretation of data, the writing of the manuscript, or the decision
to submit the manuscript for publication.
NR 36
TC 9
Z9 9
U1 1
U2 11
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0261-5614
EI 1532-1983
J9 CLIN NUTR
JI Clin. Nutr.
PD OCT
PY 2012
VL 31
IS 5
BP 659
EP 665
DI 10.1016/j.clnu.2012.01.013
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 036CP
UT WOS:000311004300011
PM 22365613
ER
PT J
AU Alam, HB
Pusateri, AE
Kindzelski, A
Egan, D
Hoots, K
Andrews, MT
Rhee, P
Tisherman, S
Mann, K
Vostal, J
Kochanek, PM
Scalea, T
Deal, V
Sheppard, F
Sopko, G
AF Alam, Hasan B.
Pusateri, Anthony E.
Kindzelski, Andrei
Egan, Debra
Hoots, Keith
Andrews, Matthew T.
Rhee, Peter
Tisherman, Samuel
Mann, Kenneth
Vostal, Jaroslav
Kochanek, Patrick M.
Scalea, Thomas
Deal, Virgil
Sheppard, Forest
Sopko, George
CA HYPOSTAT Workshop Participants
TI Hypothermia and hemostasis in severe trauma: A new crossroads workshop
report
SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY
LA English
DT Article
DE Hypothermia; trauma; coagulopathy; injury; protection
ID ISCHEMIA-REPERFUSION INJURY; PROFOUND HYPOTHERMIA; SWINE MODEL;
HEMORRHAGIC-SHOCK; LETHAL HEMORRHAGE; CARDIAC-ARREST; CIRCULATORY
ARREST; BRAIN-INJURY; EMERGENCY PRESERVATION; CARDIOPULMONARY BYPASS
AB OBJECTIVE: The hypothermia and hemostasis in severe trauma (HYPOSTAT): a new crossroads workshop was convened to evaluate the interplay among hypothermia, hemostasis, and severe trauma/hemorrhage. Trauma is the major cause of death in young individuals in the United States, with uncontrolled hemorrhage representing the major cause of preventable deaths.
DATA SOURCES: This workshop organized by the National Heart, Lung, and Blood Institute and the US Army Medical Research and Material Command as a forum for exchange of ideas among experts from diverse fields. The specific workshop goals were to (1) identify state-of-the-art and needs in knowledge of biology of hypothermia and hemostasis in the setting of significant traumatic injury; (2) provide an interdisciplinary forum to enhance knowledge regarding early detection of traumatic shock and monitoring of the level and effect of controlled hypothermia in severe trauma settings; and (3) identify future research directions of the role of therapeutic-oriented hypothermia and hemostasis in trauma with severe blood loss.
STUDY SELECTION: Not applicable.
DATA EXTRACTION: Expert opinion and literature review.
CONCLUSION: This document provides a summary of the expert opinion and highlights the recommendations that came out of the discussions at this workshop to guide scientific efforts in basic, translational, and clinical research in this area. (J Trauma Acute Care Surg. 2012;73:809-817. Copyright (C) 2012 by Lippincott Williams & Wilkins)
C1 [Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
[Alam, Hasan B.] Harvard Univ, Sch Med, Boston, MA USA.
[Pusateri, Anthony E.; Deal, Virgil; Sheppard, Forest] US Dept Def, Washington, DC 20305 USA.
[Kindzelski, Andrei; Egan, Debra; Hoots, Keith; Sopko, George] NIH, Bethesda, MD 20892 USA.
[Vostal, Jaroslav] US FDA, Silver Spring, MD USA.
[Scalea, Thomas] Univ Maryland, College Pk, MD 20742 USA.
[Andrews, Matthew T.] Univ Minnesota, Duluth, MN 55812 USA.
[Rhee, Peter] Univ Arizona, Tucson, AZ USA.
[Tisherman, Samuel; Kochanek, Patrick M.] Univ Pittsburgh, Pittsburgh, PA USA.
[Mann, Kenneth] Univ Vermont, Burlington, VT USA.
RP Alam, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA.
EM hbalam@partners.org
RI Kochanek, Patrick/D-2371-2015
OI Kochanek, Patrick/0000-0002-2627-913X
NR 87
TC 7
Z9 8
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 2163-0755
J9 J TRAUMA ACUTE CARE
JI J. Trauma Acute Care Surg.
PD OCT
PY 2012
VL 73
IS 4
BP 809
EP 817
DI 10.1097/TA.0b013e318265d1b8
PG 9
WC Critical Care Medicine; Surgery
SC General & Internal Medicine; Surgery
GA 029OL
UT WOS:000310505100003
PM 23026915
ER
PT J
AU Cantor, D
AF Cantor, David
TI Between Prevention and Therapy: Gio Batta Gori and the National Cancer
Institute's Diet, Nutrition and Cancer Programme, 1974-1978
SO MEDICAL HISTORY
LA English
DT Article
DE US National Cancer Institute; Diet; Nutrition and Cancer; Cancer
Prevention and Therapy; Select Committee on Nutrition and Human Needs
(McGovern Committee); the Candlelighters; Gio Gori
ID TOBACCO HARM REDUCTION; UNITED-STATES; PARENTERAL-NUTRITION;
HEALTH-PROGRAM; STOMACH-CANCER; CIGARETTE; ADVENTISTS; MORTALITY;
SMOKING; GENESIS
AB This paper explores the origins of the Diet, Nutrition and Cancer Programme (DNCP) of the National Cancer Institute (NCI) and its fate under its first director, Gio Batta Gori. The DNCP is used to explore the emergence of federal support for research on diet, nutrition and cancer following the 1971 Cancer Act, the complex relations between cancer prevention and therapeutics in the NCI during the 1970s, the broader politics around diet, nutrition and cancer during that decade, and their relations to Senator George McGovern's select committee on Nutrition and Human Needs. It also provides a window onto the debates and struggles over whether NCI research should be funded by contracts or grants, the nature of the patronage system within the federal cancer research agency, how a director, Gio Gori, lost patronage within that system and how a tightening of the budget for cancer research in the mid-to-late 1970s affected the DNCP.
C1 NIH, Off Hist, Bethesda, MD 20814 USA.
RP Cantor, D (reprint author), NIH, Off Hist, 1 Cloister Court,Bldg 60,Room 262, Bethesda, MD 20814 USA.
EM cantord@mail.nih.gov
FU Division of Cancer Prevention (DCP); National Cancer Institute [PO:
263-MQ-216827]
FX The research for this paper was supported by the Division of Cancer
Prevention (DCP), National Cancer Institute (PO: 263-MQ-216827). My
thanks go to Judy Grosberg for access to the NCI archives in its LION
database, to Richard Mandel for access to the National Institutes for
Health (NIH) Director's Files in the Office of the Director, NIH, to
Chin Jou for research assistance in the McGovern papers at Princeton, to
Barbara Harkins for help in tracing Gori's career at NIH and to Mark
Parascandola, Gretchen Krueger, Buhm Soon Park and the three anonymous
reviewers for comments and criticism. An earlier version of this paper
was presented at a Brown Bag Seminar at the National Library of
Medicine, 4 January 2006.
NR 124
TC 1
Z9 1
U1 1
U2 5
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0025-7273
EI 2048-8343
J9 MED HIST
JI Med. Hist.
PD OCT
PY 2012
VL 56
IS 4
BP 531
EP 561
DI 10.1017/mdh.2012.73
PG 31
WC Health Care Sciences & Services; History & Philosophy Of Science
SC Health Care Sciences & Services; History & Philosophy of Science
GA 037TX
UT WOS:000311130500006
PM 23112384
ER
PT J
AU Mischo, A
Harter, PN
Muller, K
Zachskorn, C
Kleber, S
Renner, C
Steeg, PS
Mittelbronn, M
Pestalozzi, B
AF Mischo, A.
Harter, P. N.
Mueller, K.
Zachskorn, C.
Kleber, S.
Renner, C.
Steeg, P. S.
Mittelbronn, M.
Pestalozzi, B.
TI Docetaxel pretreatment is associated with increased incidence of
CNS-metastases in a murine model of HER2-positive breast cancer
SO ONKOLOGIE
LA English
DT Meeting Abstract
C1 [Mischo, A.; Kleber, S.; Renner, C.; Pestalozzi, B.] Univ Spital Zurich, Zurich, Switzerland.
[Harter, P. N.; Mueller, K.; Zachskorn, C.; Mittelbronn, M.] Goethe Univ Frankfurt, Edinger Inst, Neurol Inst, Frankfurt, Germany.
[Steeg, P. S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0378-584X
J9 ONKOLOGIE
JI Onkologie
PD OCT
PY 2012
VL 35
SU 6
BP 64
EP 64
PG 1
GA 033BE
UT WOS:000310766700156
ER
PT J
AU Muller, TA
Dechow, R
Hennighausen, L
Peschel, C
Duyster, J
AF Mueller, T. A.
Dechow, R.
Hennighausen, L.
Peschel, C.
Duyster, J.
TI The role of STAT5 in FLT3-mediated leukemogenesis
SO ONKOLOGIE
LA English
DT Meeting Abstract
C1 [Mueller, T. A.; Dechow, R.; Peschel, C.; Duyster, J.] Tech Univ Munich, Klinikum Rechts Isar, Med Klin 3, D-8000 Munich, Germany.
[Hennighausen, L.] NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0378-584X
J9 ONKOLOGIE
JI Onkologie
PD OCT
PY 2012
VL 35
SU 6
BP 89
EP 89
PG 1
GA 033BE
UT WOS:000310766700223
ER
PT J
AU Hudecek, M
Kosasih, P
Yang, J
Einsele, H
Jensen, MC
Rader, C
Riddell, SR
AF Hudecek, M.
Kosasih, P.
Yang, J.
Einsele, H.
Jensen, M. C.
Rader, C.
Riddell, S. R.
TI Engineered T cells modified with a high-affinity ROR1-CAR confer
superior anti-tumor reactivity in vitro and in a mouse lymphoma model
SO ONKOLOGIE
LA English
DT Meeting Abstract
C1 [Hudecek, M.; Einsele, H.] Univ Klin Wurzburg, Med Klin Hamatol 2, Wurzburg, Germany.
[Hudecek, M.; Kosasih, P.; Jensen, M. C.; Riddell, S. R.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Program Immunol, Seattle, WA 98104 USA.
[Yang, J.; Rader, C.] NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
[Jensen, M. C.] Seattle Childrens Res Inst, Ctr Childhood Canc Res, Seattle, WA USA.
[Riddell, S. R.] Univ Washington, Dept Med, Seattle, WA USA.
[Riddell, S. R.] Tech Univ Munich, Inst Adv Study, Munich, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0378-584X
J9 ONKOLOGIE
JI Onkologie
PD OCT
PY 2012
VL 35
SU 6
BP 191
EP 191
PG 1
GA 033BE
UT WOS:000310766700497
ER
PT J
AU Firth, AE
Jagger, BW
Wise, HM
Nelson, CC
Parsawar, K
Wills, NM
Napthine, S
Taubenberger, JK
Digard, P
Atkins, JF
AF Firth, A. E.
Jagger, B. W.
Wise, H. M.
Nelson, C. C.
Parsawar, K.
Wills, N. M.
Napthine, S.
Taubenberger, J. K.
Digard, P.
Atkins, J. F.
TI Ribosomal frameshifting used in influenza A virus expression occurs
within the sequence UCC_UUU_CGU and is in the+1 direction
SO OPEN BIOLOGY
LA English
DT Article
DE genetic recoding; ribosomal frameshifting; mass spectrometry; influenza
virus; PA-X; translation
ID ALLOSTERIC 3-SITE MODEL; TRANSFER-RNAS; E-SITE; THYMIDINE-KINASE;
MESSENGER-RNA; MAMMALIAN ANTIZYME; ESCHERICHIA-COLI; QUALITY-CONTROL;
BUDDING YEAST; PROTEIN
AB Programmed ribosomal frameshifting is used in the expression of many virus genes and some cellular genes. In eukaryotic systems, the most well-characterized mechanism involves -1 tandem tRNA slippage on an X_XXY_YYZ motif. By contrast, the mechanisms involved in programmed +1 (or -2) slippage are more varied and often poorly characterized. Recently, a novel gene, PA-X, was discovered in influenza A virus and found to be expressed via a shift to the +1 reading frame. Here, we identify, by mass spectrometric analysis, both the site (UCC_UUU_CGU) and direction (+1) of the frameshifting that is involved in PA-X expression. Related sites are identified in other virus genes that have previously been proposed to be expressed via +1 frameshifting. As these viruses infect insects (chronic bee paralysis virus), plants (fijiviruses and amalgamaviruses) and vertebrates (influenza A virus), such motifs may form a new class of +1 frameshift-inducing sequences that are active in diverse eukaryotes.
C1 [Atkins, J. F.] Natl Univ Ireland Univ Coll Cork, BioSci Inst, Cork, Ireland.
[Firth, A. E.; Jagger, B. W.; Wise, H. M.; Napthine, S.; Digard, P.] Univ Cambridge, Div Virol, Dept Pathol, Cambridge CB2 1QP, England.
[Jagger, B. W.; Taubenberger, J. K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Wise, H. M.; Digard, P.] Univ Edinburgh, Roslin Inst, Easter Bush EH25 9RG, Midlothian, Scotland.
[Nelson, C. C.; Parsawar, K.] Univ Utah, Mass Spectrometry & Prote Core Facil, Salt Lake City, UT 84112 USA.
[Wills, N. M.] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA.
RP Atkins, JF (reprint author), Natl Univ Ireland Univ Coll Cork, BioSci Inst, Cork, Ireland.
EM j.atkins@ucc.ie
RI Digard, Paul/B-7717-2008;
OI Digard, Paul/0000-0002-0872-9440; Firth, Andrew/0000-0002-7986-9520
FU Wellcome Trust [088789]; Science Foundation Ireland [08/IN.1/B1889]; UK
Biotechnology and Biological Sciences Research Council; U.K. Medical
Research Council [G0700815]; NIH-Oxford-Cambridge Research Scholars
programme
FX A.E.F. is supported by the Wellcome Trust (088789). J.F.A. is supported
by Science Foundation Ireland (08/IN.1/B1889). P. D. is supported by
Institute Strategic Grant Funding from the UK Biotechnology and
Biological Sciences Research Council and the U.K. Medical Research
Council (G0700815). B.W.J., P.D. and J.K.T. are also thankful for the
support of the NIH-Oxford-Cambridge Research Scholars programme.
NR 60
TC 16
Z9 17
U1 0
U2 10
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 2046-2441
J9 OPEN BIOL
JI Open Biol
PD OCT
PY 2012
VL 2
AR 120109
DI 10.1098/rsob.120109
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 042TO
UT WOS:000311494100001
PM 23155484
ER
PT J
AU Blazeski, A
Zhu, RJ
Hunter, DW
Weinberg, SH
Boheler, KR
Zambidis, ET
Tung, L
AF Blazeski, Adriana
Zhu, Renjun
Hunter, David W.
Weinberg, Seth H.
Boheler, Kenneth R.
Zambidis, Elias T.
Tung, Leslie
TI Electrophysiological and contractile function of cardiomyocytes derived
from human embryonic stem cells
SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
LA English
DT Review
DE Human embryonic stem cell; Cardiac cell; Embryoid body;
Electrophysiology; Contraction Optical mapping
ID HIGHLY ENRICHED CARDIOMYOCYTES; HUMAN VENTRICULAR MYOCYTES; IN-VITRO
TRANSPLANTATION; CARDIAC DIFFERENTIATION; EXTRACELLULAR-MATRIX;
MYOCARDIAL REPAIR; ANIMAL-MODELS; RAT HEARTS; ELECTRICAL RESTITUTION;
SARCOPLASMIC-RETICULUM
AB Human embryonic stem cells have emerged as the prototypical source from which cardiomyocytes can be derived for use in drug discovery and cell therapy. However, such applications require that these cardiomyocytes (hESC-CMs) faithfully recapitulate the physiology of adult cells, especially in relation to their electrophysiological and contractile function. We review what is known about the electrophysiology of hESC-CMs in terms of beating rate, action potential characteristics, ionic currents, and cellular coupling as well as their contractility in terms of calcium cycling and contraction. We also discuss the heterogeneity in cellular phenotypes that arises from variability in cardiac differentiation, maturation, and culture conditions, and summarize present strategies that have been implemented to reduce this heterogeneity. Finally, we present original electrophysiological data from optical maps of hESC-CM clusters. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Blazeski, Adriana; Zhu, Renjun; Hunter, David W.; Weinberg, Seth H.; Tung, Leslie] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21205 USA.
[Zambidis, Elias T.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Inst Cell Engn, Baltimore, MD 21205 USA.
[Zambidis, Elias T.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Div Pediat Oncol, Baltimore, MD 21205 USA.
[Boheler, Kenneth R.] NIA, Mol Cardiol & Stem Cell Unit, Baltimore, MD 21224 USA.
RP Tung, L (reprint author), Johns Hopkins Univ, Dept Biomed Engn, 720 Rutland Ave, Baltimore, MD 21205 USA.
EM ltung@jhu.edu
FU Maryland Stem Cell Research Fund [2008-MSCRFE-0084-00,
2011-MSCRFII-0008-00, 2008-MSCRFII-0379-00]; NIH [S10 RR025544, R21
HL108210, U01HL099775, U01HL100397]; NIH NIA Intramural Research Program
FX Support for this work was provided by Maryland Stem Cell Research Fund
grants 2008-MSCRFE-0084-00 (LT), 2011-MSCRFII-0008-00 (ETZ) and
2008-MSCRFII-0379-00 (ETZ), NIH grants S10 RR025544 (LT), R21 HL108210
(LT), U01HL099775 (ETZ) and U01HL100397 (ETZ), and the NIH NIA
Intramural Research Program (KRB).
NR 212
TC 25
Z9 26
U1 0
U2 34
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0079-6107
J9 PROG BIOPHYS MOL BIO
JI Prog. Biophys. Mol. Biol.
PD OCT-NOV
PY 2012
VL 110
IS 2-3
SI SI
BP 178
EP 195
DI 10.1016/j.pbiomolbio.2012.07.012
PG 18
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 042MU
UT WOS:000311476100004
PM 22958937
ER
PT J
AU Tu, XD
Cai, H
Gao, YT
Wu, XY
Ji, BT
Yang, G
Li, HL
Zheng, W
Shu, XO
AF Tu, Xiangdong
Cai, Hui
Gao, Yu-Tang
Wu, Xiaoyan
Ji, Bu-Tian
Yang, Gong
Li, Honglan
Zheng, Wei
Shu, Xiao Ou
TI Sleep duration and its correlates in middle-aged and elderly Chinese
women: The Shanghai Women's Health Study
SO SLEEP MEDICINE
LA English
DT Article
DE Sleep duration; Socio-economic factor; Lifestyle; Health status; BMI;
Correlation; Chinese
ID CARDIOVASCULAR-DISEASE; ABDOMINAL OBESITY; INCREASED RISK;
BREAST-CANCER; UNITED-STATES; LONG-SLEEP; ASSOCIATION; ADULTS;
POPULATION; MORTALITY
AB Background: Abnormal sleep duration, either long or short, is associated with disease risk and mortality. Little information is available on sleep duration and its correlates among Chinese women.
Methods: Using information collected from 68,832 women who participated in the Shanghai Women's Health Study (SWHS), we evaluated sleep duration and its correlations with sociodemographic and lifestyle factors, health status, and anthropometric measurements and their indexes using polynomial logistic regression.
Results: The mean age of the study population was 59.6 years (SD = 9.0; range: 44.6-79.9 years) at time of sleep duration assessment. Approximately 80% of women reported sleeping 6-8 h/day, 11.5% slept 5 h or less, and 8.7% slept 9 h or more. As expected, age was the strongest predictor for sleep duration and was negatively correlated with sleep duration. In general, sleep duration was positively associated with energy intake, intakes of total meat and fruits, body mass index (BMI), waist-hip ratio (WHR), and waist circumference (WC) after adjustment for age and other factors. Both short and long sleep duration were negatively associated with education level, family income, and leisure-time physical activity and positively associated with number of live births, history of night shift work, and certain chronic diseases, compared to sleep duration around 7 h/day (6.5-7.4 h/day). Short sleep duration was related to tea consumption and passive smoking. Long sleep duration was related to menopausal status and marital status.
Conclusions: In this large, population-based study, we found that sleep duration among middle-aged and elderly Chinese women was associated with several sociodemographic and lifestyle factors and with disease status. The main limitation of the study is the cross-sectional design that does not allow us to draw any causal inference. However, this study provides information for future investigation into the nature of these associations so that recommendations can be developed to reduce sleep problems in middle-aged and elderly Chinese women. It also provides important information on potential confounders for investigation of sleep duration on health outcomes in this population. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Tu, Xiangdong; Cai, Hui; Wu, Xiaoyan; Yang, Gong; Zheng, Wei; Shu, Xiao Ou] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, IMPH, Dept Med, Nashville, TN 37203 USA.
[Tu, Xiangdong; Cai, Hui; Wu, Xiaoyan; Yang, Gong; Zheng, Wei; Shu, Xiao Ou] Vanderbilt Ingram Canc Ctr, IMPH, Nashville, TN 37203 USA.
[Tu, Xiangdong] Shekou Peoples Hosp, Dept Otorhinolaryngol, Shenzhen 518067, Guangdong, Peoples R China.
[Gao, Yu-Tang; Li, Honglan] Shanghai Jiao Tong Univ, Shanghai Canc Inst, Inst Canc, Dept Epidemiol, Shanghai 200032, Peoples R China.
[Wu, Xiaoyan] Harbin Med Univ, Coll Publ Hlth, Dept Biostat, Harbin, Peoples R China.
[Ji, Bu-Tian] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
RP Cai, H (reprint author), Vanderbilt Univ, Vanderbilt Epidemiol Ctr, IMPH, Dept Med, 2525 W End Ave,Suite 600, Nashville, TN 37203 USA.
EM hui.cai@vanderbilt.edu
FU National Institutes of Health [R37 CA070867]
FX Our study was supported by Research Grants R37 CA070867 from the
National Institutes of Health.
NR 50
TC 21
Z9 22
U1 1
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1389-9457
J9 SLEEP MED
JI Sleep Med.
PD OCT
PY 2012
VL 13
IS 9
BP 1138
EP 1145
DI 10.1016/j.sleep.2012.06.014
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 042NF
UT WOS:000311477200005
PM 22938861
ER
PT J
AU Richman, S
Gee, AP
McKenna, DH
Traverse, JH
Henry, TD
Fisk, D
Pepine, CJ
Bloom, J
Willerson, JT
Prater, K
Zhao, D
Koc, JR
Anwaruddin, S
Taylor, DA
Cogle, CR
Moye, LA
Simari, RD
Skarlatos, SI
AF Richman, Sara
Gee, Adrian P.
McKenna, David H.
Traverse, Jay H.
Henry, Timothy D.
Fisk, Diann
Pepine, Carl J.
Bloom, Jeannette
Willerson, James T.
Prater, Karen
Zhao, David
Koc, Jane Reese
Anwaruddin, Saif
Taylor, Doris A.
Cogle, Christopher R.
Moye, Lemuel A.
Simari, Robert D.
Skarlatos, Sonia I.
TI Factors affecting the turnaround time for manufacturing, testing, and
release of cellular therapy products prepared at multiple sites in
support of multicenter cardiovascular regenerative medicine protocols: a
Cardiovascular Cell Therapy Research Network (CCTRN) study
SO TRANSFUSION
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; MARROW MONONUCLEAR-CELLS; BONE-MARROW;
RATIONALE; TRIAL
AB BACKGROUND: Cellular therapy studies are often conducted at multiple clinical sites to accrue larger patient numbers. In many cases this necessitates use of localized good manufacturing practices facilities to supply the cells. To assure consistent quality, oversight by a quality assurance group is advisable. In this study we report the findings of such a group established as part of the Cardiovascular Cell Therapy Research Network (CCTRN) studies involving use of autologous bone marrow mononuclear cells (ABMMCs) to treat myocardial infarction and heart failure.
STUDY DESIGN AND METHODS: Factors affecting cell manufacturing time were studied in 269 patients enrolled on three CCTRN protocols using automated cell processing system (Sepax, Biosafe SA)-separated ABMMCs. The cells were prepared at five good manufacturing practices cell processing facilities and delivered to local treatment sites or more distant satellite centers.
RESULTS: Although the Sepax procedure takes only 90 minutes, the total time for processing was approximately 7 hours. Contributing to this were incoming testing and device preparation, release testing, patient randomization, and product delivery. The mean out-of-body time (OBT), which was to be less than 12 hours, averaged 9 hours. A detailed analysis of practices at each center revealed a variety of factors that contributed to this OBT.
CONCLUSION: We conclude that rapid cell enrichment procedures may give a false impression of the time actually required to prepare a cellular therapy product for release and administration. Institutional procedures also differ and can contribute to delays; however, in aggregate it is possible to achieve an overall manufacturing and testing time that is similar at multiple facilities.
C1 [Moye, Lemuel A.] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77030 USA.
Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
Univ Minnesota, Mol & Cellular Therapeut Facil, St Paul, MN 55108 USA.
Abbott NW Hosp, Minneapolis Heart Inst Fdn, Minneapolis, MN 55407 USA.
Shands Hosp Stem Cell Lab, Gainesville, FL USA.
Univ Florida, Coll Med, Gainesville, FL USA.
St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX USA.
Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
UHCMC Ireland Canc Ctr, Cell Therapy Serv, Cleveland, OH USA.
Cleveland Clin Fdn, Cleveland, OH 44195 USA.
Univ Minnesota, Sch Med, Ctr Cardiovasc Repair, Minneapolis, MN 55455 USA.
Mayo Clin, Rochester, MN USA.
NHLBI, Bethesda, MD 20892 USA.
RP Moye, LA (reprint author), Univ Texas Houston, Sch Publ Hlth, 1200 Herman Pressler,E815, Houston, TX 77030 USA.
EM lemmoye@msn.com
RI Cogle, Christopher/H-1746-2016
OI Cogle, Christopher/0000-0001-5422-6863
FU National Heart, Lung, and Blood Institute (NHLBI) [U01-HL-087318]; NHLBI
[N01 HB-37164, HHSN268201000008C, N01-HB-37163, HHSN268201000007C]
FX This study was supported by Grant U01-HL-087318 from the National Heart,
Lung, and Blood Institute (NHLBI). It was also supported in part by
NHLBI Contracts N01 HB-37164 and HHSN268201000008C to the Molecular and
Cellular Therapeutics Facility, University of Minnesota, and
N01-HB-37163 and HHSN268201000007C to the Cell Processing Facility,
Baylor College of Medicine.
NR 9
TC 2
Z9 2
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD OCT
PY 2012
VL 52
IS 10
BP 2225
EP 2233
DI 10.1111/j.1537-2995.2011.03543.x
PG 9
WC Hematology
SC Hematology
GA 030CM
UT WOS:000310545600023
PM 22320233
ER
PT J
AU Kilgore, N
Nuzum, EO
AF Kilgore, Nicole
Nuzum, Edwin O.
TI An Interagency Collaboration to Facilitate Development of Filovirus
Medical Countermeasures
SO VIRUSES-BASEL
LA English
DT Editorial Material
DE biodefense; Ebola; ebolavirus; FANG; Filovirida; filovirus; Filovirus
Animal Non-Clinical Group; Marburg virus; marburgvirus; medical
countermeasures
AB The Filovirus Animal Non-Clinical Group (FANG) is a US interdepartmental and interagency group established to support and facilitate the advanced development of filovirus Medical Countermeasures (MCM), both vaccines and therapeutics. It is co-led by one representative from the Department of Defense (DoD), the first author, and one from the Department of Health and Human Services (HHS), the second author. The FANG membership includes operational level program staff and Subject Matter Experts (SME) from performing organizations as well as scientific staff and program managers from DoD and HHS funding and regulatory agencies. Focus areas include animal models, assays, reagents, product manufacture and characterization, and other interagency product development issues that will support Food and Drug Administration (FDA) licensure of safe and effective filovirus MCMs. The FANG continues to develop strategies to address broadly applicable and interagency product development challenges relevant to filovirus MCM development. This paper summarizes FANG structure and accomplishments and is meant to heighten community awareness of this government-led collaborative effort.
C1 [Nuzum, Edwin O.] NIAID, Off Biodefense Res Affairs, DMID, NIH, Bethesda, MD 20892 USA.
[Kilgore, Nicole] Chem Biol Med Syst Joint Vaccine Acquisit Program, Ft Detrick, MD 21702 USA.
RP Nuzum, EO (reprint author), NIAID, Off Biodefense Res Affairs, DMID, NIH, 6610 Rockledge, Bethesda, MD 20892 USA.
EM nicole.r.kilgore.civ@mail.mil; enuzum@niaid.nih.gov
NR 5
TC 7
Z9 7
U1 0
U2 4
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD OCT
PY 2012
VL 4
IS 10
BP 2312
EP 2316
DI 10.3390/v4102312
PG 5
WC Virology
SC Virology
GA 028YP
UT WOS:000310462100022
PM 23202465
ER
PT J
AU Perry, DL
Bollinger, L
White, GL
AF Perry, Donna L.
Bollinger, Laura
White, Gary L.
TI The Baboon (Papio spp.) as a Model of Human Ebola Virus Infection
SO VIRUSES-BASEL
LA English
DT Review
DE Filoviridae; Filovirus; Baboon; Papio spp.; Ebola virus; Marburg virus;
BSL-4
ID MARBURG HEMORRHAGIC-FEVER; NONHUMAN PRIMATE MODEL; CYNOMOLGUS MACAQUES;
ESCHERICHIA-COLI; ELECTRON-MICROSCOPY; GUINEA-PIGS; PATHOGENESIS;
DISEASE; ZAIRE; RESPONSES
AB Baboons are susceptible to natural Ebola virus (EBOV) infection and share 96% genetic homology with humans. Despite these characteristics, baboons have rarely been utilized as experimental models of human EBOV infection to evaluate the efficacy of prophylactics and therapeutics in the United States. This review will summarize what is known about the pathogenesis of EBOV infection in baboons compared to EBOV infection in humans and other Old World nonhuman primates. In addition, we will discuss how closely the baboon model recapitulates human EBOV infection. We will also review some of the housing requirements and behavioral attributes of baboons compared to other Old World nonhuman primates. Due to the lack of data available on the pathogenesis of Marburg virus (MARV) infection in baboons, discussion of the pathogenesis of MARV infection in baboons will be limited.
C1 [Perry, Donna L.; Bollinger, Laura] NIAID, Integrated Res Facil, Div Clin Res, NIH, Frederick, MD USA.
[White, Gary L.] Univ Oklahoma, Univ Oklahoma Baboon Res Resource, Dept Pathol, Ft Reno Sci Pk, OK USA.
RP Perry, DL (reprint author), NIAID, Integrated Res Facil, Div Clin Res, NIH, Frederick, MD USA.
EM perrydl@niaid.nih.gov; bollingerl@niaid.nih.gov; gary-white@ouhsc.edu
FU NIAID [HHSN2722007000161]
FX The authors declare no conflict of interest. The content of this
publication does not necessarily reflect the views or policies of the
institutions and companies affiliated with the authors. DLP performed
this work as an employee of Charles River Laboratories and LB as an
employee of Battelle Memorial Institute under its prime contract
HHSN2722007000161 with the NIAID; and GW as an employee of the
University of Oklahoma.
NR 77
TC 9
Z9 10
U1 1
U2 29
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD OCT
PY 2012
VL 4
IS 10
BP 2400
EP 2416
DI 10.3390/v4102400
PG 17
WC Virology
SC Virology
GA 028YP
UT WOS:000310462100027
PM 23202470
ER
PT J
AU Cui, YF
Andersen, DK
AF Cui, YunFeng
Andersen, Dana K.
TI Diabetes and pancreatic cancer
SO ENDOCRINE-RELATED CANCER
LA English
DT Review
ID ISLET AMYLOID POLYPEPTIDE; POPULATION-BASED COHORT; RENAL-CELL
CARCINOMA; BODY-MASS INDEX; INSULIN-RESISTANCE; DUODENAL HOMEOBOX-1;
GLUCOSE-INTOLERANCE; BARIATRIC SURGERY; FECAL ELASTASE-1;
EARLY-DIAGNOSIS
AB Epidemiological studies clearly indicate that the risk of pancreatic cancer (PC) is increased in diabetic patients, but most studies focus on overall diabetes or type 2 diabetes mellitus (T2DM), and there are few studies on the risks of type 1 and type 3c (secondary) diabetes. Possible mechanisms for increased cancer risk in diabetes include cellular proliferative effects of hyperglycemia, hyperinsulinemia, and abnormalities in insulin/IGF receptor pathways. Recently, insulin and insulin secretagogues have been observed to increase the PC risk, while metformin treatment reduces the cancer risk in diabetic subjects. In addition, anticancer drugs used to treat PC may either cause diabetes or worsen coexisting diabetes. T3cDM has emerged as a major subset of diabetes and may have the highest risk of pancreatic carcinoma especially in patients with chronic pancreatitis. T3cDM is also a consequence of PC in at least 30% of patients. Distinguishing T3cDM from the more prevalent T2DM among new-onset diabetic patients can be aided by an assessment of clinical features and confirmed by finding a deficiency in postprandial pancreatic polypeptide release. In conclusion, diabetes and PC have a complex relationship that requires more clinical attention. The risk of developing PC can be reduced by aggressive prevention and treatment of T2DM and obesity and the prompt diagnosis of T3cDM may allow detection of a tumor at a potentially curable stage. Endocrine-Related Cancer (2012) 19 F9-F26
C1 [Cui, YunFeng; Andersen, Dana K.] Johns Hopkins Univ, Sch Med, Dept Surg, Johns Hopkins Bayview Med Ctr, Baltimore, MD 21205 USA.
[Cui, YunFeng] Tianjin Med Univ, Tianjin Nankai Hosp, Nankai Clin Sch Med, Dept Surg, Tianjin, Peoples R China.
RP Andersen, DK (reprint author), NIDDK, Div Digest Dis & Nutr, NIH, Bldg DEM2,Room 659,6707 Democracy Blvd, Bethesda, MD 20892 USA.
EM andersendk@niddk.nih.gov
NR 122
TC 48
Z9 50
U1 2
U2 24
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 1351-0088
EI 1479-6821
J9 ENDOCR-RELAT CANCER
JI Endocr.-Relat. Cancer
PD OCT
PY 2012
VL 19
IS 5
BP F9
EP F26
DI 10.1530/ERC-12-0105
PG 18
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA 035AH
UT WOS:000310913500003
PM 22843556
ER
PT J
AU Gonzalez, N
McKee, K
Yuste, E
Mascola, JR
Alcami, J
AF Gonzalez, N.
McKee, K.
Yuste, E.
Mascola, J. R.
Alcami, J.
TI Characterization of broadly neutralizing antibodies (bNAbs) to HIV-1
present in a cohort of long term non-progressors (LTNPs)
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Gonzalez, N.; Alcami, J.] Inst Salud Carlos III, AIDS Immunopathogenesis Unit, Madrid, Spain.
[McKee, K.; Mascola, J. R.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Yuste, E.] Hosp Clin Barcelona, Barcelona, Spain.
EM nglez@isciii.es
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 2
EP 2
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200004
ER
PT J
AU An, P
Goedert, J
Donfield, S
Buchbinder, S
Kirk, G
Detels, R
Winkler, C
AF An, P.
Goedert, J.
Donfield, S.
Buchbinder, S.
Kirk, G.
Detels, R.
Winkler, C.
TI ZNDR1 gene affects host susceptibility to HIV-1 infection
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [An, P.; Winkler, C.] SAIC Frederick Inc, NCI Frederick, Frederick, MD USA.
[Goedert, J.] NCI, Infect & Immunoepidemol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Donfield, S.] Rho Inc, Chapel Hill, NC USA.
[Buchbinder, S.] San Francisco Dept Publ Hlth, San Francisco, CA USA.
[Kirk, G.] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA.
[Detels, R.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
EM anp@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 6
EP 6
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200011
ER
PT J
AU Vinton, C
Brenchley, J
Tabb, B
Hao, XP
Hirsch, VM
Paiardini, M
Lifson, J
Silvestri, G
Estes, JD
AF Vinton, C.
Brenchley, J.
Tabb, B.
Hao, X. P.
Hirsch, V. M.
Paiardini, M.
Lifson, J.
Silvestri, G.
Estes, J. D.
TI Differential SIV infection patterns of lymph node-resident CD4 T cells
distinguishes progressive from nonprogressive SIV infection
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Vinton, C.; Brenchley, J.] NIAID, NIH, Program Barrier Immun & Repair, Bethesda, MD 20892 USA.
[Vinton, C.; Brenchley, J.] Immunopathogenesis Unit, Bethesda, MD USA.
[Vinton, C.; Brenchley, J.; Hirsch, V. M.] NIAID, NIH, Mol Microbiol Lab, Bethesda, MD 20892 USA.
[Tabb, B.; Lifson, J.; Estes, J. D.] NCI, NIH, AIDS & Canc Virus Program, Frederick, MD 21701 USA.
[Hao, X. P.] NCI, NIH, Pathol & Histotechnol Lab, Frederick, MD 21701 USA.
[Paiardini, M.; Silvestri, G.] Emory Univ, Atlanta, GA 30322 USA.
EM vintonca@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 11
EP 11
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200023
ER
PT J
AU Sampey, G
Van Duyne, R
Guendel, I
Gregg, E
Shafagati, N
Tyagi, M
Easely, R
Klase, Z
Romerio, F
Iglesias-Ussel, M
Nekhai, S
Kehn-Hall, K
Kashanchi, F
AF Sampey, G.
Van Duyne, R.
Guendel, I.
Gregg, E.
Shafagati, N.
Tyagi, M.
Easely, R.
Klase, Z.
Romerio, F.
Iglesias-Ussel, M.
Nekhai, S.
Kehn-Hall, K.
Kashanchi, F.
TI Discovery of novel transcription factors present only in infected cells
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Sampey, G.; Van Duyne, R.; Guendel, I.; Gregg, E.; Shafagati, N.; Tyagi, M.; Easely, R.; Kehn-Hall, K.; Kashanchi, F.] George Mason Univ, NCBID, Manassas, VA USA.
[Van Duyne, R.] Washington Univ, Washington, DC USA.
[Klase, Z.] NIH, Bethesda, MD 20892 USA.
[Romerio, F.; Iglesias-Ussel, M.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Nekhai, S.] Howard Univ, Washington, DC 20059 USA.
EM fkashanc@gmu.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 12
EP 12
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200026
ER
PT J
AU Lifson, J
Del Prete, G
Kiser, R
Trubey, CM
Smedley, J
Coalter, V
Oswald, K
Shoemaker, R
Fast, R
Li, Y
Lara, A
Wiles, A
Wiles, R
Macallister, R
Sanchez, R
Wai, J
Tan, C
Keele, B
Estes, J
Piatakjr, M
Hazuda, D
AF Lifson, J.
Del Prete, G.
Kiser, R.
Trubey, C. M.
Smedley, J.
Coalter, V.
Oswald, K.
Shoemaker, R.
Fast, R.
Li, Y.
Lara, A.
Wiles, A.
Wiles, R.
Macallister, R.
Sanchez, R.
Wai, J.
Tan, C.
Keele, B.
Estes, J.
Piatakjr, M.
Hazuda, D.
TI Evaluation of treatment with the histone deacetylase inhibitor
vorinostat (suberoylanilide hydroxamic acid; SAHA) in antiretroviral
drug treated, SIVmac239-infected rhesus macaques
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Lifson, J.; Del Prete, G.; Kiser, R.; Trubey, C. M.; Coalter, V.; Oswald, K.; Shoemaker, R.; Fast, R.; Li, Y.; Lara, A.; Wiles, A.; Wiles, R.; Keele, B.; Estes, J.; Piatakjr, M.] SAIC Frederick Inc, Frederick Naitonal Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA.
[Smedley, J.; Macallister, R.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Lab Anim Sci Program, Frederick, MD USA.
[Sanchez, R.; Wai, J.; Tan, C.; Hazuda, D.] Merck Res Labs, West Point, PA USA.
EM lifsonj@mail.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 2
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 17
EP 17
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200039
ER
PT J
AU Josefsson, L
Eriksson, S
Sinclair, E
Ho, T
Killian, M
Epling, L
Tan, A
Lemey, P
Faria, NR
Shao, W
Hunt, P
Somsouk, M
Douek, D
Bacchetti, P
Loeb, L
Custer, J
Poole, L
Deeks, S
Hecht, FM
Palmer, S
AF Josefsson, L.
Eriksson, S.
Sinclair, E.
Ho, T.
Killian, M.
Epling, L.
Tan, A.
Lemey, P.
Faria, N. R.
Shao, W.
Hunt, P.
Somsouk, M.
Douek, D.
Bacchetti, P.
Loeb, L.
Custer, J.
Poole, L.
Deeks, S.
Hecht, F. M.
Palmer, S.
TI Characterization of persistent HIV-1 in a broad spectrum of CD4+T cells
isolated from peripheral blood and gut associated lymphoid tissue from
patients on long-term suppressive therapy
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Josefsson, L.; Palmer, S.] Karolinska Inst, Dept Microbiol Tumor & Cellbiol, Solna, Sweden.
[Josefsson, L.; Eriksson, S.; Palmer, S.] Swedish Inst Communicable Dis Control, Dept Diagnost & Vaccinol, Solna, Sweden.
[Sinclair, E.; Ho, T.; Killian, M.; Epling, L.; Tan, A.; Hunt, P.; Somsouk, M.; Loeb, L.; Custer, J.; Poole, L.; Deeks, S.; Hecht, F. M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Lemey, P.; Faria, N. R.] Katholieke Univ Leuven, Rega Inst, Louvain, Belgium.
[Shao, W.] NCI, Adv Biomed Comp Ctr, SAIC, Frederick, MD 21701 USA.
[Douek, D.] NIAID, NIH, Immunol Lab, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Bacchetti, P.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
EM lina.josefsson@smi.se
RI Faria, Nuno/I-2975-2012
OI Faria, Nuno/0000-0001-8839-2798
NR 0
TC 0
Z9 0
U1 0
U2 5
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 18
EP 19
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200042
ER
PT J
AU Kline, C
Ndjomou, J
Franks, T
Kiser, R
Coalter, V
Piatak, M
Estes, J
Mellors, J
Lifson, J
Ambrose, Z
AF Kline, C.
Ndjomou, J.
Franks, T.
Kiser, R.
Coalter, V.
Piatak, M., Jr.
Estes, J.
Mellors, J.
Lifson, J.
Ambrose, Z.
TI Viral tissue reservoirs are determined early and little viral RNA is
detected during suppression by three or four drug regimens in the
macaque model
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Kline, C.; Ndjomou, J.; Franks, T.; Mellors, J.; Ambrose, Z.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Kiser, R.; Coalter, V.; Piatak, M., Jr.; Estes, J.; Lifson, J.] SAIC Frederick Inc, NCI Frederick, AIDS & Canc Virus Program, Frederick, MD USA.
EM zaa4@pitt.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 18
EP 18
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200041
ER
PT J
AU Madlala, P
Singh, R
Werner, L
Sibeko, S
An, P
Karim, SSA
Winkler, CA
Ndung'u, T
AF Madlala, P.
Singh, R.
Werner, L.
Sibeko, S.
An, P.
Karim, S. S. A.
Winkler, C. A.
Ndung'u, T.
TI Association of polymorphisms in the regulatory region of cyclophilin A
gene (PPIA) with disease progression and gene expression levels
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Madlala, P.; Singh, R.; Ndung'u, T.] Univ KwaZulu Natal, Nelson R Mandela Sch Med, HIV Pathogenesis Programme HPP, Durban, South Africa.
[Madlala, P.] Univ KwaZulu Natal, Pietermaritzburg, South Africa.
[Werner, L.; Sibeko, S.; Karim, S. S. A.] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Ctr AIDS Programme Res S Africa CAPRISA, Durban, South Africa.
[An, P.; Winkler, C. A.] NCI, Basic Res Lab, Frederick, MD 21701 USA.
EM madlalap@ukzn.ac.za
NR 0
TC 0
Z9 0
U1 0
U2 2
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 21
EP 22
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200049
ER
PT J
AU Introini, A
Vanpouille, C
Lisco, A
Grivel, JC
Munawwar, A
Singh, S
Margolis, L
AF Introini, A.
Vanpouille, C.
Lisco, A.
Grivel, J. -C.
Munawwar, A.
Singh, S.
Margolis, L.
TI HIV-1 transmission from semen to cervicovaginal tissue ex vivo
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Introini, A.; Vanpouille, C.; Lisco, A.; Grivel, J. -C.; Margolis, L.] NICHHD, NIH, Bethesda, MD 20892 USA.
[Munawwar, A.; Singh, S.] All India Inst Med Sci, New Delhi, India.
EM margolis@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 24
EP 24
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200056
ER
PT J
AU Nawaz, F
Cicala, C
Van Ryk, D
Wei, D
Pascuccio, M
Shrestha, S
Knox, J
Schwing, C
Hiatt, J
Chang, J
Jelicic, K
Fauci, A
Arthos, J
AF Nawaz, F.
Cicala, C.
Van Ryk, D.
Wei, D.
Pascuccio, M.
Shrestha, S.
Knox, J.
Schwing, C.
Hiatt, J.
Chang, J.
Jelicic, K.
Fauci, A.
Arthos, J.
TI The HIV-1 envelope protein gp120 mimics MAdCAM and VCAM in binding to
Integrin-alpha(4)beta(7)
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Nawaz, F.; Cicala, C.; Van Ryk, D.; Wei, D.; Pascuccio, M.; Shrestha, S.; Knox, J.; Schwing, C.; Hiatt, J.; Chang, J.; Jelicic, K.; Fauci, A.; Arthos, J.] NIAID, NIH, Bethesda, MD 20892 USA.
[Nawaz, F.] NYU, Sch Med, New York, NY USA.
EM nawazf@niaid.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 25
EP 25
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200058
ER
PT J
AU Dey, A
Kassa, A
Nandi, A
Sarkar, P
Sun, Y
Hartog, K
Labranche, C
Montefiori, D
Srivastava, I
Carfi, A
Barnett, S
AF Dey, A.
Kassa, A.
Nandi, A.
Sarkar, P.
Sun, Y.
Hartog, K.
Labranche, C.
Montefiori, D.
Srivastava, I.
Carfi, A.
Barnett, S.
TI Stabilized exposure of conserved epitopes by structure guided insertion
of disulfide bonds in HIV envelope glycoprotein
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Dey, A.; Kassa, A.; Nandi, A.; Sarkar, P.; Carfi, A.; Barnett, S.] Novartis Vaccines & Diagnost Inc, Cambridge, MD USA.
[Sun, Y.; Hartog, K.] Novartis Vaccines & Diagnost Inc, Emeryville, CA USA.
[Labranche, C.; Montefiori, D.] Duke Univ, Med Ctr, Durham, NC 27706 USA.
[Srivastava, I.] NIAID, Vaccine Res Ctr, NIH, Vaccine Prod Program Lab,VRC, Bethesda, MD 20892 USA.
EM antu.dey@novartis.com
RI Dey, Antu/A-1305-2013
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 29
EP 29
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200067
ER
PT J
AU Vaccari, M
Cameron, M
Liyanage, N
Pegu, P
Gordon, S
Doster, M
Sekaly, RP
Franchini, G
AF Vaccari, M.
Cameron, M.
Liyanage, N.
Pegu, P.
Gordon, S.
Doster, M.
Sekaly, R. -P.
Franchini, G.
TI Characterization of early gene expression profile in the blood of
macaques immunized a Thai trail-like vaccine
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Vaccari, M.; Liyanage, N.; Pegu, P.; Gordon, S.; Doster, M.; Franchini, G.] NIH, Bethesda, MD 20892 USA.
[Cameron, M.; Sekaly, R. -P.] VGTI Florida, Port St Lucie, FL USA.
EM vaccarim@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 30
EP 30
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200070
ER
PT J
AU Fitzgerald, W
Grivel, JC
AF Fitzgerald, W.
Grivel, J. -C.
TI A universal nanoparticle cell secretion capture assay for the study of
HIV-1-positive tissues
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Fitzgerald, W.; Grivel, J. -C.] NICHD, NIH, Bethesda, MD USA.
EM grivelj@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 32
EP 32
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200075
ER
PT J
AU Bulterys, P
Le, T
Quang, VM
Nelson, K
Lloyd-Smith, J
AF Bulterys, P.
Le, T.
Quang, V. M.
Nelson, K.
Lloyd-Smith, J.
TI Determinants of penicilliosis seasonality in Ho Chi Minh City, Vietnam
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Bulterys, P.] Univ Calif Los Angeles, David Geffen Sch Med, Med Sci Training Program, Los Angeles, CA 90095 USA.
[Le, T.] Univ Oxford, Clin Res Unit, Wellcome Trust Major Overseas Program, Ho Chi Minh City, Vietnam.
[Le, T.] Univ Hawaii Manoa, Hawaii Ctr AIDS, Honolulu, HI 96822 USA.
[Quang, V. M.] Hosp Trop Dis, Ho Chi Minh City, Vietnam.
[Nelson, K.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Lloyd-Smith, J.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA USA.
[Lloyd-Smith, J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
EM pbulterys@mednet.ucla.edu
RI Lloyd-Smith, James/K-4080-2012
OI Lloyd-Smith, James/0000-0001-7941-502X
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 41
EP 41
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200091
ER
PT J
AU Amorosa, V
Umbleja, T
Johnson, V
Kang, M
Luetkemeyer, A
Bardin, M
Haas, D
Chung, R
Yesmin, S
Coughlin, K
Martinez, A
Adams, MB
Alston-Smith, B
Tebas, P
Peters, M
AF Amorosa, V.
Umbleja, T.
Johnson, V.
Kang, M.
Luetkemeyer, A.
Bardin, M.
Haas, D.
Chung, R.
Yesmin, S.
Coughlin, K.
Martinez, A.
Adams, M. B.
Alston-Smith, B.
Tebas, P.
Peters, M.
TI The addition of nitazoxanide to peginterferon alfa-2a and ribavirin does
not significantly improve sustained virologic response in HCV
treatment-naive genotype 1 HIV-1/HCV co-infected subjects: results of
ACTG 5269
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Amorosa, V.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
[Amorosa, V.; Tebas, P.] Univ Penn, Philadelphia, PA 19104 USA.
[Umbleja, T.; Kang, M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Johnson, V.] Birmingham VA Med Ctr, Birmingham, AL USA.
[Johnson, V.] Univ Alabama Birmingham, Birmingham, AL USA.
[Luetkemeyer, A.; Peters, M.] Univ San Francisco, San Francisco, CA 94117 USA.
[Bardin, M.] Romark, Tampa, FL USA.
[Haas, D.] Vanderbilt Univ, Nashville, TN USA.
[Chung, R.] Harvard Univ, Sch Med, Boston, MA USA.
[Yesmin, S.] ACTG Operat Ctr, Bethesda, MD USA.
[Coughlin, K.] Frontiers Sci & Technol Res Fdn, Amherst, NY USA.
[Martinez, A.; Alston-Smith, B.] NIAID, DAIDS, NIH, Bethesda, MD 20892 USA.
[Adams, M. B.] Univ Rochester, Rochester, NY 14627 USA.
EM marion.peters@ucsf.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 47
EP 48
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200105
ER
PT J
AU Kahn, J
Xu, J
Kapogiannis, B
Rudy, B
Liu, N
Gonin, R
Wilson, C
Worrell, C
Squires, K
AF Kahn, J.
Xu, J.
Kapogiannis, B.
Rudy, B.
Liu, N.
Gonin, R.
Wilson, C.
Worrell, C.
Squires, K.
TI Immunogenicity of the HPV-6,-11,-16,-18 vaccine in HIV-positive young
women
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Kahn, J.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Xu, J.; Liu, N.; Gonin, R.] Westat Corp, Rockville, MD USA.
[Kapogiannis, B.; Worrell, C.] NICHD, PAMAB, Rockville, MD USA.
[Wilson, C.] Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL 35294 USA.
[Squires, K.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA.
[Rudy, B.] NYU, New York, NY USA.
EM jessica.kahn@cchmc.org
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 48
EP 49
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200106
ER
PT J
AU Kojic, EM
Cespedes, M
Umbleja, T
Kang, M
Aberg, J
Allen, R
Grinsztein, B
Firnhaber, C
Webster-Cyriaque, J
Palefsky, JM
Godfrey, C
Saah, AJ
Cu-Uvin, S
AF Kojic, E. M.
Cespedes, M.
Umbleja, T.
Kang, M.
Aberg, J.
Allen, R.
Grinsztein, B.
Firnhaber, C.
Webster-Cyriaque, J.
Palefsky, J. M.
Godfrey, C.
Saah, A. J.
Cu-Uvin, S.
TI Safety and immunogenicity of the quadrivalent human papillomavirus
vaccine in HIV-positive women
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Kojic, E. M.; Cu-Uvin, S.] Brown Univ, Miriam Hosp, Providence, RI USA.
[Cespedes, M.; Aberg, J.] New York Sch Med, New York, NY USA.
[Umbleja, T.; Kang, M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Allen, R.] ACTG Operat Ctr, Silver Spring, MD USA.
[Grinsztein, B.] Chagas Fiocruz, Rio De Janeiro, Brazil.
[Firnhaber, C.] Univ Witwatersrand, Johannesburg, South Africa.
[Webster-Cyriaque, J.] Univ N Carolina, Chapel Hill, NC USA.
[Palefsky, J. M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Godfrey, C.] NIAID, NIH, Bethesda, MD 20892 USA.
[Saah, A. J.] Merck Res Labs, N Wales, PA USA.
EM ekojic@lifespan.org
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 49
EP 49
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200107
ER
PT J
AU Sahasrabuddhe, V
Castle, P
Follansbee, S
Borgonovo, S
LaMere, B
Tokugawa, D
Darragh, T
Boyle, S
Sadorra, M
Tang, S
Wentzensen, N
AF Sahasrabuddhe, V.
Castle, P.
Follansbee, S.
Borgonovo, S.
LaMere, B.
Tokugawa, D.
Darragh, T.
Boyle, S.
Sadorra, M.
Tang, S.
Wentzensen, N.
TI HPV genotype attribution of anal neoplasia in HIV-positive MSM:
estimating the preventable fraction and disease misclassification
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Sahasrabuddhe, V.; Wentzensen, N.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Castle, P.] Amer Soc Clin Pathologists, Washington, DC USA.
[Follansbee, S.; Borgonovo, S.; LaMere, B.; Tokugawa, D.] Kaiser Permanente No Calif, San Francisco, CA USA.
[Darragh, T.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Boyle, S.; Sadorra, M.; Tang, S.] Roche Mol Syst, Pleasanton, CA USA.
EM vikrant.sahasrabuddhe@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 3
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 51
EP 52
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200112
ER
PT J
AU Grinsztejn, B
Hosseinipour, M
Swindells, S
Ribaudo, H
Eron, J
Chen, YQ
Wang, L
Ou, SS
Anderson, M
McCauley, M
Gamble, T
Kumarasamy, N
Hakim, J
Kumwenda, J
Pilotto, J
Godbole, S
Chariyalertsak, S
Santos, B
Mayer, K
Eshleman, S
Piwowar-Manning, E
Cottle, L
Makhema, J
Mills, L
Panchia, R
Sanne, I
Elharrar, V
Havlir, D
Cohen, MS
AF Grinsztejn, B.
Hosseinipour, M.
Swindells, S.
Ribaudo, H.
Eron, J.
Chen, Y. Q.
Wang, L.
Ou, S. -S.
Anderson, M.
McCauley, M.
Gamble, T.
Kumarasamy, N.
Hakim, J.
Kumwenda, J.
Pilotto, J.
Godbole, S.
Chariyalertsak, S.
Santos, B.
Mayer, K.
Eshleman, S.
Piwowar-Manning, E.
Cottle, L.
Makhema, J.
Mills, L.
Panchia, R.
Sanne, I.
Elharrar, V.
Havlir, D.
Cohen, M. S.
CA HPTN 052 ACTG Study Team
TI Effect of early versus delayed initiation of antiretroviral therapy
(ART) on clinical outcomes in the HPTN 052 randomized clinical trial
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Grinsztejn, B.] Fiocruz MS, Inst Pesquisa Clin Evandro Chagas, BR-21045900 Rio De Janeiro, Brazil.
[Hosseinipour, M.] UNC Project Malawi, Lilongwe, Malawi.
[Hosseinipour, M.] Univ N Carolina Chapel Hill, Lilongwe, Malawi.
[Swindells, S.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Ribaudo, H.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Eron, J.; Cohen, M. S.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Chen, Y. Q.; Wang, L.; Ou, S. -S.; Anderson, M.; Cottle, L.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[McCauley, M.] FHI 360, Washington, DC USA.
[Gamble, T.] FHI 360, Durham, NC USA.
[Kumarasamy, N.] YRG CARE Med Ctr, Madras, Tamil Nadu, India.
[Hakim, J.] Univ Zimbabwe, Dept Med, Harare, Zimbabwe.
[Kumwenda, J.] Johns Hopkins Project, Coll Med, Blantyre, Malawi.
[Pilotto, J.] Hosp Geral Nova Iguau, Rio De Janeiro, Brazil.
[Pilotto, J.] Lab AIDS & Imunol Mol IOC, Rio De Janeiro, Brazil.
[Godbole, S.] Natl AIDS Res Inst ICMR, Pune, Maharashtra, India.
[Chariyalertsak, S.] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand.
[Santos, B.] Hosp Nossa Senhora Conceiao, Porto Alegre, RS, Brazil.
[Mayer, K.] Harvard Univ, Sch Med, Fenway Hlth, Boston, MA USA.
[Eshleman, S.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA.
[Piwowar-Manning, E.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Makhema, J.] Botswana Harvard AIDS Inst, Gaborone, Botswana.
[Mills, L.] CDC, KEMRI CDC Res & Publ Hlth Collaborat, Div HIV AIDS Prevent, Kisumu, Kenya.
[Panchia, R.] Univ Witwatersrand, Perinatal HIV Res Unit PHRU, Johannesburg, South Africa.
[Sanne, I.] Univ Witwatersrand, Dept Med, Johannesburg, South Africa.
[Elharrar, V.] NIAID, NIH, Bethesda, MD 20892 USA.
[Havlir, D.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
EM beatriz.grinsztejn@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 2
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 60
EP 61
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200127
ER
PT J
AU Hazra, R
Viani, R
Acosta, E
Zheng, N
Alvero, C
O'Gara, E
Petzold, E
Heckman, B
Steimers, D
Song, I
Piscitelli, S
Wiznia, A
AF Hazra, R.
Viani, R.
Acosta, E.
Zheng, N.
Alvero, C.
O'Gara, E.
Petzold, E.
Heckman, B.
Steimers, D.
Song, I.
Piscitelli, S.
Wiznia, A.
CA P1093 Study Team
TI Pharmacokinetics, safety and efficacy of dolutegravir (DTG;
S/GSK1349572) in HIV-1-positive adolescents: preliminary analysis from
IMPAACT P1093
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Hazra, R.] NICHD, NIH, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA.
[Viani, R.] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA.
[Acosta, E.] Univ Alabama Birmingham, Med Sch Birmingham, Birmingham, AL USA.
[Zheng, N.; Alvero, C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[O'Gara, E.] NIAID, NIH, Int Maternal Adolescent & Pediat Branch, Bethesda, MD 20892 USA.
[Petzold, E.] Social & Sci Syst, Durham, NC USA.
[Steimers, D.; Song, I.; Piscitelli, S.] GlaxoSmithKline, Res Triangle Pk, NC USA.
[Wiznia, A.] Jacobi Med Ctr, Bronx, NY USA.
EM hazrar@mail.nih.gov
RI Viani, Rolando/C-3501-2013
NR 0
TC 1
Z9 1
U1 0
U2 3
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 64
EP 65
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200133
ER
PT J
AU Nielsen-Saines, K
Mirochnick, M
Kumwenda, N
Joao, EC
Kreitchmann, R
Pinto, J
Santos, B
Parsons, T
Richardson, P
Taha, T
Mofenson, L
Sato, P
Kearney, B
Fowler, MG
AF Nielsen-Saines, K.
Mirochnick, M.
Kumwenda, N.
Joao, E. C.
Kreitchmann, R.
Pinto, J.
Santos, B.
Parsons, T.
Richardson, P.
Taha, T.
Mofenson, L.
Sato, P.
Kearney, B.
Fowler, M. G.
TI Tenofovir disoproxil fumarate (TDF) pharmacokinetics (PK) with daily
dosing in the first week of life (HPTN 057)
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Nielsen-Saines, K.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Mirochnick, M.] Boston Univ, Boston, MA 02215 USA.
[Kumwenda, N.; Taha, T.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Joao, E. C.] Hosp Servidores Estado, Rio De Janeiro, Brazil.
[Kreitchmann, R.] Irmandade Santa Casa Misercordia Porto Alegre, Porto Alegre, RS, Brazil.
[Pinto, J.] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil.
[Santos, B.] Grp Hosp Conceicao, Porto Alegre, RS, Brazil.
[Parsons, T.; Richardson, P.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Mofenson, L.] NICHD, PAMAB, Bethesda, MD USA.
[Sato, P.] NIAID, Bethesda, MD 20892 USA.
[Fowler, M. G.] Johns Hopkins Med Inst, Kampala, Uganda.
EM knielsen@mednet.ucla.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 64
EP 64
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200132
ER
PT J
AU Nachman, S
Acosta, E
Zheng, N
Teppler, H
Homony, B
Xu, X
Alvero, C
Handelsman, E
Worrell, C
Graham, B
Toye, M
Petzold, E
Wiznia, A
AF Nachman, S.
Acosta, E.
Zheng, N.
Teppler, H.
Homony, B.
Xu, X.
Alvero, C.
Handelsman, E.
Worrell, C.
Graham, B.
Toye, M.
Petzold, E.
Wiznia, A.
CA P1066 Grp
TI IMPAACT P1066: raltegravir (RAL) safety and efficacy in HIV infected (+)
youth two to 18 years of age through week 48
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Nachman, S.] SUNY Stony Brook, Stony Brook, NY 11794 USA.
[Acosta, E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Zheng, N.; Alvero, C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Teppler, H.; Homony, B.; Xu, X.] Merck, N Wales, PA USA.
[Handelsman, E.] NIH, Div AIDSNIAID, Bethesda, MD 20892 USA.
[Worrell, C.] NICHHD, Bethesda, MD 20892 USA.
[Graham, B.] Frontier Sci Inc, Buffalo, NY USA.
[Toye, M.] Baystate Med Ctr, Springfield, MA 01199 USA.
[Petzold, E.] Social & Sci Syst, Durham, NC USA.
[Wiznia, A.] Albert Einstein Coll Med, Jacobi Med Ctr, Bronx, NY 10467 USA.
EM sharon.nachman@stonybrook.edu
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 67
EP 68
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200136
ER
PT J
AU Himes, S
Scheidweiler, K
Tassiopoulos, K
Kacanek, D
Hazra, R
Rich, K
Huestis, M
AF Himes, S.
Scheidweiler, K.
Tassiopoulos, K.
Kacanek, D.
Hazra, R.
Rich, K.
Huestis, M.
CA Pediat HIV AIDS Cohort Study PHAC
TI Development of the first liquid chromatography-tandem mass spectrometry
assay for antiretrovirals in meconium
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Himes, S.; Scheidweiler, K.; Huestis, M.] NIDA, Baltimore, MD USA.
[Tassiopoulos, K.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Kacanek, D.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Hazra, R.] NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA.
[Rich, K.] Univ Illinois, Dept Pediat, Chicago, IL USA.
EM sarah.himes@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 70
EP 70
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200141
ER
PT J
AU Koblin, B
Mayer, K
Eshleman, S
Wang, L
Shoptaw, S
del Rio, C
Buchbinder, S
Magnus, M
Mannheimer, S
Liu, TY
Cummings, V
Piwowar-Manning, E
Fields, S
Griffith, S
Elharrar, V
Wheeler, D
AF Koblin, B.
Mayer, K.
Eshleman, S.
Wang, L.
Shoptaw, S.
del Rio, C.
Buchbinder, S.
Magnus, M.
Mannheimer, S.
Liu, T. -Y.
Cummings, V.
Piwowar-Manning, E.
Fields, S.
Griffith, S.
Elharrar, V.
Wheeler, D.
CA HPTN 061 Study Team
TI Correlates of HIV incidence among black men who have sex with men in 6
US cities (HPTN 061)
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Koblin, B.] New York Blood Ctr, Lab Infect Dis Prevent, New York, NY 10021 USA.
[Mayer, K.] Fenway Hlth, Boston, MA USA.
[Mayer, K.] Beth Israel Deaconess Med Ctr, Boston, MA USA.
[Eshleman, S.; Cummings, V.; Piwowar-Manning, E.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Wang, L.; Liu, T. -Y.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Shoptaw, S.] Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA USA.
[del Rio, C.] Emory Univ, Rollins Sch Publ Hlth, Dept Global Hlth, Atlanta, GA 30322 USA.
[Buchbinder, S.] San Francisco Dept Publ Hlth, San Francisco, CA USA.
[Magnus, M.] George Washington Univ, Dept Epidemiol & Biostat, Sch Publ Hlth & Hlth Serv, Washington, DC USA.
[Mannheimer, S.] Columbia Univ, Dept Med, Harlem Hosp, New York, NY USA.
[Mannheimer, S.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Fields, S.] Florida Int Univ, Coll Nursing & Hlth Sci, Miami, FL 33199 USA.
[Griffith, S.] FHI 360, Res Triangle Pk, NC USA.
[Elharrar, V.] NIAID, NIH, Clin Prevent Res Branch, Bethesda, MD 20892 USA.
[Wheeler, D.] Loyola Univ, ChicagoGrad Sch Social Work, Chicago, IL 60611 USA.
EM bkoblin@nybloodcenter.org
RI del Rio, Carlos/B-3763-2012
OI del Rio, Carlos/0000-0002-0153-3517
NR 0
TC 1
Z9 1
U1 0
U2 1
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 94
EP 95
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200182
ER
PT J
AU Laeyendecker, O
Brookmeyer, R
Cousins, M
Mullis, C
Konikoff, J
Donnell, D
Celum, C
Buchbinder, S
Seage, G
Kirk, G
Mehta, S
Astemborski, J
Jacobson, L
Margolick, J
Brown, J
Quinn, T
Eshleman, S
AF Laeyendecker, O.
Brookmeyer, R.
Cousins, M.
Mullis, C.
Konikoff, J.
Donnell, D.
Celum, C.
Buchbinder, S.
Seage, G.
Kirk, G.
Mehta, S.
Astemborski, J.
Jacobson, L.
Margolick, J.
Brown, J.
Quinn, T.
Eshleman, S.
TI HIV incidence determination in clade B epidemics: a multi-assay approach
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Laeyendecker, O.; Quinn, T.] NIAID, LIR, Baltimore, MD USA.
[Cousins, M.; Eshleman, S.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Brookmeyer, R.; Konikoff, J.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA.
[Donnell, D.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Celum, C.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Celum, C.] Univ Washington, Dept Med, Seattle, WA USA.
[Buchbinder, S.] San Francisco Dept Hlth, San Francisco, CA USA.
[Seage, G.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Kirk, G.; Mehta, S.; Astemborski, J.; Jacobson, L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Margolick, J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Brown, J.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
EM olaeyen1@jhmi.edu
RI Laeyendecker, Oliver/B-9331-2009
NR 0
TC 0
Z9 0
U1 0
U2 2
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 111
EP 112
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200215
ER
PT J
AU Walensky, RP
Ross, EL
Kumarasamy, N
Wood, R
Noubary, F
Paltiel, AD
Nakamura, YM
Godbole, S
Hosseinipour, M
Hakim, JG
Kumwenda, J
Makhema, J
Akelo, V
Panchia, R
Sanne, I
Weinstein, MC
Losina, E
Mayer, KH
Grinsztejn, B
Pilotto, J
Chariyalertsak, S
Santos, B
Chen, YQ
Wang, L
Li, X
McCauley, M
Gamble, T
Piwowar-Manning, E
Cottle, L
Hoffman, I
Eron, J
Gallant, J
Swindells, S
Taha, T
Nielsen-Saines, K
Celentano, D
Essex, M
Elharrar, V
Burns, D
Seage, GR
Cohen, MS
Freedberg, KA
AF Walensky, R. P.
Ross, E. L.
Kumarasamy, N.
Wood, R.
Noubary, F.
Paltiel, A. D.
Nakamura, Y. M.
Godbole, S.
Hosseinipour, M.
Hakim, J. G.
Kumwenda, J.
Makhema, J.
Akelo, V.
Panchia, R.
Sanne, I.
Weinstein, M. C.
Losina, E.
Mayer, K. H.
Grinsztejn, B.
Pilotto, J.
Chariyalertsak, S.
Santos, B.
Chen, Y. Q.
Wang, L.
Li, X.
McCauley, M.
Gamble, T.
Piwowar-Manning, E.
Cottle, L.
Hoffman, I.
Eron, J.
Gallant, J.
Swindells, S.
Taha, T.
Nielsen-Saines, K.
Celentano, D.
Essex, M.
Elharrar, V.
Burns, D.
Seage, G. R.
Cohen, M. S.
Freedberg, K. A.
TI The cost-effectiveness of treatment as prevention: analysis of the HPTN
052 trial
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Walensky, R. P.; Ross, E. L.; Noubary, F.; Nakamura, Y. M.; Freedberg, K. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Walensky, R. P.; Freedberg, K. A.] Harvard Univ, Sch Med, Boston, MA USA.
[Losina, E.] Harvard Ctr AIDS Res, Boston, MA USA.
[Weinstein, M. C.; Essex, M.; Seage, G. R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Makhema, J.] Botswana Harvard AIDS Inst, Gaborone, Botswana.
[Walensky, R. P.; Losina, E.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Kumarasamy, N.] YR Gaitonade Ctr AIDS Res & Educ, Madras, Tamil Nadu, India.
[Wood, R.] Univ Cape Town, ZA-7925 Cape Town, South Africa.
[Wood, R.] Desmond Tutu HIV Ctr, Cape Town, South Africa.
[Paltiel, A. D.] Yale Univ, Sch Med, New Haven, CT USA.
[Godbole, S.] NARI, Pune, Maharashtra, India.
[Hosseinipour, M.] Univ N Carolina Chapel Hill, Lilongwe, Malawi.
[Hosseinipour, M.] UNC Project Malawi, Lilongwe, Malawi.
[Hakim, J. G.] Univ Zimbabwe, Dept Med, Harare, Zimbabwe.
[Kumwenda, J.] Coll Med Johns Hopkins Project, Blantyre, Malawi.
[Akelo, V.] KEMRI CDC Res & Publ Hlth Collaborat, Kisumu, Kenya.
[Panchia, R.] Univ Witwatersrand, PHRU, Johannesburg, South Africa.
[Sanne, I.] Univ Witwatersrand, Dept Med, Johannesburg, South Africa.
[Losina, E.; Freedberg, K. A.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Mayer, K. H.] Fenway Inst, Boston, MA USA.
[Grinsztejn, B.] Fiocruz MS, Inst Pesquisa Clin Evandro Chagas, BR-21045900 Rio De Janeiro, Brazil.
[Pilotto, J.] Fiocruz MS, Hosp Geral Nova Iguacu, BR-21045900 Rio De Janeiro, Brazil.
[Pilotto, J.] Fiocruz MS, Lab AIDS & Imunol Mol IOC, BR-21045900 Rio De Janeiro, Brazil.
[Chariyalertsak, S.] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand.
[Santos, B.] Hosp Nossa Senhora da Conceicao, Porto Alegre, RS, Brazil.
[Chen, Y. Q.; Wang, L.; Li, X.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[McCauley, M.] FHI 360, Washington, DC USA.
[Gamble, T.] FHI 360, Durham, NC USA.
[Piwowar-Manning, E.; Gallant, J.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Cottle, L.] SCHARP, Seattle, WA USA.
[Hoffman, I.; Eron, J.; Cohen, M. S.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Swindells, S.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Taha, T.; Celentano, D.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Nielsen-Saines, K.] Univ Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, Los Angeles, CA 90095 USA.
[Elharrar, V.; Burns, D.] NIAID, NIH, Bethesda, MD 20892 USA.
EM kfreedberg@partners.org
NR 0
TC 0
Z9 0
U1 1
U2 12
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 116
EP 117
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200220
ER
PT J
AU Valverde, E
Dinenno, E
Oster, A
Chavez, P
Thomas, P
Schulden, J
Heffelfinger, J
AF Valverde, E.
Dinenno, E.
Oster, A.
Chavez, P.
Thomas, P.
Schulden, J.
Heffelfinger, J.
TI Sexually transmitted disease diagnoses associated with exchange sex
among Hispanic migrant men who have sex with men in the United States
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Meeting Abstract
C1 [Valverde, E.; Dinenno, E.; Oster, A.; Chavez, P.; Thomas, P.; Heffelfinger, J.] Ctr Dis Control & Prevent, Div HIV AIDS, Atlanta, GA USA.
[Schulden, J.] NIDA, NIH, Bethesda, MD 20892 USA.
EM eid8@cdc.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD OCT
PY 2012
VL 15
SU 3
BP 138
EP 138
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 030RQ
UT WOS:000310588200255
ER
PT J
AU Vasudevan, K
Sztein, JM
AF Vasudevan, K.
Sztein, J. M.
TI In vitro fertility rate of 129 strain is improved by buserelin
(gonadotropin-releasing hormone) administration prior to superovulation
SO LABORATORY ANIMALS
LA English
DT Article
DE In vitro fertilization; GnRH; buserelin; fertility; superovulation
refinement
ID MOUSE EMBRYOS; OOCYTE MATURATION; GENETIC-CONTROL; HCG INJECTION;
FERTILIZATION; MICE; INVITRO; CULTURE; AGONIST; SPERM
AB The 129 mice are well recognized for their low fertility and it is speculated that this lack of fertility may be due to the oocyte condition. In this study we investigated superovulation regimens for the 129S1/SvImJ mouse strain to improve the oocyte quality and fertility rate of in vitro fertilization (IVF). Female mice were divided into four groups based on hormone and timing of injection. Group 1 received pregnant mare serum gonadotropin (PMSG) and 48 h later human chorionic gonadotropin (hCG); using the same dose, group 2 received hCG 52 h post-PMSG and group 3, 55 h post-PMSG. Group 4 received buserelin (gonadotropin-releasing hormone agonist [GnRH]) followed 24 h later by PMSG and then hCG 55 h post-PMSG. IVF was performed using 129S1/SvImJ oocytes and sperm; C57BL/6J sperm with 129S1/SvImJ oocytes was used as fertility control. The IVF fertility rate was 1% (Groups 1 and 2), 17% (Group 3) and 55% (Group 4) for 129 oocytes fertilized with 129 sperm. For 129 oocytes fertilized with C57BL/6J sperm, the fertility rate was 5% (Group 1), 10% (Group 2), 40% (Group 3) and 59% (Group 4). These results suggest that extending the interval time between PMSG and hCG and giving GnRH in addition to the standard PMSG and hCG treatments can improve IVF fertility rate of 129S1/SvImJ mouse strains significantly.
C1 [Vasudevan, K.; Sztein, J. M.] NIAID, Assisted Reprod Technol & Cryopreservat Unit, CMB, NIH, Bethesda, MD 20892 USA.
RP Sztein, JM (reprint author), NIAID, Assisted Reprod Technol & Cryopreservat Unit, CMB, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM szteinj@niaid.nih.gov
OI Sztein, Jorge Mario/0000-0001-7047-2634
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health. We thank Brenda Rae
Marshall, DPSS, NIAID, for editing. Because the authors are government
employees and this is a government work, the work is in the public
domain in the USA. Notwithstanding any other agreements, the NTH
reserves the right to provide the work to PubMedCentral for display and
use by the public, and PubMedCentral may tag or modify the work
consistent with its customary practices. Rights outside the US subject
to a government use licence can be established.
NR 28
TC 3
Z9 3
U1 0
U2 4
PU ROYAL SOC MEDICINE PRESS LTD
PI LONDON
PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND
SN 0023-6772
J9 LAB ANIM-UK
JI Lab. Anim.
PD OCT
PY 2012
VL 46
IS 4
BP 299
EP 303
DI 10.1258/la.2012.012073
PG 5
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 038RY
UT WOS:000311193000005
PM 23097563
ER
PT J
AU Xue, LY
Ren, LQ
Zou, SM
Shan, L
Liu, XY
Xie, YQ
Zhang, YM
Lu, J
Lin, DM
Dawsey, SM
Wang, GQ
Lu, N
AF Xue, Liyan
Ren, Liqun
Zou, Shuangmei
Shan, Ling
Liu, Xiuyun
Xie, Yongqiang
Zhang, Yueming
Lu, Jun
Lin, Dongmei
Dawsey, Sanford M.
Wang, Guiqi
Lu, Ning
TI Parameters predicting lymph node metastasis in patients with superficial
esophageal squamous cell carcinoma
SO MODERN PATHOLOGY
LA English
DT Article
DE endoscopic resection; esophageal cancer; lymph node metastasis;
superficial cancer; squamous cell carcinoma
ID ENDOSCOPIC MUCOSAL RESECTION; THORACIC ESOPHAGUS; CANCER; PROGNOSIS;
PATTERNS; CRITERIA
AB Endoscopic resection is a less invasive treatment than esophagectomy for superficial esophageal squamous cell carcinoma, but patients with lymph node metastasis need additional treatment after endoscopic resection. The purpose of this study was to establish a set of indicators to identify superficial esophageal squamous cell carcinoma patients at a high risk of metastasis. In all, 271 superficial esophageal squamous cell carcinoma esophagectomy cases were reviewed retrospectively. The relationships between clinicopathological parameters and immunohistochemical findings (p53, cyclin D1, EGFR and VEGF) on tissue microarrays, on the one hand, and lymph node metastasis were assessed by univariate and multivariate logistic regression analyses. Patients with intraluminal masses and ulcerated masses had a high risk of lymph node metastasis. Patients with superficial esophageal squamous cell carcinoma (1) thinner than 1200 mu m; (2) confined to the mucosa; (3) with submucosal invasion <250 mu m; (4) with submucosal invasion >= 250 mu m but with negative VEGF expression and well/moderately differentiated or basaloid histology; or (5) with submucosal invasion >= 250 mu m but with weak VEGF expression and well-differentiated histology had almost no risk of lymph node metastasis. We recommend endoscopic resection for all erosive, papillary and plaque-like superficial esophageal squamous cell carcinomas where endoscopic resection is clinically feasible, and esophagectomy for all other erosive, papillary and plaque-like cases and all intraluminal masses and ulcerated tumors. No additional treatment is needed for endoscopic resection cases with superficial esophageal squamous cell carcinoma (1) thinner than 1200 mu m; (2) confined to the mucosa; (3) with submucosal invasion <250 mu m; (4) with submucosal invasion >= 250 mu m but with negative VEGF expression and well/moderately differentiated or basaloid histology; or (5) with submucosal invasion >= 250 mu m but with weak VEGF expression and well-differentiated histology. These clinical and pathological criteria should enable more accurate selection of patients for these procedures. Modern Pathology (2012) 25, 1364-1377; doi: 10.1038/modpathol.2012.89; published online 25 May 2012
C1 [Lu, Ning] Chinese Acad Med Sci, Canc Inst Hosp, Dept Pathol, Peking Union Med Coll, Beijing 100021, Peoples R China.
[Ren, Liqun] Chengde Med Coll, Dept Pathol, Chengde, Peoples R China.
[Zhang, Yueming; Wang, Guiqi] Chinese Acad Med Sci, Canc Inst Hosp, Dept Endoscopy, Peking Union Med Coll, Beijing 100021, Peoples R China.
[Lu, Jun] Beijing Chaoyang Hosp, Dept Pathol, Beijing, Peoples R China.
[Dawsey, Sanford M.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Lu, N (reprint author), Chinese Acad Med Sci, Canc Inst Hosp, Dept Pathol, Peking Union Med Coll, Beijing 100021, Peoples R China.
EM nlu03@126.com
FU National Natural Science Foundation of the Peoples' Republic of China
[30271460, 30670964, 30770973]; Beijing Hope Run Special Fund
[LC2007B51]; Division of Cancer Epidemiology and Genetics of the
National Cancer Institute, NIH
FX The work was supported by grants from the National Natural Science
Foundation of the Peoples' Republic of China (No. 30271460, 30670964 and
30770973) and the Beijing Hope Run Special Fund (No. LC2007B51), and was
also supported in part by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics of the National Cancer
Institute, NIH.
NR 24
TC 7
Z9 9
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD OCT
PY 2012
VL 25
IS 10
BP 1364
EP 1377
DI 10.1038/modpathol.2012.89
PG 14
WC Pathology
SC Pathology
GA 016MU
UT WOS:000309523700006
PM 22627741
ER
PT J
AU Kerr, PJ
Ghedin, E
DePasse, JV
Fitch, A
Cattadori, IM
Hudson, PJ
Tscharke, DC
Read, AF
Holmes, EC
AF Kerr, Peter J.
Ghedin, Elodie
DePasse, Jay V.
Fitch, Adam
Cattadori, Isabella M.
Hudson, Peter J.
Tscharke, David C.
Read, Andrew F.
Holmes, Edward C.
TI Evolutionary History and Attenuation of Myxoma Virus on Two Continents
SO PLOS PATHOGENS
LA English
DT Article
ID RABBITS ORYCTOLAGUS-CUNICULUS; HOST-RANGE; REPLICATIVE CAPACITY;
EUROPEAN RABBITS; VIRAL-INFECTION; VIRULENCE; PROTEIN; RATES;
DETERMINANTS; COEVOLUTION
AB The attenuation of myxoma virus (MYXV) following its introduction as a biological control into the European rabbit populations of Australia and Europe is the canonical study of the evolution of virulence. However, the evolutionary genetics of this profound change in host-pathogen relationship is unknown. We describe the genome-scale evolution of MYXV covering a range of virulence grades sampled over 49 years from the parallel Australian and European epidemics, including the high-virulence progenitor strains released in the early 1950s. MYXV evolved rapidly over the sampling period, exhibiting one of the highest nucleotide substitution rates ever reported for a double-stranded DNA virus, and indicative of a relatively high mutation rate and/or a continually changing selective environment. Our comparative sequence data reveal that changes in virulence involved multiple genes, likely losses of gene function due to insertion-deletion events, and no mutations common to specific virulence grades. Hence, despite the similarity in selection pressures there are multiple genetic routes to attain either highly virulent or attenuated phenotypes in MYXV, resulting in convergence for phenotype but not genotype.
C1 [Kerr, Peter J.] CSIRO Ecosyst Sci, Canberra, ACT, Australia.
[Ghedin, Elodie; DePasse, Jay V.; Fitch, Adam] Univ Pittsburgh, Sch Med, Dept Computat & Syst Biol, Ctr Vaccine Res, Pittsburgh, PA USA.
[Cattadori, Isabella M.; Hudson, Peter J.; Read, Andrew F.; Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Tscharke, David C.] Australian Natl Univ, Res Sch Biol, Canberra, ACT, Australia.
[Read, Andrew F.; Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Kerr, PJ (reprint author), CSIRO Ecosyst Sci, Canberra, ACT, Australia.
EM ech15@psu.edu
RI Kerr, Peter/C-2463-2009; Tscharke, David/C-9133-2009;
OI Tscharke, David/0000-0001-6825-9172; Holmes, Edward/0000-0001-9596-3552
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health [R01 AI093804-01A1]; Huck Institutes of Life
Sciences, The Pennsylvania State University; Fogarty International
Center, National Institutes of Health
FX This work was funded in part by grant R01 AI093804-01A1 from the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health (http://www.niaid.nih.gov/Pages/default.aspx). We
thank members of the Research and Policy in Infectious Disease Dynamics
Program of the Science and Technology Directorate, Department of
Homeland Security (http://www.dhs.gov/index.shtm) and the Fogarty
International Center, National Institutes of Health
(http://www.fic.nih.gov/Pages/Default.aspx) for support. We also thank
the Huck Institutes of Life Sciences, The Pennsylvania State University
(http://www.huck.psu.edu/), for seed funding. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 50
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U1 2
U2 43
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD OCT
PY 2012
VL 8
IS 10
AR e1002950
DI 10.1371/journal.ppat.1002950
PG 9
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 029XH
UT WOS:000310530300016
PM 23055928
ER
PT J
AU Taha, AY
Basselin, M
Ramadan, E
Modi, HR
Rapoport, SI
Cheon, Y
AF Taha, Ameer Y.
Basselin, Mireille
Ramadan, Epolia
Modi, Hiren R.
Rapoport, Stanley I.
Cheon, Yewon
TI Altered lipid concentrations of liver, heart and plasma but not brain in
HIV-1 transgenic rats
SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
LA English
DT Article
DE HIV-1 transgenic rat; Fatty acid; Brain; Liver; Heart; Plasma;
Arachidonic; Docosahexaenoic; Polyunsaturated fatty acids (PUFA);
Concentration; Composition; Metabolism Virus
ID ALPHA-LINOLENIC ACID; POLYUNSATURATED FATTY-ACIDS;
ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HORMONE-SENSITIVE LIPASE; VIRUS
TYPE-1 GAG; DOCOSAHEXAENOIC ACID; ARACHIDONIC-ACID; ADULT-RATS;
SELECTIVE MOBILIZATION; METABOLIC SYNDROME
AB Disturbed lipid metabolism has been reported in antiretroviral-naive HIV-1-infected patients suggesting a direct effect of the virus on lipid metabolism. To test that the HIV-1 virus alone could alter lipid concentrations, we measured these concentrations in an HIV- 1 transgenic (Tg) rat model of human HIV-1 infection, which demonstrates peripheral and central pathology by 7-9 months of age. Concentrations were measured in high-energy microwaved heart, brain and liver from 7-9 month-old HIV-1 Tg and wildtype rats, and in plasma from non-microwaved rats. Plasma triglycerides and liver cholesteryl ester and total cholesterol concentrations were significantly higher in HIV-1 Tg rats than controls. Heart and plasma fatty acid concentrations reflected concentration differences in liver, which showed higher n-3 and n-6 polyunsaturated fatty acid (PUFA) concentrations in multiple lipid compartments. Fatty acid concentrations were increased or decreased in heart and liver phospholipid subfractions. Brain fatty acid concentrations differed significantly between the groups for minor fatty acids such as linoleic acid and n-3 docosapentaenoic acid. The profound changes in heart, plasma and liver lipid concentrations suggest a direct effect of chronic exposure to the HIV-1 virus on peripheral lipid (including PUFA) metabolism. Published by Elsevier Ltd.
C1 [Taha, Ameer Y.; Basselin, Mireille; Ramadan, Epolia; Modi, Hiren R.; Rapoport, Stanley I.; Cheon, Yewon] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Taha, AY (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
EM ameer.taha@nih.gov
RI Taha, Ameer/E-1979-2013
FU National Institute on Aging, National Institutes of Health
FX This work was supported entirely by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health.
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U1 2
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0952-3278
J9 PROSTAG LEUKOTR ESS
JI Prostaglandins Leukot. Essent. Fatty Acids
PD OCT-NOV
PY 2012
VL 87
IS 4-5
BP 91
EP 101
DI 10.1016/j.plefa.2012.07.006
PG 11
WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
GA 036KE
UT WOS:000311024000001
PM 22939288
ER
PT J
AU Ramsden, CE
Ringel, A
Feldstein, AE
Taha, AY
MacIntosh, BA
Hibbeln, JR
Majchrzak-Hong, SF
Faurot, KR
Rapoport, SI
Cheon, Y
Chung, YM
Berk, M
Mann, JD
AF Ramsden, Christopher E.
Ringel, Amit
Feldstein, Ariel E.
Taha, Ameer Y.
MacIntosh, Beth A.
Hibbeln, Joseph R.
Majchrzak-Hong, Sharon F.
Faurot, Keturah R.
Rapoport, Stanley I.
Cheon, Yewon
Chung, Yoon-Mi
Berk, Michael
Mann, J. Douglas
TI Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid
metabolites in humans
SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
LA English
DT Article
DE Linoleic acid; HODE; Hydroxy-octadecadienoic acid; Oxoode;
Oxo-octadecadienoic acid; Oxidation; OXLAM; PUFA; Polyunsaturated fatty
acid
ID POLYUNSATURATED FATTY-ACIDS; ADIPOSE-TISSUE COMPOSITION; LOW-DENSITY
LIPOPROTEINS; HUMAN DEPOT FAT; RAT-BRAIN; DOCOSAHEXAENOIC ACID;
UNSATURATED FAT; ABDOMINAL-PAIN; SPINAL-CORD; PHOSPHOLIPIDS
AB Linoleic acid (LA) is the most abundant polyunsaturated fatty acid in human diets, a major component of human tissues, and the direct precursor to the bioactive oxidized LA metabolites (OXLAMs), 9- and 13 hydroxy-octadecadienoic acid (9- and 13-HODE) and 9- and 13-oxo-octadecadienoic acid (9- and 13-oxoODE). These four OXIAMs have been mechanistically linked to pathological conditions ranging from cardiovascular disease to chronic pain. Plasma OXLAMs, which are elevated in Alzheimer's dementia and non-alcoholic steatohepatitis, have been proposed as biomarkers useful for indicating the presence and severity of both conditions. Because mammals lack the enzymatic machinery needed for de novo LA synthesis, the abundance of LA and OXLAMs in mammalian tissues may be modifiable via diet. To examine this issue in humans, we measured circulating LA and OXLAMs before and after a 12-week LA lowering dietary intervention in chronic headache patients. Lowering dietary LA significantly reduced the abundance of plasma OXLAMs, and reduced the LA content of multiple circulating lipid fractions that may serve as precursor pools for endogenous OXLAM synthesis. These results show that lowering dietary LA can reduce the synthesis and/or accumulation of oxidized LA derivatives that have been implicated in a variety of pathological conditions. Future studies evaluating the clinical implications of diet-induced OXLAM reductions are warranted. Published by Elsevier Ltd.
C1 [Ramsden, Christopher E.] NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
[Ramsden, Christopher E.; Faurot, Keturah R.] Univ N Carolina, Dept Phys Med & Rehabil, Program Integrat Med, Chapel Hill, NC USA.
[Feldstein, Ariel E.] Univ Calif San Diego, Dept Pediat Gastroenterol Hepatol & Nutr, San Diego, CA 92103 USA.
[Feldstein, Ariel E.; Chung, Yoon-Mi; Berk, Michael] Cleveland Clin, Dept Cell Biol, Coll Med, Cleveland, OH 44106 USA.
[Taha, Ameer Y.; Rapoport, Stanley I.; Cheon, Yewon] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD USA.
[MacIntosh, Beth A.] Univ N Carolina, Carolina Translat & Clin Sci Inst, Chapel Hill, NC USA.
[Mann, J. Douglas] Univ N Carolina, Dept Neurol, Program Integrat Med, Chapel Hill, NC USA.
RP Ramsden, CE (reprint author), NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, 31 Ctr Dr,Room 1B58,MSC 2088, Bethesda, MD 20892 USA.
EM chris.ramsden@nih.gov
RI Berk, Michael/M-7891-2013
OI Berk, Michael/0000-0002-5554-6946
FU Intramural NIH HHS [Z99 AA999999]; NCCIH NIH HHS [T32 AT003378,
T32-AT003378]; NCRR NIH HHS [UL1 RR025747, UL1RR025747]; NIDDK NIH HHS
[DK056350, P30 DK056350]
NR 54
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U2 13
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0952-3278
EI 1532-2823
J9 PROSTAG LEUKOTR ESS
JI Prostaglandins Leukot. Essent. Fatty Acids
PD OCT-NOV
PY 2012
VL 87
IS 4-5
BP 135
EP 141
DI 10.1016/j.plefa.2012.08.004
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
GA 036KE
UT WOS:000311024000006
PM 22959954
ER
PT J
AU Noseworthy, PA
Peloso, GM
Hwang, SJ
Larson, MG
Levy, D
O'Donnell, CJ
Newton-Cheh, C
AF Noseworthy, Peter A.
Peloso, Gina M.
Hwang, Shih-Jen
Larson, Martin G.
Levy, Daniel
O'Donnell, Christopher J.
Newton-Cheh, Christopher
TI QT Interval and Long-Term Mortality Risk in the Framingham Heart Study
SO ANNALS OF NONINVASIVE ELECTROCARDIOLOGY
LA English
DT Article
DE heart rate; mortality; QT interval; sudden cardiac death
ID SUDDEN CARDIAC DEATH; MIDDLE-AGED MEN; CARDIOVASCULAR MORTALITY;
GENERAL-POPULATION; COMMON VARIANTS; CORRECTED QT; ALL-CAUSE; DISEASE;
DURATION; ASSOCIATION
AB Background: The association between QT interval and mortality has been demonstrated in large, prospective population-based studies, but the strength of the association varies considerably based on the method of heart rate correction. We examined the QT-mortality relationship in the Framingham Heart Study (FHS). Methods: Participants in the first (original cohort, n = 2,365) and second generation (offspring cohort, n = 4,530) cohorts were included in this study with a mean follow up of 27.5 years. QT interval measurements were obtained manually using a reproducible digital caliper technique. Results: Using Cox proportional hazards regression adjusting for age and sex, a 20 millisecond increase in QTc (using Bazett's correction; QT/RR1/2 interval) was associated with a modest increase in risk of all-cause mortality (HR 1.14, 95% CI 1.101.18, P < 0.0001), coronary heart disease (CHD) mortality (HR 1.15, 95% CI 1.051.26, P = 0.003), and sudden cardiac death (SCD, HR 1.19, 95% CI 1.031.37, P = 0.02). However, adjustment for heart rate using RR interval in linear regression attenuated this association. The association of QT interval with all-cause mortality persisted after adjustment for cardiovascular risk factors, but associations with CHD mortality and SCD were no longer significant. Conclusion: In FHS, there is evidence of a graded relation between QTc and all-cause mortality, CHD death, and SCD; however, this association is attenuated by adjustment for RR interval. These data confirm that using Bazett's heart rate correction, QTc, overestimates the association with mortality. An association with all-cause mortality persists despite a more complete adjustment for heart rate and known cardiovascular risk factors.
C1 [Noseworthy, Peter A.; Peloso, Gina M.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Noseworthy, Peter A.; Peloso, Gina M.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Noseworthy, Peter A.; Newton-Cheh, Christopher] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Peloso, Gina M.; Hwang, Shih-Jen; Larson, Martin G.; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Levy, Daniel] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
RP Newton-Cheh, C (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St,CPZN 5-242, Boston, MA 02114 USA.
EM cnewtoncheh@chgr.mgh.harvard.edu
OI Larson, Martin/0000-0002-9631-1254
FU Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology;
NIH/NHLBI [HL080025, HL098283]; Doris Duke Charitable Foundation;
Burroughs Wellcome Fund; National Heart Lung and Blood Institute of the
National Institutes of Health; Boston University School of Medicine
[N01-HC-25195]
FX This work was supported by the Max Schaldach Fellowship in Cardiac
Pacing and Electrophysiology (P.A.N.), the NIH/NHLBI (HL080025, HL098283
C. N.-C.), the Doris Duke Charitable Foundation (C. N.-C.), and the
Burroughs Wellcome Fund (C. N.-C.). The FHS was supported by the
National Heart Lung and Blood Institute of the National Institutes of
Health and Boston University School of Medicine (Contract No.
N01-HC-25195).
NR 35
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U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1082-720X
J9 ANN NONINVAS ELECTRO
JI Ann. Noninvasive Electrocardiol.
PD OCT
PY 2012
VL 17
IS 4
BP 340
EP 348
DI 10.1111/j.1542-474X.2012.00535.x
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 026CD
UT WOS:000310248100006
PM 23094880
ER
PT J
AU Mai, PL
Malkin, D
Garber, JE
Schiffman, JD
Weitzel, JN
Strong, LC
Wyss, O
Locke, L
Means, V
Achatz, MI
Hainaut, P
Frebourg, T
Evans, DG
Bleiker, E
Patenaude, A
Schneider, K
Wilfond, B
Peters, JA
Hwang, PM
Ford, J
Tabori, U
Ognjanovic, S
Dennis, PA
Wentzensen, IM
Greene, MH
Fraumeni, JF
Savage, SA
AF Mai, Phuong L.
Malkin, David
Garber, Judy E.
Schiffman, Joshua D.
Weitzel, Jeffrey N.
Strong, Louise C.
Wyss, Oliver
Locke, Luana
Means, Von
Achatz, Maria Isabel
Hainaut, Pierre
Frebourg, Thierry
Evans, D. Gareth
Bleiker, Eveline
Patenaude, Andrea
Schneider, Katherine
Wilfond, Benjamin
Peters, June A.
Hwang, Paul M.
Ford, James
Tabori, Uri
Ognjanovic, Simona
Dennis, Phillip A.
Wentzensen, Ingrid M.
Greene, Mark H.
Fraumeni, Joseph F., Jr.
Savage, Sharon A.
TI Li-Fraumeni syndrome: report of a clinical research workshop and
creation of a research consortium
SO CANCER GENETICS
LA English
DT Article
DE Li-Fraumeni syndrome; hereditary cancer predisposition syndrome; TP53
mutations
ID TP53 MUTATION CARRIERS; BREAST-CANCER; MITOCHONDRIAL RESPIRATION;
GERMLINE MUTATIONS; FAMILIAL SYNDROME; TELOMERE LENGTH; P53 MUTATIONS;
GENE; SURVEILLANCE; NEOPLASMS
AB Li-Fraumeni syndrome (LFS) is a rare dominantly inherited cancer predisposition syndrome that was first described in 1969. In most families, it is caused by germline mutations in the TP53 gene and is characterized by early onset of multiple specific cancers and very high lifetime cumulative cancer risk. Despite significant progress in understanding the molecular biology of TP53, the optimal clinical management of this syndrome is poorly defined. We convened a workshop on November 2, 2010, at the National Institutes of Health in Bethesda, Maryland, bringing together clinicians and scientists, as well as individuals from families with LFS, to review the state of the science, address clinical management issues, stimulate collaborative research, and engage the LFS family community. This workshop also led to the creation of the Li-Fraumeni Exploration (LiFE) Research Consortium.
C1 [Mai, Phuong L.; Peters, June A.; Wentzensen, Ingrid M.; Greene, Mark H.; Fraumeni, Joseph F., Jr.; Savage, Sharon A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Malkin, David; Tabori, Uri] Univ Toronto, Hosp Sick Children, Dept Pediat, Div Hematol Oncol & Genet, Toronto, ON M5G 1X8, Canada.
[Malkin, David; Tabori, Uri] Univ Toronto, Hosp Sick Children, Dept Pediat, Genome Biol Program, Toronto, ON M5G 1X8, Canada.
[Garber, Judy E.; Schneider, Katherine] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
[Schiffman, Joshua D.] Univ Utah, Dept Pediat, Huntsman Canc Inst, Ctr Childrens Canc Res, Salt Lake City, UT USA.
[Weitzel, Jeffrey N.] City Hope Natl Med Ctr, Dept Populat Sci, Div Clin Canc Genet, Duarte, CA 91010 USA.
[Strong, Louise C.] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA.
[Achatz, Maria Isabel] Hosp AC Camargo Fund Antonio Prudente, Dept Oncogenet, Sao Paulo, Brazil.
[Achatz, Maria Isabel] Natl Inst Sci & Technol Oncogen INCITO, Sao Paulo, Brazil.
[Hainaut, Pierre] Int Prevent Res Inst, Lyon, France.
[Frebourg, Thierry] Univ Hosp, Dept Genet, INSERM, Inst Biomed Res & Innovat,U614, Rouen, Normandy, France.
[Evans, D. Gareth] Univ Manchester, St Marys Hosp, MAHSC, Manchester M13 0JH, Lancs, England.
[Bleiker, Eveline] Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands.
[Patenaude, Andrea] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Wilfond, Benjamin] Univ Washington, Sch Med, Dept Pediat, Div Bioeth, Seattle, WA 98195 USA.
[Hwang, Paul M.] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
[Ford, James] Stanford Univ, Dept Med, Sch Med, Div Oncol, Stanford, CA 94305 USA.
[Ford, James] Stanford Univ, Dept Med, Sch Med, Div Med Genet, Stanford, CA 94305 USA.
[Ognjanovic, Simona] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA.
[Ognjanovic, Simona] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA.
[Dennis, Phillip A.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Mai, PL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM maip@mail.nih.gov
RI Achatz, Maria Isabel /C-5751-2013; Oncogenomica, Inct/H-9999-2013;
Hainaut, Pierre /B-6018-2012; Savage, Sharon/B-9747-2015;
OI Achatz, Maria Isabel /0000-0001-6894-1219; Hainaut, Pierre
/0000-0002-1303-1610; Savage, Sharon/0000-0001-6006-0740; Tabori,
Uri/0000-0002-5019-2683; Evans, Gareth/0000-0002-8482-5784
FU NIH Office of Rare Diseases Research; Division of Cancer Control and
Population Sciences of the NCI; intramural research program of the
Division of Cancer Epidemiology and Genetics, NCI, NIH
FX The workshop was supported by the NIH Office of Rare Diseases Research,
the Division of Cancer Control and Population Sciences of the NCI, and
the intramural research program of the Division of Cancer Epidemiology
and Genetics, NCI, NIH.
NR 40
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U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2210-7762
J9 CANCER GENET-NY
JI Cancer Genet.
PD OCT
PY 2012
VL 205
IS 10
BP 479
EP 487
DI 10.1016/j.cancergen.2012.06.008
PG 9
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 031TQ
UT WOS:000310665600001
PM 22939227
ER
PT J
AU Liu, J
Moon, AF
Sheng, JZ
Pedersen, LC
AF Liu, Jian
Moon, Andrea F.
Sheng, Juzheng
Pedersen, Lars C.
TI Understanding the substrate specificity of the heparan sulfate
sulfotransferases by an integrated biosynthetic and crystallographic
approach
SO CURRENT OPINION IN STRUCTURAL BIOLOGY
LA English
DT Article
ID HERPES-SIMPLEX-VIRUS; D-GLUCOSAMINYL 3-O-SULFOTRANSFERASE;
ANTITHROMBIN-III; ANTICOAGULANT HEPARIN; N-SULFOTRANSFERASE;
MOLECULAR-CLONING; CRYSTAL-STRUCTURE; ENTRY RECEPTOR; EXPRESSION;
BINDING
AB Heparan sulfates (HSs) have potential therapeutic value as anti-inflammatory and antimetastasis drugs, in addition to their current use as anticoagulants. Recent advances in chemoenzymatic synthesis of HS provide a way to conveniently produce homogenous HS with different biological properties. Crystal structures of sulfotransferases involved in this process are providing atomic detail of their substrate binding clefts and interactions with their HS substrates. In theory, the flexibility of this method can be increased by modifying the specificities of the sulfotransferases based on the structures, thereby producing a new array of products.
C1 [Moon, Andrea F.; Pedersen, Lars C.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Liu, Jian; Sheng, Juzheng] Univ N Carolina, Eshelman Sch Pharm, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA.
RP Pedersen, LC (reprint author), NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
EM pederse2@niehs.nih.gov
RI Sheng, Juzheng/G-2693-2013
OI Sheng, Juzheng/0000-0003-2856-9162
FU Division of Intramural Research of the National Institute of
Environmental Health Sciences; National Institutes of Health [1 ZIA
ES102645-03, AI050050, HL094463, HL096972]
FX We thank L.G. Pedersen and R. Gosavi for critical reading of the
manuscript. This research was supported by the Division of Intramural
Research of the National Institute of Environmental Health Sciences,
National Institutes of Health (1 ZIA ES102645-03, to L. Pedersen) and
NIH grants AI050050, HL094463 and HL096972 (to J. Liu).
NR 46
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U1 2
U2 21
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-440X
J9 CURR OPIN STRUC BIOL
JI Curr. Opin. Struct. Biol.
PD OCT
PY 2012
VL 22
IS 5
BP 550
EP 557
DI 10.1016/j.sbi.2012.07.004
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 033BA
UT WOS:000310766200003
PM 22840348
ER
PT J
AU Morgan, RA
Johnson, LA
Davis, JL
Zheng, ZL
Woolard, KD
Reap, EA
Feldman, SA
Chinnasamy, N
Kuan, CT
Song, H
Zhang, W
Fine, HA
Rosenberg, SA
AF Morgan, Richard A.
Johnson, Laura A.
Davis, Jeremy L.
Zheng, Zhili
Woolard, Kevin D.
Reap, Elizabeth A.
Feldman, Steven A.
Chinnasamy, Nachimuthu
Kuan, Chien-Tsun
Song, Hua
Zhang, Wei
Fine, Howard A.
Rosenberg, Steven A.
TI Recognition of Glioma Stem Cells by Genetically Modified T Cells
Targeting EGFRvIII and Development of Adoptive Cell Therapy for Glioma
SO HUMAN GENE THERAPY
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; CHIMERIC-ANTIGEN-RECEPTOR; ANTITUMOR-ACTIVITY;
MONOCLONAL-ANTIBODIES; CANCER; IMMUNOTHERAPY; GLIOBLASTOMA; VARIANT;
EXPRESSION; GENE
AB No curative treatment exists for glioblastoma, with median survival times of less than 2 years from diagnosis. As an approach to develop immune-based therapies for glioblastoma, we sought to target antigens expressed in glioma stem cells (GSCs). GSCs have multiple properties that make them significantly more representative of glioma tumors than established glioma cell lines. Epidermal growth factor receptor variant III (EGFRvIII) is the result of a novel tumor-specific gene rearrangement that produces a unique protein expressed in approximately 30% of gliomas, and is an ideal target for immunotherapy. Using PCR primers spanning the EGFRvIII-specific deletion, we found that this tumor-specific gene is expressed in three of three GCS lines. Based on the sequence information of seven EGFRvIII-specific monoclonal antibodies (mAbs), we assembled chimeric antigen receptors (CARs) and evaluated the ability of CAR-engineered T cells to recognize EGFRvIII. Three of these anti-EGFRvIII CAR-engineered T cells produced the effector cytokine, interferon-c, and lysed antigen-expressing target cells. We concentrated development on a CAR produced from human mAb 139, which specifically recognized GSC lines and glioma cell lines expressing mutant EGFRvIII, but not wild-type EGFR and did not recognize any normal human cell tested. Using the 139-based CAR, T cells from glioblastoma patients could be genetically engineered to recognize EGFRvIII-expressing tumors and could be expanded ex vivo to large numbers, and maintained their antitumor activity. Based on these observations, a c-retroviral vector expressing this EGFRvIII CAR was produced for clinical application.
C1 [Morgan, Richard A.; Davis, Jeremy L.; Zheng, Zhili; Feldman, Steven A.; Chinnasamy, Nachimuthu; Rosenberg, Steven A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Johnson, Laura A.; Reap, Elizabeth A.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
[Woolard, Kevin D.; Song, Hua; Zhang, Wei; Fine, Howard A.] NCI, Neurooncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kuan, Chien-Tsun] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
RP Morgan, RA (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10 CRC,Room 3W5940,10 Ctr Dr, Bethesda, MD 20892 USA.
EM rmorgan@mail.nih.gov
RI Johnson, Laura/H-4861-2013
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research; Voices Against Brain Cancer (VABC)
FX This work is supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research. L. A. J. was supported by Voices Against Brain Cancer
(VABC). We thank Pamela Norberg for technical assistance. Experiments
were performed by R. A. M., L. A. J., J. L. D., Z. Z., S. A. F., and N.
C. Reagents and other experimental support was provided by K. D. W., C.
T. K., H. S., and W. Z. The manuscript was written by R. A. M., L. A.
J., K. D. W., H. A. F., and S.A.R.
NR 43
TC 85
Z9 88
U1 5
U2 19
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
J9 HUM GENE THER
JI Hum. Gene Ther.
PD OCT
PY 2012
VL 23
IS 10
BP 1043
EP 1053
DI 10.1089/hum.2012.041
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 027PE
UT WOS:000310364400480
PM 22780919
ER
PT J
AU Chandler, RJ
Venditti, CP
AF Chandler, R. J.
Venditti, C. P.
TI Increased incidence of hepatocellular carcinoma (HCC) in mice following
a single intra-hepatic injection of adeno-associated virus (AAV) in the
neonatal period
SO HUMAN GENE THERAPY
LA English
DT Meeting Abstract
CT Collaborative Congress of the
European-Society-of-Gene-and-Cell-Therapy/French-Society-of-Cell-and-Gen
e-Therapy
CY OCT 25-29, 2012
CL Versailles, FRANCE
SP European Soc Gene & Cell Therapy, French Soc Cell & Gene Therapy
C1 [Chandler, R. J.; Venditti, C. P.] Natl Human Genome Inst, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
J9 HUM GENE THER
JI Hum. Gene Ther.
PD OCT
PY 2012
VL 23
IS 10
BP A106
EP A106
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 027PE
UT WOS:000310364400317
ER
PT J
AU Kohn, D
Carbonaro, D
Shaw, K
Jin, XY
Geiger, S
Mishra, S
Cooper, A
DeOliveira, S
Sokolic, R
Candotti, F
AF Kohn, Donald
Carbonaro, Denise
Shaw, Kit
Jin, Xiangyang
Geiger, Sabine
Mishra, Suparna
Cooper, Aaron
DeOliveira, Satiro
Sokolic, Rob
Candotti, Fabio
TI Gene therapy for ADA-deficient severe combined immune deficiency
SO HUMAN GENE THERAPY
LA English
DT Meeting Abstract
CT Collaborative Congress of the
European-Society-of-Gene-and-Cell-Therapy/French-Society-of-Cell-and-Gen
e-Therapy
CY OCT 25-29, 2012
CL Versailles, FRANCE
SP European Soc Gene & Cell Therapy, French Soc Cell & Gene Therapy
C1 [Kohn, Donald; Carbonaro, Denise; Shaw, Kit; Jin, Xiangyang; Geiger, Sabine; Mishra, Suparna; Cooper, Aaron; DeOliveira, Satiro] Univ Calif Los Angeles, Los Angeles, CA USA.
[Sokolic, Rob; Candotti, Fabio] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
J9 HUM GENE THER
JI Hum. Gene Ther.
PD OCT
PY 2012
VL 23
IS 10
BP A9
EP A9
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 027PE
UT WOS:000310364400020
ER
PT J
AU Morgan, RA
Gros, A
Robbins, PF
Zheng, ZL
Feldman, SA
Yang, JC
Sherry, RM
Phan, G
Hughes, MS
Kammula, US
Miller, A
Hessman, C
Stewart, A
Restifo, NP
Rosenberg, SA
AF Morgan, Richard A.
Gros, Alena
Robbins, Paul F.
Zheng, Zhili
Feldman, Steve A.
Yang, James C.
Sherry, Richard M.
Phan, Giao
Hughes, Marybeth S.
Kammula, Udai S.
Miller, Akemi
Hessman, Crystal
Stewart, Ashley
Restifo, Nicholas P.
Rosenberg, Steven A.
TI Cancer regression and neurologic toxicity following anti-MAGE-A3 TCR
gene therapy
SO HUMAN GENE THERAPY
LA English
DT Meeting Abstract
CT Collaborative Congress of the
European-Society-of-Gene-and-Cell-Therapy/French-Society-of-Cell-and-Gen
e-Therapy
CY OCT 25-29, 2012
CL Versailles, FRANCE
SP European Soc Gene & Cell Therapy, French Soc Cell & Gene Therapy
C1 [Morgan, Richard A.; Gros, Alena; Robbins, Paul F.; Zheng, Zhili; Feldman, Steve A.; Yang, James C.; Sherry, Richard M.; Phan, Giao; Hughes, Marybeth S.; Kammula, Udai S.; Miller, Akemi; Hessman, Crystal; Stewart, Ashley; Restifo, Nicholas P.; Rosenberg, Steven A.] NCI, Surg Branch, Bethesda, MD 20892 USA.
RI Restifo, Nicholas/A-5713-2008
NR 0
TC 0
Z9 0
U1 0
U2 4
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
J9 HUM GENE THER
JI Hum. Gene Ther.
PD OCT
PY 2012
VL 23
IS 10
BP A42
EP A42
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 027PE
UT WOS:000310364400129
ER
PT J
AU Stroncek, DF
Marincola, FM
AF Stroncek, David F.
Marincola, Francisco M.
TI Dendritic cells: an immunotherapy coming of age
SO IMMUNOTHERAPY
LA English
DT Editorial Material
ID 15 KDA GRANULYSIN; T-CELLS; DIFFERENTIATION; MONOCYTES; CANCER
C1 [Stroncek, David F.] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Marincola, Francisco M.] NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Stroncek, DF (reprint author), NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM dstroncek@cc.nih.gov
FU Intramural NIH HHS [ZIA CL002120-04]
NR 9
TC 0
Z9 0
U1 0
U2 1
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1750-743X
J9 IMMUNOTHERAPY-UK
JI Immunotherapy
PD OCT
PY 2012
VL 4
IS 10
BP 973
EP 974
DI 10.2217/IMT.12.102
PG 2
WC Immunology
SC Immunology
GA 031QF
UT WOS:000310656300001
PM 23148746
ER
PT J
AU Mao, WM
Millar, JC
Wang, WH
Silverman, SM
Liu, Y
Wordinger, RJ
Rubin, JS
Pang, IH
Clark, AF
AF Mao, Weiming
Millar, J. Cameron
Wang, Wan-Heng
Silverman, Sean M.
Liu, Yang
Wordinger, Robert J.
Rubin, Jeffrey S.
Pang, Iok-Hou
Clark, Abbot F.
TI Existence of the Canonical Wnt Signaling Pathway in the Human Trabecular
Meshwork
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ELEVATES INTRAOCULAR-PRESSURE; HUMOR OUTFLOW FACILITY; BETA-CATENIN;
GLAUCOMA PROGRESSION; INHIBITOR Y-27632; PROSTATE-CANCER; EXPRESSION;
PROTEIN; CELLS; MODULATION
AB PURPOSE. We previously discovered elevated levels of secreted frizzled-related protein 1 (sFRP1), the Wnt signaling pathway inhibitor, in the glaucomatous trabecular meshwork (GTM), and found that key canonical Wnt signaling pathway genes are expressed in the trabecular meshwork (TM). The purpose of our study was to determine whether a functional canonical Wnt signaling pathway exists in the human TM (HTM).
METHODS. Western immunoblotting and/or immunofluorescent microscopy were used to study beta-catenin translocation as well as the actin cytoskeleton in transformed and primary HTM cells. A TCF/LEF luciferase assay was used to study functional canonical Wnt signaling, which was confirmed further by WNT3a-induced expression of a pathway target gene, AXIN2, via quantitative PCR. Intravitreal injection of an Ad5 adenovirus expressing Dickkopf-related protein-1 (DKK1) was used to study the in vivo effect of canonical Wnt signaling on IOP in mice.
RESULTS. WNT3a induced beta-catenin translocation in the HTM, which was blocked by co-treatment with sFRP1. Similarly, WNT3a enhanced luciferase levels in TCF/LEF luciferase assays, which also were blocked by sFRP1. Furthermore, AXIN2 expression was elevated significantly by WNT3a. However, neither WNT3a nor sFRP1 affected actin cytoskeleton organization, which theoretically could be regulated by noncanonical Wnt signaling in HTM cells. Exogenous DKK1, a specific inhibitor for the canonical Wnt signaling pathway, or sFRP1 elevated mouse IOP to equivalent levels.
CONCLUSIONS. There is a canonical Wnt signaling pathway in the TM, and this canonical Wnt pathway, but not the noncanonical Wnt signaling pathway, regulates IOP. (Invest Ophthalmol Vis Sci. 2012;53:7043-7051) DOI:10.1167/iovs.12-9664
C1 [Mao, Weiming; Silverman, Sean M.; Liu, Yang; Wordinger, Robert J.; Pang, Iok-Hou; Clark, Abbot F.] Univ N Texas, Dept Cell Biol & Anat, Hlth Sci Ctr, N Texas Eye Res Inst, Ft Worth, TX 76107 USA.
[Millar, J. Cameron; Wang, Wan-Heng; Pang, Iok-Hou] Alcon Res Ltd, Ft Worth, TX USA.
[Rubin, Jeffrey S.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Mao, WM (reprint author), Univ N Texas, Dept Cell Biol & Anat, Hlth Sci Ctr, N Texas Eye Res Inst, CBH 449,3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA.
EM weiming.mao@unthsc.edu
RI Liu, Yang/E-5865-2015;
OI Wordinger, Robert/0000-0002-2861-8967
FU Thomas R. Lee award for National Glaucoma Research, a program of the
American Health Assistance Foundation
FX Supported in part by the Thomas R. Lee award for National Glaucoma
Research, a program of the American Health Assistance Foundation (WM).
NR 45
TC 18
Z9 19
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD OCT
PY 2012
VL 53
IS 11
BP 7043
EP 7051
DI 10.1167/iovs.12-9664
PG 9
WC Ophthalmology
SC Ophthalmology
GA 030SH
UT WOS:000310589900042
PM 22956608
ER
PT J
AU Sieving, PA
AF Sieving, Paul A.
TI NEI Audacious Goals Initiative to Catalyze Innovation
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Editorial Material
ID LEBERS CONGENITAL AMAUROSIS; FACTOR-H POLYMORPHISM; MACULAR
DEGENERATION; RNA INTERFERENCE
C1 NEI, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Sieving, PA (reprint author), NEI, Natl Inst Hlth, Bethesda, MD 20892 USA.
NR 17
TC 2
Z9 2
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD OCT
PY 2012
VL 53
IS 11
BP 7149
EP 7150
DI 10.1167/iovs.12-11069
PG 2
WC Ophthalmology
SC Ophthalmology
GA 030SH
UT WOS:000310589900056
PM 23047720
ER
PT J
AU Plevka, P
Battisti, AJ
Winkler, DC
Tars, K
Holdaway, HA
Bator, CM
Rossmann, MG
AF Plevka, Pavel
Battisti, Anthony J.
Winkler, Dennis C.
Tars, Kaspars
Holdaway, Heather A.
Bator, Carol M.
Rossmann, Michael G.
TI Sample Preparation Induced Artifacts in Cryo-Electron Tomographs
SO MICROSCOPY AND MICROANALYSIS
LA English
DT Article
DE cryo-EM; microscopy; ice-vacuum interface; artifacts; virus; tomography
ID VIRUS; RECONSTRUCTIONS
AB We investigated the effects of sample preparation and of the exposure to an electron beam on particles in cryo-electron tomographs. Various virus particles with icosahedral symmetry were examined, allowing a comparison of symmetrically related components that should be identical in structure but might be affected differently by these imaging artifacts. Comparison of tomographic reconstructions with previously determined structures established by an independent method showed that neither freezing nor electron beam exposure produced a significant amount of shrinkage along the z axis (thickness). However, we observed damage to regions of the particles located close to the surface of the vitreous ice.
C1 [Plevka, Pavel; Battisti, Anthony J.; Holdaway, Heather A.; Bator, Carol M.; Rossmann, Michael G.] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
[Winkler, Dennis C.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA.
[Tars, Kaspars] Latvian Biomed Res & Study Ctr, LV-1067 Riga, Latvia.
RP Rossmann, MG (reprint author), Purdue Univ, Dept Biol Sci, 240 S Martin Jischke Dr, W Lafayette, IN 47907 USA.
EM mr@purdue.edu
RI Plevka, Pavel/H-8661-2014
OI Plevka, Pavel/0000-0003-4215-3315
FU National Institutes of Health [AI 76331]; National Institute of
Arthritis and Musculoskeletal and Skin Diseases
FX We thank Alasdair Steven not only for the use of his EM facilities but
also for an extensive amount of discussion for all parts of this
article. We thank Sheryl Kelly for help with the preparation of the
manuscript. The work was supported by National Institutes of Health
grants to M.G.R. (AI 76331). This study was supported in part by the
Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases.
NR 19
TC 1
Z9 1
U1 1
U2 9
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1431-9276
J9 MICROSC MICROANAL
JI Microsc. microanal.
PD OCT
PY 2012
VL 18
IS 5
BP 1043
EP 1048
DI 10.1017/S1431927612001298
PG 6
WC Materials Science, Multidisciplinary; Microscopy
SC Materials Science; Microscopy
GA 027AE
UT WOS:000310323400013
PM 23040048
ER
PT J
AU Kohn, EA
Yang, YA
Du, ZJ
Nagano, Y
Van Schyndle, CMH
Herrmann, MA
Heldman, M
Chen, JQ
Stuelten, CH
Flanders, KC
Wakefield, LM
AF Kohn, Ethan A.
Yang, Yu-an
Du, Zhijun
Nagano, Yoshiko
Van Schyndle, Catherine M. H.
Herrmann, Michelle A.
Heldman, Madeleine
Chen, Jin-Qiu
Stuelten, Christina H.
Flanders, Kathleen C.
Wakefield, Lalage M.
TI Biological Responses to TGF-beta in the Mammary Epithelium Show a
Complex Dependency on Smad3 Gene Dosage with Important Implications for
Tumor Progression
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID GROWTH-FACTOR-BETA; BREAST-CANCER; MESENCHYMAL TRANSITION; TRANSGENIC
MOUSE; DOWN-REGULATION; C-MYC; MICE; INDUCTION; APOPTOSIS; ROLES
AB TGF-beta plays a dual role in epithelial carcinogenesis with the potential to either suppress or promote tumor progression. We found that levels of Smad3 mRNA, a critical mediator of TGF-beta signaling, are reduced by approximately 60% in human breast cancer. We therefore used conditionally immortalized mammary epithelial cells (IMEC) of differing Smad3 genotypes to quantitatively address the Smad3 requirement for different biologic responses to TGF-beta. We found that a two-fold reduction in Smad3 gene dosage led to complex effects on TGF-beta responses; the growth-inhibitory response was retained, the pro-apoptotic response was lost, the migratory response was reduced, and the invasion response was enhanced. Loss of the pro-apoptotic response in the Smad3(+/-) IMECs correlated with loss of Smad3 binding to the Bcl-2 locus, whereas retention of the growth-inhibitory response in Smad3 IMECs correlated with retention of Smad3 binding to the c-Myc locus. Addressing the integrated outcome of these changes in vivo, we showed that reduced Smad3 levels enhanced metastasis in two independent models of metastatic breast cancer. Our results suggest that different biologic responses to TGF-beta in the mammary epithelium are differentially affected by Smad3 dosage and that a mere two-fold reduction in Smad3 is sufficient to promote metastasis. Mol Cancer Res; 10(10); 1389-99. (C) 2012 AACR.
C1 [Kohn, Ethan A.; Yang, Yu-an; Du, Zhijun; Nagano, Yoshiko; Van Schyndle, Catherine M. H.; Flanders, Kathleen C.; Wakefield, Lalage M.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Herrmann, Michelle A.; Heldman, Madeleine; Chen, Jin-Qiu] NCI, Cell Biol Lab, Collaborat Prot Technol Resource, Bethesda, MD 20892 USA.
[Stuelten, Christina H.] NCI, Ctr Canc Res, Lab Cellular & Mol Biol, Bethesda, MD 20892 USA.
RP Wakefield, LM (reprint author), NCI, Lab Canc Biol & Genet, Bldg 37,Rm 4032A,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA.
EM lw34g@nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research [Z01 BC
005785]
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research Z01 BC 005785
to L. M. Wakefield.
NR 26
TC 10
Z9 11
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD OCT
PY 2012
VL 10
IS 10
BP 1389
EP 1399
DI 10.1158/1541-7786.MCR-12-0136-T
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 031NS
UT WOS:000310649500014
PM 22878587
ER
PT J
AU Ke, RA
Lloyd-Smith, JO
AF Ke, Ruian
Lloyd-Smith, James O.
TI Evolutionary Analysis of Human Immunodeficiency Virus Type 1 Therapies
Based on Conditionally Replicating Vectors
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID DEFECTIVE INTERFERING PARTICLES; T-CELL RESPONSE; WILD-TYPE HIV-1;
LENTIVIRAL VECTOR; IN-VIVO; ANTIRETROVIRAL THERAPY; MALE CIRCUMCISION;
DRUG-RESISTANCE; COMBINATION THERAPY; CD4 LYMPHOCYTES
AB Efforts to reduce the viral load of human immunodeficiency virus type 1 (HIV-1) during long-term treatment are challenged by the evolution of anti-viral resistance mutants. Recent studies have shown that gene therapy approaches based on conditionally replicating vectors (CRVs) could have many advantages over anti-viral drugs and other approaches to therapy, potentially including the ability to circumvent the problem of evolved resistance. However, research to date has not explored the evolutionary consequences of long-term treatment of HIV-1 infections with conditionally replicating vectors. In this study, we analyze a computational model of the within-host co-evolutionary dynamics of HIV-1 and conditionally replicating vectors, using the recently proposed 'therapeutic interfering particle' as an example. The model keeps track of the stochastic process of viral mutation, and the deterministic population dynamics of T cells as well as different strains of CRV and HIV-1 particles. We show that early in the co-infection, mutant HIV-1 genotypes that escape suppression by CRV therapy appear; this is similar to the dynamics observed in drug treatments and other gene therapies. In contrast to other treatments, however, the CRV population is able to evolve and catch up with the dominant HIV-1 escape mutant and persist long-term in most cases. On evolutionary grounds, gene therapies based on CRVs appear to be a promising tool for long-term treatment of HIV-1. Our model allows us to propose design principles to optimize the efficacy of this class of gene therapies. In addition, because of the analogy between CRVs and naturally-occurring defective interfering particles, our results also shed light on the co-evolutionary dynamics of wild-type viruses and their defective interfering particles during natural infections.
C1 [Ke, Ruian; Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90024 USA.
[Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Ke, RA (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90024 USA.
EM ruian@ucla.edu
RI Lloyd-Smith, James/K-4080-2012
OI Lloyd-Smith, James/0000-0001-7941-502X
FU Bill and Melinda Gates Foundation; National Science Foundation
[EF-0928690]; De Logi Chair in Biological Sciences; RAPIDD program of
the Science & Technology Directorate of the US Department of Homeland
Security; Fogarty International Center, National Institutes of Health
FX This project was supported by the Bill and Melinda Gates Foundation and
National Science Foundation grant EF-0928690. JLS is grateful for the
support of the De Logi Chair in Biological Sciences and the RAPIDD
program of the Science & Technology Directorate of the US Department of
Homeland Security, and the Fogarty International Center, National
Institutes of Health. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 85
TC 7
Z9 7
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD OCT
PY 2012
VL 8
IS 10
AR e1002744
DI 10.1371/journal.pcbi.1002744
PG 17
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 030KE
UT WOS:000310568800039
PM 23133349
ER
PT J
AU Nussinov, R
AF Nussinov, Ruth
TI A Future Vision for PLOS Computational Biology
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Editorial Material
C1 [Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program,Frederick Natl Lab, Frederick, MD 21701 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program,Frederick Natl Lab, Frederick, MD 21701 USA.
EM NussinoR@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD OCT
PY 2012
VL 8
IS 10
AR e1002727
DI 10.1371/journal.pcbi.1002727
PG 1
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 030KE
UT WOS:000310568800023
ER
PT J
AU Rozycki, B
Boura, E
Hurley, JH
Hummer, G
AF Rozycki, Bartosz
Boura, Evzen
Hurley, James H.
Hummer, Gerhard
TI Membrane-Elasticity Model of Coatless Vesicle Budding Induced by ESCRT
Complexes
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID MIXED LIPID-MEMBRANES; MULTIVESICULAR BODIES; BAR DOMAINS; INTRAMEMBRANE
DOMAINS; GAUSSIAN CURVATURE; PROTEINS; BIOGENESIS; SCISSION; ENDOSOMES;
DEFORMATION
AB The formation of vesicles is essential for many biological processes, in particular for the trafficking of membrane proteins within cells. The Endosomal Sorting Complex Required for Transport (ESCRT) directs membrane budding away from the cytosol. Unlike other vesicle formation pathways, the ESCRT-mediated budding occurs without a protein coat. Here, we propose a minimal model of ESCRT-induced vesicle budding. Our model is based on recent experimental observations from direct fluorescence microscopy imaging that show ESCRT proteins colocalized only in the neck region of membrane buds. The model, cast in the framework of membrane elasticity theory, reproduces the experimentally observed vesicle morphologies with physically meaningful parameters. In this parameter range, the minimum energy configurations of the membrane are coatless buds with ESCRTs localized in the bud neck, consistent with experiment. The minimum energy configurations agree with those seen in the fluorescence images, with respect to both bud shapes and ESCRT protein localization. On the basis of our model, we identify distinct mechanistic pathways for the ESCRT-mediated budding process. The bud size is determined by membrane material parameters, explaining the narrow yet different bud size distributions in vitro and in vivo. Our membrane elasticity model thus sheds light on the energetics and possible mechanisms of ESCRT-induced membrane budding.
C1 [Rozycki, Bartosz; Hummer, Gerhard] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Rozycki, Bartosz] Max Planck Inst Colloids & Interfaces, Dept Theory & Biosyst, Potsdam, Germany.
[Boura, Evzen; Hurley, James H.] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Rozycki, B (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
EM Gerhard.Hummer@nih.gov
RI Rozycki, Bartosz/B-7005-2009; Hummer, Gerhard/A-2546-2013; Boura,
Evzen/I-2626-2012; Boura, Evzen/G-5275-2014
OI Rozycki, Bartosz/0000-0001-5938-7308; Hummer,
Gerhard/0000-0001-7768-746X;
FU European Community; Intramural AIDS Targeted Antiviral Program;
Intramural Research Program of the NIH, NIDDK
FX This research was supported by a Marie Curie International Outgoing
Fellowship within the 7th European Community Framework Programme (B.
R.), the Intramural AIDS Targeted Antiviral Program (J.H.H.), and the
Intramural Research Program of the NIH, NIDDK (B.R., E.B., J.H.H.,
G.H.). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 63
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Z9 17
U1 0
U2 21
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD OCT
PY 2012
VL 8
IS 10
AR e1002736
DI 10.1371/journal.pcbi.1002736
PG 9
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 030KE
UT WOS:000310568800032
PM 23093927
ER
PT J
AU Lujan, SA
Williams, JS
Pursell, ZF
Abdulovic-Cui, AA
Clark, AB
McElhinny, SAN
Kunkel, TA
AF Lujan, Scott A.
Williams, Jessica S.
Pursell, Zachary F.
Abdulovic-Cui, Amy A.
Clark, Alan B.
McElhinny, Stephanie A. Nick
Kunkel, Thomas A.
TI Mismatch Repair Balances Leading and Lagging Strand DNA Replication
Fidelity
SO PLOS GENETICS
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; POLYMERASE-EPSILON; ESCHERICHIA-COLI;
RIBONUCLEOTIDE INCORPORATION; TRINUCLEOTIDE REPEATS; GENOME INSTABILITY;
SINGLE-BASE; IN-VITRO; DELTA; ERRORS
AB The two DNA strands of the nuclear genome are replicated asymmetrically using three DNA polymerases, alpha, delta, and epsilon. Current evidence suggests that DNA polymerase epsilon (Pol epsilon) is the primary leading strand replicase, whereas Pols alpha and delta primarily perform lagging strand replication. The fact that these polymerases differ in fidelity and error specificity is interesting in light of the fact that the stability of the nuclear genome depends in part on the ability of mismatch repair (MMR) to correct different mismatches generated in different contexts during replication. Here we provide the first comparison, to our knowledge, of the efficiency of MMR of leading and lagging strand replication errors. We first use the strand-biased ribonucleotide incorporation propensity of a Pol epsilon mutator variant to confirm that Pol epsilon is the primary leading strand replicase in Saccharomyces cerevisiae. We then use polymerase-specific error signatures to show that MMR efficiency in vivo strongly depends on the polymerase, the mismatch composition, and the location of the mismatch. An extreme case of variation by location is a T-T mismatch that is refractory to MMR. This mismatch is flanked by an AT-rich triplet repeat sequence that, when interrupted, restores MMR to >95% efficiency. Thus this natural DNA sequence suppresses MMR, placing a nearby base pair at high risk of mutation due to leading strand replication infidelity. We find that, overall, MMR most efficiently corrects the most potentially deleterious errors (indels) and then the most common substitution mismatches. In combination with earlier studies, the results suggest that significant differences exist in the generation and repair of Pol alpha, delta, and epsilon replication errors, but in a generally complementary manner that results in high-fidelity replication of both DNA strands of the yeast nuclear genome.
C1 [Lujan, Scott A.; Williams, Jessica S.; Clark, Alan B.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
[Lujan, Scott A.; Williams, Jessica S.; Clark, Alan B.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
[Pursell, Zachary F.] Tulane Univ, Dept Biochem, New Orleans, LA 70118 USA.
[Abdulovic-Cui, Amy A.] Augusta State Univ, Dept Biol, Augusta, GA USA.
[McElhinny, Stephanie A. Nick] USA, Res Off, Res Triangle Pk, NC 27709 USA.
RP Lujan, SA (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
EM kunkel@niehs.nih.gov
OI Pursell, Zachary/0000-0001-5871-7192
FU Division of Intramural Research of the National Institutes of Health,
National Institute of Environmental Health Sciences [Z01 ES065089]
FX This work was supported by Project Z01 ES065089 to TAK, from the
Division of Intramural Research of the National Institutes of Health,
National Institute of Environmental Health Sciences. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 56
TC 32
Z9 32
U1 0
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD OCT
PY 2012
VL 8
IS 10
AR e1003016
DI 10.1371/journal.pgen.1003016
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 029WR
UT WOS:000310528400038
PM 23071460
ER
PT J
AU Parikh, AR
Olnes, MJ
Barrett, AJ
AF Parikh, Ankur R.
Olnes, Matthew J.
Barrett, A. John
TI Immunomodulatory Treatment of Myelodysplastic Syndromes: Antithymocyte
Globulin, Cyclosporine, and Alemtuzumab
SO SEMINARS IN HEMATOLOGY
LA English
DT Article
ID IMMUNOSUPPRESSIVE THERAPY; APLASTIC-ANEMIA; BONE-MARROW;
REFRACTORY-ANEMIA; PHASE-II; T-CELLS; MDS; AUTOIMMUNITY; RAPAMYCIN;
PREDICTS
AB It is now well accepted that a subgroup of patients with myelodysplastic syndromes (MDS) can recover from pancytopenia following immunosuppressive treatment (IST). For many years immunosuppression with antilymphocyte antibodies has been a standard treatment approach for patients with severe aplastic anemia (SAA). The initial concept of using immunosuppression to treat pancytopenic patients with MDS was based on the premise that MDS might share with SAA an autoimmune basis for the bone marrow failure common to both conditions. The idea was supported by reports of favorable outcomes in occasional cases of MDS treated with antithymocyte globulin (ATG). Today, various forms of IST have been successfully used to restore hematopoiesis in MDS in many centers worldwide. In this review we outline the rationale for use of IST in MDS, and describe studies which help to define the patients with MDS likely to respond to IST. We summarize 18 published clinical trials using IST for MDS and discuss how these studies have helped to define the MDS subgroups likely to respond to treatment, the nature and durability of the response, the impact of IST on long-term outcome, and the best treatment approach. Semin Hematol 49:304-311. Published by Elsevier Inc.
C1 [Parikh, Ankur R.; Olnes, Matthew J.; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Olnes, Matthew J.] Transnatl Inst, Hlth Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD USA.
RP Barrett, AJ (reprint author), NHLBI, Hematol Branch, NIH, CRC Bldg 10,Room 3-5322,10 Ctr Dr,MSC 1202, Bethesda, MD 20892 USA.
EM barrettj@nhlbi.nih.gov
FU Intramural NIH HHS [ZIA HL006106-03]
NR 47
TC 7
Z9 7
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0037-1963
J9 SEMIN HEMATOL
JI Semin. Hematol.
PD OCT
PY 2012
VL 49
IS 4
BP 304
EP 311
DI 10.1053/j.seminhematol.2012.07.004
PG 8
WC Hematology
SC Hematology
GA 031RU
UT WOS:000310660800004
PM 23079060
ER
PT J
AU Kuehn, D
Aros, S
Cassorla, F
Avaria, M
Unanue, N
Henriquez, C
Kleinsteuber, K
Conca, B
Avila, A
Carter, TC
Conley, MR
Troendle, J
Mills, JL
AF Kuehn, Devon
Aros, Sofia
Cassorla, Fernando
Avaria, Maria
Unanue, Nancy
Henriquez, Cecilia
Kleinsteuber, Karin
Conca, Barbara
Avila, Alejandra
Carter, Tonia C.
Conley, Mary R.
Troendle, James
Mills, James L.
TI A Prospective Cohort Study of the Prevalence of Growth, Facial, and
Central Nervous System Abnormalities in Children with Heavy Prenatal
Alcohol Exposure
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Alcohol; Pregnancy; Fetal Alcohol Spectrum Disorders; Growth
Restriction; Neurodevelopment
ID ATTENTION-DEFICIT HYPERACTIVITY; SPECTRUM DISORDERS; BINGE-DRINKING;
RISK-FACTORS; FETAL; PREGNANCY; IDENTIFICATION; DIAGNOSIS; RATS
AB Background Most children who are exposed to large quantities of alcohol in utero do not develop fetal alcohol syndrome (FAS). Population-based prospective data on the risk of developing components of fetal alcohol spectrum disorders (FASD), however, are limited. Methods This was a prospective cohort study of 9,628 women screened during their first prenatal appointment in Chile, which identified 101 who consumed at least 4 drinks/d (exposed) matched with 101 women with no reported alcohol consumption during pregnancy (unexposed). Detailed alcohol consumption data were collected during the pregnancy. Children were evaluated up to 8.5 years of age by clinicians masked to exposure status. Results One or more functional central nervous system abnormalities were present in 44.0% (22/50) of the exposed children compared to 13.6% (6/44) of the unexposed (p = 0.002). Growth restriction was present in 27.2% (25/92) of the exposed and 12.5% (12/96) of the unexposed (p = 0.02). Abnormal facial features were present in 17.3% (14/81) of the exposed children compared to 1.1% (1/89) of the unexposed children (p = 0.0002) by direct examination. Of the 59 exposed children with data available to detect at least 1 abnormality, 12 (20.3%) had no abnormalities. Binge drinking from conception to recognition of pregnancy (OR = 1.48 per day, 95% CI: 1.15 to 1.91, p = 0.002) and after recognition of pregnancy (OR= 1.41 per day, 95% CI: 1.01 to 1.95, p = 0.04) and total number of drinks consumed per week from conception to recognition of pregnancy (OR = 1.02 per drink, 95% CI: 1.01 to 1.04, p = 0.0009) were significantly associated with abnormal child outcome. Conclusions After exposure to heavy alcohol consumption during pregnancy, 80% of children had 1 or more abnormalities associated with alcohol exposure. Patterns of alcohol use that posed the greatest risk of adverse outcomes were binge drinking and high total weekly intake. Functional neurologic impairment occurred most frequently and may be the only sign to alert physicians to prenatal alcohol exposure.
C1 [Kuehn, Devon; Carter, Tonia C.; Conley, Mary R.; Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bethesda, MD USA.
[Kuehn, Devon] Natl Capital Consortium, Dept Pediat, Bethesda, MD USA.
[Aros, Sofia; Cassorla, Fernando; Avaria, Maria; Unanue, Nancy; Henriquez, Cecilia; Kleinsteuber, Karin; Conca, Barbara; Avila, Alejandra] San Borja Arriaran Clin Hosp, Dept Pediat, Santiago, Chile.
[Cassorla, Fernando] Univ Chile, Fac Med, Inst Maternal & Child Res IDIMI, Santiago, Chile.
[Troendle, James] NHLBI, Div Cardiovasc Sci, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Mills, JL (reprint author), NICHD NIH, Room 7B03,6100 Execut Blvd, Bethesda, MD 20892 USA.
EM millsj@mail.nih.gov
FU Intramural Research Program of the National Institute of Health, Eunice
Kennedy Shriver National Institute of Child Health and Human Development
FX The authors wish to thank Susan Astley for her very insightful
suggestions, and Susan Astley and Sterling Clarren for their extensive
work on the photographic analysis of the children. This work was
supported by the Intramural Research Program of the National Institute
of Health, Eunice Kennedy Shriver National Institute of Child Health and
Human Development.
NR 24
TC 22
Z9 22
U1 1
U2 29
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD OCT
PY 2012
VL 36
IS 10
BP 1811
EP 1819
DI 10.1111/j.1530-0277.2012.01794.x
PG 9
WC Substance Abuse
SC Substance Abuse
GA 014QM
UT WOS:000309390800016
PM 22823161
ER
PT J
AU Mei, H
Gu, DF
Hixson, JE
Rice, TK
Chen, J
Shimmin, LC
Schwander, K
Kelly, TN
Liu, DP
Chen, SF
Huang, JF
Jaquish, CE
Rao, DC
He, J
AF Mei, Hao
Gu, Dongfeng
Hixson, James E.
Rice, Treva K.
Chen, Jing
Shimmin, Lawrence C.
Schwander, Karen
Kelly, Tanika N.
Liu, De-Pei
Chen, Shufeng
Huang, Jian-feng
Jaquish, Cashell E.
Rao, Dabeeru C.
He, Jiang
TI Genome-wide Linkage and Positional Association Study of Blood Pressure
Response to Dietary Sodium Intervention The GenSalt Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE allelic association; blood pressure; genetic linkage; salt sensitivity
ID VISININ-LIKE PROTEIN-1; SALT-SENSITIVITY; ESSENTIAL-HYPERTENSION;
CHROMOSOME 2P24-P25; FAMILY; POLYMORPHISMS; TESTS; POPULATION;
POTASSIUM; PEDIGREES
AB The authors conducted a genome-wide linkage scan and positional association analysis to identify the genetic determinants of salt sensitivity of blood pressure (BP) in a large family-based, dietary-feeding study. The dietary intervention was conducted among 1,906 participants in rural China (20032005). A 7-day low-sodium intervention was followed by a 7-day high-sodium intervention. Salt sensitivity was defined as BP responses to low- and high-sodium interventions. Signals of the logarithm of the odds to the base 10 (LOD epsilon 3) were detected at 3342 centimorgans of chromosome 2 (2p24.3-2p24.1), with a maximum LOD score of 3.33 for diastolic blood pressure responses to high-sodium intervention. LOD scores were 2.352.91 for mean arterial pressure (MAP) and 0.801.49 for systolic blood pressure responses in this region, respectively. Correcting for multiple tests, single nucleotide polymorphism (SNP) rs11674786 (2.7 kilobases upstream of the family with sequence similarity 84, member A, gene (FAM84A)) in the linkage region was significantly associated with diastolic blood pressure (P 0.0007) and MAP responses (P 0.0007), and SNP rs16983422 (2.8 kilobases upstream of the visinin-like 1 gene (VSNL1)) was marginally associated with diastolic blood pressure (P 0.005) and MAP responses (P 0.005). An additive interaction between SNPs rs11674786 and rs16983422 was observed, with P 7.00 10(5) and P 7.23 10(5) for diastolic blood pressure and MAP responses, respectively. The authors concluded that genetic region 2p24.3-2p24.1 might harbor functional variants for the salt sensitivity of BP.
C1 [Mei, Hao] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA.
[Gu, Dongfeng; Chen, Shufeng; Huang, Jian-feng] Cardiovasc Inst, Beijing, Peoples R China.
[Gu, Dongfeng; Chen, Shufeng; Huang, Jian-feng] Fuwai Hosp, Beijing, Peoples R China.
[Hixson, James E.; Shimmin, Lawrence C.] Univ Texas Sch Publ Hlth, Hlth Sci Ctr, Houston, TX USA.
[Rice, Treva K.; Schwander, Karen; Rao, Dabeeru C.] Washington Univ, Div Biostat, St Louis, MO USA.
[Liu, De-Pei] Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100730, Peoples R China.
[Liu, De-Pei] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Jaquish, Cashell E.] NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA.
RP Mei, H (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 1440 Canal St, New Orleans, LA 70112 USA.
EM hmei@tulane.edu
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, Maryland [U01HL072507, R01HL087263, R01HL090682]
FX The Genetic Epidemiology Network of Salt Sensitivity is supported by
research grants (U01HL072507, R01HL087263, and R01HL090682) from the
National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, Maryland.
NR 40
TC 2
Z9 2
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD OCT 1
PY 2012
VL 176
SU 7
BP S81
EP S90
DI 10.1093/aje/kws290
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 018TM
UT WOS:000309686100008
PM 22865701
ER
PT J
AU Aggarwal, R
Reed, AM
Ascherman, DP
Barohn, RJ
Feldman, BM
Miller, FW
Rider, LG
Harris-Love, M
Levesque, MC
Oddis, CV
AF Aggarwal, Rohit
Reed, Ann M.
Ascherman, Dana P.
Barohn, Richard J.
Feldman, Brian M.
Miller, Frederick W.
Rider, Lisa G.
Harris-Love, Michael
Levesque, Marc C.
Oddis, Chester V.
CA RIM Study Grp
TI Clinical and Serologic Predictors of Response in Rituximab-Treated
Refractory Adult and Juvenile Dermatomyositis (DM) and Adult
Polymyositis (PM) - the RIM Study.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Aggarwal, Rohit; Levesque, Marc C.; Oddis, Chester V.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Reed, Ann M.] Mayo Clin, Rochester, MN USA.
[Ascherman, Dana P.] Univ Miami, Miami, FL USA.
[Barohn, Richard J.] Univ Kansas, Dept Neurol, Med Ctr, Kansas City, KS USA.
[Feldman, Brian M.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Miller, Frederick W.; Rider, Lisa G.] NIEHS, NIH, Bethesda, MD USA.
[Harris-Love, Michael] VA Med Ctr, Washington, DC USA.
NR 0
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 1598
BP S682
EP S683
PG 2
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748303319
ER
PT J
AU Aranow, C
Dall'Era, M
Massarotti, EM
Mackay, MC
Coca, A
Koumpouras, F
Levesque, MC
Chatham, WW
Clowse, MEB
Criscione-Schreiber, LG
Callahan, S
Goldmuntz, EA
Keyes-Elstein, L
Diamond, B
Kamen, DL
AF Aranow, Cynthia
Dall'Era, Maria
Massarotti, Elena M.
Mackay, Meggan C.
Coca, Andreea
Koumpouras, Fotios
Levesque, Marc C.
Chatham, W. Winn
Clowse, Megan E. B.
Criscione-Schreiber, Lisa G.
Callahan, Sherri
Goldmuntz, Ellen A.
Keyes-Elstein, Lynette
Diamond, Betty
Kamen, Diane L.
TI A Double-Blind Randomized Placebo-Controlled Trial of the Effect of
Vitamin D3 On the Interferon Signature in Patients with Systemic Lupus
Erythematosus
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Aranow, Cynthia] Feinstein Inst Med Res, Manhasset, NY USA.
[Dall'Era, Maria] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Massarotti, Elena M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Mackay, Meggan C.] Feinstein Inst, Manhasset, NY USA.
[Koumpouras, Fotios] West Penn Hosp, Pittsburgh, PA USA.
[Coca, Andreea] Univ Rochester, Rochester, NY USA.
[Levesque, Marc C.] Univ Pittsburgh, Pittsburgh, PA USA.
[Chatham, W. Winn] Univ Alabama Birmingham, Birmingham, AL USA.
[Clowse, Megan E. B.; Criscione-Schreiber, Lisa G.] Duke Univ, Med Ctr, Durham, NC USA.
[Callahan, Sherri; Goldmuntz, Ellen A.] NIAID NIH Rm 6807, Bethesda, MD USA.
[Keyes-Elstein, Lynette] Rho Fed Syst Inc, Chapel Hill, NC USA.
[Keyes-Elstein, Lynette] Feinstein Inst Med Rsch, Manhasset, NY USA.
[Kamen, Diane L.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Charleston, SC USA.
NR 0
TC 3
Z9 3
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2619
BP S1110
EP S1110
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748306129
ER
PT J
AU Assassi, S
Weisman, MH
Chen, ZX
Rahbar, M
Clegg, DO
Colbert, RA
Deodhar, AA
Savage, LM
Graham, T
Witter, JP
Reveille, JD
AF Assassi, Shervin
Weisman, Michael H.
Chen, Zhongxue
Rahbar, Mohammad
Clegg, Daniel O.
Colbert, Robert A.
Deodhar, Atul A.
Savage, Laurie M.
Graham, Tiffany
Witter, James P.
Reveille, John D.
TI Correlates of Inflammatory Back Pain in a Nationally Representative
Sample of the US Population
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Assassi, Shervin; Chen, Zhongxue; Rahbar, Mohammad; Graham, Tiffany; Reveille, John D.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
[Weisman, Michael H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Clegg, Daniel O.] George E Wahlen VA Med Ctr, Salt Lake City, UT USA.
[Colbert, Robert A.] NIAMS, NIH, Bethesda, MD USA.
[Deodhar, Atul A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Savage, Laurie M.] Spondylitis Assoc Amer, Van Nuys, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 545
BP S237
EP S238
PG 2
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748301084
ER
PT J
AU Bakir-Gungor, B
Remmers, E
Kastner, DL
Meguro, A
Mizuki, N
Gul, A
Sezerman, OU
AF Bakir-Gungor, Burcu
Remmers, Elaine
Kastner, Daniel L.
Meguro, Akira
Mizuki, Nobuhisa
Gul, Ahmet
Sezerman, Osman Ugur
TI The Identification of Pathway Markers in Behcet's Disease Using
Genomewide Association Data From Two Different Populations.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Bakir-Gungor, Burcu] Bahcesehir Univ, Istanbul, Turkey.
[Remmers, Elaine; Kastner, Daniel L.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Meguro, Akira; Mizuki, Nobuhisa] Yokohama City Univ, Grad Sch Med, Yokohama, Kanagawa 232, Japan.
[Gul, Ahmet] Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey.
[Sezerman, Osman Ugur] Sabanci Univ, Istanbul, Turkey.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 1005
BP S434
EP S435
PG 2
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748302080
ER
PT J
AU Baldini, C
Rossi, C
Santini, E
Ferro, F
Gallo, A
Martini, D
Sernissi, F
Donati, V
Giacomelli, C
Luciano, N
Solini, A
Bombardieri, S
AF Baldini, Chiara
Rossi, Chiara
Santini, Eleonora
Ferro, Francesco
Gallo, Alessia
Martini, Daniela
Sernissi, Francesca
Donati, Valentina
Giacomelli, Camillo
Luciano, Nicoletta
Solini, Anna
Bombardieri, Stefano
TI The Axis P2X7 Receptor-Inflammasome: A Role in Modulating Inflammatory
Response in Primary Sjogren's Syndrome?
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Baldini, Chiara; Rossi, Chiara; Santini, Eleonora; Ferro, Francesco; Martini, Daniela; Sernissi, Francesca; Donati, Valentina; Giacomelli, Camillo; Luciano, Nicoletta; Solini, Anna; Bombardieri, Stefano] Univ Pisa, Rheumatol Unit, Pisa, Italy.
[Gallo, Alessia] NIDCR, Bethesda, MD USA.
RI Giacomelli, Camillo/J-5866-2016
OI Giacomelli, Camillo/0000-0002-2904-1450
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 529
BP S231
EP S231
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748301068
ER
PT J
AU Carlsen, AL
Schetter, AJ
Nielsen, CT
Lood, C
Knudsen, S
Voss, A
Harris, CC
Hellmark, T
Segelmark, M
Jacobsen, S
Bengtsson, AA
Heegaard, NHH
AF Carlsen, Anting L.
Schetter, Aaron J.
Nielsen, Christoffer T.
Lood, Christian
Knudsen, Steen
Voss, Anne
Harris, Curtis C.
Hellmark, Thomas
Segelmark, Marten
Jacobsen, Soren
Bengtsson, Anders A.
Heegaard, Niels H. H.
TI Signature of Circulating Micro-RNA in Systemic Lupus Erythematosus.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Carlsen, Anting L.; Nielsen, Christoffer T.; Heegaard, Niels H. H.] Statens Serum Inst, Copenhagen S, Denmark.
[Schetter, Aaron J.; Harris, Curtis C.] NCI, NIH, Bethesda, MD 20892 USA.
[Bengtsson, Anders A.] Dept Clin Sci Lund, Rheumatol Sect, Lund, Sweden.
[Knudsen, Steen] Med Prognosis Inst, Horsholm, Denmark.
[Voss, Anne] Odense Univ Hosp, Odense C, Denmark.
[Jacobsen, Soren] Copenhagen Univ Hosp, Copenhagen, Denmark.
NR 0
TC 0
Z9 0
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2276
BP S963
EP S963
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748305196
ER
PT J
AU Chen, YQ
Liu, Y
Huang, Y
Yee, C
MacBride, A
Bowcock, A
Lowes, M
Goldbach-Mansky, RT
AF Chen, Yongqing
Liu, Yin
Huang, Yan
Yee, Carole
MacBride, Alison
Bowcock, Anne
Lowes, Michelle
Goldbach-Mansky, Raphaela T.
TI Immune Activating Effects of Co-Stimulation of TLR Agonists and
Cytokines On Primary and Immortalized Keratinocytes From a Patient with
a CARD14 Mediated Pustular Psoriasis (CAMPS) and Healthy Controls
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Chen, Yongqing; Huang, Yan; Goldbach-Mansky, Raphaela T.] NIAMS, Translat Autoinflammatory Dis Sect, Off Clin Director, Bethesda, MD USA.
[Yee, Carole] NCI, NIH, Bethesda, MD 20892 USA.
[MacBride, Alison] NIAID, NIH, Bethesda, MD 20892 USA.
[Bowcock, Anne] Washington Univ, St Louis, MO USA.
[Lowes, Michelle] Rockefeller Univ, Invest Dermatol Lab, New York, NY 10021 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 1808
BP S769
EP S770
PG 2
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748304085
ER
PT J
AU Criswell, LA
Taylor, KE
McHugh, C
Laurie, C
Doheny, K
Lam, MY
Nititham, J
Bierut, L
Harris, EL
Baer, AN
Challacombe, S
Dong, Y
Lanfranchi, H
Schiodt, M
Srinivasan, M
Sugai, S
Umehara, H
Vivino, FB
Yan, Z
Shiboski, S
Daniels, T
Greenspan, JS
Shiboski, C
AF Criswell, Lindsey A.
Taylor, Kimberly E.
McHugh, Caitlin
Laurie, Cathy
Doheny, Kimberly
Lam, Mi Y.
Nititham, Joanne
Bierut, Laura
Harris, Emily L.
Baer, Alan N.
Challacombe, Stephen
Dong, Yi
Lanfranchi, Hector
Schiodt, Morten
Srinivasan, M.
Sugai, Susumu
Umehara, Hisanori
Vivino, Frederick B.
Yan, Zhao
Shiboski, Steve
Daniels, Troy
Greenspan, John S.
Shiboski, Caroline
CA SICCA
TI Genome-Wide Association Analysis Reveals Genetic Heterogeneity of
Sjogren's Syndrome (SS) According to Specific Subphenotypes and Ancestry
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Daniels, Troy] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA.
[McHugh, Caitlin; Laurie, Cathy] Univ Washington, Seattle, WA 98195 USA.
[Doheny, Kimberly] Ctr Inherited Dis Res, Baltimore, MD USA.
[Nititham, Joanne] Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA USA.
[Bierut, Laura] Washington Univ, St Louis, MO USA.
[Harris, Emily L.] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA.
[Baer, Alan N.] Johns Hopkins Univ, Baltimore, MD USA.
[Challacombe, Stephen] Kings Coll London, London WC2R 2LS, England.
[Dong, Yi; Yan, Zhao] Peking Univ, Med Coll Hosp, Beijing 100871, Peoples R China.
[Lanfranchi, Hector] Univ Buenos Aires, Buenos Aires, DF, Argentina.
[Schiodt, Morten] Rigshosp, DK-2100 Copenhagen, Denmark.
[Srinivasan, M.] Aravind Eye Hosp, Madurai, Tamil Nadu, India.
[Sugai, Susumu; Umehara, Hisanori] Kanazawa Med Univ, Kanazawa, Ishikawa, Japan.
[Vivino, Frederick B.] Penn Presbyt Med Ctr, Philadelphia, PA USA.
[Daniels, Troy] Univ Calif San Francisco, Sch Dent, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2672
BP S1133
EP S1134
PG 2
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748306182
ER
PT J
AU Danielides, S
Dema, B
Rivera, J
Illei, GG
AF Danielides, Stamatina
Dema, Barbara
Rivera, Juan
Illei, Gabor G.
TI IgE Autoantibodies Against SSA and SSB in Patients with Sjogren's
Syndrome and Healthy Controls.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Dema, Barbara; Rivera, Juan] NIAMS, Immunogenet Mol Lab, NIH, Bethesda, MD USA.
[Illei, Gabor G.] NIDCR, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2200
BP S930
EP S930
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748305120
ER
PT J
AU de Jesus, AA
Liu, Y
Montealegre, GA
Reinhardt, AL
Brown, D
Torrelo, A
Casano, AV
Das, L
Chen, YQ
Huang, Y
Stone, D
Chapelle, DC
Plass, N
Zuckerman, SH
Macias, W
Goldbach-Mansky, RT
AF de Jesus, Adriana Almeida
Liu, Yin
Montealegre, Gina A.
Reinhardt, Adam L.
Brown, Diane
Torrelo, Antonio
Casano, Angel V.
Das, Lena
Chen, Yongqing
Huang, Yan
Stone, Deborah
Chapelle, Dawn C.
Plass, Nicole
Zuckerman, Steven H.
Macias, William
Goldbach-Mansky, Raphaela T.
TI A Subset of up-Regulated IFN Regulated Genes in Candle Patients Decrease
with Treatment with a JAK Inhibitor
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [de Jesus, Adriana Almeida] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Reinhardt, Adam L.] Childrens Hosp Omaha UNMC, Omaha, NE USA.
[Brown, Diane] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Torrelo, Antonio] Hosp Nino Jesus, Dept Pediat Dermatol, Madrid, Spain.
[Casano, Angel V.] Meditex Spain, Malaga, Spain.
[Das, Lena] Womens & Childrens Hosp, Singapore, Singapore.
[Chen, Yongqing; Huang, Yan] Off Clin Director NIAMS, Translat Autoinflammatory Dis Sect, Bethesda, MD USA.
[Plass, Nicole] Natl Inst Hlth Clin Ctr, Bethesda, MD USA.
[Zuckerman, Steven H.] Lilly Res Labs, Indianapolis, IN USA.
[Macias, William] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Goldbach-Mansky, Raphaela T.] NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2653
BP S1124
EP S1124
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748306163
ER
PT J
AU Edwan, JH
Tran, TM
Abu-Asab, M
Goldbach-Mansky, RT
Colbert, RA
AF Edwan, Jehad H.
Tran, Tri M.
Abu-Asab, Mones
Goldbach-Mansky, Raphaela T.
Colbert, Robert A.
TI STAT3 Plays a Central Role in NLRP3 Inflammasome-Mediated IL-1 beta
Production and Pyronecrosis.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Goldbach-Mansky, Raphaela T.] NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD USA.
[Abu-Asab, Mones] NEI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 310
BP S136
EP S136
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748300311
ER
PT J
AU Gallo, A
Tandon, M
Jang, SI
Ong, HL
Ambudkar, I
Illei, GG
Alevizos, I
AF Gallo, Alessia
Tandon, Mayank
Jang, Shyh-Ing
Ong, Hwei Ling
Ambudkar, Indu
Illei, Gabor G.
Alevizos, Ilias
TI Ebv-Mir-Bart13 Affects the Expression of AQP5 in Human Salivary Gland
Cell Lines Contributing to the Pathogenesis of Sjogren's Syndrome
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Illei, Gabor G.; Alevizos, Ilias] NIDCR, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 506
BP S222
EP S222
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748301045
ER
PT J
AU Golding, A
Hasni, SA
Illei, GG
Shevach, EM
AF Golding, Amit
Hasni, Sarfaraz A.
Illei, Gabor G.
Shevach, Ethan M.
TI Expression of Helios Facilitates Distinction Between FoxP3(+) Treg and
FoxP3(+) Activated T Conventional Cells in Patients with Systemic Lupus
Erythematosus
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Golding, Amit; Hasni, Sarfaraz A.; Shevach, Ethan M.] NIAID, NIH, Bethesda, MD 20892 USA.
[Illei, Gabor G.] NIDCR, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2506
BP S1058
EP S1058
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748306016
ER
PT J
AU Gorelik, M
Bushnell, D
Goldbach-Mansky, RT
Hoffman, HM
Hirsch, R
AF Gorelik, Mark
Bushnell, Daniel
Goldbach-Mansky, Raphaela T.
Hoffman, Hal M.
Hirsch, Raphael
TI Elevated Serum Follistatin-Like Protein 1 Suggests an Interleukin-1
Independent Pathway for Inflammation in Patients with Cryopyrin
Associated Periodic Syndromes
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Gorelik, Mark] Univ Pittsburgh, Childrens Hosp, Med Ctr, Pittsburgh, PA 15260 USA.
[Bushnell, Daniel; Hirsch, Raphael] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA.
[Goldbach-Mansky, Raphaela T.] NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD USA.
[Hoffman, Hal M.] Univ Calif San Diego, La Jolla, CA 92093 USA.
NR 0
TC 2
Z9 2
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2656
BP S1125
EP S1126
PG 2
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748306166
ER
PT J
AU Haroon, N
Inman, RD
Learch, TJ
Weisman, MH
Ward, MM
Reveille, JD
Gensler, LS
AF Haroon, Nigil
Inman, Robert D.
Learch, Thomas J.
Weisman, Michael H.
Ward, Michael M.
Reveille, John D.
Gensler, Lianne S.
TI Anti-TNF Therapy Slows Radiographic Progression of Ankylosing
Spondylitis
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Haroon, Nigil] Univ Toronto, Toronto Western Res Inst, Univ Hlth Network, Toronto, ON, Canada.
[Learch, Thomas J.] Cedars Sinai, Los Angeles, CA USA.
[Weisman, Michael H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Ward, Michael M.] NIAMS, NIH, Bethesda, MD USA.
[Reveille, John D.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
[Gensler, Lianne S.] UCSF, San Francisco, CA USA.
NR 0
TC 2
Z9 2
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 782
BP S339
EP S340
PG 2
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748301319
ER
PT J
AU Huber, AM
Mamyrova, G
Lee, JA
Lachenbruch, PA
Targoff, IN
Miller, FW
Rider, LG
AF Huber, Adam M.
Mamyrova, Gulnara
Lee, Julia A.
Lachenbruch, Peter A.
Targoff, Ira N.
Miller, Frederick W.
Rider, Lisa G.
CA Childhood Myositis Heterogeneity S
TI Illness Features Associated with an Increased Risk of Mortality in
Children with Juvenile Idiopathic Inflammatory Myopathies.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Huber, Adam M.] Dalhousie Univ, Halifax, NS, Canada.
[Mamyrova, Gulnara] George Washington Univ, Washington, DC USA.
[Lachenbruch, Peter A.; Miller, Frederick W.; Rider, Lisa G.] NIEHS, NIH, Bethesda, MD USA.
[Targoff, Ira N.] Oklahoma Med Res Foun, Oklahoma City, OK USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 291
BP S127
EP S128
PG 2
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748300292
ER
PT J
AU Kirino, Y
Zhou, Q
Ishigatsubo, Y
Mizuki, N
Tugal-Tutkun, I
Seyahi, E
Ozyazgan, Y
Sacli, FS
Erer, B
Emrence, Z
Cakar, A
Ustek, D
Meguro, A
Ueda, A
Takeno, M
Ombrello, MJ
Satorius, C
Maskeri, B
Mullikin, J
Sun, HW
Gutierrez-Cruz, G
Kim, Y
Gul, A
Kastner, DL
Remmers, EF
AF Kirino, Yohei
Zhou, Qing
Ishigatsubo, Yoshiaki
Mizuki, Nobuhisa
Tugal-Tutkun, Ilknur
Seyahi, Emire
Ozyazgan, Yilmaz
Sacli, F. Sevgi
Erer, Burak
Emrence, Zeliha
Cakar, Atilla
Ustek, Duran
Meguro, Akira
Ueda, Atsuhisa
Takeno, Mitsuhiro
Ombrello, Michael J.
Satorius, Colleen
Maskeri, Baishali
Mullikin, Jim
Sun, Hong-Wei
Gutierrez-Cruz, Gustavo
Kim, Yoonhee
Gul, Ahmet
Kastner, Daniel L.
Remmers, Elaine F.
TI Targeted Deep Re-Sequencing Implicates Rare and Low Frequency Coding
Variants in IL23R, MEFV, TLR4, and NOD2 in Behcet's Disease
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Kirino, Yohei; Zhou, Qing; Ombrello, Michael J.; Satorius, Colleen; Kastner, Daniel L.; Remmers, Elaine F.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Ishigatsubo, Yoshiaki; Mizuki, Nobuhisa; Meguro, Akira; Ueda, Atsuhisa; Takeno, Mitsuhiro] Yokohama City Univ, Grad Sch Med, Yokohama, Kanagawa 232, Japan.
[Seyahi, Emire; Ozyazgan, Yilmaz; Sacli, F. Sevgi] Istanbul Univ, Cerrahpasa Fac Med, Istanbul, Turkey.
[Erer, Burak; Gul, Ahmet] Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey.
[Emrence, Zeliha; Cakar, Atilla; Ustek, Duran] Istanbul Univ, Inst Expt Med, Istanbul, Turkey.
[Maskeri, Baishali; Mullikin, Jim] NHGRI, NIH, Rockville, MD USA.
[Sun, Hong-Wei; Gutierrez-Cruz, Gustavo] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Kim, Yoonhee] NHGRI, NIH, Baltimore, MD USA.
RI Ustek, Duran/C-3484-2009
OI Ustek, Duran/0000-0002-0060-2859
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 1611
BP S688
EP S688
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748303332
ER
PT J
AU Lessard, CJ
Li, H
Adrianto, I
Ice, JA
Jonsson, R
Illei, GG
Rischmueller, M
Nordmark, G
Mariette, X
Miceli-Richard, C
Wahren-Herlenius, M
Witte, T
Brennan, MT
Omdal, R
Gaffney, PM
Lessard, JA
Ng, WF
Rhodus, NL
Segal, BM
Scofield, RH
James, JA
Anaya, JM
Harley, JB
Montgomery, CG
Sivils, KM
AF Lessard, Christopher J.
Li, He
Adrianto, Indra
Ice, John A.
Jonsson, Roland
Illei, Gabor G.
Rischmueller, Maureen
Nordmark, Gunnel
Mariette, Xavier
Miceli-Richard, Corinne
Wahren-Herlenius, Marie
Witte, Torsten
Brennan, Michael T.
Omdal, Roald
Gaffney, Patrick M.
Lessard, James A.
Ng, Wan-Fai
Rhodus, Nelson L.
Segal, Barbara M.
Scofield, R. Hal
James, Judith A.
Anaya, Juan-Manuel
Harley, John B.
Montgomery, Courtney G.
Sivils, Kathy Moser
TI A Genome-Wide Association Study Establishes Muliple Susceptibility Loci
for Sjogren's Syndrome
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Lessard, Christopher J.; James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, Oklahoma City, OK USA.
[Jonsson, Roland] Univ Bergen, Bergen, Norway.
[Illei, Gabor G.] NIDCR, NIH, Bethesda, MD USA.
[Rischmueller, Maureen] Queen Elizabeth Hosp, Adelaide, SA, Australia.
[Mariette, Xavier] Univ Paris 11, Le Kremlin Bicetre, France.
[Miceli-Richard, Corinne] Hop Bicetre, Le Kremlin Bicetre, France.
[Wahren-Herlenius, Marie] Karolinska Inst, Stockholm, Sweden.
[Witte, Torsten] Hannover Med Sch, Hannover, Germany.
[Brennan, Michael T.] Carolinas Med Ctr, Charlotte, NC 28203 USA.
[Omdal, Roald] Stavanger Univ Hosp, Clin Immunol Unit, Dept Internal Med, Stavanger, Norway.
[Gaffney, Patrick M.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA.
[Lessard, James A.] Valley Bone & Joint Clin, Grand Forks, ND USA.
[Ng, Wan-Fai] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Rhodus, Nelson L.] Univ Minnesota, Minneapolis, MN USA.
[Segal, Barbara M.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA.
[Anaya, Juan-Manuel] Univ Rosario Corp Invest Biol, Bogota, Colombia.
[Harley, John B.] US Dept Vet Affairs, Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
RI Adrianto, Indra/D-4214-2013; Witte, Torsten/B-5783-2016; Anaya,
Juan-Manuel/J-1960-2016
OI Adrianto, Indra/0000-0002-9973-3057; Anaya,
Juan-Manuel/0000-0002-6444-1249
NR 0
TC 1
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2671
BP S1133
EP S1133
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748306181
ER
PT J
AU Lukkahatai, N
Walitt, BT
Benjamin, M
Alves, G
Saligan, L
AF Lukkahatai, Nada
Walitt, Brian T.
Benjamin, Majors
Alves, Gelio
Saligan, Leorey
TI Genomic Categories of Fatigue in Women with Fibromyalgia
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Lukkahatai, Nada; Benjamin, Majors; Saligan, Leorey] NINR, NIH, Bethesda, MD 20892 USA.
[Walitt, Brian T.] Washington Hosp Ctr, Washington, DC 20010 USA.
[Alves, Gelio] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 1874
BP S796
EP S797
PG 2
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748304151
ER
PT J
AU Maksymowych, WP
Learch, TJ
Lambert, RGW
Ward, MM
Haroon, N
Salonen, D
Inman, RD
Weisman, MH
AF Maksymowych, Walter P.
Learch, Thomas J.
Lambert, Robert G. W.
Ward, Michael M.
Haroon, Nigil
Salonen, David
Inman, Robert D.
Weisman, Michael H.
TI Validation of a Reference Imaging Module for Calibration of Readers
Scoring with the Modified Stoke Ankylosing Spondylitis Spine Score.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Maksymowych, Walter P.; Lambert, Robert G. W.] Univ Alberta, Edmonton, AB, Canada.
[Learch, Thomas J.] Cedars Sinai, Los Angeles, CA USA.
[Ward, Michael M.] NIAMS, NIH, Bethesda, MD USA.
[Haroon, Nigil; Inman, Robert D.] Univ Toronto, Univ Hlth Network, Toronto Western Res Inst, Toronto, ON, Canada.
[Weisman, Michael H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 542
BP S236
EP S236
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748301081
ER
PT J
AU Mamyrova, G
Katz, JD
Jones, RV
Lachenbruch, PA
Shah, M
Jones, OY
Chahal, A
Agrawal, S
Miller, FW
Rider, LG
AF Mamyrova, Gulnara
Katz, James D.
Jones, Robert V.
Lachenbruch, Peter A.
Shah, Mona
Jones, Olcay Y.
Chahal, Anupam
Agrawal, Seema
Miller, Frederick W.
Rider, Lisa G.
CA Childhood Myositis Heterogeneity G
TI Clinical and Laboratory Features Distinguishing Juvenile Polymyositis
and Muscular Dystrophy in Children.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Mamyrova, Gulnara; Katz, James D.; Jones, Robert V.; Jones, Olcay Y.; Chahal, Anupam; Agrawal, Seema] George Washington Univ, Washington, DC USA.
[Lachenbruch, Peter A.; Shah, Mona; Miller, Frederick W.; Rider, Lisa G.] NIEHS, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 282
BP S123
EP S123
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748300283
ER
PT J
AU Manno, RL
Gelber, AC
Seo, P
Levine, SM
Ghazarian, SR
Chen, PH
Stewart, KJ
Metter, J
Ferrucci, L
Fontaine, KR
AF Manno, Rebecca L.
Gelber, Allan C.
Seo, Philip
Levine, Stuart M.
Ghazarian, Sharon R.
Chen, Po-Han
Stewart, Kerry J.
Metter, Jeffrey
Ferrucci, Luigi
Fontaine, Kevin R.
TI Body Composition, Strength, and Function in Elderly Patients with Giant
Cell Arteritis
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Manno, Rebecca L.; Gelber, Allan C.; Levine, Stuart M.; Stewart, Kerry J.] Johns Hopkins Univ, Baltimore, MD USA.
[Seo, Philip] Johns Hopkins Vasculitis Ctr, Baltimore, MD USA.
[Metter, Jeffrey; Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA.
[Fontaine, Kevin R.] Univ Alabama Birmingham, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2395
BP S1009
EP S1009
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748305315
ER
PT J
AU Martin, KR
Van Domelen, D
Pantell, M
Hung, MY
Harris, TB
Patel, K
AF Martin, Kathryn Remmes
Van Domelen, Dane
Pantell, Matthew
Hung, Ming-yang
Harris, Tamara B.
Patel, Kushang
TI Association of Arthritis and Joint Pain with Accelerometer-Measured
Physical Activity in Adults Aged 50 and Older in the United States:
Findings From the National Health and Nutrition Examination Survey
(2003-2004)
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Martin, Kathryn Remmes; Van Domelen, Dane; Pantell, Matthew; Hung, Ming-yang; Harris, Tamara B.] NIA, NIH, Bethesda, MD 20892 USA.
[Patel, Kushang] Univ Washington, Seattle, WA 98195 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2513
BP S1061
EP S1061
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748306023
ER
PT J
AU Martin, KR
Kuh, D
Harris, TB
Guralnik, JM
Coggon, D
Wills, AK
AF Martin, Kathryn Remmes
Kuh, Diana
Harris, Tamara B.
Guralnik, Jack M.
Coggon, David
Wills, Andrew K.
TI BMI, Occupational Activity, and Leisure-Time Physical Activity: an
Exploration of Risk Factors and Modifiers for Knee Osteoarthritis.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Martin, Kathryn Remmes; Harris, Tamara B.] NIA, NIH, Bethesda, MD 20892 USA.
[Kuh, Diana] MRC, London, England.
[Guralnik, Jack M.] Univ Maryland, Baltimore, MD 21201 USA.
[Coggon, David] Univ Southampton, Southampton, Hants, England.
[Wills, Andrew K.] Univ Bristol, Bristol, Avon, England.
NR 0
TC 0
Z9 0
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 800
BP S348
EP S348
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748301337
ER
PT J
AU Montealegre, GA
de Jesus, AA
Chapelle, DC
Dancey, P
Frenkel, J
van Royen-Kerkhoff, A
Herzog, R
Ciocca, G
Rivas-Chacon, RF
Reed, AM
Plass, N
Aksentijevich, I
Ferguson, PJ
Hill, SC
Cowen, E
Goldbach-Mansky, RT
AF Montealegre, Gina A.
de Jesus, Adriana Almeida
Chapelle, Dawn C.
Dancey, Paul
Frenkel, Joost
van Royen-Kerkhoff, Annet
Herzog, Ronit
Ciocca, Giovanna
Rivas-Chacon, Rafael F.
Reed, Ann M.
Plass, Nicole
Aksentijevich, Ivona
Ferguson, Polly J.
Hill, Suvimol C.
Cowen, Edward
Goldbach-Mansky, Raphaela T.
TI Safety and Efficacy of Anakinra in Patients with Deficiency of
Interleukin-1 Receptor Antagonist
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Montealegre, Gina A.; Chapelle, Dawn C.; Goldbach-Mansky, Raphaela T.] NIAMS, NIH, Translat Autoinflammatory Dis Sect, Bethesda, MD USA.
[de Jesus, Adriana Almeida] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Dancey, Paul] Mem Univ Newfoundland, St John, NF, Canada.
[Frenkel, Joost; van Royen-Kerkhoff, Annet] Univ Utrecht, Utrecht, Netherlands.
[Herzog, Ronit] Cornell Univ, New York, NY 10021 USA.
[Ciocca, Giovanna; Rivas-Chacon, Rafael F.] Miami Childrens Hosp, Miami, FL USA.
[Reed, Ann M.] Mayo Clin, Rochester, MN USA.
[Plass, Nicole; Hill, Suvimol C.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Aksentijevich, Ivona] NHGRI, NIH, Bethesda, MD 20892 USA.
[Ferguson, Polly J.] Univ Iowa, Carver Coll Med, Iowa City, IA USA.
[Cowen, Edward] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2031
BP S861
EP S861
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748304308
ER
PT J
AU Mountz, JD
Wang, JH
New, JS
Yang, P
Wu, Q
Luo, B
Li, J
Druey, KM
Hsu, HC
AF Mountz, John D.
Wang, John H.
New, James S.
Yang, PingAr
Wu, Qi
Luo, Bao
Li, Jun
Druey, Kirk M.
Hsu, Hui-Chen
TI Inhibition of Pathogenic Autoantibodies by Accelerating the Exit of
Germinal Center B Cells Via Manipulation of Regulator of G-Protein
Signaling
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Mountz, John D.; New, James S.; Yang, PingAr; Wu, Qi; Luo, Bao; Li, Jun; Hsu, Hui-Chen] Univ Alabama Birmingham, Birmingham, AL USA.
[Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL USA.
[Wang, John H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Druey, Kirk M.] NIAID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2575
BP S1090
EP S1090
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748306085
ER
PT J
AU Nakayamada, S
Kanno, Y
Vahedi, G
O'Shea, JJ
Tanaka, Y
AF Nakayamada, Shingo
Kanno, Yuka
Vahedi, Golnaz
O'Shea, John J.
Tanaka, Yoshiya
TI Dynamic Regulation of T Follicular Helper Cell Differentiation Through
STAT Signaling
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Nakayamada, Shingo; Tanaka, Yoshiya] Univ Occupat & Environm Hlth, Dept Internal Med 1, Kitakyushu, Fukuoka 807, Japan.
[Kanno, Yuka; Vahedi, Golnaz; O'Shea, John J.] NIAMSD, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2322
BP S980
EP S980
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748305242
ER
PT J
AU Ombrello, AK
Hoffmann, PM
Jones, A
Barron, KS
Kastner, DL
AF Ombrello, Amanda K.
Hoffmann, Patrycja M.
Jones, Anne
Barron, Karyl S.
Kastner, Daniel L.
TI Evaluation of Anakinra Therapy in Seven Adults After Suboptimal Response
to Etanercept Therapy for Tumor Necrosis Factor Receptor-Associated
Periodic Fever Syndrome.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Ombrello, Amanda K.; Hoffmann, Patrycja M.; Jones, Anne; Kastner, Daniel L.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Barron, Karyl S.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 179
BP S77
EP S78
PG 2
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748300180
ER
PT J
AU Ombrello, MJ
Remmers, E
Grom, AA
Thomson, W
Martini, A
Gattorno, M
Ozen, S
Prahalad, S
Bohnsack, JF
Zeft, A
Ilowite, NT
Mellins, ED
Russo, RAG
Len, C
Oliveira, SK
Yeung, RS
Wedderburn, LR
Lopez, JA
Sato-Rius, C
Tachmazidou, I
Langefeld, CD
Zeggini, E
Thompson, SD
Woo, P
Kastner, DL
AF Ombrello, Michael J.
Remmers, Elaine
Grom, Alexei A.
Thomson, Wendy
Martini, Alberto
Gattorno, Marco
Ozen, Seza
Prahalad, Sampath
Bohnsack, John F.
Zeft, Andrew
Ilowite, Norman T.
Mellins, Elizabeth D.
Russo, Ricardo A. G.
Len, Claudio
Oliveira, Sheila K.
Yeung, Rae S. M.
Wedderburn, Lucy R.
Lopez, Jordi Anton
Sato-Rius, Colleen
Tachmazidou, Ioanna
Langefeld, Carl D.
Zeggini, Eleftheria
Thompson, Susan D.
Woo, Patricia
Kastner, Daniel L.
TI Genome-Wide Association Meta-Analysis of Eight Independent Systemic
Juvenile Idiopathic Arthritis Collections Reveals Regional Association
Spanning the Major Histocompatibility Complex Class II and III Gene
Cluster
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Ombrello, Michael J.; Kastner, Daniel L.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Grom, Alexei A.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Thomson, Wendy] Arthrit Res UK Epidemiol Unit, Manchester, Lancs, England.
[Martini, Alberto] Univ Genoa, Genoa, Italy.
[Gattorno, Marco] Ist Giannina Gaslini, I-16148 Genoa, Italy.
[Ozen, Seza] Hacettepe Univ, Ankara, Turkey.
[Prahalad, Sampath] Emory Childrens Ctr, Atlanta, GA USA.
[Bohnsack, John F.] Univ Utah, Salt Lake City, UT USA.
[Zeft, Andrew] Cleveland Clin, Cleveland, OH 44106 USA.
[Ilowite, Norman T.] Childrens Hosp Montefiore, Bronx, NY USA.
[Mellins, Elizabeth D.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA.
[Russo, Ricardo A. G.] Hosp Pediatria Garrahan, Buenos Aires, DF, Argentina.
[Len, Claudio] Univ Fed Sao Paulo, UNIFESP, Sao Paulo, Brazil.
[Oliveira, Sheila K.] Univ Fed Rio de Janeiro, IPPMG, Rio De Janeiro, Brazil.
[Yeung, Rae S. M.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Wedderburn, Lucy R.; Woo, Patricia] UCL, London, England.
[Lopez, Jordi Anton] Univ Childrenxs Hosp, Barcelona, Spain.
[Tachmazidou, Ioanna; Zeggini, Eleftheria] Wellcome Trust Sanger Inst, Cambridge, England.
[Langefeld, Carl D.] Wake Forest Sch Med, Winston Salem, NC USA.
RI Oliveira, Sheila/F-5213-2016
OI Oliveira, Sheila/0000-0002-2426-716X
NR 0
TC 0
Z9 0
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2657
BP S1126
EP S1126
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748306167
ER
PT J
AU Osborn, T
Matteson, E
Ernste, F
Crowson, CS
Hoganson, DD
Whitt, IZ
AF Osborn, Thomas
Matteson, Eric
Ernste, Floranne
Crowson, Cynthia S.
Hoganson, Deana D.
Whitt, Irene Z.
TI Fingertip Skin Hardness in Limited Scleroderma: Durometry versus Manual
Assessment.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Osborn, Thomas; Matteson, Eric; Crowson, Cynthia S.] Mayo Clin, Rochester, MN USA.
[Hoganson, Deana D.] Mercy Arthrit & Osteoporosis Ctr, Urbandale, IA USA.
[Whitt, Irene Z.] NIEHS, NIH, Environm Autoimmun Grp, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 709
BP S304
EP S304
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748301247
ER
PT J
AU Oswald, M
Aranow, C
Kamen, DL
Mackay, MC
Goldmuntz, EA
Diamond, B
Gregersen, PK
AF Oswald, Michaela
Aranow, Cynthia
Kamen, Diane L.
Mackay, Meggan C.
Goldmuntz, Ellen A.
Diamond, Betty
Gregersen, Peter K.
CA ALE02 Study Team
TI Modular Microarray Analysis Fails to Reveal a Significant Biological
Effect of Vitamin D3 Treatment in Patients Participating in a
Double-Blind Randomized Placebo-Controlled Trial of the Effect of
Vitamin D3 On the Interferon Signature in Patients with Systemic Lupus
Erythematosus
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Oswald, Michaela; Aranow, Cynthia; Diamond, Betty; Gregersen, Peter K.] Feinstein Inst Med Res, Manhasset, NY USA.
[Kamen, Diane L.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Charleston, SC USA.
[Mackay, Meggan C.] Feinstein Inst, Manhasset, NY USA.
[Goldmuntz, Ellen A.] NIAID, NIH, Bethesda, MD 20892 USA.
[Gregersen, Peter K.] N Shore Long Isl Jewish Hlth Syst, Manhasset, NY USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2687
BP S1139
EP S1140
PG 2
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748306197
ER
PT J
AU Ota, Y
Kawaguchi, Y
Kitani, A
Takagi, K
Ichida, H
Katsumata, Y
Gono, T
Hanaoka, M
Okamoto, Y
Yamanaka, H
AF Ota, Yuko
Kawaguchi, Yasushi
Kitani, Atsushi
Takagi, Kae
Ichida, Hisae
Katsumata, Yasuhiro
Gono, Takahisa
Hanaoka, Masanori
Okamoto, Yuko
Yamanaka, Hisashi
TI IL-13 Receptors and Signaling in the Dermal Fibroblasts From Patients
with Systemic Sclerosis
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Ota, Yuko; Kawaguchi, Yasushi; Takagi, Kae; Ichida, Hisae; Katsumata, Yasuhiro; Gono, Takahisa; Hanaoka, Masanori; Okamoto, Yuko; Yamanaka, Hisashi] Tokyo Womens Med Univ, Inst Rheumatol, Tokyo, Japan.
[Kitani, Atsushi] NIAID, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 1492
BP S640
EP S640
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748303213
ER
PT J
AU Remmers, EF
Kirino, Y
Bertsias, G
Ishigatsubo, Y
Kim, Y
Ombrello, MJ
Tugal-Tutkun, I
Seyahi, E
Ozyazgan, Y
Sacli, FS
Erer, B
Emrence, Z
Cakar, A
Abaci, N
Ustek, D
Satorius, C
Takeno, M
Gul, A
Kastner, DL
AF Remmers, Elaine F.
Kirino, Yohei
Bertsias, George
Ishigatsubo, Yoshiaki
Kim, Yoonhee
Ombrello, Michael J.
Tugal-Tutkun, Ilknur
Seyahi, Emire
Ozyazgan, Yilmaz
Sacli, F. Sevgi
Erer, Burak
Emrence, Zeliha
Cakar, Atilla
Abaci, Neslihan
Ustek, Duran
Satorius, Colleen
Takeno, Mitsuhiro
Gul, Ahmet
Kastner, Daniel L.
TI Genome-Wide Analysis Reveals a Recessive Association of ERAP1 Variants
with Behcet's Disease and Epistasis Between ERAP1 and HLA-B*51.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Remmers, Elaine F.; Kirino, Yohei; Bertsias, George; Kim, Yoonhee; Ombrello, Michael J.; Satorius, Colleen; Kastner, Daniel L.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Ishigatsubo, Yoshiaki; Takeno, Mitsuhiro] Yokohama City Univ, Grad Sch Med, Yokohama, Kanagawa 232, Japan.
[Tugal-Tutkun, Ilknur; Erer, Burak; Gul, Ahmet] Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey.
[Seyahi, Emire; Ozyazgan, Yilmaz; Sacli, F. Sevgi] Istanbul Univ, Cerrahpasa Fac Med, Istanbul, Turkey.
[Emrence, Zeliha; Cakar, Atilla; Abaci, Neslihan; Ustek, Duran] Istanbul Univ, Inst Expt Med, Istanbul, Turkey.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 989
BP S428
EP S428
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748302064
ER
PT J
AU Rider, LG
Yip, AL
Horkayne-Szakaly, I
Volochayev, R
Shrader, JA
Turner, ML
Kong, HH
Jain, MS
Jansen, AV
Oddis, CV
Fleisher, TA
Miller, FW
AF Rider, Lisa G.
Yip, Adrienne L.
Horkayne-Szakaly, Iren
Volochayev, Rita
Shrader, Joseph A.
Turner, Maria L.
Kong, Heidi H.
Jain, Minal S.
Jansen, Anna V.
Oddis, Chester V.
Fleisher, Thomas A.
Miller, Frederick W.
TI Clinical, Laboratory, and Cellular Responses in the Rituximab in
Myositis Trial in Patients Enrolled At the National Institutes of Health
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Rider, Lisa G.; Yip, Adrienne L.; Volochayev, Rita; Jansen, Anna V.; Miller, Frederick W.] NIEHS, NIH, Bethesda, MD USA.
[Horkayne-Szakaly, Iren] Joint Pathol Ctr, Silver Spring, MD USA.
[Shrader, Joseph A.; Jain, Minal S.; Fleisher, Thomas A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Turner, Maria L.; Kong, Heidi H.] NCI, NIH, Bethesda, MD 20892 USA.
[Oddis, Chester V.] Univ Pittsburgh, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 206
BP S88
EP S88
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748300207
ER
PT J
AU Srinivasalu, H
Hill, SC
Sanchez, GAM
Brundidge, AD
Ward, MM
Colbert, RA
AF Srinivasalu, Hemalatha
Hill, Suvimol C.
Sanchez, Gina A. Montealegre
Brundidge, April D.
Ward, Michael M.
Colbert, Robert A.
TI Whole Body Magnetic Resonance Imaging in Evaluation of Enthesitis in
Spondyloarthropathy.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Srinivasalu, Hemalatha; Sanchez, Gina A. Montealegre; Brundidge, April D.; Ward, Michael M.; Colbert, Robert A.] NIAMS, NIH, Bethesda, MD USA.
[Hill, Suvimol C.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2000
BP S848
EP S848
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748304277
ER
PT J
AU Tjarnlund, A
Bottai, M
Rider, LG
Werth, VP
Pilkington, CA
de Visser, M
Alfredsson, L
Amato, AA
Barohn, RJ
Liang, MH
Singh, JA
Miller, FW
Lundberg, IE
AF Tjarnlund, Anna
Bottai, Matteo
Rider, Lisa G.
Werth, Victoria P.
Pilkington, Clarissa A.
de Visser, Marianne
Alfredsson, Lars
Amato, Anthony A.
Barohn, Richard J.
Liang, Matthew H.
Singh, Jasvinder A.
Miller, Frederick W.
Lundberg, Ingrid E.
CA Int Myositis Classification Criter
TI Progress Report On Development of Classification Criteria for Adult and
Juvenile Idiopathic Inflammatory Myopathies.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Tjarnlund, Anna] Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Solna, Sweden.
[Bottai, Matteo; Alfredsson, Lars] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Rider, Lisa G.; Miller, Frederick W.] NIEHS, NIH, Bethesda, MD USA.
[Werth, Victoria P.] Univ Penn, Philadelphia, PA 19104 USA.
[Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Pilkington, Clarissa A.] Great Ormond St Hosp Sick Children, London WC1N 3JH, England.
[de Visser, Marianne] Univ Amsterdam, Acad Med Ctr, Dept Neurol, NL-1105 AZ Amsterdam, Netherlands.
[Amato, Anthony A.; Liang, Matthew H.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Amato, Anthony A.] Harvard Univ, Sch Med, Boston, MA USA.
[Barohn, Richard J.] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, MO USA.
[Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA.
NR 0
TC 4
Z9 4
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 753
BP S323
EP S324
PG 2
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748301290
ER
PT J
AU Tomasson, G
Monach, PA
Tanriverdi, K
Specks, U
Stone, JH
Ding, LN
Fervenza, F
Hoffman, GS
Kallenberg, CGM
Langford, CA
Phippard, DJ
Seo, P
Spiera, RF
St Clair, EW
Tchao, N
Freedman, JE
Merkel, PA
AF Tomasson, Gunnar
Monach, Paul A.
Tanriverdi, Kahraman
Specks, Ulrich
Stone, John H.
Ding, Linna
Fervenza, Fernando
Hoffman, Gary S.
Kallenberg, Cees G. M.
Langford, Carol A.
Phippard, Deborah J.
Seo, Philip
Spiera, Robert F.
St Clair, E. William
Tchao, Nadia
Freedman, Jane E.
Merkel, Peter A.
TI Predictive Value of Selected Markers of Inflammation and Platelet
Activation for Complete Remission in ANCA-Associated Vasculitis
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Tomasson, Gunnar] Univ Iceland, Reykjavik, Iceland.
[Monach, Paul A.] Boston Univ, Boston, MA 02215 USA.
[Tanriverdi, Kahraman; Freedman, Jane E.] Univ Massachusetts, Wochester, MA USA.
[Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Specks, Ulrich; Fervenza, Fernando] Mayo Clin, Rochester, MN USA.
[Ding, Linna] NIAID, Bethesda, MD 20892 USA.
[Hoffman, Gary S.; Langford, Carol A.] Cleveland Clin, Cleveland, OH 44106 USA.
[Kallenberg, Cees G. M.] Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands.
[Phippard, Deborah J.; Tchao, Nadia] Immune Tolerance Network, Bethesda, MD USA.
[Seo, Philip] Johns Hopkins Vasculitis Ctr, Baltimore, MD USA.
[Spiera, Robert F.] Hosp Special Surg, New York, NY 10021 USA.
[St Clair, E. William] Duke Univ, Med Ctr, Durham, NC USA.
[Merkel, Peter A.] Univ Penn, Philadelphia, PA 19104 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2567
BP S1085
EP S1086
PG 2
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748306077
ER
PT J
AU Usategui, A
Miranda, V
Criado, G
Del Rey, MJ
Izquierdo, E
Leonard, WJ
Pablos, JL
AF Usategui, Alicia
Miranda, Vanessa
Criado, Gabriel
Del Rey, Manuel J.
Izquierdo, Elena
Leonard, Warren J.
Pablos, Jose L.
TI TSLP Receptor Deficiency Reduces IL-13 Expression and Prevents Fibrosis
in Experimental Scleroderma.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Usategui, Alicia; Miranda, Vanessa; Criado, Gabriel; Del Rey, Manuel J.; Izquierdo, Elena; Pablos, Jose L.] Inst Invest Hosp 12 Octubre I 12, Madrid, Spain.
[Leonard, Warren J.] NHLBI, NIH, Bethesda, MD 20892 USA.
RI Del Rey, Manuel /O-6114-2014; Usategui, Alicia/O-6476-2014
OI Del Rey, Manuel /0000-0002-8180-1584;
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 1513
BP S648
EP S649
PG 2
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748303234
ER
PT J
AU Yao, L
Yip, AL
Mesdaghinia, S
Shademan, A
Shrader, JA
Jansen, AV
Miller, FW
Rider, LG
AF Yao, Lawrence
Yip, Adrienne L.
Mesdaghinia, Sepehr
Shademan, Ashkan
Shrader, Joseph A.
Jansen, Anna V.
Miller, Frederick W.
Rider, Lisa G.
TI Magnetic Resonance Imaging (MRI) Assessment of Inflammatory Myopathy:
Quantitative Fat-Corrected Muscle T2 and Conventional T2 Measurement
Versus Standard MRI and Clinical Metrics.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Yao, Lawrence; Shrader, Joseph A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Yip, Adrienne L.; Mesdaghinia, Sepehr; Shademan, Ashkan; Jansen, Anna V.; Miller, Frederick W.; Rider, Lisa G.] NIEHS, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 1037
BP S449
EP S450
PG 2
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748302112
ER
PT J
AU Yazdany, J
Feldman, CH
Liu, J
Ward, MM
Fischer, MA
Costenbader, KH
AF Yazdany, Jinoos
Feldman, Candace H.
Liu, Jun
Ward, Michael M.
Fischer, Michael A.
Costenbader, Karen H.
TI Assessment of Quality of Care for Incident Lupus Nephritis in the US
Medicaid Population
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Yazdany, Jinoos] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Liu, Jun; Costenbader, Karen H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Ward, Michael M.] NIAMS, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2600
BP S1100
EP S1101
PG 2
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748306110
ER
PT J
AU Yin, HG
Cabrera-Perez, J
Lai, ZN
Michael, D
Weller, M
Swaim, B
Rana, N
Liu, XB
Alevizos, I
Ambudkar, I
Chiorini, JA
AF Yin, Hongen
Cabrera-Perez, Javier
Lai, Zhennan
Michael, Drew
Weller, Melodie
Swaim, Bill
Rana, Noreen
Liu, Xibao
Alevizos, Ilias
Ambudkar, Indu
Chiorini, John A.
TI Overexpression of BMP6 Is Associated with Loss of Salivary Gland
Activity in Sjogren's Syndrome Patients and Mice.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Yin, Hongen; Cabrera-Perez, Javier; Lai, Zhennan; Michael, Drew; Weller, Melodie; Swaim, Bill; Rana, Noreen; Liu, Xibao; Chiorini, John A.] NIDCR, NIH, Bethesda, MD USA.
[Alevizos, Ilias] NIDCR, NIH 10 1N110, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 517
BP S226
EP S226
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748301056
ER
PT J
AU Zhou, H
Hasni, SA
Tandon, M
Jang, SI
Austin, HA
Balow, JE
Alevizos, I
Illei, GG
AF Zhou, Hua
Hasni, Sarfaraz A.
Tandon, Mayank
Jang, Shyh-Ing
Austin, Howard A.
Balow, James E.
Alevizos, Ilias
Illei, Gabor G.
TI Mirorna Mir-150 Contributes to Chronic Kidney Injury in Lupus Nephritis
by Increasing the Synthesis of Fibrotic Proteins Via Downregulation of
SOCS1.
SO ARTHRITIS AND RHEUMATISM
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR)
and Association-of-Rheumatology-Health-Professionals (ARHP)
CY NOV 09-14, 2012
CL Washington, DC
SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP)
C1 [Zhou, Hua; Tandon, Mayank; Jang, Shyh-Ing; Alevizos, Ilias; Illei, Gabor G.] NIDCR, NIH, Bethesda, MD USA.
[Hasni, Sarfaraz A.] NIAMS, NIH, Bethesda, MD USA.
[Austin, Howard A.; Balow, James E.] NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
SU S
MA 2501
BP S1056
EP S1056
PG 1
WC Rheumatology
SC Rheumatology
GA 019OD
UT WOS:000309748306011
ER
PT J
AU Chan, PYS
von Leupoldt, A
Bradley, MM
Lang, PJ
Davenport, PW
AF Chan, Pei-Ying S.
von Leupoldt, Andreas
Bradley, Margaret M.
Lang, Peter J.
Davenport, Paul W.
TI The effect of anxiety on respiratory sensory gating measured by
respiratory-related evoked potentials
SO BIOLOGICAL PSYCHOLOGY
LA English
DT Article
DE Respiratory perception; Anxiety; Affective state; Mechanosensation; RREP
ID OBSTRUCTIVE PULMONARY-DISEASE; INSPIRATORY RESISTIVE LOADS; SYMPTOM
PERCEPTION; PSYCHOLOGICAL-ASPECTS; PANIC DISORDER; ASTHMA;
SCHIZOPHRENIA; ILLNESS; DYSPNEA; ATTACKS
AB Respiratory sensory gating is evidenced by decreased amplitudes of the respiratory-related evoked potentials (RREP) N1 peak for the second (S2) compared to the first occlusion (S1) when two paired occlusions are presented with a 500-millisecond (ms) inter-stimulus-interval during one inspiration. Because anxiety is prevalent in respiratory diseases and associated with altered respiratory perception, we tested whether anxiety can modulate individuals' respiratory neural gating mechanism.
By using high-density EEG, RREPs were measured in a paired inspiratory occlusion paradigm in 11 low and 10 higher anxious individuals with normal lung function.
The N1 peak gating S2/S1 ratio and the N1 S2 amplitudes were greater in higher compared to low anxious individuals (p's < 0.05). In addition, higher anxiety levels were correlated with greater S2/S1 ratios (r=0.54, p < 0.05) and 52 amplitudes (r=-0.49, p < 0.05).
The results demonstrate that anxiety is associated with reduced respiratory sensory gating which might underlie altered respiratory symptom perception in anxious individuals. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Chan, Pei-Ying S.] Chang Gung Univ, Dept Occupat Therapy, Tao Yuan, Taiwan.
[Chan, Pei-Ying S.; von Leupoldt, Andreas; Davenport, Paul W.] Univ Florida, Coll Vet Med, Dept Physiol Sci, Gainesville, FL 32610 USA.
[von Leupoldt, Andreas] Univ Med Ctr Hamburg Eppendorf, Dept Syst Neurosci, Hamburg, Germany.
[von Leupoldt, Andreas] Univ Hamburg, Dept Psychol, Hamburg, Germany.
[Bradley, Margaret M.; Lang, Peter J.] Univ Florida, NIMH Ctr Study Emot & Attent, Gainesville, FL USA.
RP Chan, PYS (reprint author), Chang Gung Univ, Dept Occupat Therapy, Tao Yuan, Taiwan.
EM chanp@mail.cgu.edu.tw
FU NIMH NIH HHS [P50 MH072850, R21 MH082702, P50 MH 72850]
NR 53
TC 21
Z9 21
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0301-0511
J9 BIOL PSYCHOL
JI Biol. Psychol.
PD OCT
PY 2012
VL 91
IS 2
BP 185
EP 189
DI 10.1016/j.biopsycho.2012.07.001
PG 5
WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology,
Experimental
SC Psychology; Behavioral Sciences
GA 028JM
UT WOS:000310418600003
PM 22781313
ER
PT J
AU Wecker, M
Gilbert, P
Russell, N
Hural, J
Allen, M
Pensiero, M
Chulay, J
Chiu, YL
Karim, SSA
Burke, DS
AF Wecker, M.
Gilbert, P.
Russell, N.
Hural, J.
Allen, M.
Pensiero, M.
Chulay, J.
Chiu, Ya-Lin
Karim, S. S. Abdool
Burke, D. S.
CA HVTN 040 059 Protocol Team
NIAID HIV Vaccine Trials Network
TI Phase I Safety and Immunogenicity Evaluations of an Alphavirus Replicon
HIV-1 Subtype C gag Vaccine in Healthy HIV-1-Uninfected Adults
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID EQUINE ENCEPHALITIS-VIRUS; MAJOR ENVELOPE PROTEINS;
IMMUNODEFICIENCY-VIRUS; NEUTRALIZING ANTIBODIES; ARTERITIS VIRUS;
EBOLA-VIRUS; PROTECTION; MYRISTOYLATION; PARTICLES; EXPRESSION
AB On the basis of positive preclinical data, we evaluated the safety and immunogenicity of an alphavirus replicon HIV-1 subtype C gag vaccine (AVX101), expressing a nonmyristoylated form of Gag, in two double-blind, randomized, placebo-controlled clinical trials in healthy HIV-1-uninfected adults. Escalating doses of AVX101 or placebo were administered subcutaneously to participants in the United States and Southern Africa. Because of vaccine stability issues, the first trial was halted prior to completion of all dose levels and a second trial was implemented. The second trial was also stopped prematurely due to documentation issues with the contract manufacturer. Safety and immunogenicity were evaluated through assessments of reactogenicity, reports of adverse events, and assessment of replication-competent and Venezuelan equine encephalitis (VEE) viremia. Immunogenicity was measured using the following assays: enzyme-linked immunosorbent assay (ELISA), chromium 51 (Cr-51)-release cytotoxic T lymphocyte (CTL), gamma interferon (IFN-gamma) ELISpot, intracellular cytokine staining (ICS), and lymphoproliferation assay (LPA). Anti-vector antibodies were also measured. AVX101 was well tolerated and exhibited only modest local reactogenicity. There were 5 serious adverse events reported during the trials; none were considered related to the study vaccine. In contrast to the preclinical data, immune responses in humans were limited. Only low levels of binding antibodies and T-cell responses were seen at the highest doses. This trial also highlighted the difficulties in developing a novel vector for HIV.
C1 [Wecker, M.; Gilbert, P.; Russell, N.; Hural, J.; Chiu, Ya-Lin] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Allen, M.; Pensiero, M.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Chulay, J.] AlphaVax Inc, Res Triangle Pk, NC USA.
[Karim, S. S. Abdool] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Ctr AIDS Programme Res S Africa CAPRISA, Durban, South Africa.
[Burke, D. S.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Wecker, M (reprint author), Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
EM mwecker@fhcrc.org
RI Abdool Karim, Salim Safurdeen/N-5947-2013;
OI Abdool Karim, Salim Safurdeen/0000-0002-4986-2133; Allen,
Mary/0000-0001-8163-0714; /0000-0002-5704-8094
FU Division of AIDS, National Institute of Allergy and Infectious Diseases,
National Institutes of Health [5 U01 AI550771-02, N01-AI-30029,
5-U01-AI-47976, 5-U01-AI-47980, 5-U01-AI-47985, 5-U01-AI-48013,
5-U01-AI-48023, 5-U01-AI-46747, U01 AI046703, 3U01 AIO46747]
FX Financial support was provided by the Division of AIDS, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, including grants 5 U01 AI550771-02, N01-AI-30029,
5-U01-AI-47976, 5-U01-AI-47980, 5-U01-AI-46747, 5-U01-AI-47985,
5-U01-AI-48013, 5-U01-AI-48023, 5-U01-AI-46747, U01 AI046703, and 3U01
AIO46747.
NR 20
TC 15
Z9 17
U1 0
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD OCT
PY 2012
VL 19
IS 10
BP 1651
EP 1660
DI 10.1128/CVI.00258-12
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 016TE
UT WOS:000309541600013
PM 22914365
ER
PT J
AU Prensner, JR
Chinnaiyan, AM
Srivastava, S
AF Prensner, John R.
Chinnaiyan, Arul M.
Srivastava, Sudhir
TI Systematic, evidence-based discovery of biomarkers at the NCI
SO CLINICAL & EXPERIMENTAL METASTASIS
LA English
DT Article
DE Biomarker; Prostate cancer; Bioinformatics; Early detection
ID PROSTATE-SPECIFIC ANTIGEN; GENE FUSIONS; CLINICAL UTILITY; CANCER
DETECTION; URINE ASSAY; IMPROVE; SERUM; DESIGN; PCA3; REARRANGEMENTS
AB In the past decade, biomarker discovery has become ubiquitous in cancer research. However, despite this interest in biomarker research, few newly-characterized biomarkers have emerged as clinically-used entities. Here, we review the current state of biomarker research in cancer and identify challenges that stall many biomarker discovery efforts. We outline a model for systematic biomarker discovery, exemplified by recent efforts in prostate cancer, in which bioinformatics plays a central role in identifying promising new candidate biomarkers. Finally, we review the role of the National Cancer Institute's Early Detection Research Network (EDRN) in biomarker studies and the importance of EDRN-led efforts to establish a research standard for more effective biomarker discovery efforts.
C1 [Prensner, John R.; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA.
[Srivastava, Sudhir] NCI, Canc Biomarkers Res Grp, Canc Prevent Div, Rockville, MD 20852 USA.
RP Srivastava, S (reprint author), NCI, Canc Biomarkers Res Grp, Canc Prevent Div, 6130 Execut Blvd,Suite 3142, Rockville, MD 20852 USA.
EM srivasts@mail.nih.gov
FU Early Detection Research Network [U01 CA 11275]; Department of Defense
[PC100171, PC094290]; NIH Prostate Specialized Program of Research
Excellence [P50CA69568]; Doris Duke Charitable Foundation Clinical
Scientist Award; Prostate Cancer Foundation; American Cancer Society;
Howard Hughes Medical Institute
FX We would like to acknowledge the numerous labs, authors, and
publications that we were unable to cite in this review due to space
restrictions. This work was supported by the Early Detection Research
Network Grant U01 CA 11275 (to A. M. C.), the Department of Defense
Grants PC100171 (to A. M. C.) and PC094290 (to J. R. P.), NIH Prostate
Specialized Program of Research Excellence grant P50CA69568 (to A. M.
C.). A. M. C. is supported by the Doris Duke Charitable Foundation
Clinical Scientist Award, the Prostate Cancer Foundation, the American
Cancer Society, and the Howard Hughes Medical Institute. J. R. P. is a
Fellow of the University of Michigan Medical Scientist Training Program.
A. M. C. is a Taubman Scholar of the University of Michigan.
NR 48
TC 11
Z9 11
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0262-0898
EI 1573-7276
J9 CLIN EXP METASTAS
JI Clin. Exp. Metastasis
PD OCT
PY 2012
VL 29
IS 7
BP 645
EP 652
DI 10.1007/s10585-012-9507-z
PG 8
WC Oncology
SC Oncology
GA 028ZO
UT WOS:000310464700003
PM 22868876
ER
PT J
AU Bisono, GM
Simmons, L
Volk, RJ
Meyer, D
Quinn, TC
Rosenthal, SL
AF Bisono, Gabriela M.
Simmons, Lisa
Volk, Robert J.
Meyer, Dodi
Quinn, Thomas C.
Rosenthal, Susan L.
TI Attitudes and Decision Making About Neonatal Male Circumcision in a
Hispanic Population in New York City
SO CLINICAL PEDIATRICS
LA English
DT Article
DE circumcision; Hispanic; sexually transmitted infection; attitudes
ID HUMAN-PAPILLOMAVIRUS INFECTION; HIV PREVENTION; NEWBORN CIRCUMCISION;
FEMALE PARTNERS; MEN; TRIAL; RISK; ACCEPTABILITY; INTERVENTION;
ACQUISITION
AB Objective. To understand attitudes and decision making regarding neonatal male circumcision. Methods. Parents (n = 150) with a son 3 years old were interviewed regarding demographics, communication with a medical provider, attitudes, and process by which the neonatal circumcision decision was made. Results. Thirty-three percent of sons were circumcised. In univariate analyses, choosing male circumcision was associated with parents being interviewed in English, the father being circumcised, positive attitudes, being informed of the advantages of circumcision, making a decision before birth, and being offered a choice. In the final model, parents who came from a culture and family that believed in circumcision and who believed that it was not too risky were more likely to circumcise their sons. Conclusions. Decisions regarding circumcision appear to be influenced by values, risk perceptions, and medical providers. Future research should address ways of ensuring that families have the opportunity to make an informed decision.
C1 [Rosenthal, Susan L.] Columbia Univ, Med Ctr, Dept Pediat, New York, NY 10032 USA.
[Bisono, Gabriela M.; Simmons, Lisa; Meyer, Dodi; Rosenthal, Susan L.] NewYork Presbyterian Morgan Stanley Childrens Hos, New York, NY USA.
[Volk, Robert J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Quinn, Thomas C.] NIH, Bethesda, MD 20892 USA.
RP Rosenthal, SL (reprint author), Columbia Univ, Med Ctr, Dept Pediat, 630 W 168th St,Room 9-401B, New York, NY 10032 USA.
EM slr2154@columbia.edu
OI Volk, Robert/0000-0001-8811-5854
FU Intramural NIH HHS [ZIA AI000361-28]; NICHD NIH HHS [R24 HD042854]
NR 33
TC 7
Z9 7
U1 3
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0009-9228
J9 CLIN PEDIATR
JI Clin. Pediatr.
PD OCT
PY 2012
VL 51
IS 10
BP 956
EP 963
DI 10.1177/0009922812441662
PG 8
WC Pediatrics
SC Pediatrics
GA 027TZ
UT WOS:000310378000009
PM 22511191
ER
PT J
AU Kramer-Marek, G
Longmire, MR
Choyke, PL
Kobayashi, H
AF Kramer-Marek, G.
Longmire, M. R.
Choyke, P. L.
Kobayashi, H.
TI Recent Advances in Optical Cancer Imaging of EGF Receptors
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Review
DE Optical imaging; cancer; epidermal growth factor receptor; HER2;
positron emission tomography; fluorescence; multiple color imaging;
monoclonal antibody; affibody; activatable imaging probe; near infrared;
molecular imaging; radionuclide imaging
ID GROWTH-FACTOR-RECEPTOR; METASTATIC BREAST-CANCER; LABELED
MONOCLONAL-ANTIBODIES; SQUAMOUS-CELL CARCINOMA; IN-VIVO; AFFIBODY
MOLECULES; MALIGNANT-TUMORS; OVER-EXPRESSION; OVARIAN-CANCER; THERAPY
AB Epidermal growth factor (EGF) receptors are commonly expressed on the cell membrane of cancer cells and activity of these receptors results in accelerated cell growth and carcinogenesis. A variety of targeted molecules have been developed to block ligand binding and/or inhibit the function of these receptor tyrosine kinases, and several have proven therapeutic benefits. Along with the advent of new therapeutic agents comes a need for non-invasive tools to diagnose, characterize, and monitor tumor responsiveness to therapy. Imaging EGF receptors with radionuclides has been performed for decades. However, recently this area has advanced considerably with the development of EGF receptor-targeted optical imaging probes. Herein, we review recent advances in molecular imaging of the EGF receptor family, focusing specifically on optical imaging. Such agents provide the opportunity for earlier diagnosis, improved tumor characterization, and the ability to measure and monitor tumor responsiveness to anti-EGF receptor treatment strategies.
C1 [Longmire, M. R.; Choyke, P. L.; Kobayashi, H.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Kramer-Marek, G.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, NIH, Bldg 10,Room B3B69,MSC 1088, Bethesda, MD 20892 USA.
EM Kobayash@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Cancer Institute; Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, and Center for
Cancer Research.
NR 65
TC 3
Z9 4
U1 3
U2 33
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 0929-8673
J9 CURR MED CHEM
JI Curr. Med. Chem.
PD OCT
PY 2012
VL 19
IS 28
BP 4759
EP 4766
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 019NE
UT WOS:000309745800005
PM 22873662
ER
PT J
AU Blanchet, EM
Millo, C
Martucci, V
Chen, C
Bluemke, DA
Pacak, K
AF Blanchet, E. M.
Millo, C.
Martucci, V.
Chen, C.
Bluemke, D. A.
Pacak, K.
TI Simultaneous whole-body PET/MRI for paraganglioma: initial NIH results.
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Meeting Abstract
CT 25th Annual Congress of the European-Association-of-Nuclear-Medicine
(EANM)
CY OCT 27-31, 2012
CL Milan, ITALY
SP European Assoc Nucl Med (EANM)
C1 [Blanchet, E. M.; Martucci, V.; Pacak, K.] NICHD, NIH, Bethesda, MD USA.
[Millo, C.; Chen, C.] NIH, Dept Nucl Med, Bethesda, MD USA.
[Bluemke, D. A.] NIH, Dept Radiol, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD OCT
PY 2012
VL 39
SU 2
MA OP118
BP S174
EP S175
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 019GW
UT WOS:000309726600068
ER
PT J
AU Zheng, K
Zhu, Z
Shi, J
Du, Y
Xing, H
Jia, B
Sun, Y
Cai, J
Luo, Y
Ma, Y
Dang, Y
Ba, J
Chen, X
Li, F
AF Zheng, K.
Zhu, Z.
Shi, J.
Du, Y.
Xing, H.
Jia, B.
Sun, Y.
Cai, J.
Luo, Y.
Ma, Y.
Dang, Y.
Ba, J.
Chen, X.
Li, F.
TI Ga-68-PRGD2 PET/CT for integrin receptor imaging of lung cancer: a
translational study
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Meeting Abstract
CT 25th Annual Congress of the European-Association-of-Nuclear-Medicine
(EANM)
CY OCT 27-31, 2012
CL Milan, ITALY
SP European Assoc Nucl Med (EANM)
C1 [Zheng, K.; Zhu, Z.; Du, Y.; Xing, H.; Sun, Y.; Cai, J.; Luo, Y.; Ma, Y.; Dang, Y.; Ba, J.; Li, F.] Beijing Union Med Coll Hosp, Beijing, Peoples R China.
[Shi, J.; Jia, B.] Peiking Univ, Med Isotopes Ctr, Beijing, Peoples R China.
[Chen, X.] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD OCT
PY 2012
VL 39
SU 2
MA OP535
BP S262
EP S262
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 019GW
UT WOS:000309726600389
ER
PT J
AU Kristinsson, SY
Pfeiffer, RM
Bjorkholm, M
Schulman, S
Landgren, O
AF Kristinsson, Sigurdur Y.
Pfeiffer, Ruth M.
Bjorkholm, Magnus
Schulman, Sam
Landgren, Ola
TI Thrombosis is associated with inferior survival in multiple myeloma
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Article
DE multiple myeloma; venous thromboembolism; survival; arterial thrombosis;
thalidomide; lenalidomide; aspirin; low-molecular weight heparin;
warfarin; prophylaxis
ID DEEP-VEIN THROMBOSIS; VENOUS THROMBOSIS; UNDETERMINED SIGNIFICANCE;
MONOCLONAL GAMMOPATHY; PLUS DEXAMETHASONE; POPULATION; THALIDOMIDE;
LENALIDOMIDE; THERAPY; THROMBOEMBOLISM
AB Patients with multiple myeloma are at an increased risk of venous thromboembolism and arterial thrombosis. We assessed the impact of venous and arterial thrombosis on survival in a population-based study of 9,399 multiple myeloma patients diagnosed in Sweden from 1987 to 2005. We found multiple myeloma patients with venous thromboembolism to have a higher mortality at 1-, 5-, and 10-years of follow up compared with those without, with hazard ratios of 2.9 (95% confidence interval (CI) 2.4-3.5), 1.6 (95% CI: 1.5-1.8), and 1.6 (95% CI: 1.4-1.7), respectively. There was an increase in risk of death among multiple myeloma patients with arterial thrombosis, with hazard ratios of 3.4 (95% CI: 3.0-3.8), 2.2 (95% CI: 2.0-2.3), and 2.1 (95% CI: 1.9-2.1), respectively. In landmark analyses at six months, early arterial but not venous thromboembolism was associated with a higher risk of death. Thus, in contrast to prior smaller studies, we found the development of thrombosis to be associated with significantly poorer survival. The prevention of thrombosis in multiple myeloma is an important goal in the management of these patients.
C1 [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus; Schulman, Sam; Landgren, Ola] Karolinska Univ, Hosp Solna, Div Hematol, Dept Med, SE-17176 Stockholm, Sweden.
[Kristinsson, Sigurdur Y.; Bjorkholm, Magnus; Schulman, Sam; Landgren, Ola] Karolinska Inst, Stockholm, Sweden.
[Pfeiffer, Ruth M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Schulman, Sam] McMaster Univ, Dept Med, Hamilton, ON, Canada.
[Landgren, Ola] NCI, Multiple Myeloma Sect, Metab Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Kristinsson, SY (reprint author), Karolinska Univ, Hosp Solna, Div Hematol, Dept Med, SE-17176 Stockholm, Sweden.
EM sigurdur.kristinsson@karolinska.se
RI Kristinsson, Sigurdur /M-2910-2015;
OI Kristinsson, Sigurdur /0000-0002-4964-7476; Schulman,
Sam/0000-0002-8512-9043
FU regional agreement on medical training and clinical research (ALF)
between Stockholm County Council; regional agreement on medical training
and clinical research (ALF) between Karolinska Institutet; Cancer
Society in Stockholm; Intramural Research Program of the NIH, NCI
FX this research was supported by grants from the regional agreement on
medical training and clinical research (ALF) between Stockholm County
Council and Karolinska Institutet, the Cancer Society in Stockholm, and
the Intramural Research Program of the NIH, NCI. The authors thank the
Medical Product Agency in Sweden.
NR 24
TC 16
Z9 16
U1 0
U2 0
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD OCT
PY 2012
VL 97
IS 10
BP 1603
EP 1607
DI 10.3324/haematol.2012.064444
PG 5
WC Hematology
SC Hematology
GA 025QZ
UT WOS:000310208400026
PM 22511493
ER
PT J
AU Ziegler, RG
AF Ziegler, Regina G.
TI Following Up Folate and Its Function in Colorectal Carcinogenesis
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID CANCER-RISK; FOLIC-ACID; GENETIC-VARIANTS; UNITED-STATES; VITAMIN-B-6;
PREVENTION; TRIAL
C1 NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Ziegler, RG (reprint author), NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH, Execut Plaza S 8098, Bethesda, MD 20892 USA.
EM regina.ziegler@nih.gov
FU Intramural NIH HHS
NR 19
TC 3
Z9 3
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD OCT
PY 2012
VL 104
IS 20
BP 1525
EP 1527
DI 10.1093/jnci/djs412
PG 3
WC Oncology
SC Oncology
GA 025UN
UT WOS:000310220700001
PM 23066165
ER
PT J
AU Shim, JS
Rao, R
Beebe, K
Neckers, L
Han, I
Nahta, R
Liu, JO
AF Shim, Joong Sup
Rao, Rajini
Beebe, Kristin
Neckers, Len
Han, Inkyu
Nahta, Rita
Liu, Jun O.
TI Selective Inhibition of HER2-Positive Breast Cancer Cells by the HIV
Protease Inhibitor Nelfinavir
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID RECEPTOR TYROSINE KINASES; C-TERMINAL DOMAIN; PANCREATIC-CANCER; HSP90
INHIBITOR; LUNG-CANCER; IN-VIVO; GROWTH; TRASTUZUMAB; RADIATION; COMPLEX
AB Human epidermal growth factor receptor 2 (HER2)positive breast cancer is highly aggressive and has higher risk of recurrence than HER2-negative cancer. With few treatment options available, new drug targets specific for HER2-positive breast cancer are needed.
We conducted a pharmacological profiling of seven genotypically distinct breast cancer cell lines using a subset of inhibitors of breast cancer cells from a screen of the Johns Hopkins Drug Library. To identify molecular targets of nelfinavir, identified in the screen as a selective inhibitor of HER2-positive cells, we conducted a genome-wide screen of a haploinsufficiency yeast mutant collection. We evaluated antitumor activity of nelfinavir with xenografts in athymic nude mouse models (n 46 per group) of human breast cancer and repeated mixed-effects regression analysis. All statistical tests were two-sided.
Pharmacological profiling showed that nelfinavir, an anti-HIV drug, selectively inhibited the growth of HER2-positive breast cancer cells in vitro. A genome-wide screening of haploinsufficiency yeast mutants revealed that nelfinavir inhibited heat shock protein 90 (HSP90) function. Further characterization using proteolytic footprinting experiments indicated that nelfinavir inhibited HSP90 in breast cancer cells through a novel mechanism. In vivo, nelfinavir selectively inhibited the growth of HER2-positive breast cancer cells (tumor volume index of HCC1954 cells on day 29, vehicle vs nelfinavir, mean 14.42 vs 5.16, difference 9.25, 95% confidence interval [CI] 5.93 to 12.56, P < .001; tumor volume index of BT474 cells on day 26, vehicle vs nelfinavir, mean 2.21 vs 0.90, difference 1.31, 95% CI 0.83 to 1.78, P < .001). Moreover, nelfinavir inhibited the growth of trastuzumab- and/or lapatinib-resistant, HER2-positive breast cancer cells in vitro at clinically achievable concentrations.
Nelfinavir was found to be a new class of HSP90 inhibitor and can be brought to HER2-breast cancer treatment trials with the same dosage regimen as that used among HIV patients.
C1 [Shim, Joong Sup; Liu, Jun O.] Johns Hopkins Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA.
[Liu, Jun O.] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[Rao, Rajini] Johns Hopkins Sch Med, Dept Physiol, Baltimore, MD 21205 USA.
[Han, Inkyu] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA.
[Beebe, Kristin; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Nahta, Rita] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA.
RP Liu, JO (reprint author), Johns Hopkins Sch Med, Dept Pharmacol & Mol Sci, 725 N Wolfe St,Hunterian Bldg 516, Baltimore, MD 21205 USA.
EM joliu@jhu.edu
RI Shim, Joong Sup/G-8383-2011; Shim, Joong Sup/O-2848-2016
OI Shim, Joong Sup/0000-0003-0167-7307; Shim, Joong Sup/0000-0003-0167-7307
FU National Cancer Institute [CA122814]; Flight Attendant Medical Research
Institute (FAMRI); Commonwealth Foundation; National Institutes of
Health (NIH) [R01AI065983]; National Center for Research Resources, a
component of the NIH; NIH Roadmap for Medical Research [UL1 RR 025005]
FX National Cancer Institute (CA122814); Flight Attendant Medical Research
Institute (FAMRI); the Commonwealth Foundation (to JOL); the National
Institutes of Health (NIH) (R01AI065983 to RR); National Center for
Research Resources, a component of the NIH and NIH Roadmap for Medical
Research (UL1 RR 025005 to Johns Hopkins School of Medicine).
NR 46
TC 31
Z9 31
U1 1
U2 15
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD OCT
PY 2012
VL 104
IS 20
BP 1576
EP 1590
DI 10.1093/jnci/djs396
PG 15
WC Oncology
SC Oncology
GA 025UN
UT WOS:000310220700009
PM 23042933
ER
PT J
AU Shiels, MS
Pfeiffer, RM
Chaturvedi, AK
Kreimer, AR
Engels, EA
AF Shiels, Meredith S.
Pfeiffer, Ruth M.
Chaturvedi, Anil K.
Kreimer, Aimee R.
Engels, Eric A.
TI Impact of the HIV Epidemic on the Incidence Rates of Anal Cancer in the
United States
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID SQUAMOUS INTRAEPITHELIAL LESIONS; HUMAN-PAPILLOMAVIRUS INFECTION;
COST-EFFECTIVENESS; HPV INFECTION; POSITIVE MEN; RISK-FACTORS; WOMEN;
AIDS; METAANALYSIS; PREVALENCE
AB The risk of anal cancer is substantially increased in HIV-infected individuals. Thus, the HIV epidemic may have influenced the increasing anal cancer trends in the United States. We estimated the impact of the HIV epidemic on trends in anal cancer incidence in the United States during 19802005.
Data on anal cancer cases with and without AIDS were obtained from the HIV/AIDS Cancer Match Study. The number of HIV-infected anal cancer cases without AIDS was estimated from the number of anal cancers occurring before diagnosis of AIDS. The proportion of anal cancer cases with HIV infection in the general population was calculated. We estimated temporal trends in the incidence rates of anal cancer in the general population overall and after exclusion of HIV-infected cancer cases by calculating annual percent changes and 95% confidence intervals (CIs) using a Joinpoint log-linear model. All incidence rates were standardized to the 2000 US population by age, sex, and race.
During 19802005, of the 20 533 estimated anal cancer cases, 1665 (8.1%) were HIV-infected. During 20012005, the proportion of anal cancer cases with HIV infection was the highest1.2% (95% CI 0.93 to 1.4%) among females and 28.4% (95% CI 26.6 to 29.4%) among males. During 19802005, HIV infection did not have an impact on the trends in anal cancer among females (incidence rates increased by 3.3% [95% CI 3.0 to 3.7%] annually overall, and by 3.3% [95% CI 2.9 to 3.6%] annually without HIV-infected anal cancer cases) but had a strong impact on the trends in anal cancer among males (incidence rates increased by 3.4% [95% CI 2.9 to 3.9%] annually overall, and by 1.7% [95% CI 1.2 to 2.3%] annually without HIV infection).
During 19802005, the increasing anal cancer incidence rates in the United States were strongly influenced by the HIV epidemic in males but were independent of HIV infection in females.
C1 [Shiels, Meredith S.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
RP Shiels, MS (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7059, Rockville, MD 20892 USA.
EM shielsms@mail.nih.gov
RI Kreimer, Aimee/H-1687-2015; Chaturvedi, Anil/J-2024-2015
OI Chaturvedi, Anil/0000-0003-2696-8899
FU National Cancer Institute
FX This study was funded by the Intramural Research Program of the National
Cancer Institute.
NR 47
TC 31
Z9 31
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD OCT
PY 2012
VL 104
IS 20
BP 1591
EP 1598
DI 10.1093/jnci/djs371
PG 8
WC Oncology
SC Oncology
GA 025UN
UT WOS:000310220700010
PM 23042932
ER
PT J
AU Lin, ZN
Lin, YC
Zhang, XM
Kadlubar, S
Tuo, JS
Green, B
Deng, HL
Ning, BT
AF Lin, Zhong-Ning
Lin, Yu-Chun
Zhang, Xuemei
Kadlubar, Susan
Tuo, Jingsheng
Green, Bridgett
Deng, Helen
Ning, Baitang
TI Differential promoter activities of functional haplotypes in the 5
'-flanking region of human Sulfotransferase 1A1
SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
LA English
DT Article
DE SULT1A1; Polymorphism; Haplotypes; Functional Genome; Promoter
ID HUMAN PHENOL SULFOTRANSFERASE; SULT1A1 GENE; BIOCHEMICAL-PROPERTIES;
ENZYMATIC-ACTIVITY; EXPRESSION; POLYMORPHISMS; ASSOCIATION; ENZYMES;
BRAIN; CELLS
AB Previously, we reported five common single nucleotide polymorphisms (SNPs), -624G>C, -396G>A, -358A>C, -341C>G, and -294T>C, and six common haplotypes (CGACT, GAACT, GGAGC, GGACC, CAACT, and GAACC) in the 5'-flanking region of the SULT1A1 gene that were associated with altered enzymatic activity. In the present study, we performed in vitro assays to determine the functional impact of these genetic variations on the promoter activity. Dual luciferase reporter assays revealed that these SNPs are located in a negative regulatory fragment of the SULT1A1 gene. Further experiments demonstrated that these SNPs and haplotypes affected promoter activities of SULT1A1. Electrophoretic mobility shift assays showed distinctive binding patterns for the SNPs -396G>A and -294T>C, due to differential binding affinities of the G/A alleles and the T/C alleles to nuclear proteins extracted from the liver carcinoma cell lines, HepG2 and Huh7. (c) 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:422428, 2012; View this article online at wileyonlinelibrary.com. DOI 10:1002/jbt.21437
C1 [Lin, Zhong-Ning; Green, Bridgett; Ning, Baitang] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Lin, Zhong-Ning; Lin, Yu-Chun] Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou 510275, Guangdong, Peoples R China.
[Zhang, Xuemei; Kadlubar, Susan] Univ Arkansas Med Sci, Colege Med, Div Med Genet, Little Rock, AR 72205 USA.
[Tuo, Jingsheng] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Deng, Helen] Arkansas Dept Hlth, Little Rock, AR 72205 USA.
RP Ning, BT (reprint author), US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
EM baitang.ning@fda.hhs.gov
OI Tuo, Jingsheng/0000-0002-1372-7810
FU U.S. Food and Drug Administration [E0715801]
FX Contract Grant Sponsor: U.S. Food and Drug Administration.; Contract
Grant Number: E0715801.
NR 18
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1095-6670
J9 J BIOCHEM MOL TOXIC
JI J. Biochem. Mol. Toxicol.
PD OCT
PY 2012
VL 26
IS 10
BP 422
EP 428
DI 10.1002/jbt.21437
PG 7
WC Biochemistry & Molecular Biology; Toxicology
SC Biochemistry & Molecular Biology; Toxicology
GA 027BQ
UT WOS:000310327200006
PM 23080433
ER
PT J
AU Kim, H
Stotts, NA
Froelicher, ES
Engler, MM
Porter, C
Kwak, H
AF Kim, Hyunjung
Stotts, Nancy A.
Froelicher, Erika S.
Engler, Marguerite M.
Porter, Carol
Kwak, Heejeong
TI Adequacy of early enteral nutrition in adult patients in the intensive
care unit
SO JOURNAL OF CLINICAL NURSING
LA English
DT Article
DE critical care; enteral nutrition; nursing practice; overfeeding;
underfeeding
ID CRITICALLY-ILL PATIENTS; RECEIVING MECHANICAL VENTILATION; RESTING
ENERGY-EXPENDITURE; ICU PATIENTS; CALORIC-INTAKE; DELIVERY; SUPPORT;
GUIDELINES; REQUIREMENTS; OUTCOMES
AB Aims and objectives. To evaluate the adequacy of energy and protein intake of patients in a Korean intensive care unit in the first four days after initiation of enteral feeding and to investigate the factors that had impact on adequate intake. Background. Underfeeding is a common problem for patients hospitalised in the intensive care unit and is associated with severe negative consequences, including increased morbidity and mortality. Design. A prospective, cohort study was conducted in a medical intensive care unit of a university hospital in Korea. Methods. A total of 34 adult patients who had a primary medical diagnosis and who had received bolus enteral nutrition for the first four days after initiation of enteral nutrition were enrolled in this study. The data on prescription and intake of energy and protein, feeding method and feeding interruption were recorded during the first four days after enteral feeding initiation. Underfeeding was defined as the intake <90% of required energy and protein. Results. Most patients (62%) received insufficient energy, although some (29%) received adequate energy. More than half of patients (56%) had insufficient protein intake during the first four days after enteral feeding was initiated. Logistic regression analysis showed that the factors associated with underfeeding of energy were early initiation of enteral nutrition, under-prescription of energy and prolonged interruption of prescribed enteral nutrition. Conclusion. Underfeeding is frequent in Korean critically ill patients owing to early initiation, under-prescription and prolonged interruption of enteral feeding. Relevance to clinical practice. Interventions need to be developed and tested that address early initiation, under-prescription and prolonged interruption of enteral nutrition. Findings from this study are important as they form the foundation for the development of evidence-based care that is badly needed to eliminate underfeeding in this large vulnerable Korean intensive care unit population.
C1 [Stotts, Nancy A.; Froelicher, Erika S.] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA.
[Kim, Hyunjung] Hallym Univ, Div Nursing, Chunchon, South Korea.
[Engler, Marguerite M.] NINR, NIH, Bethesda, MD 20892 USA.
[Porter, Carol] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
[Kwak, Heejeong] Konyang Univ Hosp, Taejon, South Korea.
RP Stotts, NA (reprint author), Univ Calif San Francisco, Dept Physiol Nursing, 2 Koret Way,Box 0610, San Francisco, CA 94143 USA.
EM nancy.stotts@nursing.ucsf.edu
FU Hallym University [HRF-201203-012]; Global Korean Nursing Foundation
FX This study was supported by Hallym University Research Fund, 2012
(HRF-201203-012) and Global Korean Nursing Foundation. The authors are
grateful to the nurses from the medical ICU of the Konyang University
Hospital for their support. We also thank Dr. Steven Paul, a
statistician at the UCSF School of Nursing for his statistical
consultation.
NR 45
TC 4
Z9 4
U1 1
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0962-1067
J9 J CLIN NURS
JI J. Clin. Nurs.
PD OCT
PY 2012
VL 21
IS 19-20
BP 2860
EP 2869
DI 10.1111/j.1365-2702.2012.04218.x
PG 10
WC Nursing
SC Nursing
GA 008CV
UT WOS:000308935800019
PM 22845617
ER
PT J
AU Waldman, M
Austin, HA
AF Waldman, Meryl
Austin, Howard A., III
TI Treatment of Idiopathic Membranous Nephropathy
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Review
ID RANDOMIZED CONTROLLED-TRIAL; COMPARING METHYLPREDNISOLONE PLUS;
PROLIFERATIVE LUPUS NEPHRITIS; CONVERTING ENZYME-INHIBITION; LONG-TERM
TREATMENT; MYCOPHENOLATE-MOFETIL; NEPHROTIC SYNDROME;
WEGENERS-GRANULOMATOSIS; UNTREATED PATIENTS; HEYMANN NEPHRITIS
AB Exciting progress recently has been made in our understanding of idiopathic membranous nephropathy, as well as treatment of this disease. Here, we review important advances regarding the pathogenesis of membranous nephropathy. We will also review the current approach to treatment and its limitations and will highlight new therapies that are currently being explored for this disease including Rituximab, mycophenolate mofetil, and adrenocorticotropic hormone, with an emphasis on results of the most recent clinical trials.
C1 [Waldman, Meryl; Austin, Howard A., III] NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA.
RP Waldman, M (reprint author), NIDDKD, Kidney Dis Sect, NIH, 10 Ctr Dr,CRC 5-5750, Bethesda, MD 20892 USA.
EM waldmanm@niddk.nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health
FX This research was supported in part by the Intramural Research Program
of the National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health.
NR 89
TC 26
Z9 32
U1 0
U2 20
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD OCT
PY 2012
VL 23
IS 10
BP 1617
EP 1630
DI 10.1681/ASN.2012010058
PG 14
WC Urology & Nephrology
SC Urology & Nephrology
GA 019JO
UT WOS:000309736000007
PM 22859855
ER
PT J
AU Wei, LY
Malhotra, SV
AF Wei, Linyi
Malhotra, Sanjay V.
TI Synthesis and cytotoxicity evaluation of novel pyrido[3,4-d]pyrimidine
derivatives as potential anticancer agents
SO MEDCHEMCOMM
LA English
DT Article
ID ANTIMALARIAL PROPERTIES; KINASE INHIBITORS; LCK KINASE; CANCER;
DISCOVERY; CELLS
AB A new series of 4-substituted 2-amino pyrido[3,4-d]pyrimidine derivatives has been designed and synthesized as potential anticancer agents. These compounds were prepared from a common intermediate, 4-chloro-8-methoxy pyrido[3,4-d]pyrimidin-2-amine, followed by palladium catalyzed cross-coupling reactions or nucleophilic aromatic substitutions at the C-4 position. Evaluation of the representative analogs using the US National Cancer Institute's 60 human cancer cell line (NCI 60) panel identified some of these compounds as exhibiting highly selective activities against breast cancer and renal cancer cell lines. A structure-activity relationship (SAR) study was explored to facilitate further development of this new class of compounds.
C1 [Wei, Linyi; Malhotra, Sanjay V.] SAIC Frederick Inc, Lab Synthet Chem, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Malhotra, SV (reprint author), SAIC Frederick Inc, Lab Synthet Chem, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM malhotrasa@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX The authors would like to thank the NCI Developmental Therapeutics
Program for the 60 cell line screen of compounds described in this
paper. This project has been funded in whole or in part with federal
funds from the National Cancer Institute, National Institutes of Health,
under contract no. HHSN261200800001E. The content of this publication
does not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government.
NR 25
TC 9
Z9 9
U1 1
U2 7
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2040-2503
J9 MEDCHEMCOMM
JI MedChemComm
PD OCT
PY 2012
VL 3
IS 10
BP 1250
EP 1257
DI 10.1039/c2md20097j
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Medicinal
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 028LK
UT WOS:000310423600007
PM 25429348
ER
PT J
AU Wu, C
Kraft, P
Zhai, K
Chang, J
Wang, ZM
Li, Y
Hu, ZB
He, ZH
Jia, WH
Abnet, CC
Liang, LM
Hu, N
Miao, XP
Zhou, YF
Liu, ZH
Zhan, QM
Liu, Y
Qiao, Y
Zhou, YL
Jin, GF
Guo, CH
Lu, CD
Yang, HJ
Fu, JH
Yu, DK
Freedman, ND
Ding, T
Tan, W
Goldstein, AM
Wu, TC
Shen, HB
Ke, Y
Zeng, YX
Chanock, SJ
Taylor, PR
Lin, DX
AF Wu, Chen
Kraft, Peter
Zhai, Kan
Chang, Jiang
Wang, Zhaoming
Li, Yun
Hu, Zhibin
He, Zhonghu
Jia, Weihua
Abnet, Christian C.
Liang, Liming
Hu, Nan
Miao, Xiaoping
Zhou, Yifeng
Liu, Zhihua
Zhan, Qimin
Liu, Yu
Qiao, Yan
Zhou, Yuling
Jin, Guangfu
Guo, Chuanhai
Lu, Changdong
Yang, Haijun
Fu, Jianhua
Yu, Dianke
Freedman, Neal D.
Ding, Ti
Tan, Wen
Goldstein, Alisa M.
Wu, Tangchun
Shen, Hongbing
Ke, Yang
Zeng, Yixin
Chanock, Stephen J.
Taylor, Philip R.
Lin, Dongxin
TI Genome-wide association analyses of esophageal squamous cell carcinoma
in Chinese identify multiple susceptibility loci and gene-environment
interactions
SO NATURE GENETICS
LA English
DT Article
ID RISK-FACTORS; HEPATOCELLULAR-CARCINOMA; ALCOHOL-DRINKING; GASTRIC
CANCERS; MESSENGER-RNA; BETA-CATENIN; COLON-CANCER; MOUSE MODEL;
EXPRESSION; GROWTH
AB We conducted a genome-wide association study (GWAS) and a genome-wide gene-environment interaction analysis of esophageal squamous-cell carcinoma (ESCC) in 2,031 affected individuals (cases) and 2,044 controls with independent validation in 8,092 cases and 8,620 controls. We identified nine new ESCC susceptibility loci, of which seven, at chromosomes 4q23, 16q12.1, 17q21, 22q12, 3q27, 17p13 and 18p11, had a significant marginal effect (P = 1.78 x 10(-39) to P = 2.49 x 10(-11)) and two of which, at 2q22 and 13q33, had a significant association only in the gene-alcohol drinking interaction (gene-environment interaction P (P-G x E) = 4.39 x 10(-11) and P-G x E = 4.80 x 10(-8), respectively). Variants at the 4q23 locus, which includes the ADH cluster, each had a significant interaction with alcohol drinking in their association with ESCC risk (P-G x E = 2.54 x 10(-7) to P-G x E = 3.23 x 10(-2)). We confirmed the known association of the ALDH2 locus on 12q24 to ESCC, and a joint analysis showed that drinkers with both of the ADH1B and ALDH2 risk alleles had a fourfold increased risk for ESCC compared to drinkers without these risk alleles. Our results underscore the direct genetic contribution to ESCC risk, as well as the genetic contribution to ESCC through interaction with alcohol consumption.
C1 [Wu, Chen; Zhai, Kan; Chang, Jiang; Liu, Zhihua; Zhan, Qimin; Liu, Yu; Qiao, Yan; Zhou, Yuling; Lu, Changdong; Yu, Dianke; Tan, Wen; Lin, Dongxin] Chinese Acad Med Sci, State Key Lab Mol Oncol, Canc Inst & Hosp, Beijing 100730, Peoples R China.
[Wu, Chen; Zhai, Kan; Chang, Jiang; Liu, Zhihua; Zhan, Qimin; Liu, Yu; Qiao, Yan; Zhou, Yuling; Yu, Dianke; Tan, Wen; Lin, Dongxin] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Wu, Chen; Kraft, Peter; Liang, Liming] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Wang, Zhaoming; Abnet, Christian C.; Hu, Nan; Freedman, Neal D.; Goldstein, Alisa M.; Chanock, Stephen J.; Taylor, Philip R.] NCI, Div Canc Epidemiol & Genet, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Wang, Zhaoming; Chanock, Stephen J.] NCI, Core Genotyping Facil, SAIC Frederick, Frederick, MD 21701 USA.
[Li, Yun] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Hu, Zhibin; Jin, Guangfu; Shen, Hongbing] Nanjing Med Univ, Dept Epidemiol & Biostat, Ctr Canc, Nanjing, Jiangsu, Peoples R China.
[He, Zhonghu; Guo, Chuanhai; Ke, Yang] Peking Univ, Key Lab Carcinogenesis & Translat Res, Minist Educ, Sch Oncol,Beijing Canc Hosp & Inst, Beijing 100871, Peoples R China.
[Jia, Weihua; Fu, Jianhua; Zeng, Yixin] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol So China, Guangzhou 510275, Guangdong, Peoples R China.
[Miao, Xiaoping; Wu, Tangchun] Huazhong Univ Sci & Technol, Sch Publ Hlth, Key Lab Environm & Hlth, Minist Educ, Wuhan 430074, Hubei, Peoples R China.
[Zhou, Yifeng] Soochow Univ, Lab Canc Mol Genet, Coll Med, Suzhou, Jiangsu, Peoples R China.
[Lu, Changdong; Yang, Haijun] Anyang Canc Hosp, Anyang, Henan, Peoples R China.
[Ding, Ti] Shanxi Canc Hosp, Taiyuan, Shanxi, Peoples R China.
RP Lin, DX (reprint author), Chinese Acad Med Sci, State Key Lab Mol Oncol, Canc Inst & Hosp, Beijing 100730, Peoples R China.
EM lindx72@cicams.ac.cn
RI miao, xiaoping/C-4336-2011; Abnet, Christian/C-4111-2015; Freedman,
Neal/B-9741-2015
OI miao, xiaoping/0000-0002-6818-9722; Abnet,
Christian/0000-0002-3008-7843; Freedman, Neal/0000-0003-0074-1098
FU National High-Tech Research and Development Program of China
[2009AA022706]; National Basic Research Program of China [2011CB504303];
National Natural Science Foundation of China [30721001]; Intramural
Research Program of the US National Institutes of Health, NCI; Division
of Cancer Epidemiology and Genetics
FX This work was funded by the National High-Tech Research and Development
Program of China (2009AA022706 to D.L.), the National Basic Research
Program of China (2011CB504303 to D.L. and W.T.), the National Natural
Science Foundation of China (30721001 to D.L., Q.Z. and Z.L.) and the
Intramural Research Program of the US National Institutes of Health, NCI
and the Division of Cancer Epidemiology and Genetics.
NR 46
TC 101
Z9 108
U1 3
U2 38
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD OCT
PY 2012
VL 44
IS 10
BP 1090
EP +
DI 10.1038/ng.2411
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 016WJ
UT WOS:000309550200007
PM 22960999
ER
PT J
AU Su, Z
Gay, LJ
Strange, A
Palles, C
Band, G
Whiteman, DC
Lescai, F
Langford, C
Nanji, M
Edkins, S
van der Winkel, A
Levine, D
Sasieni, P
Bellenguez, C
Howarth, K
Freeman, C
Trudgill, N
Tucker, AT
Pirinen, M
Peppelenbosch, MP
van der Laan, LJW
Kuipers, EJ
Drenth, JPH
Peters, WH
Reynolds, JV
Kelleher, DP
McManus, R
Grabsch, H
Prenen, H
Bisschops, R
Krishnadath, K
Siersema, PD
van Baal, JWPM
Middleton, M
Petty, R
Gillies, R
Burch, N
Bhandari, P
Paterson, S
Edwards, C
Penman, I
Vaidya, K
Ang, Y
Murray, I
Patel, P
Ye, WM
Mullins, P
Wu, AH
Bird, NC
Dallal, H
Shaheen, NJ
Murray, LJ
Koss, K
Bernstein, L
Romero, Y
Hardie, LJ
Zhang, R
Winter, H
Corley, DA
Panter, S
Risch, HA
Reid, BJ
Sargeant, I
Gammon, MD
Smart, H
Dhar, A
McMurtry, H
Ali, H
Liu, G
Casson, AG
Chow, WH
Rutter, M
Tawil, A
Morris, D
Nwokolo, C
Isaacs, P
Rodgers, C
Ragunath, K
MacDonald, C
Haigh, C
Monk, D
Davies, G
Wajed, S
Johnston, D
Gibbons, M
Cullen, S
Church, N
Langley, R
Griffin, M
Alderson, D
Deloukas, P
Hunt, SE
Gray, E
Dronov, S
Potter, SC
Tashakkori-Ghanbaria, A
Anderson, M
Brooks, C
Blackwell, JM
Bramon, E
Brown, MA
Casas, JP
Corvin, A
Duncanson, A
Markus, HS
Mathew, CG
Palmer, CNA
Plomin, R
Rautanen, A
Sawcer, SJ
Trembath, RC
Viswanathan, AC
Wood, N
Trynka, G
Wijmenga, C
Cazier, JB
Atherfold, P
Nicholson, AM
Gellatly, NL
Glancy, D
Cooper, SC
Cunningham, D
Lind, T
Hapeshi, J
Ferry, D
Rathbone, B
Brown, J
Love, S
Attwood, S
MacGregor, S
Watson, P
Sanders, S
Ek, W
Harrison, RF
Moayyedi, P
de Caestecker, J
Barr, H
Stupka, E
Vaughan, TL
Peltonen, L
Spencer, CCA
Tomlinson, I
Donnelly, P
Jankowski, JAZ
AF Su, Zhan
Gay, Laura J.
Strange, Amy
Palles, Claire
Band, Gavin
Whiteman, David C.
Lescai, Francesco
Langford, Cordelia
Nanji, Manoj
Edkins, Sarah
van der Winkel, Anouk
Levine, David
Sasieni, Peter
Bellenguez, Celine
Howarth, Kimberley
Freeman, Colin
Trudgill, Nigel
Tucker, Art T.
Pirinen, Matti
Peppelenbosch, Maikel P.
van der Laan, Luc J. W.
Kuipers, Ernst J.
Drenth, Joost P. H.
Peters, Wilbert H.
Reynolds, John V.
Kelleher, Dermot P.
McManus, Ross
Grabsch, Heike
Prenen, Hans
Bisschops, Raf
Krishnadath, Kausila
Siersema, Peter D.
van Baal, Jantine W. P. M.
Middleton, Mark
Petty, Russell
Gillies, Richard
Burch, Nicola
Bhandari, Pradeep
Paterson, Stuart
Edwards, Cathryn
Penman, Ian
Vaidya, Kishor
Ang, Yeng
Murray, Iain
Patel, Praful
Ye, Weimin
Mullins, Paul
Wu, Anna H.
Bird, Nigel C.
Dallal, Helen
Shaheen, Nicholas J.
Murray, Liam J.
Koss, Konrad
Bernstein, Leslie
Romero, Yvonne
Hardie, Laura J.
Zhang, Rui
Winter, Helen
Corley, Douglas A.
Panter, Simon
Risch, Harvey A.
Reid, Brian J.
Sargeant, Ian
Gammon, Marilie D.
Smart, Howard
Dhar, Anjan
McMurtry, Hugh
Ali, Haythem
Liu, Geoffrey
Casson, Alan G.
Chow, Wong-Ho
Rutter, Matt
Tawil, Ashref
Morris, Danielle
Nwokolo, Chuka
Isaacs, Peter
Rodgers, Colin
Ragunath, Krish
MacDonald, Chris
Haigh, Chris
Monk, David
Davies, Gareth
Wajed, Saj
Johnston, David
Gibbons, Michael
Cullen, Sue
Church, Nicholas
Langley, Ruth
Griffin, Michael
Alderson, Derek
Deloukas, Panos
Hunt, Sarah E.
Gray, Emma
Dronov, Serge
Potter, Simon C.
Tashakkori-Ghanbaria, Avazeh
Anderson, Mark
Brooks, Claire
Blackwell, Jenefer M.
Bramon, Elvira
Brown, Matthew A.
Casas, Juan P.
Corvin, Aiden
Duncanson, Audrey
Markus, Hugh S.
Mathew, Christopher G.
Palmer, Colin N. A.
Plomin, Robert
Rautanen, Anna
Sawcer, Stephen J.
Trembath, Richard C.
Viswanathan, Ananth C.
Wood, Nicholas
Trynka, Gosia
Wijmenga, Cisca
Cazier, Jean-Baptiste
Atherfold, Paul
Nicholson, Anna M.
Gellatly, Nichola L.
Glancy, Deborah
Cooper, Sheldon C.
Cunningham, David
Lind, Tore
Hapeshi, Julie
Ferry, David
Rathbone, Barrie
Brown, Julia
Love, Sharon
Attwood, Stephen
MacGregor, Stuart
Watson, Peter
Sanders, Scott
Ek, Weronica
Harrison, Rebecca F.
Moayyedi, Paul
de Caestecker, John
Barr, Hugh
Stupka, Elia
Vaughan, Thomas L.
Peltonen, Leena
Spencer, Chris C. A.
Tomlinson, Ian
Donnelly, Peter
Jankowski, Janusz A. Z.
CA Esophageal Adenocarcinoma Genetics
Wellcome Trust Case Control Consor
TI Common variants at the MHC locus and at chromosome 16q24.1 predispose to
Barrett's esophagus
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; GASTROESOPHAGEAL-REFLUX DISEASE; SUSCEPTIBILITY
LOCI; RISK-FACTORS; ADENOCARCINOMA; CANCER; OBESITY; METAANALYSIS;
POPULATION; METAPLASIA
AB Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P-combined = 4.09 x 10(-9); odds ratio (OR) = 1.21, 95% confidence interval (CI) = 1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P-combined = 2.74 x 10(-10); OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
C1 [Gay, Laura J.; Nanji, Manoj; Nicholson, Anna M.; Gellatly, Nichola L.; Stupka, Elia; Jankowski, Janusz A. Z.] Queen Mary Univ London, Ctr Digest Dis, Blizard Inst, London, England.
[Su, Zhan; Strange, Amy; Palles, Claire; Band, Gavin; Bellenguez, Celine; Howarth, Kimberley; Freeman, Colin; Pirinen, Matti; Rautanen, Anna; Cazier, Jean-Baptiste; Spencer, Chris C. A.; Tomlinson, Ian; Donnelly, Peter] Wellcome Trust Ctr Human Genet, Oxford, England.
[Palles, Claire; Tomlinson, Ian] Oxford Natl Inst Hlth Res, Comprehens Biomed Res Ctr, Oxford, England.
[Whiteman, David C.; MacGregor, Stuart; Ek, Weronica] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Lescai, Francesco; Stupka, Elia] UCL, Inst Canc, London, England.
[Langford, Cordelia; Edkins, Sarah; Deloukas, Panos; Hunt, Sarah E.; Gray, Emma; Dronov, Serge; Potter, Simon C.; Tashakkori-Ghanbaria, Avazeh] Wellcome Trust Sanger Inst, Cambridge, England.
[van der Winkel, Anouk; Peppelenbosch, Maikel P.; Kuipers, Ernst J.] Erasmus Univ, Med Ctr, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands.
[Levine, David; Zhang, Rui] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Sasieni, Peter] Barts & London Queen Marys Sch Med & Dent, Ctr Canc Prevent, Wolfson Inst Prevent Med, London, England.
[Trudgill, Nigel; Cooper, Sheldon C.] Sandwell Gen Hosp, Dept Gastroenterol, Lyndon, England.
[Tucker, Art T.] Queen Mary Univ London, Ctr Clin Pharmacol, William Harvey Res Inst, London, England.
[van der Laan, Luc J. W.] Erasmus Univ, Med Ctr, Dept Surg, Rotterdam, Netherlands.
[Drenth, Joost P. H.; Peters, Wilbert H.] Radboud Univ Nijmegen, Med Ctr, Dept Gastroenterol & Hepatol, NL-6525 ED Nijmegen, Netherlands.
[Reynolds, John V.] St James Hosp, Dept Surg, Inst Mol Med, Dublin 8, Ireland.
[Reynolds, John V.; Kelleher, Dermot P.; McManus, Ross] Trinity Coll Dublin, Dublin, Ireland.
[Kelleher, Dermot P.; McManus, Ross] St James Hosp, Inst Mol Med, Dept Clin Med, Dublin 8, Ireland.
[Grabsch, Heike] Univ Leeds, St Jamess Univ Hosp, Leeds Inst Mol Med, Sect Pathol & Tumour Biol, Leeds, W Yorkshire, England.
[Prenen, Hans; Bisschops, Raf] Univ Hosp Gasthuisberg, Dept Digest Oncol, B-3000 Louvain, Belgium.
[Krishnadath, Kausila] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol & Hepatol, NL-1105 AZ Amsterdam, Netherlands.
[Siersema, Peter D.; van Baal, Jantine W. P. M.] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Middleton, Mark; Gillies, Richard; Jankowski, Janusz A. Z.] Univ Oxford, Dept Med Oncol, Churchill Hosp, Oxford, England.
[Petty, Russell] Univ Aberdeen, Inst Med Sci, Sch Med & Dent, Aberdeen, Scotland.
[Burch, Nicola; Glancy, Deborah; Rathbone, Barrie; Jankowski, Janusz A. Z.] Leicester Royal Infirm, Ctr Digest Dis, Leicester, Leics, England.
[Bhandari, Pradeep] Queen Alexandra Hosp, Gastroenterol & Hepatol Serv, Portsmouth, Hants, England.
[Paterson, Stuart] Forth Valley Royal Hosp, Dept Gastroenterol, Larbert, England.
[Edwards, Cathryn] Torbay Hosp, Dept Gastroenterol, Torquay, England.
[Penman, Ian] Western Gen Hosp, Gastrointestinal Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
[Penman, Ian] Royal Infirm Edinburgh NHS Trust, Gastrointestinal Unit, Edinburgh, Midlothian, Scotland.
[Vaidya, Kishor] Victoria Hosp, Gastrointestinal Unit, Kirkcaldy, England.
[Ang, Yeng] Natl Hlth Serv NHS Trust, Dept Gastroenterol, Royal Albert Edward Infirm, Wigan, England.
[Murray, Iain] Royal Cornwall Hosp, Dept Gastroenterol, Truro, England.
[Patel, Praful] Southampton Univ Hosp, NHS Trust, Dept Gastroenterol, Southampton, Hants, England.
[Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Mullins, Paul] NHS Trust Royal Blackburn Hosp, E Lancashire Hosp, Dept Gastroenterol, Blackburn, Lancs, England.
[Wu, Anna H.] Univ So Calif, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA.
[Bird, Nigel C.] Univ Sheffield, Sch Med, Dept Oncol, Sheffield, S Yorkshire, England.
[Dallal, Helen] S Tees NHS Fdn Trust, Middlesbrough, Cleveland, England.
[Shaheen, Nicholas J.] Univ N Carolina, Sch Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA.
[Murray, Liam J.] Queens Univ, Ctr Publ Hlth, Belfast, Antrim, North Ireland.
[Koss, Konrad] Macclesfield Gen Hosp, Dept Gastroenterol, Macclesfield, Cheshire, England.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA.
[Bernstein, Leslie] City Hope Comprehens Canc Ctr, Duarte, CA USA.
[Romero, Yvonne] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA.
[Hardie, Laura J.] Univ Leeds, Div Epidemiol, Leeds, W Yorkshire, England.
[Winter, Helen] Great Western Hosp, Dept Oncol, Swindon, Wilts, England.
[Corley, Douglas A.] Kaiser Permanente, Oakland Med Ctr, Div Res, Oakland, CA USA.
[Panter, Simon] S Tyneside Dist Hosp, Dept Gastroenterol, S Shields, England.
[Risch, Harvey A.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Reid, Brian J.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98104 USA.
[Sargeant, Ian] Lister Hosp, Gastroenterol & Hepatol Serv, London, England.
[Gammon, Marilie D.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Smart, Howard] Royal Liverpool Univ Hosp, Dept Gastroenterol, Liverpool, Merseyside, England.
[Smart, Howard] Royal Liverpool Univ Hosp, Dept Hepatol, Liverpool, Merseyside, England.
[Dhar, Anjan] Cty Durham & Darlington NHS Fdn Trust, Darlington, Durham, England.
[McMurtry, Hugh] Lancashire Teaching Hosp NHS Fdn Trust, Chorley, England.
[Ali, Haythem] Maidstone Hlth Author, Dept Surg, Maidstone, Kent, England.
[Liu, Geoffrey] Univ Toronto, Dept Med, Princess Margaret Hosp, Univ Hlth Network,Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Liu, Geoffrey] Univ Toronto, Dept Med Biophys, Princess Margaret Hosp, Univ Hlth Network,Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Liu, Geoffrey] Univ Toronto, Div Epidemiol, Princess Margaret Hosp, Univ Hlth Network,Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Casson, Alan G.] Univ Saskatchewan, Dept Surg, Saskatoon, SK, Canada.
[Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Rutter, Matt] Univ Hosp N Tees, Dept Gastroenterol, Stockton On Tees, England.
[Tawil, Ashref] N Devon Dist Hosp, Gastroenterol & Hepatol Serv, Barnstaple, England.
[Morris, Danielle] E&N Herts NHS Trust, Queen Elizabeth Hosp, Dept Gastroenterol, Welwyn Garden City, Herts, England.
[Nwokolo, Chuka] Univ Hosp Coventry, Dept Gastroenterol, Coventry, W Midlands, England.
[Isaacs, Peter] Blackpool Victoria Hosp, Gastroenterol & Hepatol Serv, Blackpool, England.
[Rodgers, Colin] Antrim & Whiteabbey United Hosp, Dept Gastroenterol, Whiteabbey, Antrim, North Ireland.
[Ragunath, Krish] Queens Med Ctr, Wolfson Digest Dis Ctr, Nottingham NG7 2UH, England.
[MacDonald, Chris] Cumberland Infirm, Gastroenterol Clin, Carlisle, England.
[Haigh, Chris] Wansbeck Gen Hosp, Dept Gastroenterol, Ashington, England.
[Monk, David] Countess Chester Hosp, Dept Gen Surg, Chester, Cheshire, England.
[Davies, Gareth] Harrogate Dist Hosp, Gastroenterol & Hepatol Serv, Harrogate, England.
[Wajed, Saj] Royal Devon & Exeter NHS Fdn Trust, Dept Thorac & Upper Gastrointestinal Surg, Exeter, Devon, England.
[Johnston, David] Ninewells Hosp, Dept Gastroenterol, Dundee DD1 9SY, Scotland.
[Gibbons, Michael] Craigavon Area Hosp, Dept Gastroenterol, Craigavon, England.
[Cullen, Sue] Wycombe Hosp, Dept Gastroenterol, High Wycombe, Bucks, England.
[Church, Nicholas] Royal Edinburgh Infirm, Ctr Liver & Digest Dis, Edinburgh, Midlothian, Scotland.
[Langley, Ruth] MRC, Clin Trials Unit, London, England.
[Griffin, Michael] Royal Victoria Infirm, No Osophago Gastirc Unit, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
[Alderson, Derek] Univ Birmingham, Queen Elizabeth Hosp, Acad Dept Surg, Sch Canc Sci,Coll Med & Dent Sci, Birmingham B15 2TH, W Midlands, England.
[Anderson, Mark] City Hosp Birmingham, Gastrointestinal Unit, Birmingham, W Midlands, England.
[Brooks, Claire] Univ Oxford, Dept Oncol, Oncol Clin Trials Off, Oxford, England.
[Blackwell, Jenefer M.] Univ Western Australia, Telethon Inst Child Hlth Res, Ctr Child Hlth Res, Perth, WA 6009, Australia.
[Blackwell, Jenefer M.] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England.
[Bramon, Elvira] Kings Coll London, Dept Psychoisis Studies, Natl Inst Hlth Res, Biomed Res Ctr Mental Hlth,Inst Psychiat, London WC2R 2LS, England.
[Bramon, Elvira] S London & Maudsley NHS Fdn Trust, London, England.
[Brown, Matthew A.] Univ Queensland, Diamantina Inst, Princess Alexandra Hosp, Brisbane, Qld, Australia.
[Casas, Juan P.] UCL, Dept Epidemiol & Publ Hlth, London, England.
[Casas, Juan P.] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England.
[Corvin, Aiden] Trinity Coll Dublin, Neuropsychiat Genet Res Grp, Inst Mol Med, Dublin, Ireland.
[Duncanson, Audrey] Wellcome Trust Res Labs, London, England.
[Markus, Hugh S.] St Georges Univ London, Ctr Clin Neurosci, London, England.
[Mathew, Christopher G.; Trembath, Richard C.] Guys Hosp, Dept Med & Mol Genet, Kings Coll London, London SE1 9RT, England.
[Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Ctr, Dundee DD1 9SY, Scotland.
[Plomin, Robert] Kings Coll London, Social Genet & Dev Psychiat Ctr, Inst Psychiat, London WC2R 2LS, England.
[Sawcer, Stephen J.] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England.
[Viswanathan, Ananth C.] Moorfields Eye Hosp NHS Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr Ophthalmol, London, England.
[Viswanathan, Ananth C.] UCL, Inst Ophthalmol, London, England.
[Wood, Nicholas] UCL, Dept Mol Neurosci, Inst Neurol, London, England.
[Trynka, Gosia; Wijmenga, Cisca] Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands.
[Trynka, Gosia; Wijmenga, Cisca] Univ Groningen, Groningen, Netherlands.
[Atherfold, Paul] UCB Pharma, Slough, Berks, England.
[Atherfold, Paul] Univ Oxford, Dept Clin Pharmacol, Oxford, England.
[Cunningham, David] Royal Marsden Hosp, Gastrointestinal Unit, London SW3 6JJ, England.
[Lind, Tore] AstraZeneca, Res & Dev, Lund, Sweden.
[Hapeshi, Julie] Gloucestershire Royal Hosp, Gloucestershire Res & Dev Support Unit, Gloucester GL1 3NN, England.
[Ferry, David] Royal Wolverhampton Hosp NHS Trust, New Cross Hosp, Dept Oncol, Wolverhampton, W Midlands, England.
[Brown, Julia] Leeds Inst Mol Med, Clin Trial Res Unit, Leeds, W Yorkshire, England.
[Love, Sharon] Ctr Stat Med, Oxford Clin Trials Res Unit, Oxford, England.
[Sanders, Scott] Warwick Hosp, Dept Cellular Pathol, Warwick, England.
[Harrison, Rebecca F.] Leicester Royal Infirm, Dept Pathol, Leicester LE2 7LX, Leics, England.
[Moayyedi, Paul] McMaster Univ, Med Ctr, Dept Med, Div Gastroenterol, Hamilton, ON L8N 3Z5, Canada.
[de Caestecker, John] Leicester Gen Hosp, Dept Gastroenterol, Leicester LE5 4PW, Leics, England.
[Barr, Hugh] Gloucestershire Royal Hosp, Dept Upper Gastrointestinal Surg, Gloucester GL1 3NN, England.
[Stupka, Elia] Ist Sci San Raffaele, Ctr Translat Genom & Bioinformat, I-20132 Milan, Italy.
[Vaughan, Thomas L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Donnelly, Peter] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
[Jankowski, Janusz A. Z.] Univ Oxford, Gastrointestinal Canc Grp, Oxford, England.
RP Jankowski, JAZ (reprint author), Queen Mary Univ London, Ctr Digest Dis, Blizard Inst, London, England.
EM iant@well.ox.ac.uk; donnelly@well.ox.ac.uk; j.a.jankowski@qmul.ac.uk
RI Liu, Geoffrey/N-4421-2016; Blackwell, Jenefer/H-3015-2015; Drenth,
J.P.H./H-8025-2014; Peters, W.H.M./L-4572-2015; Mathew,
Christopher/G-3434-2015; Whiteman, David/P-2728-2014; Palmer,
Colin/C-7053-2008; Shaheen, Nicholas/A-1898-2013; Deloukas,
Panos/B-2922-2013; Macgregor, Stuart/C-6442-2009; Rutter,
Michael/C-8570-2013; Wijmenga, Cisca/D-2173-2009; Barr,
Hugh/G-4673-2014; Moayyedi, Paul/M-6178-2014; Jankowski,
Janusz/H-2706-2012
OI McManus, Ross/0000-0002-0529-9617; Trembath,
Richard/0000-0003-0550-3400; van der Laan, Luc/0000-0002-0651-5334;
Lescai, Francesco/0000-0002-6399-9101; Wood,
Nicholas/0000-0002-9500-3348; Pirinen, Matti/0000-0002-1664-1350;
Cunningham, David/0000-0001-5158-1069; Murray, Iain/0000-0002-1795-3647;
Trynka, Gosia/0000-0002-6955-9529; Corvin, Aiden/0000-0001-6717-4089;
Hunt, Sarah/0000-0002-8350-1235; Stupka, Elia/0000-0003-3154-4011;
Plomin, Robert/0000-0002-0756-3629; Wijmenga, Cisca/0000-0002-5635-1614;
Mathew, Christopher/0000-0003-4178-1838; Whiteman,
David/0000-0003-2563-9559; Palmer, Colin/0000-0002-6415-6560; Deloukas,
Panos/0000-0001-9251-070X; Macgregor, Stuart/0000-0001-6731-8142; Barr,
Hugh/0000-0002-2919-5660; Moayyedi, Paul/0000-0002-3616-9292; Jankowski,
Janusz/0000-0003-2130-9181
FU WTCCC2 project [085475/B/08/Z, 085475/Z/08/Z]; Wellcome Trust
[072894/Z/03/Z, 090532/Z/09/Z, 075491/Z/04/B, 068545/Z/02];
Wolfson-Royal Society Merit Award; Australian Research Council;
Australian National Health & Medical Research Council (NHMRC) Career
Development Award; Wellcome Trust Fellowship [097364/Z/11/Z]; UK Medical
Research Council [G0000934]; UK National Blood Service controls;
Esophageal Adenocarcinoma GenE Consortia incorporating the ChOPIN
project [C548/A5675]; AspECT [HDRMJQ0]; BOSS clinical trials project
[MGAG1G7R]; Cancer Research UK (AspECT) [C548/A4584, D9612L00090];
Histological AssessmeNt Determining EpitheliaL Response (HANDEL)
[C548/A9085]; AstraZeneca UK educational grant; University Hospitals of
Leicester R and D grant; US National Institutes of Health
[R01CA13672501]; Health Research Board and the Wellcome Trust; Science
Foundation Ireland [09/IN.1/B2640]
FX We acknowledge the individuals with Barrett's esophagus who participated
in the study and the physicians who helped in recruitment. We thank the
many research nurses who also helped recruit, including S. Prew. We
thank S. Bertrand, J. Bryant, S. L. Clark, J. S. Conquer, T. Dibling, J.
C. Eldred, S. Gamble, C. Hind, A. Wilk, C. R. Stribling and S. Taylor of
the Wellcome Trust Sanger Institute's Sample and Genotyping Facilities
for technical assistance. We also thank J. Barrett for design of the
Immunochip array. Funding for this study was provided by the WTCCC2
project (085475/B/08/Z and 085475/Z/08/Z) and the Wellcome Trust
(072894/Z/03/Z, 090532/Z/09/Z and 075491/Z/04/B). P. Donnelly was
supported in part by a Wolfson-Royal Society Merit Award. D.C.W. is
supported by a Future Fellowship from the Australian Research Council.
S.M. is supported by an Australian National Health & Medical Research
Council (NHMRC) Career Development Award. C.C.A.S. was supported by a
Wellcome Trust Fellowship (097364/Z/11/Z). We acknowledge use of the
British 1958 Birth Cohort DNA collection, funded by the UK Medical
Research Council (grant G0000934) and the Wellcome Trust (grant
068545/Z/02), the UK National Blood Service controls, funded by the
Wellcome Trust, and the People of the British Isles collection, funded
by the Wellcome Trust. This work was also supported by the Esophageal
Adenocarcinoma GenE Consortia incorporating the ChOPIN project (grant
C548/A5675) and Inherited Predisposition of neoplasia analysis of
genomic DNA (IPOD) from AspECT and BOSS clinical trials project (grant
MGAG1G7R); Cancer Research UK (AspECT, grants C548/A4584 and
D9612L00090, and Histological AssessmeNt Determining EpitheliaL Response
(HANDEL), grant C548/A9085); AstraZeneca UK educational grant;
University Hospitals of Leicester R and D grant; and AspECT (T91 5211
University of Oxford grant HDRMJQ0). The Barrett's and Esophageal
Adenocarcinoma Genetic Susceptibility Study (BEAGESS) within the BEACON
Consortium was supported by US National Institutes of Health grant
R01CA13672501. We acknowledge the Dublin Centre for Clinical Research
(funded by the Health Research Board and the Wellcome Trust) for support
in sample collection and the Irish Blood Transfusion Service and TCD DNA
Biobank for provision of control samples. R.M. is supported by the
Science Foundation Ireland grant 09/IN.1/B2640.
NR 47
TC 68
Z9 68
U1 1
U2 25
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD OCT
PY 2012
VL 44
IS 10
BP 1131
EP +
DI 10.1038/ng.2408
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 016WJ
UT WOS:000309550200014
PM 22961001
ER
PT J
AU Holliday, EG
Maguire, JM
Evans, TJ
Koblar, SA
Jannes, J
Sturm, JW
Hankey, GJ
Baker, R
Golledge, J
Parsons, MW
Malik, R
McEvoy, M
Biros, E
Lewis, MD
Lincz, LF
Peel, R
Oldmeadow, C
Smith, W
Moscato, P
Barlera, S
Bevan, S
Bis, JC
Boerwinkle, E
Boncoraglio, GB
Brott, TG
Brown, RD
Cheng, YC
Cole, JW
Cotlarciuc, I
Devan, WJ
Fornage, M
Furie, KL
Gretarsdottir, S
Gschwendtner, A
Ikram, MA
Longstreth, WT
Meschia, JF
Mitchell, BD
Mosley, TH
Nalls, MA
Parati, EA
Psaty, BM
Sharma, P
Stefansson, K
Thorleifsson, G
Thorsteinsdottir, U
Traylor, M
Verhaaren, BFJ
Wiggins, KL
Worrall, BB
Sudlow, C
Rothwell, PM
Farrall, M
Dichgans, M
Rosand, J
Markus, HS
Scott, RJ
Levi, C
Attia, J
AF Holliday, Elizabeth G.
Maguire, Jane M.
Evans, Tiffany-Jane
Koblar, Simon A.
Jannes, Jim
Sturm, Jonathan W.
Hankey, Graeme J.
Baker, Ross
Golledge, Jonathan
Parsons, Mark W.
Malik, Rainer
McEvoy, Mark
Biros, Erik
Lewis, Martin D.
Lincz, Lisa F.
Peel, Roseanne
Oldmeadow, Christopher
Smith, Wayne
Moscato, Pablo
Barlera, Simona
Bevan, Steve
Bis, Joshua C.
Boerwinkle, Eric
Boncoraglio, Giorgio B.
Brott, Thomas G.
Brown, Robert D., Jr.
Cheng, Yu-Ching
Cole, John W.
Cotlarciuc, Ioana
Devan, William J.
Fornage, Myriam
Furie, Karen L.
Gretarsdottir, Solveig
Gschwendtner, Andreas
Ikram, M. Arfan
Longstreth, W. T., Jr.
Meschia, James F.
Mitchell, Braxton D.
Mosley, Thomas H.
Nalls, Michael A.
Parati, Eugenio A.
Psaty, Bruce M.
Sharma, Pankaj
Stefansson, Kari
Thorleifsson, Gudmar
Thorsteinsdottir, Unnur
Traylor, Matthew
Verhaaren, Benjamin F. J.
Wiggins, Kerri L.
Worrall, Bradford B.
Sudlow, Cathie
Rothwell, Peter M.
Farrall, Martin
Dichgans, Martin
Rosand, Jonathan
Markus, Hugh S.
Scott, Rodney J.
Levi, Christopher
Attia, John
CA Australian Stroke Genetics Collabo
International Stroke Genetics Cons
Wellcome Trust Case Control Consor
TI Common variants at 6p21.1 are associated with large artery
atherosclerotic stroke
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; L GENE-CLUSTER; ISCHEMIC-STROKE;
ATRIAL-FIBRILLATION; GENOTYPE DATA; HERITABILITY; METAANALYSIS; RISK;
CLASSIFICATION; VISUALIZATION
AB Genome-wide association studies (GWAS) have not consistently detected replicable genetic risk factors for ischemic stroke, potentially due to etiological heterogeneity of this trait. We performed GWAS of ischemic stroke and a major ischemic stroke subtype (large artery atherosclerosis, LAA) using 1,162 ischemic stroke cases (including 421 LAA cases) and 1,244 population controls from Australia. Evidence for a genetic influence on ischemic stroke risk was detected, but this influence was higher and more significant for the LAA subtype. We identified a new LAA susceptibility locus on chromosome 6p21.1 (rs556621: odds ratio (OR) = 1.62, P = 3.9 x 10(-8)) and replicated this association in 1,715 LAA cases and 52,695 population controls from 10 independent population cohorts (meta-analysis replication OR = 1.15, P = 3.9 x 10(-4); discovery and replication combined OR = 1.21, P = 4.7 x 10(-8)). This study identifies a genetic risk locus for LAA and shows how analyzing etiological subtypes may better identify genetic risk alleles for ischemic stroke.
C1 [Holliday, Elizabeth G.; McEvoy, Mark; Peel, Roseanne; Attia, John] Univ Newcastle, Sch Med & Publ Hlth, Ctr Clin Epidemiol & Biostat, Newcastle, NSW 2300, Australia.
[Holliday, Elizabeth G.; Evans, Tiffany-Jane; Moscato, Pablo; Scott, Rodney J.; Attia, John] Hunter Med Res Inst, Ctr Bioinformat Biomarker Discovery & Informat Ba, Newcastle, NSW, Australia.
[Maguire, Jane M.] Univ Newcastle, Sch Nursing & Midwifery, Newcastle, NSW 2300, Australia.
[Maguire, Jane M.; Parsons, Mark W.; Lincz, Lisa F.; Levi, Christopher] Univ Newcastle, Ctr Brain & Mental Hlth Res, Newcastle, NSW 2300, Australia.
[Maguire, Jane M.; Sturm, Jonathan W.] Gosford Hosp, Cent Coast Area Hlth, Dept Neurosci, Gosford, NSW, Australia.
[Evans, Tiffany-Jane; Lincz, Lisa F.; Scott, Rodney J.] Univ Newcastle, Sch Biomed Sci & Pharm, Newcastle, NSW 2300, Australia.
[Koblar, Simon A.; Jannes, Jim; Lewis, Martin D.] Univ Adelaide, Sch Med, Stroke Res Program, Adelaide, SA, Australia.
[Koblar, Simon A.; Jannes, Jim] Queen Elizabeth Hosp, Dept Neurol, Stroke Unit, Adelaide, SA, Australia.
[Hankey, Graeme J.] Royal Perth Hosp, Dept Neurol, Perth, WA, Australia.
[Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.
[Baker, Ross] Royal Perth Hosp, Dept Haematol, Perth, WA, Australia.
[Baker, Ross] Murdoch Univ, Ctr Thrombosis & Haemophilia, Perth, WA, Australia.
[Golledge, Jonathan; Biros, Erik] James Cook Univ, Sch Med & Dent, Vasc Biol Unit, Townsville, Qld, Australia.
[Golledge, Jonathan] Townsville Hosp, Dept Vasc Surg, Townsville, Qld, Australia.
[Malik, Rainer; Gschwendtner, Andreas; Dichgans, Martin] Univ Munich, Inst Stroke & Dementia Res ISD, Med Ctr, Klinikum Univ Munchen, Munich, Germany.
[McEvoy, Mark; Peel, Roseanne; Smith, Wayne] Hunter Med Res Inst, Publ Hlth Res Program, Newcastle, NSW, Australia.
[Lewis, Martin D.] Univ Adelaide, Discipline Genet, Sch Mol & Biomed Sci, Adelaide, SA, Australia.
[Lincz, Lisa F.] Calvary Mater Newcastle Hosp, Hunter Haematol Res Grp, Newcastle, NSW, Australia.
[Oldmeadow, Christopher] Hunter Med Res Inst, Clin Res Design IT & Stat Support Unit, Newcastle, NSW, Australia.
[Moscato, Pablo] Univ Newcastle, Sch Elect Engn & Comp Sci, Newcastle, NSW 2300, Australia.
[Barlera, Simona] Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
[Bevan, Steve; Traylor, Matthew; Markus, Hugh S.] St Georges Univ London, Stroke & Dementia Res Ctr, London, England.
[Bis, Joshua C.; Psaty, Bruce M.; Wiggins, Kerri L.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Boerwinkle, Eric; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA.
[Boerwinkle, Eric; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX USA.
[Boncoraglio, Giorgio B.; Parati, Eugenio A.] Ist Neurol Carlo Besta, Dept Cerebrovasc Dis, Fdn Ist Ricovero & Cura Carattere Sci IRCCS, Milan, Italy.
[Brott, Thomas G.; Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
[Brown, Robert D., Jr.] Mayo Clin, Dept Neurol, Rochester, MN USA.
[Cheng, Yu-Ching; Mitchell, Braxton D.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA.
[Cole, John W.] Baltimore Vet Affairs Med Ctr, Baltimore, MD USA.
[Cole, John W.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Cotlarciuc, Ioana; Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, ICCRU, London, England.
[Devan, William J.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Devan, William J.; Furie, Karen L.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Devan, William J.; Furie, Karen L.; Rosand, Jonathan] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Gretarsdottir, Solveig; Stefansson, Kari; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur] deCODE Genet, Reykjavik, Iceland.
[Ikram, M. Arfan; Verhaaren, Benjamin F. J.] Univ Med Ctr, Erasmus Med Ctr MC, Dept Epidemiol, Rotterdam, Netherlands.
[Ikram, M. Arfan] Erasmus MC Univ Med Ctr, Dept Neurol, Rotterdam, Netherlands.
[Ikram, M. Arfan; Verhaaren, Benjamin F. J.] Erasmus MC Univ Med Ctr, Dept Radiol, Rotterdam, Netherlands.
[Longstreth, W. T., Jr.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Longstreth, W. T., Jr.] Univ Washington, Dept Med, Seattle, WA USA.
[Longstreth, W. T., Jr.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Nalls, Michael A.] NIA, Lab Neurogenet, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth, Seattle, WA USA.
[Stefansson, Kari; Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA.
[Sudlow, Cathie] Univ Edinburgh, Div Clin Neurosci, Edinburgh, Midlothian, Scotland.
[Sudlow, Cathie] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
[Rothwell, Peter M.] John Radcliffe Hosp, Dept Clin Neurol, Oxford OX3 9DU, England.
[Farrall, Martin] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Farrall, Martin] Univ Oxford, Dept Cardiovasc Med, Oxford, England.
[Scott, Rodney J.] Hunter Area Pathol Serv, Div Genet, Newcastle, NSW, Australia.
RP Holliday, EG (reprint author), Univ Newcastle, Sch Med & Publ Hlth, Ctr Clin Epidemiol & Biostat, Newcastle, NSW 2300, Australia.
EM liz.holliday@newcastle.edu.au
RI Scott, Rodney/B-2827-2013; MOSCATO, PABLO/G-7668-2013; Peel,
Roseanne/G-7726-2013; golledge, jonathan/I-2371-2013; Attia,
John/F-5376-2013; EVANS, TIFFANY-JANE/G-8001-2013; Parsons,
Mark/G-3750-2014; Hankey, Graeme /H-4968-2014; Boncoraglio,
Giorgio/B-8647-2011;
OI Lewis, Martin/0000-0002-3332-3776; Koblar, Simon/0000-0002-8667-203X;
Mitchell, Braxton/0000-0003-4920-4744; Scott,
Rodney/0000-0001-7724-3404; Traylor, Matthew/0000-0001-6624-8621; Bevan,
Steve/0000-0003-0490-6830; Peel, Roseanne/0000-0001-9912-3198; Attia,
John/0000-0001-9800-1308; EVANS, TIFFANY-JANE/0000-0001-7525-461X;
Hankey, Graeme /0000-0002-6044-7328; Ikram, Mohammad
Arfan/0000-0003-0372-8585
FU University of Newcastle; Australian National Health and Medical Research
Council (NHMRC) [569257]; Australian National Heart Foundation (NHF) [G
04S 1623]; Gladys M Brawn Fellowship scheme; Vincent Fairfax Family
Foundation in Australia; Australian Office of Health and Medical
Research; Wellcome Trust [085475/B/08/Z, 085475/Z/08/Z, WT084724MA,
090532/Z/09/Z]; European Community [LSHM-CT-2007037273]; AstraZeneca; US
National Institute of Neurological Disorders and Stroke [U01NS069208];
Netherlands Heart Foundation [2009B102]
FX A complete list of funding acknowledgments is included in the
Supplementary Note. We are grateful to the participants with ischemic
stroke and also to their families for participating in this study.
Australian population control data were derived from the Hunter
Community Study. We also thank the University of Newcastle for funding
and the men and women of the Hunter region who participated in this
study. This research was funded by grants from the Australian National
Health and Medical Research Council (NHMRC; project grant 569257), the
Australian National Heart Foundation (NHF; project grant G 04S 1623),
the University of Newcastle, the Gladys M Brawn Fellowship scheme and
the Vincent Fairfax Family Foundation in Australia. E.G.H. is supported
by the Australian NHMRC Fellowship scheme. J.G. is supported by a
Practitioner Fellowship from the NHMRC and a Senior Clinical Research
Fellowship from the Australian Office of Health and Medical Research.
The principal funding for the Wellcome Trust Case Control Consortium 2
(WTCCC2) ischemic stroke study was provided by the Wellcome Trust, as
part of the WTCCC2 project (085475/B/08/Z, 085475/Z/08/Z and
WT084724MA). This work was also supported by the European Community's
Sixth Framework Programme (LSHM-CT-2007037273), the Wellcome Trust core
award (090532/Z/09/Z) and AstraZeneca. M. Farrall is a member of the
Oxford British Heart Foundation (BHF) Centre of Research Excellence. The
Siblings with Ischemic Stroke Study (SWISS) and the Ischemic Stroke
Genetics Study (ISGS) were funded by grants from the US National
Institute of Neurological Disorders and Stroke. Additional funding was
provided by the US National Institute of Neurological Disorders and
Stroke (U01NS069208). The Rotterdam Study received principal funding for
this report from the Netherlands Heart Foundation (grant 2009B102).
NR 37
TC 75
Z9 77
U1 1
U2 16
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD OCT
PY 2012
VL 44
IS 10
BP 1147
EP +
DI 10.1038/ng.2397
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 016WJ
UT WOS:000309550200017
PM 22941190
ER
PT J
AU Block, ML
Elder, A
Auten, RL
Bilbo, SD
Chen, HL
Chen, JC
Cory-Slechta, DA
Costa, D
Diaz-Sanchez, D
Dorman, DC
Gold, DR
Gray, K
Jeng, HA
Kaufman, JD
Kleinman, MT
Kirshner, A
Lawler, C
Miller, DS
Nadadur, SS
Ritz, B
Semmens, EO
Tonelli, LH
Veronesi, B
Wright, RO
Wright, RJ
AF Block, Michelle L.
Elder, Alison
Auten, Richard L.
Bilbo, Staci D.
Chen, Honglei
Chen, Jiu-Chiuan
Cory-Slechta, Deborah A.
Costa, Daniel
Diaz-Sanchez, David
Dorman, David C.
Gold, Diane R.
Gray, Kimberly
Jeng, Hueiwang Anna
Kaufman, Joel D.
Kleinman, Michael T.
Kirshner, Annette
Lawler, Cindy
Miller, David S.
Nadadur, Srikanth S.
Ritz, Beate
Semmens, Erin O.
Tonelli, Leonardo H.
Veronesi, Bellina
Wright, Robert O.
Wright, Rosalind J.
TI The outdoor air pollution and brain health workshop
SO NEUROTOXICOLOGY
LA English
DT Review
DE Air pollution; Brain; Particulate matter; Ozone; Central nervous system;
Susceptibility; Epidemiology; Neuroinflammation; Neurotoxicity; Behavior
ID CENTRAL-NERVOUS-SYSTEM; AMBIENT PARTICULATE MATTER; DIESEL EXHAUST
PARTICLES; HEART-RATE-VARIABILITY; EARLY ENVIRONMENTAL-REGULATION;
RECEPTOR GENE-EXPRESSION; LEFT-VENTRICULAR MASS; GENOMIC TARGET SITES;
LONG-TERM EXPOSURE; RAT NASAL-MUCOSA
AB Accumulating evidence suggests that outdoor air pollution may have a significant impact on central nervous system (CNS) health and disease. To address this issue, the National Institute of Environmental Health Sciences/National Institute of Health convened a panel of research scientists that was assigned the task of identifying research gaps and priority goals essential for advancing this growing field and addressing an emerging human health concern. Here, we review recent findings that have established the effects of inhaled air pollutants in the brain, explore the potential mechanisms driving these phenomena, and discuss the recommended research priorities/approaches that were identified by the panel. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Block, Michelle L.] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA 23298 USA.
[Elder, Alison; Cory-Slechta, Deborah A.] Univ Rochester, Dept Environm Med, Rochester, NY USA.
[Auten, Richard L.] Duke Univ, Dept Pediat, Div Neonatol, Durham, NC 27706 USA.
[Bilbo, Staci D.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA.
[Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Chen, Jiu-Chiuan] Univ So Calif, Keck Sch Med, Dept Preventat Med, Los Angeles, CA 90033 USA.
[Costa, Daniel] US EPA, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
[Diaz-Sanchez, David] US EPA, Environm Publ Hlth Div, NHEERL, Res Triangle Pk, NC 27711 USA.
[Dorman, David C.] N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC USA.
[Gold, Diane R.] Harvard Univ, Brigham & Womens Hosp, Channing Lab, Dept Med,Med Sch, Boston, MA 02115 USA.
[Jeng, Hueiwang Anna] Old Dominion Univ, Coll Hlth Sci, Sch Community & Environm Hlth, Norfolk, VA USA.
[Kaufman, Joel D.] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA.
[Kleinman, Michael T.] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA.
[Miller, David S.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Ritz, Beate] Univ Calif Los Angeles, Dept Epidemiol, Ctr Occupat & Environm Hlth, Los Angeles, CA USA.
[Semmens, Erin O.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Tonelli, Leonardo H.] Univ Maryland, Sch Med, Mood & Anxiety Program LT, Dept Psychiat, Baltimore, MD 21201 USA.
[Veronesi, Bellina] US EPA, Natl Hlth & Environm Effects Lab, Integrated Syst Toxicol Div, Res Triangle Pk, NC 27711 USA.
[Wright, Robert O.; Wright, Rosalind J.] Mt Sinai Sch Med, New York, NY USA.
RP Block, ML (reprint author), Virginia Commonwealth Univ, Dept Anat & Neurobiol, Med Campus,Box 980709, Richmond, VA 23298 USA.
EM mblock@vcu.edu
RI Ritz, Beate/E-3043-2015; Kaufman, Joel/B-5761-2008; Chen,
JC/I-2261-2016; Bilbo, Staci/L-5076-2016;
OI Kaufman, Joel/0000-0003-4174-9037; Bilbo, Staci/0000-0001-6736-7841;
Chen, Honglei/0000-0003-3446-7779
FU NIEHS/NIH-DERT
FX This work was supported by NIEHS/NIH-DERT.
NR 196
TC 73
Z9 74
U1 9
U2 52
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0161-813X
J9 NEUROTOXICOLOGY
JI Neurotoxicology
PD OCT
PY 2012
VL 33
IS 5
BP 972
EP 984
DI 10.1016/j.neuro.2012.08.014
PG 13
WC Neurosciences; Pharmacology & Pharmacy; Toxicology
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology
GA 028BA
UT WOS:000310396600002
PM 22981845
ER
PT J
AU Messing, SAJ
Ton-Hoang, B
Hickman, AB
McCubbin, AJ
Peaslee, GF
Ghirlando, R
Chandler, M
Dyda, F
AF Messing, Simon A. J.
Ton-Hoang, Bao
Hickman, Alison B.
McCubbin, Andrew J.
Peaslee, Graham F.
Ghirlando, Rodolfo
Chandler, Michael
Dyda, Fred
TI The processing of repetitive extragenic palindromes: the structure of a
repetitive extragenic palindrome bound to its associated nuclease
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID CONJUGATIVE RELAXASE TRWC; STRANDED-DNA BINDING; ESCHERICHIA-COLI;
NEISSERIA-MENINGITIDIS; INSERTION SEQUENCES; TN10 TRANSPOSITION;
BACTERIAL GENOMES; IMMUNE-SYSTEM; RECOGNITION; CLEAVAGE
AB Extragenic sequences in genomes, such as microRNA and CRISPR, are vital players in the cell. Repetitive extragenic palindromic sequences (REPs) are a class of extragenic sequences, which form nucleotide stem-loop structures. REPs are found in many bacterial species at a high copy number and are important in regulation of certain bacterial functions, such as Integration Host Factor recruitment and mRNA turnover. Although a new clade of putative transposases (RAYTs or TnpA(REP)) is often associated with an increase in these repeats, it is not clear how these proteins might have directed amplification of REPs. We report here the structure to 2.6 A of TnpA(REP) from Escherichia coli MG1655 bound to a REP. Sequence analysis showed that TnpA(REP) is highly related to the IS200/IS605 family, but in contrast to IS200/IS605 transposases, TnpA(REP) is a monomer, is auto-inhibited and is active only in manganese. These features suggest that, relative to IS200/IS605 transposases, it has evolved a different mechanism for the movement of discrete segments of DNA and has been severely down-regulated, perhaps to prevent REPs from sweeping through genomes.
C1 [Messing, Simon A. J.; Hickman, Alison B.; Ghirlando, Rodolfo; Dyda, Fred] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Ton-Hoang, Bao; Chandler, Michael] CNRS, Lab Microbiol & Genet Mol, F-31062 Toulouse, France.
[McCubbin, Andrew J.; Peaslee, Graham F.] Hope Coll, Dept Chem, Holland, MI 49423 USA.
RP Dyda, F (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM fred.dyda@nih.gov
OI Chandler, Michael/0000-0002-0292-6662
FU National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institutes of Health; NIDDK; CNRS (France); ANR [285051]; US
Department of Energy, Basic Energy Sciences, Office of Science
[W-31-109-Eng-38]
FX Intramural Program of the National Institute of Diabetes and Digestive
and Kidney Diseases of the National Institutes of Health (F.D., in
part); Nancy Nossal Fellowship award from NIDDK (to S.M.); Postdoctoral
Intramural Research Training Award from NIDDK (to S.M.); CNRS (France,
the work in Toulouse was supported by intramural funding); ANR [285051
to M.C.] and US Department of Energy, Basic Energy Sciences, Office of
Science [Contract No. W-31-109-Eng-38, use of APS]. Funding for open
access charge: Intramural Program of the National Institute of Diabetes
and Digestive and Kidney Diseases of the National Institutes of Health.
NR 74
TC 12
Z9 13
U1 0
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD OCT
PY 2012
VL 40
IS 19
BP 9964
EP 9979
DI 10.1093/nar/gks741
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 027TT
UT WOS:000310377200056
PM 22885300
ER
PT J
AU Kim, JW
Marshall, JL
AF Kim, Joseph W.
Marshall, John L.
TI Improving Harmonious Precision JOSEPH Article Reviewed
SO ONCOLOGY-NEW YORK
LA English
DT Editorial Material
ID CELL LUNG-CANCER; HETEROGENEITY
C1 [Kim, Joseph W.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Kim, Joseph W.] NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA.
[Marshall, John L.] Georgetown Univ, Med Ctr, Ruesch Ctr Cure GI Canc, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
RP Kim, JW (reprint author), NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
NR 6
TC 0
Z9 0
U1 0
U2 0
PU UBM MEDICA
PI NORWALK
PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA
SN 0890-9091
J9 ONCOLOGY-NY
JI Oncology-NY
PD OCT
PY 2012
VL 26
IS 10
BP 949
EP +
PG 2
WC Oncology
SC Oncology
GA 028LP
UT WOS:000310424100016
PM 23176007
ER
PT J
AU Jancel, TJ
Penzak, SR
Olivier, KN
Uzel, G
Holland, SM
AF Jancel, Timothy J.
Penzak, Scott R.
Olivier, Kenneth N.
Uzel, Gulbu
Holland, Steven M.
TI Three cases of iatrogenic adrenal insufficiency due to concomitant
administration of posaconazole and budesonide
SO PHARMACOTHERAPY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-College-of-Clinical-Pharmacy (ACCP)
CY OCT 21-24, 2012
CL Hollywood, FL
SP Amer Coll Clin Pharm (ACCP)
C1 [Jancel, Timothy J.; Penzak, Scott R.] NIH, Bethesda, MD 20892 USA.
[Olivier, Kenneth N.; Uzel, Gulbu; Holland, Steven M.] NIAID, LCID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-0008
J9 PHARMACOTHERAPY
JI Pharmacotherapy
PD OCT
PY 2012
VL 32
IS 10
BP E240
EP E241
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 015NH
UT WOS:000309452700215
ER
PT J
AU Jancel, TJ
Penzak, SR
Shaw, PA
Hallahan, CW
Malech, HL
Freeman, AF
Olivier, KN
Holland, SM
AF Jancel, Timothy J.
Penzak, Scott R.
Shaw, Pamela A.
Hallahan, Claire W.
Malech, Harry L.
Freeman, Alexandra F.
Olivier, Kenneth N.
Holland, Steven M.
TI Therapeutic drug monitoring of posaconazole in adults: a retrospective
analysis.
SO PHARMACOTHERAPY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-College-of-Clinical-Pharmacy (ACCP)
CY OCT 21-24, 2012
CL Hollywood, FL
SP Amer Coll Clin Pharm (ACCP)
C1 [Jancel, Timothy J.; Penzak, Scott R.] NIH, Bethesda, MD 20892 USA.
[Shaw, Pamela A.; Hallahan, Claire W.] NIAID, BRB, Bethesda, MD 20892 USA.
[Malech, Harry L.] NIAID, LHD, Bethesda, MD 20892 USA.
[Freeman, Alexandra F.; Olivier, Kenneth N.; Holland, Steven M.] NIAID, LCID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-0008
J9 PHARMACOTHERAPY
JI Pharmacotherapy
PD OCT
PY 2012
VL 32
IS 10
MA 123
BP E213
EP E214
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 015NH
UT WOS:000309452700124
ER
PT J
AU George, PJ
Anuradha, R
Kumar, NP
Kumaraswami, V
Nutman, TB
Babu, S
AF George, Palakkal Jovvian
Anuradha, Rajamanickam
Kumar, Nathella Pavan
Kumaraswami, Vasanthapuram
Nutman, Thomas B.
Babu, Subash
TI Evidence of Microbial Translocation Associated with Perturbations in T
Cell and Antigen-Presenting Cell Homeostasis in Hookworm Infections
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID CYTOKINE PRODUCTION; IMMUNE-RESPONSES; ENTERIC NEMATODE; ENDOTOXEMIA;
SCHISTOSOMIASIS; INFLAMMATION; ACTIVATION; HELMINTHS; PRODUCTS; HIV
AB Background: Microbial translocation (MT) is the process by which microbes or microbial products translocate from the intestine to the systemic circulation. MT is a common cause of systemic immune activation in HIV infection and is associated with reduced frequencies of CD4(+) T cells; no data exist, however, on the role of MT in intestinal helminth infections.
Methods: We measured the plasma levels of MT markers, acute-phase proteins, and pro- and anti - inflammatory cytokines in individuals with or without hookworm infections. We also estimated the absolute counts of CD4(+) and CD8(+) T cells as well as the frequencies of memory T cell and dendritic cell subsets. Finally, we also measured the levels of all of these parameters in a subset of individuals following treatment of hookworm infection.
Results: Our data suggest that hookworm infection is characterized by increased levels of markers associated with MT but not acute-phase proteins nor pro-inflammatory cytokines. Hookworm infections were also associated with increased levels of the anti - inflammatory cytokine - IL-10, which was positively correlated with levels of lipopolysaccharide (LPS). In addition, MT was associated with decreased numbers of CD8(+) T cells and diminished frequencies of particular dendritic cell subsets. Antihelmintic treatment of hookworm infection resulted in reversal of some of the hematologic and microbiologic alterations.
Conclusions: Our data provide compelling evidence for MT in a human intestinal helminth infection and its association with perturbations in the T cell and antigen-presenting cell compartments of the immune system. Our data also reveal that at least one dominant counter-regulatory mechanism i.e. increased IL-10 production might potentially protect against systemic immune activation in hookworm infections.
C1 [George, Palakkal Jovvian; Anuradha, Rajamanickam; Kumar, Nathella Pavan; Babu, Subash] Natl Inst Hlth, Int Ctr Excellence Res, Madras, Tamil Nadu, India.
[Kumaraswami, Vasanthapuram] Natl Inst Res TB, Madras, Tamil Nadu, India.
[Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Babu, Subash] SAIC Frederick Inc, NCI Frederick, Frederick, MD USA.
RP George, PJ (reprint author), Natl Inst Hlth, Int Ctr Excellence Res, Madras, Tamil Nadu, India.
EM sbabu@mail.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health. The funders had no
role in study design, data collection and analysis, decision to publish
or preparation of manuscript.
NR 37
TC 7
Z9 7
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD OCT
PY 2012
VL 6
IS 10
AR e1830
DI 10.1371/journal.pntd.0001830
PG 10
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 029WH
UT WOS:000310527200008
PM 23056659
ER
PT J
AU Nussinov, R
Tsai, CJ
Xin, FX
Radivojac, P
AF Nussinov, Ruth
Tsai, Chung-Jung
Xin, Fuxiao
Radivojac, Predrag
TI Allosteric post-translational modification codes
SO TRENDS IN BIOCHEMICAL SCIENCES
LA English
DT Review
DE allostery; propagation; signaling proteins; conformational ensembles;
signaling pathways; protein structure; population shift; conformational
selection; induced fit
ID CONFORMATIONAL-CHANGE; HISTONE MODIFICATIONS; MASS-SPECTROMETRY;
PROTEIN; PHOSPHORYLATION; UBIQUITIN; ACETYLATION; ACTIVATION; RECEPTOR;
COMPLEX
AB Post-translational modifications (PTMs) have been recognized to impact protein function in two ways: (i) orthosterically, via direct recognition by protein domains or through interference with binding; and (ii) allosterically, via conformational changes induced at the functional sites. Because different chemical types of PTMs elicit different structural alterations, the effects of combinatorial codes of PTMs are vastly larger than previously believed. Combined with orthosteric PTMs, the impact of PTMs on cellular regulation is immense. From an evolutionary standpoint, harnessing this immense, yet highly specific, PTM code is an extremely efficient vehicle that can save a cell several-fold in gene number and speed up its response to environmental change.
C1 [Nussinov, Ruth; Tsai, Chung-Jung] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program,Frederick Natl Lab, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Dept Human Genet & Mol Med, Sackler Sch Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
[Xin, Fuxiao; Radivojac, Predrag] Indiana Univ, Sch Informat & Comp, Bloomington, IN 47405 USA.
RP Nussinov, R (reprint author), NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program,Frederick Natl Lab, Frederick, MD 21702 USA.
EM NussinoR@helix.nih.gov
RI Xin, Fuxiao/I-2405-2013
FU National Cancer Institute, National Institutes of Health (NIH)
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research; National Science Foundation (NSF) [DBI-0644017]
FX This project was funded, in whole or in part, with Federal funds from
the National Cancer Institute, National Institutes of Health (NIH),
under contract number HHSN261200800001E. This research was supported (in
part) by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research, and National Science Foundation
(NSF) award DBI-0644017.
NR 74
TC 63
Z9 63
U1 0
U2 35
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0968-0004
J9 TRENDS BIOCHEM SCI
JI Trends Biochem.Sci.
PD OCT
PY 2012
VL 37
IS 10
BP 447
EP 455
DI 10.1016/j.tibs.2012.07.001
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 028KC
UT WOS:000310420200007
PM 22884395
ER
PT J
AU Duckworth, BP
Wilson, DJ
Nelson, KM
Boshoff, HI
Barry, CE
Aldrich, CC
AF Duckworth, Benjamin P.
Wilson, Daniel J.
Nelson, Kathryn M.
Boshoff, Helena I.
Barry, Clifton E., III
Aldrich, Courtney C.
TI Development of a Selective Activity-Based Probe for Adenylating Enzymes:
Profiling MbtA Involved in Siderophore Biosynthesis from Mycobacterium
tuberculosis
SO ACS CHEMICAL BIOLOGY
LA English
DT Article
ID DRUG-RESISTANT TUBERCULOSIS; IRON ACQUISITION; GENE-CLUSTER; INHIBITION;
TARGETS; IDENTIFICATION; MOLECULES; DOMAIN
AB MbtA is an adenylating enzyme from Mycobacterium tuberculosis that catalyzes the first step in the biosynthesis of the mycobactins. A bisubstrate inhibitor of MbtA (Sal-AMS) was previously described that displays potent antitubercular activity under iron-replete as well as iron-deficient growth conditions. This finding is surprising since mycobactin biosynthesis is not required under iron-replete conditions and suggests off-target inhibition of additional biochemical pathways. As a first step toward a complete understanding of the mechanism of action of Sal-AMS, we have designed and validated an activity-based probe (ABP) for studying Sal-AMS inhibition in M. tuberculosis. This probe labels pure MbtA as well as MbtA in mycobacterial lysate, and labeling can be completely inhibited by preincubation with Sal-AMS. Furthermore, this probe provides a prototypical core scaffold for the creation of ABPs to profile any of the other 66 adenylating enzymes in Mtb or the multitude of adenylating enzymes in other pathogenic bacteria.
C1 [Duckworth, Benjamin P.; Wilson, Daniel J.; Nelson, Kathryn M.; Aldrich, Courtney C.] Univ Minnesota, Ctr Drug Design, Minneapolis, MN 55455 USA.
[Nelson, Kathryn M.] Univ Minnesota, Dept Med Chem, Minneapolis, MN 55455 USA.
[Boshoff, Helena I.; Barry, Clifton E., III] NIAID, TB Res Sect, Bethesda, MD 20892 USA.
RP Aldrich, CC (reprint author), Univ Minnesota, Ctr Drug Design, Minneapolis, MN 55455 USA.
EM aldri015@umn.edu
RI Barry, III, Clifton/H-3839-2012
FU National Institutes of Health [AI070219, F32 AI084326]; Intrmural
Research Program of the NIAID, NIH; University of Minnesota Office of
the Vice President for Research; Medical School; College of Biological
Science, NIH, NSF; Minnesota Medical Foundation
FX This work was supported by National Institutes of Health Grants AI070219
(to C.C.A.), F32 AI084326 (to B.P.D.), and the Intrmural Research
Program of the NIAID, NIH (to C.E.B.). Funding for the 850 MHz NMR
instrumentation was provided by the University of Minnesota Office of
the Vice President for Research, the Medical School, the College of
Biological Science, NIH, NSF, and the Minnesota Medical Foundation.
NR 28
TC 23
Z9 23
U1 1
U2 30
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1554-8929
J9 ACS CHEM BIOL
JI ACS Chem. Biol.
PD OCT
PY 2012
VL 7
IS 10
BP 1653
EP 1658
DI 10.1021/cb300112x
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 022IL
UT WOS:000309951400006
PM 22796950
ER
PT J
AU Lateef, TM
Kriss, R
Carpenter, K
Nelson, KB
AF Lateef, Tarannum M.
Kriss, Rebecca
Carpenter, Karen
Nelson, Karin B.
TI Neurologic complaints in young children in the ED: when is cranial
computed tomography helpful?
SO AMERICAN JOURNAL OF EMERGENCY MEDICINE
LA English
DT Article
ID PEDIATRIC EMERGENCY-DEPARTMENT; ONSET AFEBRILE SEIZURES; BLUNT HEAD
TRAUMA; RADIATION-EXPOSURE; AMERICAN-ACADEMY; BRAIN-INJURIES; DECISION
RULE; RISING USE; CT; SYNCOPE
AB Main Objective: The objective of this study is to describe the use of emergent head computed tomography (CT) in young children and ask in which circumstances scans contributed to immediate management.
Methods: We reviewed electronic records of children, aged 1 month through 6 years, who received a head CT at a large suburban emergency department between February 2008 and February 2009. Age, sex, chief complaint, history, physical examination, indication for and results of head CT, red flags in history or physical examination, final disposition, and number of head CT scans performed to date were recorded. Abnormalities on CT scans were classified as significant or incidental, and subsequent interventions were documented.
Results: Emergent head CTs were performed on 394 children. The most common indications were trauma, 65%; seizure, 11%; and headache, 6%. Computed tomographic abnormalities were found in 40% (154 children): 32 significant findings, 104 incidental findings, and 22 preexisting abnormalities. Four children with significant findings required immediate intervention. They all had red flags in both history and physical examination, and 3 of 4 children had known preexisting pathology; 1 child had nonaccidental trauma. Only 1 child had a significantly abnormal CT with no identifiable red flags; this child was admitted for observation and was discharged within 24 hours. Approximately a third of children had no readily identifiable red flag for the CT scans that they received. Of note, 20% of the young children had received more than 1 head CT scan to date, and 6% had between 6 and 20 scans.
Conclusions: Every child in this sample who required emergency intervention had red flags on history and physical examination. The 35% of CT scans performed in young children without red flags did not contribute usefully to their acute management. (c) 2012 Published by Elsevier Inc.
C1 [Lateef, Tarannum M.] George Washington Univ, Childrens Natl Med Ctr, Sch Med, Dept Neurol, Washington, DC 20010 USA.
[Lateef, Tarannum M.; Kriss, Rebecca; Carpenter, Karen] Inova Fairfax Hosp Children, Falls Church, VA 22042 USA.
[Nelson, Karin B.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Lateef, TM (reprint author), George Washington Univ, Childrens Natl Med Ctr, Sch Med, Dept Neurol, Washington, DC 20010 USA.
EM tlateef@childrensnational.org
NR 42
TC 2
Z9 2
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0735-6757
EI 1532-8171
J9 AM J EMERG MED
JI Am. J. Emerg. Med.
PD OCT
PY 2012
VL 30
IS 8
BP 1507
EP 1514
DI 10.1016/j.ajem.2011.12.018
PG 8
WC Emergency Medicine
SC Emergency Medicine
GA 020MI
UT WOS:000309813900028
PM 22386353
ER
PT J
AU Rubio-Tapia, A
Ludvigsson, JF
Brantner, TL
Murray, JA
Everhart, JE
AF Rubio-Tapia, Alberto
Ludvigsson, Jonas F.
Brantner, Tricia L.
Murray, Joseph A.
Everhart, James E.
TI The Prevalence of Celiac Disease in the United States
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID RECOMBINANT TISSUE TRANSGLUTAMINASE; HEALTHY BLOOD-DONORS; AT-RISK;
ANTIBODIES; MULTICENTER; DIAGNOSIS; MANAGEMENT; MORTALITY; CHILDREN;
FINLAND
AB OBJECTIVES: The prevalence of celiac disease (CD) in the United States is unknown. We sought to estimate CD prevalence nationwide by using a nationally representative sample.
METHODS: This study included 7,798 persons aged 6 years or older who participated in the National Health and Nutrition Examination Survey 2009-2010. Serum samples from all participants were tested for immunoglobulin A (IgA) tissue transglutaminase antibodies and, if findings were abnormal, also for IgA endomysial antibodies. Information about prior diagnosis of CD and use of a gluten-free diet (GFD) was obtained by direct interview. CD was defined as having either double-positive serology (serologically diagnosed CD) or a reported diagnosis of CD by a doctor or other health-care professional and being on a GFD (reported clinical diagnosis of CD).
RESULTS: CD was found in 35 participants, 29 of whom were unaware of their diagnosis. Median age was 45 years (interquartile range, 23-66 years); 20 were women and 29 were non-Hispanic white. The prevalence of CD in the United States was 0.71% (95% confidence interval (CI), 0.58-0.86%), with 1.01% (95% CI, 0.78-1.31%) among non-Hispanic whites. In all, 55 participants reported following a GFD, which corresponded to a prevalence of 0.63% (95% CI, 0.36-1.07%).
CONCLUSIONS: The prevalence of CD in the United States was 0.71% (1 in 141), similar to that found in several European countries. However, most cases were undiagnosed. CD was rare among minority groups but affected 1% of non-Hispanic whites. Most persons who were following a GFD did not have a diagnosis of CD.
C1 [Rubio-Tapia, Alberto; Brantner, Tricia L.; Murray, Joseph A.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN 55905 USA.
[Ludvigsson, Jonas F.] Orebro Univ Hosp, Dept Pediat, Orebro, Sweden.
[Ludvigsson, Jonas F.] Karolinska Univ Hosp, Dept Med, Stockholm, Sweden.
[Ludvigsson, Jonas F.] Karolinska Inst, Stockholm, Sweden.
[Everhart, James E.] NIDDKD, US Dept HHS, NIH, Bethesda, MD 20892 USA.
RP Murray, JA (reprint author), Mayo Clin, Div Gastroenterol & Hepatol, 200 1st St SW, Rochester, MN 55905 USA.
EM murray.joseph@mayo.edu
RI Ludvigsson, Jonas/A-8560-2012;
OI Ludvigsson, Jonas/0000-0003-1024-5602; murray,
joseph/0000-0003-1941-9090
FU Centers for Disease Control [M26561]; American College of
Gastroenterology Junior Faculty Development Award; Swedish Research
Council; Fulbright Commission
FX This work was supported by the Centers for Disease Control Contract No.
M26561, American College of Gastroenterology Junior Faculty Development
Award (A.R.-T.), the Swedish Research Council and the Fulbright
Commission (J.F.L.).
NR 53
TC 185
Z9 188
U1 7
U2 51
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD OCT
PY 2012
VL 107
IS 10
BP 1538
EP 1544
DI 10.1038/ajg.2012.219
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 018XK
UT WOS:000309701000013
PM 22850429
ER
PT J
AU Browne, ML
Carter, TC
Kay, DM
Kuehn, D
Brody, LC
Romitti, PA
Liu, AY
Caggana, M
Druschel, CM
Mills, JL
AF Browne, Marilyn L.
Carter, Tonia C.
Kay, Denise M.
Kuehn, Devon
Brody, Lawrence C.
Romitti, Paul A.
Liu, Aiyi
Caggana, Michele
Druschel, Charlotte M.
Mills, James L.
TI Evaluation of Genes Involved in Limb Development, Angiogenesis, and
Coagulation as Risk Factors for Congenital Limb Deficiencies
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE limb deficiencies; polymorphisms; FGF10
ID MALFORMATIONS; DEFECTS; FGF10; MUTATIONS; VARIANTS
AB We conducted a population-based case-control study of single nucleotide polymorphisms (SNPs) in selected genes to find common variants that play a role in the etiology of limb deficiencies (LDs). Included in the study were 389 infants with LDs of unknown cause and 980 unaffected controls selected from all births in New York State (NYS) for the years 1998-2005. We used cases identified from the NYS Department of Health (DOH) Congenital Malformations Registry. Genotypes were obtained for 132 SNPs in genes involved in limb development (SHH, WNT7A, FGF4, FGF8, FGF10, TBX3, TBX5, SALL4, GREM1, GDF5, CTNNB1, EN1, CYP26A1, CYP26B1), angiogenesis (VEGFA, HIF1A, NOS3), and coagulation (F2, F5, MTHFR). Genotype call rates were >97% and SNPs were tested for departure from Hardy-Weinberg expectations by race/ethnic subgroups. For each SNP, odds ratios (OR)s and confidence intervals (CI)s were estimated and corrected for multiple comparisons for all LDs combined and for LD subtypes. Among non-Hispanic white infants, associations between FGF10 SNPs rs10805683 and rs13170645 and all LDs combined were statistically significant following correction for multiple testing (OR = 1.99; 95% CI = 1.43-2.77; uncorrected P = 0.000043 for rs10805683 heterozygous genotype, and OR = 2.37; 95% CI = 1.48-3.78; uncorrected P = 0.00032 for rs13170645 homozygous minor genotype). We also observed suggestive evidence for associations with SNPs in other genes including CYP26B1 and WNT7A. Animal studies have shown that FGF10 induces formation of the apical ectodermal ridge and is necessary for limb development. Our data suggest that common variants in FGF10 increase the risk for a wide range of non-syndromic limb deficiencies. (C) 2012 Wiley Periodicals, Inc.
C1 [Browne, Marilyn L.; Druschel, Charlotte M.] New York State Dept Hlth, Congenital Malformat Registry, Troy, NY USA.
[Browne, Marilyn L.; Druschel, Charlotte M.] SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Rensselaer, NY USA.
[Carter, Tonia C.; Kuehn, Devon; Liu, Aiyi; Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Bethesda, MD USA.
[Kay, Denise M.; Caggana, Michele] New York State Dept Hlth, Div Genet, Wadsworth Ctr, Albany, NY USA.
[Kuehn, Devon] USUHS, Dept Pediat, Bethesda, MD USA.
[Brody, Lawrence C.] NHGRI, Genome Technol Branch, NIH, DHHS, Bethesda, MD 20892 USA.
[Romitti, Paul A.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA.
RP Browne, ML (reprint author), ESP, NYSDOH, Corning Tower,Room 1203, Albany, NY 12237 USA.
EM mlb10@health.state.ny.us
OI Kay, Denise/0000-0002-9928-2698; Liu, Aiyi/0000-0002-6618-5082
FU National Institutes of Health [HHSN267200703431C]; Eunice Kennedy
Shriver National Institute of Child Health and Human Development NICHD
[N01-DK-7-3431]; National Human Genome Research Institute
FX Research support: Intramural Research Program of the National Institutes
of Health; Contract number: HHSN267200703431C; Research support: Eunice
Kennedy Shriver National Institute of Child Health and Human Development
NICHD; Contract number: N01-DK-7-3431; Research support: National Human
Genome Research Institute.
NR 21
TC 6
Z9 7
U1 2
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD OCT
PY 2012
VL 158A
IS 10
BP 2463
EP 2472
DI 10.1002/ajmg.a.35565
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 023XK
UT WOS:000310070700014
PM 22965740
ER
PT J
AU Lee, SM
Romero, R
Lee, YJ
Park, IS
Park, CW
Yoon, BH
AF Lee, Seung Mi
Romero, Roberto
Lee, You Jeong
Park, In Sook
Park, Chan-Wook
Yoon, Bo Hyun
TI Systemic inflammatory stimulation by microparticles derived from hypoxic
trophoblast as a model for inflammatory response in preeclampsia
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE hypoxia; inflammation; microparticles; preeclampsia; trophoblast
ID SYNCYTIOTROPHOBLAST MICROVILLOUS MEMBRANES; NORMAL-PREGNANCY;
ENDOTHELIAL-CELLS; EXPRESSION; PLACENTA; INVASION; WOMEN; MODULATION;
APOPTOSIS; ARTERIES
AB OBJECTIVE: To determine whether trophoblast-derived microparticles can induce different inflammatory responses of the peripheral blood mononuclear cells depending upon the state of trophoblast when the microparticles are generated.
STUDY DESIGN: A trophoblast-derived cell line (ATCC no. CRL-1584) was cultured under normal or hypoxic conditions. Microparticles were isolated from the cell culture supernatants (microparticles from normal trophoblast; microparticles from hypoxic trophoblast). Peripheral blood mononuclear cells were cultured alone or cocultured with either microparticles from normal trophoblast or microparticles from hypoxic trophoblast.
RESULTS: After 48 hours, the peripheral blood mononuclear cells cocultured with microparticles from normal trophoblast released higher concentrations of interleukin-6 than peripheral blood mononuclear cells cultured alone. The peripheral blood mononuclear cells cocultured with microparticles from hypoxic trophoblast showed higher concentration of interleukin-6 and tumor necrosis factor alpha than peripheral blood mononuclear cells cocultured with microparticles from normal trophoblast, after 24 hours and 48 hours.
CONCLUSION: More intense and rapid inflammatory response of peripheral blood mononuclear cells was observed with microparticles from hypoxic trophoblast than with microparticles from normal trophoblast. This difference might explain the exaggerated systemic inflammatory response as a result of placental hypoxia in preeclampsia.
C1 [Park, In Sook; Park, Chan-Wook; Yoon, Bo Hyun] Seoul Natl Univ, Dept Obstet & Gynecol, Coll Med, Seoul 110744, South Korea.
Seoul Natl Univ, Dept Pathol, Coll Med, Seoul 110744, South Korea.
Seoul Natl Univ, Boramae Med Ctr, Seoul Metropolitan Govt, Dept Obstet & Gynecol, Seoul 110744, South Korea.
[Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
RP Yoon, BH (reprint author), Seoul Natl Univ, Dept Obstet & Gynecol, Coll Med, Seoul 110744, South Korea.
EM yoonbh@snu.ac.kr
RI Park, Chan-Wook/J-5498-2012
FU National Research Foundation of Korea (NRF) [2011-0000195]; Government
of Korea (MEST)
FX This research was supported by the National Research Foundation of Korea
(NRF) grant number 2011-0000195, funded by the Government of Korea
(MEST).
NR 43
TC 2
Z9 3
U1 0
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD OCT
PY 2012
VL 207
IS 4
AR 337.e1
DI 10.1016/j.ajog.2012.06.047
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 025SA
UT WOS:000310212000046
PM 23021701
ER
PT J
AU Carter, LG
Lewis, KN
Wilkerson, DC
Tobia, CM
Tenlep, SYN
Shridas, P
Garcia-Cazarin, ML
Wolff, G
Andrade, FH
Charnigo, RJ
Esser, KA
Egan, JM
de Cabo, R
Pearson, KJ
AF Carter, Lindsay G.
Lewis, Kaitlyn N.
Wilkerson, Donald C.
Tobia, Christine M.
Tenlep, Sara Y. Ngo
Shridas, Preetha
Garcia-Cazarin, Mary L.
Wolff, Gretchen
Andrade, Francisco H.
Charnigo, Richard J.
Esser, Karyn A.
Egan, Josephine M.
de Cabo, Rafael
Pearson, Kevin J.
TI Perinatal exercise improves glucose homeostasis in adult offspring
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE running; pregnancy; programming; mice
ID HIGH-FAT DIET; GESTATIONAL DIABETES-MELLITUS; SIGNALING PROTEIN
EXPRESSION; SHORT-TERM-MEMORY; LOW-BIRTH-WEIGHT; DEVELOPMENTAL ORIGINS;
INSULIN-RESISTANCE; PHYSICAL-ACTIVITY; ENVIRONMENTAL ENRICHMENT;
MATERNAL EXERCISE
AB Carter LG, Lewis KN, Wilkerson DC, Tobia CM, Tenlep SY, Shridas P, Garcia-Cazarin ML, Wolff G, Andrade FH, Charnigo RJ, Esser KA, Egan JM, de Cabo R, Pearson KJ. Perinatal exercise improves glucose homeostasis in adult offspring. Am J Physiol Endocrinol Metab 303: E1061-E1068, 2012. First published August 28, 2012; doi: 10.1152/ajpendo.00213.2012.-Emerging research has shown that subtle factors during pregnancy and gestation can influence long-term health in offspring. In an attempt to be proactive, we set out to explore whether a nonpharmacological intervention, perinatal exercise, might improve offspring health. Female mice were separated into sedentary or exercise cohorts, with the exercise cohort having voluntary access to a running wheel prior to mating and during pregnancy and nursing. Offspring were weaned, and analyses were performed on the mature offspring that did not have access to running wheels during any portion of their lives. Perinatal exercise caused improved glucose disposal following an oral glucose challenge in both female and male adult offspring (P < 0.05 for both). Blood glucose concentrations were reduced to lower values in response to an intraperitoneal insulin tolerance test for both female and male adult offspring of parents with access to running wheels (P < 0.05 and P < 0.01, respectively). Male offspring from exercised dams showed increased percent lean mass and decreased fat mass percent compared with male offspring from sedentary dams (P < 0.01 for both), but these parameters were unchanged in female offspring. These data suggest that short-term maternal voluntary exercise prior to and during healthy pregnancy and nursing can enhance long-term glucose homeostasis in offspring.
C1 [Carter, Lindsay G.; Wilkerson, Donald C.; Tobia, Christine M.; Tenlep, Sara Y. Ngo; Pearson, Kevin J.] Univ Kentucky, Grad Ctr Nutr Sci, Coll Med, Lexington, KY 40536 USA.
[Lewis, Kaitlyn N.; de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
[Lewis, Kaitlyn N.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
[Lewis, Kaitlyn N.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA.
[Wilkerson, Donald C.] Owensboro Canc Res Program, Owensboro, KY USA.
[Shridas, Preetha] Univ Kentucky, Dept Internal Med, Coll Med, Lexington, KY 40536 USA.
[Garcia-Cazarin, Mary L.; Wolff, Gretchen; Andrade, Francisco H.; Esser, Karyn A.] Univ Kentucky, Dept Physiol, Coll Med, Lexington, KY 40536 USA.
[Charnigo, Richard J.] Univ Kentucky, Dept Biostat, Coll Publ Hlth, Lexington, KY 40536 USA.
[Egan, Josephine M.] NIA, Lab Clin Invest, NIH, Baltimore, MD 21224 USA.
RP Pearson, KJ (reprint author), Univ Kentucky, Grad Ctr Nutr Sci, Coll Med, Wethington Bldg,Rm 591,900 S Limestone St, Lexington, KY 40536 USA.
EM kevin.pearson@uky.edu
RI Andrade, Francisco/F-1258-2011; de Cabo, Rafael/J-5230-2016;
OI Andrade, Francisco/0000-0002-2460-5798; de Cabo,
Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
FU National Institutes of Health [NIH] [NIAMS-AR-55246, R01-EY-012998,
R01-DK-090460]; National Institutes of Health [research core of the
COBRE on Obesity and Cardiovascular Diseases from the National Center
for Research Resources] [5P20-RR-021954-05]; National Institutes of
Health [National Institute of General Medical Sciences]
[8P20-GM-103527-05]; NIH training grant [DK-07778]; Intramural Research
Program of the NIA, NIH
FX This study was supported by the National Institutes of Health [NIH;
NIAMS-AR-55246 to K. A. Esser, R01-EY-012998 to F. H. Andrade,
R01-DK-090460 to K. J. Pearson, and the research core of the COBRE on
Obesity and Cardiovascular Diseases from the National Center for
Research Resources (5P20-RR-021954-05) and the National Institute of
General Medical Sciences (8P20-GM-103527-05)]. L. G. Carter was
supported by an NIH training grant (DK-07778). This research was
supported in part by the Intramural Research Program of the NIA, NIH.
NR 49
TC 26
Z9 26
U1 6
U2 16
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD OCT
PY 2012
VL 303
IS 8
BP E1061
EP E1068
DI 10.1152/ajpendo.00213.2012
PG 8
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 022SG
UT WOS:000309982000012
PM 22932781
ER
PT J
AU Gao, XH
Yu, LD
Castro, L
Tucker, CJ
Moore, AB
Xiao, H
Dixon, D
AF Gao, Xiaohua
Yu, Linda
Castro, Lysandra
Tucker, Charles J.
Moore, Alicia B.
Xiao, Hang
Dixon, Darlene
TI An essential role of p27 downregulation in fenvalerate-induced cell
growth in human uterine leiomyoma and smooth muscle cells
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE fibroids; endocrine-disrupting chemical
ID BREAST-CANCER CELLS; PROGNOSTIC-SIGNIFICANCE; INHIBITOR P27(KIP1);
UP-REGULATION; CYCLE ARREST; EXPRESSION; DEREGULATION; PATHWAY;
PHOSPHORYLATION; PROLIFERATION
AB Gao X, Yu L, Castro L, Tucker CJ, Moore AB, Xiao H, Dixon D. An essential role of p27 downregulation in fenvalerate-induced cell growth in human uterine leiomyoma and smooth muscle cells. Am J Physiol Endocrinol Metab 303: E1025-E1035, 2012. First published July 31, 2012; doi: 10.1152/ajpendo.00107.2012.-Previously, we reported that fenvalerate (Fen) promotes proliferation of human uterine leiomyoma (UtLM) cells by enhancing progression of cells from G(0)-G(1) to S phase through molecular mechanisms independent of estrogen receptor-alpha and -beta. The cyclin-dependent kinase (CDK) inhibitor p27, which blocks G(1) to S phase transitions and is an important regulator of CDK2, is often decreased in hormonally regulated diseases, including uterine leiomyomas. Therefore, we were interested in whether Fen could regulate the expression of p27 and whether p27 might play a role in Fen-induced cell proliferation. Expression of p27 in Fentreated UtLM and uterine smooth muscle cells (UtSMCs) was examined. We found that p27 mRNA was significantly downregulated and that protein levels were decreased in both cell types treated with 10 mu M Fen for 24 h compared with respective controls. Overexpression of p27 in UtLM cells and UtSMCs using an adenovirus doxycycline (Dox)-regulated Tet-off system abrogated the proliferative effects of Fen, as evidenced by decreased total cell numbers and BrdU incorporation. Fen treatment increased CDK2 mRNA expression levels; however, overexpression of p27 also abolished this effect. In contrast, Dox treatment dramatically restored the above muted responses. Finally, we utilized siRNA to knock down p27 expression. After transfection, mRNA levels of p27 were downregulated in UtLM cells and UtSMCs and total cell numbers and BrdU incorporation increased significantly compared with nontransfected cells. Fen treatment in the presence of p27 silencing enhanced the increased cell counts and BrdU labeling in UtLM cells and UtSMCs. Taken together, these results indicate that p27 downregulation is critical for Fen-induced cell proliferation.
C1 [Gao, Xiaohua; Yu, Linda; Castro, Lysandra; Moore, Alicia B.; Dixon, Darlene] NIEHS, Mol Pathogenesis Grp, Natl Toxicol Program, Branch Lab,NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Tucker, Charles J.] NIEHS, Lab Signal Transduct, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Gao, Xiaohua; Xiao, Hang] Nanjing Med Univ, Sch Publ Hlth, Dept Toxicol, Nanjing, Jiangsu, Peoples R China.
RP Dixon, D (reprint author), NIEHS, Mol Pathogenesis Grp, Natl Toxicol Program, Branch Lab,NIH,Dept Hlth & Human Serv, POB 12233,MD B3-06,111 TW Alexander Dr,Bldg 101,R, Res Triangle Pk, NC 27709 USA.
EM dixon@niehs.nih.gov
FU National Institutes of Health, the National Institute of Environmental
Health Sciences; National Toxicology Program
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, the National Institute of Environmental
Health Sciences, and the National Toxicology Program.
NR 31
TC 6
Z9 6
U1 1
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
EI 1522-1555
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD OCT
PY 2012
VL 303
IS 8
BP E1025
EP E1035
DI 10.1152/ajpendo.00107.2012
PG 11
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 022SG
UT WOS:000309982000009
PM 22850687
ER
PT J
AU Covian, R
Balaban, RS
AF Covian, Raul
Balaban, Robert S.
TI Cardiac mitochondrial matrix and respiratory complex protein
phosphorylation
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Review
DE kinase; phosphatase; citric acid cycle; oxidative phosphorylation;
protein transport; mitochondria intermembrane space; phosphohistidine;
adenine nucleotide translocase; pyruvate dehydrogenase; branched chain
alpha-ketoacid dehydrogenase
ID CYTOCHROME-C-OXIDASE; ALPHA-KETO ACID; BOVINE HEART-MITOCHONDRIA;
DEPENDENT ANION CHANNEL; IRON-SULFUR PROTEIN; ELECTRON-TRANSFER
FLAVOPROTEIN; SITE-SPECIFIC PHOSPHORYLATION; PERFUSED RAT-HEART; BC(1)
COMPLEX; PYRUVATE-DEHYDROGENASE
AB Covian R, Balaban RS. Cardiac mitochondrial matrix and respiratory complex protein phosphorylation. Am J Physiol Heart Circ Physiol 303: H940-H966, 2012. First published August 10, 2012; doi:10.1152/ajpheart.00077.2012.-It has become appreciated over the last several years that protein phosphorylation within the cardiac mitochondrial matrix and respiratory complexes is extensive. Given the importance of oxidative phosphorylation and the balance of energy metabolism in the heart, the potential regulatory effect of these classical signaling events on mitochondrial function is of interest. However, the functional impact of protein phosphorylation and the kinase/phosphatase system responsible for it are relatively unknown. Exceptions include the well-characterized pyruvate dehydrogenase and branched chain alpha-ketoacid dehydrogenase regulatory system. The first task of this review is to update the current status of protein phosphorylation detection primarily in the matrix and evaluate evidence linking these events with enzymatic function or protein processing. To manage the scope of this effort, we have focused on the pathways involved in energy metabolism. The high sensitivity of modern methods of detecting protein phosphorylation and the low specificity of many kinases suggests that detection of protein phosphorylation sites without information on the mole fraction of phosphorylation is difficult to interpret, especially in metabolic enzymes, and is likely irrelevant to function. However, several systems including protein translocation, adenine nucleotide translocase, cytochrome c, and complex IV protein phosphorylation have been well correlated with enzymatic function along with the classical dehydrogenase systems. The second task is to review the current understanding of the kinase/phosphatase system within the matrix. Though it is clear that protein phosphorylation occurs within the matrix, based on P-32 incorporation and quantitative mass spectrometry measures, the kinase/phosphatase system responsible for this process is ill-defined. An argument is presented that remnants of the much more labile bacterial protein phosphoryl transfer system may be present in the matrix and that the evaluation of this possibility will require the application of approaches developed for bacterial cell signaling to the mitochondria.
C1 [Covian, Raul; Balaban, Robert S.] NHLBI, Cardiac Energet Lab, Bethesda, MD 20817 USA.
RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, 9000 Rockville Pike, Bethesda, MD 20817 USA.
EM physiology@hotmail.com
FU Intramural NIH HHS [Z99 HL999999]
NR 237
TC 40
Z9 41
U1 1
U2 14
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
EI 1522-1539
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD OCT
PY 2012
VL 303
IS 8
BP H940
EP H966
DI 10.1152/ajpheart.00077.2012
PG 27
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 022SC
UT WOS:000309981600003
PM 22886415
ER
PT J
AU Li, LL
Lai, EY
Huang, YN
Eisner, C
Mizel, D
Wilcox, CS
Schnermann, J
AF Li, Lingli
Lai, En Yin
Huang, Yuning
Eisner, Christoph
Mizel, Diane
Wilcox, Christopher S.
Schnermann, Jurgen
TI Renal afferent arteriolar and tubuloglomerular feedback reactivity in
mice with conditional deletions of adenosine 1 receptors
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE stop flow pressure; cre recombinase; nestin; smooth muscle actin
ID INTERMEDIATE-FILAMENT PROTEIN; GLOMERULAR-FILTRATION-RATE; RAT MESANGIAL
CELLS; SMOOTH-MUSCLE; A(2A) RECEPTORS; DEFICIENT MICE; BLOOD-PRESSURE;
NITRIC-OXIDE; EXPRESSION; CALCIUM
AB Li L, Lai EY, Huang Y, Eisner C, Mizel D, Wilcox CS, Schnermann J. Renal afferent arteriolar and tubuloglomerular feedback reactivity in mice with conditional deletions of adenosine 1 receptors. Am J Physiol Renal Physiol 303: F1166-F1175, 2012. First published August 15, 2012; doi:10.1152/ajprenal.00222.2012.-Adenosine 1 receptors (A1AR) have been shown in previous experiments to play a major role in the tubuloglomerular feedback (TGF) constrictor response of afferent arterioles (AA) to increased loop of Henle flow. Overexpression studies have pointed to a critical role of vascular A1AR, but it has remained unclear whether selective deletion of A1AR from smooth muscle cells is sufficient to abolish TGF responsiveness. To address this question, we have determined TGF response magnitude in mice in which vascular A1AR deletion was achieved using the loxP recombination approach with cre recombinase being controlled by a smooth muscle actin promoter (SmCre/A1ARff). Effective vascular deletion of A1AR was affirmed by absence of vasoconstrictor responses to adenosine or cyclohexyl adenosine (CHA) in microperfused AA. Elevation of loop of Henle flow from 0 to 30 nl/min caused a 22.1 +/- 3.1% reduction of stop flow pressure in control mice and of 7.2 +/- 1.5% in SmCre/A1ARff mice (P < 0.001). Maintenance of residual TGF activity despite absence of A1AR-mediated responses in AA suggests participation of extravascular A1AR in TGF. Support for this notion comes from the observation that deletion of A1ARff by nestin-driven cre causes an identical TGF response reduction (7.3 +/- 2.4% in NestinCre/A1ARff vs. 20.3 +/- 2.7% in controls), whereas AA responsiveness was reduced but not abolished. A1AR on AA smooth muscle cells are primarily responsible for TGF activation, but A1AR on extravascular cells, perhaps mesangial cells, appear to contribute to the TGF response.
C1 [Li, Lingli; Huang, Yuning; Eisner, Christoph; Mizel, Diane; Schnermann, Jurgen] NIDDKD, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA.
[Lai, En Yin; Wilcox, Christopher S.] Georgetown Univ, Div Nephrol & Hypertens, Kidney & Vasc Res Ctr, Washington, DC USA.
RP Schnermann, J (reprint author), NIDDKD, Kidney Dis Branch, NIH, Bldg 10,Rm 4D51,10 Ctr Dr,MSC 1370, Bethesda, MD 20892 USA.
EM jurgens@intra.niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Institutes of Health [DK-36079, DK-49870, HL-68686]
FX This work was supported by the intramural research program of the
National Institute of Diabetes and Digestive and Kidney Diseases. C. S.
Wilcox was supported by National Institutes of Health Grants DK-36079,
DK-49870, and HL-68686.
NR 35
TC 8
Z9 8
U1 0
U2 7
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD OCT
PY 2012
VL 303
IS 8
BP F1166
EP F1175
DI 10.1152/ajprenal.00222.2012
PG 10
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 022SA
UT WOS:000309981400007
PM 22896040
ER
PT J
AU Rogers, NM
Yao, MY
Novelli, EM
Thomson, AW
Roberts, DD
Isenberg, JS
AF Rogers, Natasha M.
Yao, Mingyi
Novelli, Enrico M.
Thomson, Angus W.
Roberts, David D.
Isenberg, Jeffrey S.
TI Activated CD47 regulates multiple vascular and stress responses:
implications for acute kidney injury and its management
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Review
DE thrombospondin-1; CD47; kidney injury; nitric oxide; reactive oxygen
species; ischemia-reperfusion injury; transplant
ID ISCHEMIA-REPERFUSION INJURY; INTEGRIN-ASSOCIATED PROTEIN; SOLUBLE
GUANYLATE-CYCLASE; TUBULAR EPITHELIAL-CELLS; FIBROTIC RENAL-DISEASE;
NITRIC-OXIDE SYNTHASE; TGF-BETA; ISCHEMIA/REPERFUSION INJURY; OXIDATIVE
STRESS; TUBULOINTERSTITIAL FIBROSIS
AB Rogers NM, Yao M, Novelli EM, Thomson AW, Roberts DD, Isenberg JS. Activated CD47 regulates multiple vascular and stress responses: implications for acute kidney injury and its management. Am J Physiol Renal Physiol 303: F1117-F1125, 2012. First published August 8, 2012; doi:10.1152/ajprenal.00359.2012.-Ischemia-reperfusion injury (IRI) remains a significant source of early and delayed renal transplant failure. Therapeutic interventions have yet to resolve this ongoing clinical challenge although the reasons for this remain unclear. The cell surface receptor CD47 is widely expressed on vascular cells and in tissues. It has one known soluble ligand, the stress-released matricellular protein thrombospondin-1 (TSP1). The TSP1-CD47 ligand receptor axis controls a number of important cellular processes, inhibiting survival factors such as nitric oxide, cGMP, cAMP, and VEGF, while activating injurious pathways such as production of reactive oxygen species. A role of CD47 in renal IRI was recently revealed by the finding that the TSP1-CD47 axis is induced in renal tubular epithelial cells (RTEC) under hypoxia and following IRI. The absence of CD47 in knockout mice increases survival, mitigates RTEC damage, and prevents subsequent kidney failure. Conversely, therapeutic blockade of TSP1-CD47 signaling provides these same advantages to wild-type animals. Together, these findings suggest an important role for CD47 in renal IRI as a proximate promoter of injury and as a novel therapeutic target.
C1 [Rogers, Natasha M.; Yao, Mingyi; Novelli, Enrico M.; Isenberg, Jeffrey S.] Univ Pittsburgh, Sch Med, Vasc Med Inst, Pittsburgh, PA USA.
[Isenberg, Jeffrey S.] Univ Pittsburgh, Sch Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA.
[Isenberg, Jeffrey S.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA.
[Rogers, Natasha M.; Thomson, Angus W.] Univ Pittsburgh, Sch Med, Starzl Transplantat Inst, Pittsburgh, PA USA.
[Roberts, David D.] NCI, NIH, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Isenberg, JS (reprint author), E1240 Biomed Sci Tower,Rm E1258,200 Lothrop St, Pittsburgh, PA 15261 USA.
EM jsi5@pitt.edu
RI Roberts, David/A-9699-2008
OI Roberts, David/0000-0002-2481-2981
FU National Institutes of Health (NIH) [R01 HL-108954, 1P01HL103455-01];
American Heart Association [11BGIA7210001]; Institute for Transfusion
Medicine; Hemophilia Center of Western Pennsylvania; National Cancer
Institute; Australian NHMRC [APP1016276]
FX This work was supported by the National Institutes of Health (NIH)
Grants R01 HL-108954 (to J. S. Isenberg) and 1P01HL103455-01, the
American Heart Association (11BGIA7210001 to J. S. Isenberg), the
Institute for Transfusion Medicine and the Hemophilia Center of Western
Pennsylvania (to J. S. Isenberg), the Intramural Research Program of the
National Cancer Institute (to D. D. Roberts), and by the Australian
NHMRC (APP1016276 C. J. Martin Award to N. M. Rogers).
NR 105
TC 10
Z9 10
U1 0
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD OCT
PY 2012
VL 303
IS 8
BP F1117
EP F1125
DI 10.1152/ajprenal.00359.2012
PG 9
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 022SA
UT WOS:000309981400001
PM 22874763
ER
PT J
AU Ayode, D
McBride, CM
de Heer, H
Watanabe, E
Gebreyesus, T
Tadele, G
Tora, A
Davey, G
AF Ayode, Desta
McBride, Colleen M.
de Heer, Hendrik
Watanabe, Emi
Gebreyesus, Tsega
Tadele, Getnet
Tora, Abebayehu
Davey, Gail
TI The Association of Beliefs About Heredity with Preventive and
Interpersonal Behaviors in Communities Affected by Podoconiosis in Rural
Ethiopia
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID NON-FILARIAL ELEPHANTIASIS; SOUTHERN ETHIOPIA; SELF-REGULATION; HEALTH
BEHAVIOR; DISEASE; PERSPECTIVE; GENOMICS; STIGMA; MODEL; INFORMATION
AB Little is known about how beliefs about heredity as a cause of health conditions might influence preventive and interpersonal behaviors among those individuals with low genetic and health literacy. We explored causal beliefs about podoconiosis, a neglected tropical disease (NTD) endemic in Ethiopia. Podoconiosis clusters in families but can be prevented if individuals at genetically high risk wear shoes consistently. Adults (N = 242) from four rural Ethiopian communities participated in qualitative assessments of beliefs about the causes of podoconiosis. Heredity was commonly mentioned, with heredity being perceived as (1) the sole cause of podoconiosis, (2) not a causal factor, or (3) one of multiple causes. These beliefs influenced the perceived controllability of podoconiosis and in turn, whether individuals endorsed preventive and interpersonal stigmatizing behaviors. Culturally informed education programs that increase the perceived controllability of stigmatized hereditary health conditions like podoconiosis have promise for increasing preventive behaviors and reducing interpersonal stigma.
C1 [McBride, Colleen M.; Watanabe, Emi] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Ayode, Desta; Tadele, Getnet] Univ Addis Ababa, Coll Social Sci, Addis Ababa, Ethiopia.
[de Heer, Hendrik] No Arizona Univ, Coll Hlth & Human Serv, Dept Phys Therapy & Athlet Training, Flagstaff, AZ 86011 USA.
[Gebreyesus, Tsega] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
[Tora, Abebayehu] Wolaita Sodo Univ, Dept Sociol, Sodo, Ethiopia.
[Davey, Gail] Brighton & Sussex Med Sch, Brighton, E Sussex, England.
RP McBride, CM (reprint author), NHGRI, Social & Behav Res Branch, NIH, Bldg 31,MSC 2073,31 Ctr Dr,Room B1B54, Bethesda, MD 20892 USA.
EM destaayode@yahoo.com; cmcbride@mail.nih.gov; hendrik.deheer@nau.edu;
watanabee@mail.nih.gov; tgebreye@jhsph.edu; getnett2001@yahoo.com;
abezed@yahoo.com; G.Davey@bsms.ac.uk
RI de Heer, Hendrik/D-3192-2013;
OI de Heer, Hendrik/0000-0002-9241-5021; Davey, Gail/0000-0003-2796-7468
FU Intramural Research Program of the Social & Behavioral Science Branch
(SBRB); National Human Genome Research Institutes, National Institutes
of Health
FX This project was supported by the Intramural Research Program of the
Social & Behavioral Science Branch (SBRB). The SBRB is supported by the
National Human Genome Research Institutes, National Institutes of
Health.
NR 39
TC 13
Z9 13
U1 0
U2 5
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD OCT
PY 2012
VL 87
IS 4
BP 623
EP 630
DI 10.4269/ajtmh.2012.12-0204
PG 8
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 020FS
UT WOS:000309795000007
PM 22826482
ER
PT J
AU Cukras, CA
Wong, WT
Caruso, R
Cunningham, D
Zein, W
Sieving, P
AF Cukras, Catherine A.
Wong, Wai T.
Caruso, Rafael
Cunningham, Denise
Zein, Wadih
Sieving, Paul
TI Fundus Autofluorescence Patterns in Stargardt Disease Over Time Reply
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Letter
C1 [Cukras, Catherine A.] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA.
[Cukras, Catherine A.; Caruso, Rafael; Zein, Wadih; Sieving, Paul] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Wong, Wai T.] NEI, Off Sci Director, NIH, Bethesda, MD 20892 USA.
[Cunningham, Denise] NEI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
RP Cukras, CA (reprint author), NEI, Div Epidemiol & Clin Res, NIH, 10 Ctr Dr,Bldg 10,Room 10C438, Bethesda, MD 20892 USA.
EM cukrasc@nei.nih.gov
RI Wong, Wai/B-6118-2017
OI Wong, Wai/0000-0003-0681-4016
NR 1
TC 0
Z9 0
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD OCT
PY 2012
VL 130
IS 10
BP 1354
EP 1355
PG 2
WC Ophthalmology
SC Ophthalmology
GA 016TX
UT WOS:000309543500032
PM 23753838
ER
PT J
AU Cookson, MR
AF Cookson, Mark R.
TI Cellular effects of LRRK2 mutations
SO BIOCHEMICAL SOCIETY TRANSACTIONS
LA English
DT Article
DE autophagy; cell death; inclusion body; leucine-rich repeat kinase 2
(LRRK2); neurite; Parkinson's disease
ID REPEAT KINASE 2; PARKINSONS-DISEASE; NEURONAL TOXICITY; ALPHA-SYNUCLEIN;
PROTEIN; AUTOPHAGY; LOCALIZATION; MICE; NEURODEGENERATION; DEGRADATION
AB Mutations in LRRK2 (leucine-rich repeat kinase 2) are a relatively common cause of inherited PD (Parkinson's disease), but the mechanism(s) by which mutations lead to disease are poorly understood. In the present paper, I discuss what is known about LRRK2 in cellular models, focusing specifically on assays that have been used to tease apart the effects of LRRK2 mutations on cellular phenotypes. LRRK2 expression has been suggested to cause loss of neuronal viability, although because it also has a strong effect on the length of neurites on these cells, whether this is true toxicity or not is unclear. Also, LRRK2 mutants can promote the redistribution of LRRK2 from diffuse cytosolic staining to more discrete structures, at least at high expression levels achieved in transfection experiments. The relevance of these phenotypes for PD is not yet clear, and a great deal of work is needed to understand them in more depth.
C1 NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, Bethesda, MD 20892 USA.
RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, 35 Convent Dr, Bethesda, MD 20892 USA.
EM cookson@mail.nih.gov
FU National Institutes of Health, National Institute on Aging
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute on Aging.
NR 49
TC 10
Z9 10
U1 1
U2 8
PU PORTLAND PRESS LTD
PI LONDON
PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND
SN 0300-5127
J9 BIOCHEM SOC T
JI Biochem. Soc. Trans.
PD OCT
PY 2012
VL 40
BP 1070
EP 1073
DI 10.1042/BST20120165
PN 5
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 016JD
UT WOS:000309513200025
PM 22988867
ER
PT J
AU Thomas, JD
Cui, HT
North, PJ
Hofer, T
Rader, C
Burke, TR
AF Thomas, Joshua D.
Cui, Huiting
North, Patrick J.
Hofer, Thomas
Rader, Christoph
Burke, Terrence R., Jr.
TI Application of Strain-Promoted Azide-Alkyne Cycloaddition and Tetrazine
Ligation to Targeted Fc-Drug Conjugates
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID FREE CLICK CHEMISTRY; BIOCONJUGATION; REACTIVITY; CANCER; COPPER;
FUNCTIONALIZATION; ANTIBODIES; LINKER
AB We have previously described an approach whereby antibody Fc fragments harboring a single C-terminal selenocysteine residue (Fc-Sec) are directed against a variety of targets by changing the peptide or small molecule to which they are conjugated. In the present work, we describe methodology for improving the efficacy of these Fc-Sec conjugates by incorporating cytotoxic drugs. The Fc-Sec protein is first programmed to target specific tumor cell types by attachment of a bifunctional linker that contains a "clickable" handle (e.g., cyclobutane or cyclooctyne) in addition to a tumor cell-binding peptide or small molecule. Following Fc-Sec conjugation, a cytotoxic warhead is then attached by cycloaddition reactions of tetrazine or azide-containing linker. To validate this approach, we used a model system in which folic acid (FA) is the targeting moiety and a disulfide-linked biotin moiety serves as a cytotoxic drug surrogate. We demonstrated successful targeting of Fc-Sec proteins to folate-receptor expressing tumor cells. Tetrazine ligation was found to be an efficient method for biotin "arming" of the folate-targeted Fc-Sec proteins. We also report novel bioconjugation methodologies that use [4 + 2] cycloaddition reactions between tetrazines and cyclooctynes.
C1 [Thomas, Joshua D.; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, NIH, Frederick, MD 21701 USA.
[Cui, Huiting; North, Patrick J.; Hofer, Thomas; Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
RP Burke, TR (reprint author), NCI, Biol Chem Lab, NIH, Frederick, MD 21701 USA.
EM tburke@helix.nih.gov
RI Burke, Terrence/N-2601-2014
FU NIH, Center for Cancer Research, Frederick National Laboratory for
Cancer Research; National Cancer Institute, National Institutes of
Health
FX This work was supported by the Intramural Research Program of the NIH,
Center for Cancer Research, Frederick National Laboratory for Cancer
Research and the National Cancer Institute, National Institutes of
Health. The content of this publication does not necessarily reflect the
views or policies of the Department of Health and Human Services, nor
does mention of trade names, commercial products, or organizations imply
endorsement by the U.S. Government.
NR 30
TC 19
Z9 19
U1 0
U2 74
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD OCT
PY 2012
VL 23
IS 10
BP 2007
EP 2013
DI 10.1021/bc300052u
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 020ZL
UT WOS:000309855000002
PM 22988967
ER
PT J
AU Morris, SK
Awasthi, S
Khera, A
Bassani, DG
Kang, G
Parashar, UD
Kumar, R
Shet, A
Glass, RI
Jha, P
AF Morris, Shaun K.
Awasthi, Shally
Khera, Ajay
Bassani, Diego G.
Kang, Gagandeep
Parashar, Umesh D.
Kumar, Rajesh
Shet, Anita
Glass, Roger I.
Jha, Prabhat
CA Million Death Study Collaborators
TI Rotavirus mortality in India: estimates based on a nationally
representative survey of diarrhoeal deaths
SO BULLETIN OF THE WORLD HEALTH ORGANIZATION
LA English
DT Article
ID CHILD-MORTALITY; VACCINE; DISEASE; EFFICACY; SAFETY; GASTROENTERITIS;
IMMUNIZATION; INEQUITY; INFANTS
AB Objective To estimate the number of rotavirus-associated deaths among Indian children younger than five years.
Methods We surveyed more than 23 000 child deaths from a nationally representative survey of 1.1 million Indian households during 2001-2003. Diarrhoeal deaths were characterized by region, age and sex and were combined with the proportion of deaths attributable to rotavirus, as determined by hospital microbiologic data collected by the Indian Rotavirus Strain Surveillance Network from December 2005 to November 2007. Rotavirus vaccine efficacy data from clinical trials in developing countries were used to estimate the number of deaths preventable by a national vaccination programme. Data were analysed using Stata SE version 10.
Findings Rotavirus caused an estimated 113 000 deaths (99% confidence interval, CI: 86 000-155 000); 50% (54 700) and 75% (85 400) occurred before one and two years of age, respectively. One child in 242 died from rotavirus infection before five years of age. Rotavirus-associated mortality rates overall, among girls and among boys were 4.14 (99% CI: 3.14-5.68), 4.89 (99% CI: 3.75-6.79) and 3.45 (99% CI: 2.58-4.66) deaths per 1000 live births, respectively. Rates were highest in Bihar, Uttar Pradesh and Madhya Pradesh, which together accounted for >50% of deaths (64 400) nationally. Rotavirus vaccine could prevent 41 000-48 000 deaths among children aged 3-59 months.
Conclusion The burden of rotavirus-associated mortality is high among Indian children, highlighting the potential benefits of rotavirus vaccination.
C1 [Morris, Shaun K.] Univ Toronto, Hosp Sick Children, Div Infect Dis, Toronto, ON M5G 1X8, Canada.
[Awasthi, Shally] King Georges Med Univ, Dept Paediat, Lucknow, Uttar Pradesh, India.
[Khera, Ajay] Govt India, Minist Hlth & Family Welf, New Delhi, India.
[Bassani, Diego G.] Univ Toronto, Hosp Sick Children, Dept Paediat, Toronto, ON M5G 1X8, Canada.
[Kang, Gagandeep] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India.
[Parashar, Umesh D.] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
[Kumar, Rajesh] Post Grad Inst Med Educ, Sch Publ Hlth, Chandigarh, India.
[Shet, Anita] St Johns Natl Acad Hlth Sci, Dept Paediat, Bangalore, Karnataka, India.
[Glass, Roger I.] Fogarty Int Ctr, Bethesda, MD USA.
[Jha, Prabhat] Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Ctr Global Hlth Res, Toronto, ON M5G 1X8, Canada.
RP Morris, SK (reprint author), Univ Toronto, Hosp Sick Children, Div Infect Dis, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
EM shaun.morris@mail.utoronto.ca
OI Shet, Anita/0000-0002-7204-8164; Kang, Gagandeep/0000-0002-3656-564X
FU Fogarty International Centre of the United States National Institutes of
Health [R01 TW05991-01]; Canadian Institute of Health Research
[IEG-53506]; International Development Research Centre [102172]; Li Ka
Shing Knowledge Institute; Keenan Research Centre at St Michael's
Hospital, University of Toronto; United States Fund from the Bill &
Melinda Gates Foundation [50140]; Canada Research Chair programme;
Paediatric Scientist Development Program; Sick Kids Foundation;
Paediatric Chairs of Canada; March of Dimes
FX This work was supported by the Fogarty International Centre of the
United States National Institutes of Health (grant R01 TW05991-01), the
Canadian Institute of Health Research, (grant IEG-53506), the
International Development Research Centre (grant 102172), the Li Ka
Shing Knowledge Institute and Keenan Research Centre at St Michael's
Hospital, University of Toronto, and the United States Fund for the
United Nations Children's Fund (subgrant 50140, via a grant from the
Bill & Melinda Gates Foundation for the Child Health Epidemiology
Reference Group). Authors received support from the Canada Research
Chair programme (PJ) and from the Paediatric Scientist Development
Program, the Sick Kids Foundation, the Paediatric Chairs of Canada and
the March of Dimes (SKM). The funders had no role in study design, data
collection and analysis, decision to publish or preparation of the
manuscript.
NR 28
TC 20
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U1 0
U2 9
PU WORLD HEALTH ORGANIZATION
PI GENEVA 27
PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND
SN 0042-9686
J9 B WORLD HEALTH ORGAN
JI Bull. World Health Organ.
PD OCT
PY 2012
VL 90
IS 10
BP 720
EP 727
DI 10.2471/BLT.12.101873
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 021NY
UT WOS:000309893500005
PM 23109739
ER
PT J
AU Jorgensen, TJ
Ruczinski, I
Shugart, YY
Wheless, L
Schaad, YB
Kessing, B
Hoffman-Bolton, J
Helzlsouer, KJ
Kao, WHL
Francis, L
Alani, RM
Strickland, PT
Smith, MW
Alberg, AJ
AF Jorgensen, Timothy J.
Ruczinski, Ingo
Shugart, Yin Yao
Wheless, Lee
Schaad, Yvette Berthier
Kessing, Bailey
Hoffman-Bolton, Judith
Helzlsouer, Kathy J.
Kao, W. H. Linda
Francis, Lesley
Alani, Rhoda M.
Strickland, Paul T.
Smith, Michael W.
Alberg, Anthony J.
TI A population-based study of hedgehog pathway gene variants in relation
to the dual risk of basal cell carcinoma plus another cancer
SO CANCER EPIDEMIOLOGY
LA English
DT Article
DE Skin cancer; Genetics; Polymorphisms; Hedgehog; Vitamin D receptor; Fas
ID NONMELANOMA SKIN-CANCER; SIGNALING PATHWAY; POLYMORPHISM; ASSOCIATION;
SUSCEPTIBILITY; BCC
AB Introduction: A personal history of basal cell carcinoma (BCC) is associated with increased risk of other malignancies, but the reason is unknown. The hedgehog pathway is critical to the etiology of BCC, and is also believed to contribute to susceptibility to other cancers. This study tested the hypothesis that hedgehog pathway and pathway-related gene variants contribute to the increased risk of subsequent cancers among those with a history of BCC. Methods: The study was nested within the ongoing CLUE II cohort study, established in 1989 in Washington County, Maryland, USA. The study consisted of a cancer-free control group (n = 2296) compared to three different groups of cancer cases ascertained through 2007, those diagnosed with: (1) Other (non-BCC) cancer only (n = 2349); (2) BCC only (n = 534); and (3) BCC plus other cancer (n = 446). The frequencies of variant alleles were compared among these four groups for 20 single nucleotide polymorphisms (SNPs) in 6 hedgehog pathway genes (SHH, IHH, PTCH2, SMO, GLI1, SUFU), and also 22 SNPs in VDR and 8 SNPs in FAS, which have cross-talk with the hedgehog pathway. Results: Comparing those with both BCC and other cancer versus those with no cancer, no significant associations were observed for any of the hedgehog pathway SNPs, or for the FAS SNPs. One VDR SNP was nominally significantly associated with the BCC cancer-prone phenotype, rs11574085 [ per minor allele odds ratio (OR) 1.38, 95% confidence interval (CI) 1.05-1.82; p-value = 0.02]. Conclusion: The hedgehog pathway gene SNPs studied, along with the VDR and FAS SNPs studied, are not strongly associated with the BCC cancer-prone phenotype. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Wheless, Lee; Francis, Lesley; Alberg, Anthony J.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA.
[Wheless, Lee; Francis, Lesley; Alberg, Anthony J.] Med Univ S Carolina, Dept Med, Div Epidemiol & Biostat, Charleston, SC 29425 USA.
[Jorgensen, Timothy J.] Georgetown Univ, Sch Med, Dept Radiat Med, Washington, DC USA.
[Ruczinski, Ingo] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Shugart, Yin Yao] NIMH, Div Intramural Res Program, Bethesda, MD USA.
[Schaad, Yvette Berthier; Hoffman-Bolton, Judith; Kao, W. H. Linda; Strickland, Paul T.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Schaad, Yvette Berthier; Kessing, Bailey] NCI, SAIC Frederick Inc, Lab Genom Div, Frederick, MD 21701 USA.
[Hoffman-Bolton, Judith] George W Comstock Ctr Publ Hlth Res & Prevent, Washington Cty, MD USA.
[Helzlsouer, Kathy J.] St Johns Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA.
[Alani, Rhoda M.] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA.
[Strickland, Paul T.] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Smith, Michael W.] NCI, SAIC Frederick Inc, Adv Technol Program, Genet & Genom Grp, Frederick, MD 21701 USA.
RP Alberg, AJ (reprint author), Med Univ S Carolina, Hollings Canc Ctr, 86 Jonathan Lucas St,POB 250955, Charleston, SC 29425 USA.
EM alberg@musc.edu
OI Alani, Rhoda/0000-0003-2741-2665
FU National Cancer Institute (NCI) [R01 CA105069, HHSN26120080001E]; NCI,
Center for Cancer Research; State of Maryland; Maryland Cigarette
Restitution Fund; National Program of Cancer Registries of the CDC
FX This work was supported by the National Cancer Institute (NCI) (R01
CA105069, HHSN26120080001E) and the Intramural Research Program of the
NCI, Center for Cancer Research. This publication does not necessarily
reflect the views or policies of the NCI, NIMH, NIH, U.S. DHHS, the U.S.
government, or the Maryland Cancer Registry, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. government.; Cancer incidence data were provided by the Maryland
Cancer Registry, Center for Cancer Surveillance and Control, Department
of Health and Mental Hygiene, which is funded by the State of Maryland,
the Maryland Cigarette Restitution Fund, and the National Program of
Cancer Registries of the CDC to make the cancer registry data available.
NR 23
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Z9 7
U1 0
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1877-7821
J9 CANCER EPIDEMIOL
JI Cancer Epidemiol.
PD OCT
PY 2012
VL 36
IS 5
BP E288
EP E293
DI 10.1016/j.canep.2012.05.001
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 020NP
UT WOS:000309818500004
PM 22677152
ER
PT J
AU Altiok, E
Aksoy, F
Perk, Y
Taylan, F
Kim, PW
Ilikkan, B
Asal, GT
Goldbach-Mansky, R
Sanal, O
AF Altiok, Ender
Aksoy, Figen
Perk, Yildiz
Taylan, Fulya
Kim, Peter W.
Ilikkan, Barbaros
Asal, Gulten Turkkani
Goldbach-Mansky, Raphaela
Sanal, Ozden
TI A novel mutation in the interleukin-1 receptor antagonist associated
with intrauterine disease onset
SO CLINICAL IMMUNOLOGY
LA English
DT Article
DE Autoinflammatory syndrome; Deficiency of interleukin-1 receptor
antagonist; Intrauterine onset; Immunodeficiency
ID AUTOINFLAMMATORY DISEASE; DEFICIENCY; IL1RN; MANIFESTATIONS;
INFLAMMASOME; PUSTULOSIS; DISORDERS; DELETION
AB Deficiency of the IL-1 receptor antagonist (DIRA) is a recently described rare autoinflammatory disease, caused by loss of function mutations in IL1RN leading to the unopposed activation of the IL-1 pathway. We describe a novel nonsense mutation in the IL1RN gene, associated with early intrauterine onset, death and multiorgan involvement in a prematurely born baby. The protein prediction model indicated that the novel Q119X mutation would result in a nonfunctional protein by impairing the ability of the IL-1Ra to bind and antagonize signaling through the IL-1R. Since the disorder may mimic severe bacterial infections and the treatment with anakinra is life saving, we intend to raise awareness of the syndrome and the possibility of a founder mutation that may lead to the diagnosis of additional cases in Turkey. The clinical suspicion of DIRA is critical to avoid improper management of the patients with antibiotics alone and death from multiorgan failure. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Sanal, Ozden] Hacettepe Univ, Sch Med, Div Pediat Immunol, TR-06100 Ankara, Turkey.
[Kim, Peter W.; Goldbach-Mansky, Raphaela] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Taylan, Fulya] Acibadem Genet, Istanbul, Turkey.
[Perk, Yildiz; Ilikkan, Barbaros] Cerrahpasa Med Sch, Neonatol Unit, Istanbul, Turkey.
[Aksoy, Figen] Cerrahpasa Med Sch, Dept Pathol, Istanbul, Turkey.
[Altiok, Ender] Acibadem Univ, Fac Med, Dept Med Biol, Istanbul, Turkey.
RP Sanal, O (reprint author), Hacettepe Univ, Sch Med, Div Pediat Immunol, TR-06100 Ankara, Turkey.
EM altioke@gmail.com; ctfpatoloji@gmail.com; perky@istanbul.edu.tr;
fulyataylan@gmail.com; kimp@mail.nih.gov; goldbacr@mail.nih.gov;
sanaloz@gmail.com
OI Taylan, Fulya/0000-0002-2907-0235
FU Intramural NIH HHS [ZIA AR041138-08]
NR 19
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U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1521-6616
J9 CLIN IMMUNOL
JI Clin. Immunol.
PD OCT
PY 2012
VL 145
IS 1
BP 77
EP 81
DI 10.1016/j.clim.2012.08.003
PG 5
WC Immunology
SC Immunology
GA 024FH
UT WOS:000310094600012
PM 22940634
ER
PT J
AU Anjuere, F
Bekri, S
Bihl, F
Braud, VM
Cuburu, N
Czerkinsky, C
Hervouet, C
Luci, C
AF Anjuere, F.
Bekri, S.
Bihl, F.
Braud, V. M.
Cuburu, N.
Czerkinsky, C.
Hervouet, C.
Luci, C.
TI B cell and T cell immunity in the female genital tract: Potential of
distinct mucosal routes of vaccination and role of tissue-associated
dendritic cells and natural killer cells
SO CLINICAL MICROBIOLOGY AND INFECTION
LA English
DT Review
DE Dendritic cells; genital immunity; mucosal vaccines; natural killer
cells; tissue-associated memory T cells
ID SIMPLEX-VIRUS TYPE-2; CHOLERA-TOXIN; IN-VIVO; NKT CELLS; IMMUNIZATION;
INFECTION; RESPONSES; ADJUVANT; PROTECTION; INDUCTION
AB Clin Microbiol Infect 2012; 18 (Suppl. 5): 117122 Abstract The female genital mucosa constitutes the major port of entry of sexually transmitted infections. Most genital microbial pathogens represent an enormous challenge for developing vaccines that can induce genital immunity that will prevent their transmission. It is now established that long-lasting protective immunity at mucosal surfaces has to involve local B-cell and T-cell effectors as well as local memory cells. Mucosal immunization constitutes an attractive way to generate systemic and genital B-cell and T-cell immune responses that can control early infection by sexually transmitted pathogens. Nevertheless, no mucosal vaccines against sexually transmitted infections are approved for human use. The mucosa-associated immune system is highly compartmentalized and the selection of any particular route or combinations of routes of immunization is critical when defining vaccine strategies against genital infections. Furthermore, mucosal surfaces are complex immunocompetent tissues that comprise antigen-presenting cells and also innate immune effectors and non-immune cells that can act as natural adjuvants or negative immune modulators. The functions of these cells have to be taken into account when designing tissue-specific antigen-delivery systems and adjuvants. Here, we will discuss data that compare different mucosal routes of immunization to generate B-cell and T-cell responses in the genital tract, with a special emphasis on the newly described sublingual route of immunization. We will also summarize data on the understanding of the effector and induction mechanisms of genital immunity that may influence the development of vaccine strategies against genital infections.
C1 [Anjuere, F.; Bekri, S.; Bihl, F.; Braud, V. M.; Luci, C.] UMR7275 CNRS UNS, Inst Pharmacol Mol & Cellulaire, Valbonne, France.
[Anjuere, F.; Bekri, S.; Bihl, F.; Braud, V. M.; Luci, C.] Univ Nice Sophia Antipolis, Nice, France.
[Cuburu, N.] NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA.
[Czerkinsky, C.] Int Vaccine Inst, Seoul, South Korea.
[Hervouet, C.] Kings Coll London, Dept Immunobiol, London WC2R 2LS, England.
RP Anjuere, F (reprint author), CNRS UNSA UMR 7275, Inst Pharmacol Mol & Cellulaire, 660 Route Lucioles, F-06560 Valbonne, France.
EM anjuere@unice.fr
RI braud, veronique/I-4597-2013; CZERKINSKY, CECIL/G-6520-2015;
Anjuere-Casile, Fabienne/O-5779-2016;
OI braud, veronique/0000-0001-8213-3947; Anjuere-Casile,
Fabienne/0000-0003-3144-8652; LUCI, Carmelo/0000-0001-9687-4164; Bekri,
Selma/0000-0003-2045-386X
FU Centre National de la Recherche Scientifique (France); Institut National
de la Sante et de la Recherche Medicale (France); EU-FP7 Euroneut41
project; Agence Nationale de Recherche sur le SIDA (France); SIDACTION
(France); Association de Recherche sur le Cancer (ARC); Fondation de
l'Avenir (France)
FX Our work is supported by Centre National de la Recherche Scientifique
(France), Institut National de la Sante et de la Recherche Medicale
(France), EU-FP7 Euroneut41 project, the Agence Nationale de Recherche
sur le SIDA (France), the SIDACTION (France), the Association de
Recherche sur le Cancer (ARC) and the Fondation de l'Avenir (France).
NR 57
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U1 6
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1198-743X
J9 CLIN MICROBIOL INFEC
JI Clin. Microbiol. Infect.
PD OCT
PY 2012
VL 18
SU 5
SI SI
BP 117
EP 122
DI 10.1111/j.1469-0691.2012.03995.x
PG 6
WC Infectious Diseases; Microbiology
SC Infectious Diseases; Microbiology
GA 019DI
UT WOS:000309716900016
PM 22882377
ER
PT J
AU Miller, FG
AF Miller, Franklin G.
TI Clinical equipoise and risk-benefit assessment
SO CLINICAL TRIALS
LA English
DT Article
ID BENIGN PROSTATIC HYPERPLASIA; PLACEBO-CONTROLLED TRIALS; DOUBLE-BLIND;
ETHICS; CRITIQUE
AB Clinical equipoise is widely regarded as an ethical requirement for the design and conduct of randomized controlled trials (RCTs). Underlying clinical equipoise is the norm that no patient should be randomized to treatment known (or believed by the expert clinical community) to be inferior to the established standard of care. This implies that patient-subjects should not be exposed to net risks in control groups of randomized trials - risks that are not compensated by the prospect of direct medical benefits from the control intervention. However, proponents of clinical equipoise have no moral objections to permitting net risks for 'nontherapeutic' research procedures employed in clinical trials. This differential assessment makes risk-benefit assessment of randomized trials incoherent. In this article, I examine critically four arguments in defense of clinical equipoise as a requirement for risk-benefit assessment. Each of these arguments fails to support clinical equipoise, leading to the conclusion that we should dispense with this principle in risk-benefit assessment of RCTs. Clinical Trials 2012; 9: 621-627. http://ctj.sagepub.com
C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Miller, FG (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM fmiller@nih.gov
FU Intramural Research Program of the Clinical Center, National Institutes
of Health
FX This research was supported by the Intramural Research Program of the
Clinical Center, National Institutes of Health.
NR 21
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U1 1
U2 7
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
J9 CLIN TRIALS
JI Clin. Trials
PD OCT
PY 2012
VL 9
IS 5
BP 621
EP 627
DI 10.1177/1740774512450952
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 019HX
UT WOS:000309730200008
PM 22777654
ER
PT J
AU Miller, FG
AF Miller, Franklin G.
TI Is anything lost if we give up clinical equipoise? RESPONSE
SO CLINICAL TRIALS
LA English
DT Editorial Material
ID ETHICS
C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Miller, FG (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM fmiller@nih.gov
FU Intramural NIH HHS
NR 5
TC 0
Z9 0
U1 1
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
J9 CLIN TRIALS
JI Clin. Trials
PD OCT
PY 2012
VL 9
IS 5
BP 632
EP 633
DI 10.1177/1740774512455262
PG 2
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 019HX
UT WOS:000309730200011
PM 23060322
ER
PT J
AU Rasmussen-Torvik, LJ
Pacheco, JA
Wilke, RA
Thompson, WK
Ritchie, MD
Kho, AN
Muthalagu, A
Hayes, MG
Armstrong, LL
Scheftner, DA
Wilkins, JT
Zuvich, RL
Crosslin, D
Roden, DM
Denny, JC
Jarvik, GP
Carlson, CS
Kullo, IJ
Bielinski, SJ
McCarty, CA
Li, RL
Manolio, TA
Crawford, DC
Chisholm, RL
AF Rasmussen-Torvik, Laura J.
Pacheco, Jennifer A.
Wilke, Russell A.
Thompson, William K.
Ritchie, Marylyn D.
Kho, Abel N.
Muthalagu, Arun
Hayes, M. Geoff
Armstrong, Loren L.
Scheftner, Douglas A.
Wilkins, John T.
Zuvich, Rebecca L.
Crosslin, David
Roden, Dan M.
Denny, Joshua C.
Jarvik, Gail P.
Carlson, Christopher S.
Kullo, Iftikhar J.
Bielinski, Suzette J.
McCarty, Catherine A.
Li, Rongling
Manolio, Teri A.
Crawford, Dana C.
Chisholm, Rex L.
TI High Density GWAS for LDL Cholesterol in African Americans Using
Electronic Medical Records Reveals a Strong Protective Variant in APOE
SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE
LA English
DT Article
DE GWAS; LDL; electronic medical records
ID GENOME-WIDE ASSOCIATION; HEART-DISEASE RISK; GENETIC-VARIANTS; EMERGE
NETWORK; LIPID-LEVELS; BLOOD-LIPIDS; POPULATION; LOCI; TOOL;
IDENTIFICATION
AB Only one low-density lipoprotein cholesterol (LDL-C) genome-wide association study (GWAS) has been previously reported in -African Americans. We performed a GWAS of LDL-C in African Americans using data extracted from electronic medical records (EMR) in the eMERGE network. African Americans were genotyped on the Illumina 1M chip. All LDL-C measurements, prescriptions, and diagnoses of concomitant disease were extracted from EMR. We created two analytic datasets; one dataset having median LDL-C calculated after the exclusion of some lab values based on comorbidities and medication (n= 618) and another dataset having median LDL-C calculated without any exclusions (n= 1,249). SNP rs7412 in APOE was strongly associated with LDL-C in both datasets (p < 5 x 10-8). In the dataset with exclusions, a decrease of 20.0 mg/dL per minor allele was observed. The effect size was attenuated (12.3 mg/dL) in the dataset without any lab values excluded. Although other signals in APOE have been detected in previous GWAS, this large and important SNP association has not been well detected in large GWAS because rs7412 was not included on many genotyping arrays. Use of median LDL-C extracted from EMR after exclusions for medications and comorbidities increased the percentage of trait variance explained by genetic variation. Clin Trans Sci 2012; Volume 5: 394399
C1 [Rasmussen-Torvik, Laura J.; Wilkins, John T.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Pacheco, Jennifer A.; Thompson, William K.; Muthalagu, Arun; Chisholm, Rex L.] Northwestern Univ, Feinberg Sch Med, Ctr Genet Med, Chicago, IL 60611 USA.
[Wilke, Russell A.; Roden, Dan M.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
[Ritchie, Marylyn D.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
[Kho, Abel N.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Hayes, M. Geoff; Armstrong, Loren L.; Scheftner, Douglas A.] Northwestern Univ, Div Endocrinol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Zuvich, Rebecca L.; Crawford, Dana C.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Ctr Human Genet Res, Nashville, TN 37232 USA.
[Crosslin, David] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Roden, Dan M.] Vanderbilt Univ, Dept Pharmacol, Nashville, TN USA.
[Denny, Joshua C.] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN USA.
[Jarvik, Gail P.] Univ Washington, Dept Med Med Genet, Seattle, WA 98195 USA.
[Jarvik, Gail P.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Carlson, Christopher S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Kullo, Iftikhar J.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA.
[Bielinski, Suzette J.] Mayo Clin, Div Epidemiol, Rochester, MN USA.
[McCarty, Catherine A.] Essentia Inst Rural Hlth, Duluth, MN USA.
[Li, Rongling; Manolio, Teri A.] NHGRI, Off Populat Genom, Bethesda, MD 20892 USA.
RP Rasmussen-Torvik, LJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
EM ljrtorvik@northwestern.edu
RI Ritchie, Marylyn/C-1114-2012; Crawford, Dana/C-1054-2012; Jarvik,
Gail/N-6476-2014; Bielinski, Suzette/A-2238-2009;
OI Jarvik, Gail/0000-0002-6710-8708; Bielinski,
Suzette/0000-0002-2905-5430; Pacheco, Jennifer/0000-0001-8021-5818
FU NHGRI; NIGMS [U01-HG-004610, U01-HG-004608, U01-HG-04599, U01HG004609,
U01-HG-04603]; State of Washington Life Sciences Discovery Fund
FX The eMERGE Network was initiated and funded by NHGRI, with additional
funding from NIGMS through the following grants: U01-HG-004610 (Group
Health Cooperative); U01-HG-004608 (Marshfield Clinic); U01-HG-04599
(Mayo Clinic); U01HG004609 (Northwestern University); U01-HG-04603
(Vanderbilt University), and the State of Washington Life Sciences
Discovery Fund award to the Northwest Institute of Medical Genetics.
NR 32
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U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1752-8054
J9 CTS-CLIN TRANSL SCI
JI CTS-Clin. Transl. Sci.
PD OCT
PY 2012
VL 5
IS 5
BP 394
EP 399
DI 10.1111/j.1752-8062.2012.00446.x
PG 6
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 023YX
UT WOS:000310075000004
PM 23067351
ER
PT J
AU Karschner, EL
Schwope, DM
Schwilke, EW
Goodwin, RS
Kelly, DL
Gorelick, DA
Huestis, MA
AF Karschner, Erin L.
Schwope, David M.
Schwilke, Eugene W.
Goodwin, Robert S.
Kelly, Deanna L.
Gorelick, David A.
Huestis, Marilyn A.
TI Predictive model accuracy in estimating last
Delta(9)-tetrahydrocannabinol (THC) intake from plasma and whole blood
cannabinoid concentrations in chronic, daily cannabis smokers
administered subchronic oral THC
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Delta(9)-tetrahydrocannabinol; Chronic; Cannabis; Predictive models;
Cannabinoids; Marijuana
ID MARIJUANA; DELTA-9-TETRAHYDROCANNABINOL; INGESTION; TIME;
11-HYDROXY-THC; SMOKING; THCCOOH; HUMANS; USERS
AB Background: Determining time since last cannabis/Delta(9)-tetrahydrocannabinol (THC) exposure is important in clinical, workplace, and forensic settings. Mathematical models calculating time of last exposure from whole blood concentrations typically employ a theoretical 0.5 whole blood-to-plasma (WB/P) ratio. No studies previously evaluated predictive models utilizing empirically-derived WB/P ratios, or whole blood cannabinoid pharmacokinetics after subchronic THC dosing.
Methods: Ten male chronic, daily cannabis smokers received escalating around-the-clock oral THC (40-120 mg daily) for 8 days. Cannabinoids were quantified in whole blood and plasma by two-dimensional gas chromatography-mass spectrometry.
Results: Maximum whole blood THC occurred 3.0 h after the first oral THC dose and 103.5 h (4.3 days) during multiple THC dosing. Median WB/P ratios were THC 0.63 (n = 196), 11-hydroxy-THC 0.60 (n = 189), and 11-nor-9-carboxy-THC (THCCOOH) 0.55 (n = 200). Predictive models utilizing these WB/P ratios accurately estimated last cannabis exposure in 96% and 100% of specimens collected within 1-5 h after a single oral THC dose and throughout multiple dosing, respectively. Models were only 60% and 12.5% accurate 12.5 and 22.5 h after the last THC dose, respectively.
Conclusions: Predictive models estimating time since last cannabis intake from whole blood and plasma cannabinoid concentrations were inaccurate during abstinence, but highly accurate during active THC dosing. THC redistribution from large cannabinoid body stores and high circulating THCCOOH concentrations create different pharmacokinetic profiles than those in less than daily cannabis smokers that were used to derive the models. Thus, the models do not accurately predict time of last THC intake in individuals consuming THC daily. Published by Elsevier Ireland
C1 [Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Kelly, Deanna L.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Catonsville, MD 21228 USA.
RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Biomed Res Ctr, 251 Bayview Blvd,Room 05A721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program, NIH, National Institute on Drug Abuse; NIDA
Residential Research Support Services Contract [HHSN271200599091CADB];
Cooperative Research and Development Agreement between Sanofi-aventis;
National Institutes of Health
FX Funding for this study was provided by the Intramural Research Program,
NIH, National Institute on Drug Abuse; NIDA Residential Research Support
Services Contract HHSN271200599091CADB (D. Kelly, PI) to the Maryland
Psychiatric Research Center (MPRC); and a Cooperative Research and
Development Agreement between Sanofi-aventis and the National Institutes
of Health. NIDA and MPRC had no further role in the study design; in the
collection, analysis, and interpretation of data; in the writing of the
report; or in the decision to submit the paper for publication.
Sanofi-aventis contributed to study design and data management, but
played no further role in the collection, analysis, and interpretation
of data, in the writing of the report; or in the decision to submit the
paper for publication.
NR 19
TC 11
Z9 11
U1 3
U2 23
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD OCT 1
PY 2012
VL 125
IS 3
BP 313
EP 319
DI 10.1016/j.drugalcdep.2012.03.005
PG 7
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 024NL
UT WOS:000310115800019
PM 22464363
ER
PT J
AU Singer, N
Eapen, M
Grillon, C
Ungerleider, LG
Hendler, T
AF Singer, Neomi
Eapen, Mariam
Grillon, Christian
Ungerleider, Leslie G.
Hendler, Talma
TI Through the Eyes of Anxiety: Dissecting Threat Bias via
Emotional-Binocular Rivalry
SO EMOTION
LA English
DT Article
DE social anxiety disorder; panic disorder; threat bias; binocular rivalry;
information processing
ID FACIAL EXPRESSIONS; SOCIAL PHOBIA; ATTENTIONAL BIAS; PANIC DISORDER;
INDIVIDUAL-DIFFERENCES; SELECTIVE ATTENTION; STRATEGIC PROCESSES;
FEARFUL FACES; INFORMATION; STIMULI
AB An extensive body of research has demonstrated that anxious individuals abnormally process threat-related content. Yet, the manner in which clinical anxiety affects the selection of threatening signals and their maintenance within consciousness is yet to be explored. The present study used an emotional binocular rivalry (e-BR) procedure, in which pictures of faces depicting either fearful or neutral expressions competed with pictures of a house for conscious perception. We assumed that first- or cumulative-preferred perception of faces with fearful over neutral expression (i.e., initial or sustained threat bias, respectively) stand for preferential selection or maintenance of fear content in awareness, correspondingly. Unmedicated patients with social anxiety disorder (SAD) and panic disorder (PAD) were compared to healthy controls for threat-related perceptual biases in the e-BR. At first perception of face, both SAD and PAD patients showed a greater initial threat bias than healthy controls. In contrast, at cumulative dwell-time of face, patient groups demonstrated a diminished sustained threat bias relative to healthy controls, yet in a different manner. SAD patients showed a sustained threat bias, though it was smaller than in healthy controls. Furthermore, increased levels of reported anxiety among SAD patients were associated with enhanced sustained perception of neutral faces. PAD patients, on the other hand, showed no sustained threat bias and a diminished cumulative perception of fearful faces with increased levels of anxiety traits. These findings indicate that anxiety disorders commonly involve an initially enhanced selection of threat signals into awareness, followed by disorder-specific manifestation of diminished preferred maintenance of threat in awareness.
C1 [Singer, Neomi; Hendler, Talma] Tel Aviv Sourasky Med Ctr, Funct Brain Ctr, Wohl Inst Adv Imaging, IL-64239 Tel Aviv, Israel.
[Singer, Neomi; Hendler, Talma] Tel Aviv Univ, Dept Psychol, Tel Aviv, Israel.
[Eapen, Mariam; Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Grillon, Christian] NIMH, Sect Neurobiol Fear & Anxiety, NIH, Bethesda, MD 20892 USA.
[Hendler, Talma] Tel Aviv Univ, Dept Physiol & Pharmacol, Sackler Fac Med, Tel Aviv, Israel.
RP Hendler, T (reprint author), Tel Aviv Sourasky Med Ctr, Funct Brain Ctr, Wohl Inst Adv Imaging, 6 Weizmann St, IL-64239 Tel Aviv, Israel.
EM talma@tasmc.health.gov.il
FU Intramural NIH HHS [ZIA MH002798-10]
NR 74
TC 12
Z9 12
U1 8
U2 17
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 1528-3542
J9 EMOTION
JI Emotion
PD OCT
PY 2012
VL 12
IS 5
BP 960
EP 969
DI 10.1037/a0027070
PG 10
WC Psychology, Experimental
SC Psychology
GA 022GQ
UT WOS:000309946200014
PM 22390706
ER
PT J
AU Shechner, T
Pelc, T
Pine, DS
Fox, NA
Bar-Haim, Y
AF Shechner, Tomer
Pelc, Tatiana
Pine, Daniel S.
Fox, Nathan A.
Bar-Haim, Yair
TI Flexible Attention Deployment in Threatening Contexts: An Instructed
Fear Conditioning Study
SO EMOTION
LA English
DT Article
DE Attention bias; acute stress; instructed fear conditioning; attention
training
ID POTENTIATED STARTLE; PREFRONTAL CORTEX; INCREASED ANXIETY; SOCIAL
ANXIETY; BIAS; SUPPRESSION; CAPTURE; INDIVIDUALS; PLASTICITY; DISORDERS
AB Factors leading humans to shift attention away from danger cues remain poorly understood. Two laboratory experiments reported here show that context interacts with learning experiences to shape attention avoidance of mild danger cues. The first experiment exposed 18 participants to contextual threat of electric shock. Attention allocation to mild danger cues was then assessed with the dot-probe task. Results showed that contextual threat caused subjects to avert attention from danger cues. In the second experiment, 36 participants were conditioned to the same contextual threat used in Experiment I. These subjects then were randomly assigned to either an experimental group. trained to shift attention toward danger cues, or a placebo group exposed to the same stimuli without the training component. As in Experiment 1, contextual threat again caused attention allocation away from danger in the control group. However, this did not occur in the experimental group. These experiments show that acute contextual threat and learning experiences interact to shape the deployment of attention away from danger cues.
C1 [Shechner, Tomer] NIMH, Sect Dev Affect Neurosci Emot & Dev Branch, Bethesda, MD 20892 USA.
[Shechner, Tomer; Pelc, Tatiana; Bar-Haim, Yair] Tel Aviv Univ, Dept Psychol, Tel Aviv, Israel.
[Fox, Nathan A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA.
RP Shechner, T (reprint author), NIMH, Sect Dev Affect Neurosci Emot & Dev Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM shechnert@mail.nih.gov
OI Pelc, Tatiana/0000-0001-8870-6179
FU Intramural NIH HHS [ZIA MH002780-11, ZIA MH002782-11, ZIA MH002781-11]
NR 39
TC 13
Z9 13
U1 3
U2 17
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 1528-3542
J9 EMOTION
JI Emotion
PD OCT
PY 2012
VL 12
IS 5
BP 1041
EP 1049
DI 10.1037/a0027072
PG 9
WC Psychology, Experimental
SC Psychology
GA 022GQ
UT WOS:000309946200023
PM 22390711
ER
PT J
AU Shumay, E
Logan, J
Volkow, ND
Fowler, JS
AF Shumay, Elena
Logan, Jean
Volkow, Nora D.
Fowler, Joanna S.
TI Evidence that the methylation state of the monoamine oxidase A (MAOA)
gene predicts brain activity of MAO A enzyme in healthy men
SO EPIGENETICS
LA English
DT Article
DE monoamine oxidase A; DNA methylation; MAOA genotype; positron emission
tomography
ID POSITRON-EMISSION-TOMOGRAPHY; DNA METHYLATION; FUNCTIONAL POLYMORPHISM;
MONOZYGOTIC TWINS; L-DEPRENYL; ASSOCIATION; PROMOTER; BINDING; DISORDER;
GENOTYPE
AB Human brain function is mediated by biochemical processes, many of which can be visualized and quantified by positron emission tomography (PET). PET brain imaging of monoamine oxidase A (MAO A)-an enzyme metabolizing neurotransmitters-revealed that MAO A levels vary widely between healthy men and this variability was not explained by the common MAOA genotype (VNTR genotype), suggesting that environmental factors, through epigenetic modifications, may mediate it. Here, we analyzed MAOA methylation in white blood cells (by bisulphite conversion of genomic DNA and subsequent sequencing of cloned DNA products) and measured brain MAO A levels (using PET and [C-11]clorgyline, a radiotracer with specificity for MAO A) in 34 healthy non-smoking male volunteers. We found significant interindividual differences in methylation status and methylation patterns of the core MAOA promoter. The VNTR genotype did not influence the methylation status of the gene or brain MAO A activity. In contrast, we found a robust association of the regional and CpG site-specific methylation of the core MAOA promoter with brain MAO A levels. These results suggest that the methylation status of the MAOA promoter (detected in white blood cells) can reliably predict the brain endophenotype. Therefore, the status of MAOA methylation observed in healthy males merits consideration as a variable contributing to interindividual differences in behavior.
C1 [Shumay, Elena; Logan, Jean; Fowler, Joanna S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Volkow, Nora D.] NIDA, NIH, Bethesda, MD 20892 USA.
RP Shumay, E (reprint author), Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
EM eshumay@bnl.gov
OI Logan, Jean/0000-0002-6993-9994
FU Brookhaven National Laboratory [DE-AC02-98CH10886]; CeNeRx BioPharma;
Valeant Pharmaceuticals International; National Institutes of Health
[KO1 DA02580, K05DA020001]; NIAAA intramural program at Brookhaven
National Laboratory (NDV); NIH grant from the General Research Clinical
Centers (Stony Brook University) [MO1RR10710]
FX This study was performed at Brookhaven National Laboratory under
contract DE-AC02-98CH10886 with infrastructure support from its Office
of Biological and Environmental Research. Support for the MAO A studies
came in part from CeNeRx BioPharma and Valeant Pharmaceuticals
International and in part by the National Institutes of Health: NIDA
awards KO1 DA02580 for ES and K05DA020001 for JSF; the NIAAA intramural
program at Brookhaven National Laboratory (NDV) and by NIH grant
MO1RR10710 from the General Research Clinical Centers (Stony Brook
University). We are grateful to Dr Beth Milligan, Alice Shanklin and
Alexander Scalia for technical assistance in conducting experimental
tests, Joan Terry and Hai-Dee Lee for CRC operations, to Donald Warner,
Michael Schueller and David Schlyer for PET and cyclotron operations,
Payton King and David Alexoff for plasma analysis and to Colleen Shea,
Lisa Muench and Youwen Xu for radiotracer synthesis. We are also
grateful to the individuals who volunteered for these studies.
NR 52
TC 30
Z9 31
U1 0
U2 14
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1559-2294
J9 EPIGENETICS-US
JI Epigenetics
PD OCT
PY 2012
VL 7
IS 10
BP 1151
EP 1160
DI 10.4161/epi.21976
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 022LJ
UT WOS:000309960600008
PM 22948232
ER
PT J
AU Imamichi, H
Lempicki, RA
Adelsberger, JW
Hasley, RB
Rosenberg, A
Roby, G
Rehm, CA
Nelson, A
Krishnan, S
Pavlick, M
Woods, CJ
Baseler, MW
Lane, HC
AF Imamichi, Hiromi
Lempicki, Richard A.
Adelsberger, Joseph W.
Hasley, Rebecca B.
Rosenberg, Alice
Roby, Gregg
Rehm, Catherine A.
Nelson, Amy
Krishnan, Sonya
Pavlick, Mark
Woods, Christian J.
Baseler, Michael W.
Lane, H. Clifford
TI The CD8+HLA-DR+ T cells expanded in HIV-1 infection are qualitatively
identical to those from healthy controls
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Activated CD8+T cells; Cell cycle; HIV; HLA-DR; Immune activation
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HLA-DR; ACTIVATION ANTIGENS; IMMUNE
ACTIVATION; FOLLOW-UP; EXPRESSION; AIDS; LYMPHOCYTES; PHENOTYPE;
APOPTOSIS
AB HIV-induced immune activation leads to expansion of a subset of human CD8+ T cells expressing HLA-DR antigens. Expansion of CD8+HLA-DR+ T cells can be also observed in non-HIV settings including several autoimmune diseases and aging. Although these cells are felt to represent immune exhaustion and/or to be anergic, their precise role in host defense has remained unclear. Here, we report that this subset of cells exhibits a restricted repertoire, shows evidence of multiple rounds of division, but lacks markers of recent TCR engagement. Detailed cell cycle analysis revealed that compared with their CD8+HLA-DR- counterpart, the CD8+HLA-DR+ T-cell pool contained an increased fraction of cells in S-phase with elevated levels of the G2/M regulators: cyclin A2, CDC25C, Cdc2 (CDK1), indicating that these cells are not truly anergic but rather experiencing proliferation in vivo. Together, these data support a hypothesis that antigen stimulation leads to the initial expansion of a CD8+ pool of cells in vivo that undergo further expansion independent of ongoing TCR engagement. No qualitative differences were noted between CD8+HLA-DR+ cells from HIV+ and HIV- donors, indicating that the generation of CD8+HLA-DR+ T cells is a part of normal immune regulation that is exaggerated in the setting of HIV-1 infection.
C1 [Imamichi, Hiromi; Hasley, Rebecca B.; Roby, Gregg; Rehm, Catherine A.; Nelson, Amy; Pavlick, Mark; Lane, H. Clifford] NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD USA.
[Lempicki, Richard A.; Adelsberger, Joseph W.; Baseler, Michael W.] SAIC Frederick Inc, Clin Serv Program, Appl Dev Res Directorate, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Rosenberg, Alice; Krishnan, Sonya] SAIC Frederick Inc, Clin Monitoring Res Program, Clin Res Directorate, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Woods, Christian J.] Washington Hosp Ctr, Washington, DC 20010 USA.
RP Imamichi, H (reprint author), NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD USA.
EM himamichi@nih.gov
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
FU National Institute of Allergy and Infectious Diseases of the National
Institutes of Health (Bethesda, Maryland); National Cancer Institute,
National Institutes of Health [HHSN261200800001E]
FX The authors would like to thank all study participants. We also would
like to thank Jeanette Higgins, Valerie Hill, and Virginia Simpson for
assistance with the Wright-Giemsa staining, Cathy Watkins and Cathi
Yeager for assistance on the flow cytometry analyses, Dr. Douglas Kuhns
and Dara Riva for assistance on the photomicrographs, and Dr. Hong Kiang
for assistance on cytospins. This work was funded through the intramural
research program of the National Institute of Allergy and Infectious
Diseases of the National Institutes of Health (Bethesda, Maryland) and
in part with federal funds from the National Cancer Institute, National
Institutes of Health, under Contract No. HHSN261200800001E. The content
of this publication does not necessarily reflect the views or policies
of the Department of Health and Human Services, nor does mention of
trade names, commercial products, or organizations imply endorsement by
the U.S. Government.
NR 37
TC 5
Z9 6
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD OCT
PY 2012
VL 42
IS 10
BP 2608
EP 2620
DI 10.1002/eji.201142046
PG 13
WC Immunology
SC Immunology
GA 017SC
UT WOS:000309610200009
PM 22777759
ER
PT J
AU Hodge, DL
Reynolds, D
Cerban, FM
Correa, SG
Baez, NS
Young, HA
Rodriguez-Galan, MC
AF Hodge, Deborah L.
Reynolds, Della
Cerban, Fabio M.
Correa, Silvia G.
Baez, Natalia S.
Young, Howard A.
Cecilia Rodriguez-Galan, Maria
TI MCP-1/CCR2 interactions direct migration of peripheral B and T
lymphocytes to the thymus during acute infectious/inflammatory processes
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE IL-12 and IL-18; Infection; MCP-1; Peripheral B and T cells; Thymus
reentry
ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; IN-VIVO; TRYPANOSOMA-CRUZI; ADOPTIVE
TRANSFER; CELLS MIGRATE; ADULT THYMUS; IFN-GAMMA; TOLERANCE; IL-18; MICE
AB Mature lymphocyte immigration into the thymus has been documented in mouse, rat, and pig models, and highly increases when cells acquire an activated phenotype. Entrance of peripheral B and T cells into the thymus has been described in healthy and pathological situations. However, it has not been proposed that leukocyte recirculation to the thymus could be a common feature occurring during the early phase of a Th1 inflammatory/infectious process when a large number of peripheral cells acquire an activated phenotype and the cellularity of the thymus is seriously compromised. The data we present here demonstrate that in well-established Th1 models triggered by different types of immunogens, for example, LPS treatment (a bacterial product), Candida albicans infection (a fungus), and after Trypanosoma cruzi infection (a parasite), a large number of mature peripheral B and T cells enter the thymus. This effect is dependent on, but not exclusive of, the available space in the thymus. Our data also demonstrate that MCP-1/CCR2 (where MCP-1 is monocyte chemoattractant protein-1) interaction is responsible for the infiltration of peripheral cells to the thymus in these Th1-inflammatory/infectious situations. Finally, systemic expression of IL-12 and IL-18 produced during the inflammatory process is ultimately responsible for these migratory events.
C1 [Cerban, Fabio M.; Correa, Silvia G.; Baez, Natalia S.; Cecilia Rodriguez-Galan, Maria] Univ Nacl Cordoba, Fac Ciencias Quim, CIBICI CONICET, RA-5000 Cordoba, Argentina.
[Hodge, Deborah L.; Reynolds, Della; Young, Howard A.] NIH, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res,Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Rodriguez-Galan, MC (reprint author), Univ Nacl Cordoba, Fac Ciencias Quim, CIBICI CONICET, RA-5000 Cordoba, Argentina.
EM crodri@bioclin.fcq.unc.edu.ar
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute (NCI), National Institutes of Health; Agencia Nacional
de Promocion Cientifica y Tecnologica (Argentina); Secretaria de Ciencia
y Tecnica de la Universidad Nacional de Cordoba (SeCyT-UNC)
FX This project has been funded in part with federal funds from the
Intramural Research Program of the Center for Cancer Research, National
Cancer Institute (NCI), National Institutes of Health, and also by
Agencia Nacional de Promocion Cientifica y Tecnologica (Argentina) and
Secretaria de Ciencia y Tecnica de la Universidad Nacional de Cordoba
(SeCyT-UNC).
NR 42
TC 15
Z9 15
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD OCT
PY 2012
VL 42
IS 10
BP 2644
EP 2654
DI 10.1002/eji.201242408
PG 11
WC Immunology
SC Immunology
GA 017SC
UT WOS:000309610200012
PM 22740067
ER
PT J
AU Kreitzer, MA
Jacoby, J
Naylor, E
Baker, A
Grable, T
Tran, E
Booth, SE
Qian, HH
Malchow, RP
AF Kreitzer, Matthew A.
Jacoby, Jason
Naylor, Ethan
Baker, Adam
Grable, Trent
Emma Tran
Booth, Sophie Erwin
Qian, Haohua
Malchow, Robert Paul
TI Distinctive patterns of alterations in proton efflux from goldfish
retinal horizontal cells monitored with self-referencing H plus
-selective electrodes
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE feedback; horizontal cell; pH; retina
ID CONE PHOTORECEPTORS; CALCIUM; PH; MODULATION; FEEDBACK; TRANSMISSION;
DEPOLARIZATION; GLUTAMATE; CHANNELS; CATFISH
AB The H+ hypothesis of lateral feedback inhibition in the outer retina predicts that depolarizing agents should increase H+ release from horizontal cells. To test this hypothesis, self-referencing H+-selective microelectrodes were used to measure extracellular H+ fluxes from isolated goldfish horizontal cells. We found a more complex pattern of cellular responses than previously observed from horizontal cells of other species examined using this technique. One class of cells had an initial standing signal indicative of high extracellular H+ adjacent to the cell membrane; challenge with glutamate, kainate or high extracellular potassium induced an extracellular alkalinization. This alkalinization was reduced by the calcium channel blockers nifedipine and cobalt. A second class of cells displayed spontaneous oscillations in extracellular H+ that were abolished by cobalt, nifedipine and low extracellular calcium. A strong correlation between changes in intracellular calcium and extracellular proton flux was detected in experiments simultaneously monitoring intracellular calcium and extracellular H+. A third set of cells was characterized by a standing extracellular alkalinization which was turned into an acidic signal by cobalt. In this last set of cells, addition of glutamate or high extracellular potassium did not significantly alter the proton signal. Taken together, the response characteristics of all three sets of neurons are most parsimoniously explained by activation of a plasma membrane Ca2+ ATPase pump, with an extracellular alkalinization resulting from exchange of intracellular calcium for extracellular H+. These findings argue strongly against the hypothesis that H+ release from horizontal cells mediates lateral inhibition in the outer retina.
C1 [Kreitzer, Matthew A.; Naylor, Ethan; Baker, Adam; Grable, Trent] Indiana Wesleyan Univ, Dept Biol, Marion, IN 46953 USA.
[Jacoby, Jason; Malchow, Robert Paul] Univ Illinois, Dept Biol Sci, Chicago, IL 60680 USA.
[Emma Tran] Univ Texas Austin, Austin, TX 78712 USA.
[Booth, Sophie Erwin] Univ Colorado, Colorado Springs, CO 80907 USA.
[Qian, Haohua] NEI, Bethesda, MD 20892 USA.
[Malchow, Robert Paul] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL USA.
RP Kreitzer, MA (reprint author), Indiana Wesleyan Univ, Dept Biol, 4201 S Washington St, Marion, IN 46953 USA.
EM matthew.kreitzer@indwes.edu
FU National Science Foundation [0924372, 0924383]; Marine Biological
Laboratory; Midwest Eye-Banks
FX We thank Richard Sanger and Mark Messerli of the MBL for assistance with
self-referencing and calcium imaging at the Marine Biological Laboratory
and without whose help this work could not have been done. We thank
Blair Rossetti and Louis Kerr at the MBL and Jim McIlvain and Chris
Rieken of Zeiss Corp. for assistance with confocal microscopy, and
undergraduate students Blair Skinner, Tom Cully, Luke Montgomery, Karisa
Burkholder, Paul Garverick, Matthew Decker, Sonja Vogel, Kyle Mazellan
and Meredith Osborn at Indiana Wesleyan University for their
contribution to the self-referencing measurements reported. This work
was supported by National Science Foundation Grants 0924372 and 0924383,
a Laura and Arthur Colwin Summer Fellowship from the Marine Biological
Laboratory, and the Midwest Eye-Banks.
NR 23
TC 2
Z9 2
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-816X
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD OCT
PY 2012
VL 36
IS 8
BP 3040
EP 3050
DI 10.1111/j.1460-9568.2012.08226.x
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 021WY
UT WOS:000309917300004
PM 22809323
ER
PT J
AU Andrade, LR
Lins, U
Farina, M
Kachar, B
Thalmann, R
AF Andrade, Leonardo R.
Lins, Ulysses
Farina, Marcos
Kachar, Bechara
Thalmann, Ruediger
TI Immunogold TEM of otoconin 90 and otolin - relevance to mineralization
of otoconia, and pathogenesis of benign positional vertigo
SO HEARING RESEARCH
LA English
DT Article
ID INNER-EAR; MATRIX PROTEINS; MAJOR PROTEIN; OSTEOPOROSIS; OSTEOPENIA;
CONTAINS; BALANCE
AB Implementation of the deep-etch technique enabled unprecedented definition of substructural elements of otoconia, including the fibrillar meshwork of the inner core with its globular attachments. Subsequently the effects of the principal soluble otoconial protein, otoconin 90, upon calcite crystal growth in vitro were determined, including an increased rate of nucleation, inhibition of growth kinetics and significant morphologic changes. The logical next step, ultrastructural localization of otoconin 90, by means of immunogold TEM in young mature mice, demonstrated a high density of gold particles in the inner core in spite of a relatively low level of mineralization. Here gold particles are typically arranged in oval patterns implying that otoconin 90 is attached to a scaffold consisting of the hexagonal fibrillar meshwork, characteristic of otolin. The level of mineralization is much higher in the outer cortex where mineralized fiber bundles are arranged parallel to the surface. Following decalcification, gold particles, as well as matrix fibrils, presumed to consist of a linear structural phenotype of otolin, are aligned in identical direction, suggesting that they serve as scaffold to guide mineralization mediated by otoconin 90. In the faceted tips, the level of mineralization is highest, even though the density of gold particles is relatively low, conceivably due to the displacement by the dense mineral phase. TEM shows that individual crystallites assemble into iso-oriented columns. Columns are arranged in parallel lamellae which convert into mineralized blocks for hierarchical assembly into the complex otoconial mosaic.
Another set of experiments based on immunogold TEM in young mice demonstrates that the fibrils interconnecting otoconia consist of the short chain collagen otolin. By two years of age the superficial layer of mouse otoconia (corresponding to mid-life human) has become demineralized resulting in weakening or loss of anchoring of the fibrils interconnecting otoconia. Consequently, otoconia detached from each other may be released into the endolymphatic space by minor mechanical disturbances. In humans, benign positional vertigo (BPV) is believed to result from translocation of otoconia from the endolymphatic space into the semi-circular canals rendering their receptors susceptible to stimulation by gravity causing severe attacks of vertigo. The combinations of these observations in humans, together with the presented animal experiments, provide a tentative pathogenetic basis of the early stage of BPV. (c) 2012 Elsevier B.V. All rights reserved.
C1 [Thalmann, Ruediger] Washington Univ, Sch Med, Dept Otolaryngol, St Louis, MO 63110 USA.
[Andrade, Leonardo R.; Kachar, Bechara] NIDCD, Lab Cell Struct & Dynam, NIH, Bethesda, MD 20892 USA.
[Andrade, Leonardo R.; Farina, Marcos] Univ Fed Rio de Janeiro, CCS, Inst Ciencias Biomed, BR-21941590 Rio De Janeiro, RJ, Brazil.
[Lins, Ulysses] Univ Fed Rio de Janeiro, CCS, Inst Microbiol Prof Paulo de Goes, BR-21941590 Rio De Janeiro, RJ, Brazil.
RP Thalmann, R (reprint author), Washington Univ, Sch Med, Dept Otolaryngol, 660 S Euclid Ave, St Louis, MO 63110 USA.
EM thalmannr@ent.wustl.edu
RI Andrade, Leonardo/C-9554-2011; Inbeb, Inct/K-2317-2013; Farina,
Marcos/I-3744-2014; Lins, Ulysses/N-7282-2015
OI Andrade, Leonardo/0000-0002-0004-5677; Lins, Ulysses/0000-0002-1786-1144
FU National Institutes of Health (NIH) Intramural Research Fund
[Z01-DC000002-22]; NIH [R21DC 009320, RO1 DC 011614]; FAPERJ; CNPq
FX We thank Dr. S. Brian Andrews from NINDS-NIH for the use of the Zeiss
912 analytical TEM. We would also like to thank Endrit Agastra for
assistance with the preparation of the manuscript. This work was
supported by National Institutes of Health (NIH) Intramural Research
Fund Z01-DC000002-22 (B.K.), NIH awards R21DC 009320 and RO1 DC 011614
(RT), and the Brazilian Agencies FAPERJ (UL) and CNPq (MF).
NR 32
TC 11
Z9 12
U1 2
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5955
J9 HEARING RES
JI Hear. Res.
PD OCT
PY 2012
VL 292
IS 1-2
BP 14
EP 25
DI 10.1016/j.heares.2012.07.003
PG 12
WC Audiology & Speech-Language Pathology; Neurosciences;
Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Neurosciences & Neurology;
Otorhinolaryngology
GA 024GJ
UT WOS:000310097400002
PM 22841569
ER
PT J
AU Li, XL
Chen, XJ
Yao, JH
Zhang, X
Yang, F
Tian, J
AF Li, Xiuli
Chen, Xinjian
Yao, Jianhua
Zhang, Xing
Yang, Fei
Tian, Jian
TI Automatic Renal Cortex Segmentation Using Implicit Shape Registration
and Novel Multiple Surfaces Graph Search
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE Implicit shape registration; multiple surfaces graph searching; physical
constraints; renal cortex; segmentation
ID KIDNEY SEGMENTATION; CT IMAGES; MODEL; INFORMATION; ALGORITHMS;
VOLUMETRY; SOFTWARE; MRI
AB In this paper, we present an automatic renal cortex segmentation approach using the implicit shape registration and novel multiple surfaces graph search. The proposed approach is based on a hierarchy system. First, the whole kidney is roughly initialized using an implicit shape registration method, with the shapes embedded in the space of Euclidean distance functions. Second, the outer and inner surfaces of renal cortex are extracted utilizing multiple surfaces graph searching, which is extended to allow for varying sampling distances and physical constraints to better separate the renal cortex and renal column. Third, a renal cortex refining procedure is applied to detect and reduce incorrect segmentation pixels around the renal pelvis, further improving the segmentation accuracy. The method was evaluated on 17 clinical computed tomography scans using the leave-one-out strategy with five metrics: Dice similarity coefficient (DSC), volumetric overlap error (OE), signed relative volume difference (SVD), average symmetric surface distance (D-avg), and average symmetric rms surface distance (D-rms). The experimental results of DSC, OE, SVD, D-avg, and D-rms were 90.50% +/- 1.19% 4.38% +/- 3.93%, 2.37% +/- 1.72%, 0.14 mm +/- 0.09 mm, and 0.80 mm +/- 0.64 mm, respectively. The results showed the feasibility, efficiency, and robustness of the proposed method.
C1 [Li, Xiuli; Zhang, Xing; Yang, Fei; Tian, Jian] Chinese Acad Sci, Intelligent Med Res Ctr, Inst Automat, Beijing 100190, Peoples R China.
[Chen, Xinjian; Yao, Jianhua] NIH, Ctr Clin, Radiol & Imaging Sci Dept, Bethesda, MD 20814 USA.
RP Tian, J (reprint author), Chinese Acad Sci, Intelligent Med Res Ctr, Inst Automat, Beijing 100190, Peoples R China.
EM tian@ieee.org
RI Tian, Jie/H-1190-2011; Tian, MITK/M-5549-2013; Chen, Xinjian/E-8592-2016
OI Tian, Jie/0000-0003-0498-0432;
FU National Basic Research Program of China (973 Program) [2011CB707700];
National Natural Science Foundation of China [81071218, 60910006,
30873462]; Chinese Academy of Sciences [KSCX2-YW-R-262, 2010Y2GA03,
2010T2G36, 2010A090100032]; Guangdong Province [2010A090100032]
FX This work was supported in part by the National Basic Research Program
of China (973 Program) under Grant 2011CB707700, in part by the National
Natural Science Foundation of China under Grant 81071218, Grant
60910006, and Grant 30873462, in part by the Knowledge Innovation
Project of the Chinese Academy of Sciences under Grant KSCX2-YW-R-262,
in part by the Fellowship for Young International Scientists of the
Chinese Academy of Sciences under Grant 2010Y2GA03, in part by the
Chinese Academy of Sciences Visiting Professorship for Senior
International Scientists under Grant 2010T2G36, and in part by the
strategic cooperation project jointly funded by Guangdong Province and
the Chinese Academy of Sciences 2010A090100032.
NR 40
TC 8
Z9 9
U1 1
U2 9
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0278-0062
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD OCT
PY 2012
VL 31
IS 10
BP 1849
EP 1860
DI 10.1109/TMI.2012.2203922
PG 12
WC Computer Science, Interdisciplinary Applications; Engineering,
Biomedical; Engineering, Electrical & Electronic; Imaging Science &
Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Imaging Science & Photographic
Technology; Radiology, Nuclear Medicine & Medical Imaging
GA 024ZB
UT WOS:000310149700002
PM 22695346
ER
PT J
AU Linguraru, MG
Richbourg, WJ
Liu, JF
Watt, JM
Pamulapati, V
Wang, SJ
Summers, RM
AF Linguraru, Marius George
Richbourg, William J.
Liu, Jianfei
Watt, Jeremy M.
Pamulapati, Vivek
Wang, Shijun
Summers, Ronald M.
TI Tumor Burden Analysis on Computed Tomography by Automated Liver and
Tumor Segmentation
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE Cancer; contrast-enhanced computed tomography (CT); liver;
parameterization; segmentation; shape; tumor burden
ID FEATURE-SELECTION; SHAPE MODEL; CT; IMAGES; TRANSPLANTATION;
OPTIMIZATION; REGISTRATION; ENHANCEMENT; METASTASIS; LYMPHOMA
AB The paper presents the automated computation of hepatic tumor burden from abdominal computed tomography (CT) images of diseased populations with images with inconsistent enhancement. The automated segmentation of livers is addressed first. A novel 3-D affine invariant shape parameterization is employed to compare local shape across organs. By generating a regular sampling of the organ's surface, this parameterization can be effectively used to compare features of a set of closed 3-D surfaces point-to-point, while avoiding common problems with the parameterization of concave surfaces. From an initial segmentation of the livers, the areas of atypical local shape are determined using training sets. A geodesic active contour corrects locally the segmentations of the livers in abnormal images. Graph cuts segment the hepatic tumors using shape and enhancement constraints. Liver segmentation errors are reduced significantly and all tumors are detected. Finally, support vector machines and feature selection are employed to reduce the number of false tumor detections. The tumor detection true position fraction of 100% is achieved at 2.3 false positives/case and the tumor burden is estimated with 0.9% error. Results from the test data demonstrate the method's robustness to analyze livers from difficult clinical cases to allow the temporal monitoring of patients with hepatic cancer.
C1 [Linguraru, Marius George] Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA.
[Linguraru, Marius George] NIH, Ctr Clin, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Richbourg, William J.; Liu, Jianfei; Watt, Jeremy M.; Pamulapati, Vivek; Wang, Shijun; Summers, Ronald M.] NIH, Ctr Clin, Imaging Biomarkers & Comp Aided Diag Lab, Bethesda, MD 20892 USA.
RP Linguraru, MG (reprint author), Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA.
EM mlin-gura@childrensnational.org; rms@nih.gov
FU National Institutes of Health, Clinical Center
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, Clinical Center.
NR 66
TC 24
Z9 24
U1 2
U2 10
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0278-0062
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD OCT
PY 2012
VL 31
IS 10
BP 1965
EP 1976
DI 10.1109/TMI.2012.2211887
PG 12
WC Computer Science, Interdisciplinary Applications; Engineering,
Biomedical; Engineering, Electrical & Electronic; Imaging Science &
Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Imaging Science & Photographic
Technology; Radiology, Nuclear Medicine & Medical Imaging
GA 024ZB
UT WOS:000310149700012
PM 22893379
ER
PT J
AU Egger, M
Ekouevi, DK
Williams, C
Lyamuya, RE
Mukumbi, H
Braitstein, P
Hartwell, T
Graber, C
Chi, BH
Boulle, A
Dabis, F
Wools-Kaloustian, K
AF Egger, Matthias
Ekouevi, Didier K.
Williams, Carolyn
Lyamuya, Rita Elias
Mukumbi, Henri
Braitstein, Paula
Hartwell, Tyler
Graber, Claire
Chi, Benjamin H.
Boulle, Andrew
Dabis, Francois
Wools-Kaloustian, Kara
TI Cohort Profile: The international epidemiological databases to evaluate
AIDS (IeDEA) in sub-Saharan Africa
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Editorial Material
ID HIV-INFECTED PATIENTS; ANTIRETROVIRAL TREATMENT PROGRAM;
RESOURCE-LIMITED SETTINGS; SCALE-UP PROGRAMS; FOLLOW-UP; PATIENTS LOST;
SOUTH-AFRICA; WESTERN KENYA; THERAPY; MORTALITY
C1 [Egger, Matthias] Univ Bern, ISPM, Div Int & Environm Hlth, CH-3012 Bern, Switzerland.
[Egger, Matthias; Boulle, Andrew] Univ Cape Town, Sch Publ Hlth & Family Med, Infect Dis Epidemiol Unit, ZA-7700 Rondebosch, South Africa.
[Ekouevi, Didier K.] Programme PAC CI, Abidjan, Cote Ivoire.
[Williams, Carolyn] NIAID, Epidemiol Branch, Div Aids, Bethesda, MD 20892 USA.
[Lyamuya, Rita Elias] Morogoro Reg Hosp, Morogoro, Tanzania.
[Mukumbi, Henri] AMOCONGO ARV Ambulatory Treatment Ctr, Kinshasa, Zaire.
[Braitstein, Paula; Wools-Kaloustian, Kara] Indiana Univ Sch Med, Indianapolis, IN USA.
[Braitstein, Paula] Moi Univ, Sch Med, Eldoret, Kenya.
[Braitstein, Paula] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Hartwell, Tyler] RTI Int, Dept Stat & Epidemiol, Durham, NC USA.
[Chi, Benjamin H.] Ctr Infect Dis Res Zambia, Lusaka, Zambia.
[Dabis, Francois] Univ Bordeaux Segalen, ISPED, INSERM, U897, Bordeaux, France.
RP Egger, M (reprint author), Univ Bern, ISPM, Div Int & Environm Hlth, Finkenhubelweg 11, CH-3012 Bern, Switzerland.
EM egger@ispm.unibe.ch
RI EKOUEVI, Didier/E-7960-2014
FU NIAID NIH HHS [U01 AI069919, U01 AI069924]
NR 40
TC 71
Z9 71
U1 0
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD OCT
PY 2012
VL 41
IS 5
BP 1256
EP 1264
DI 10.1093/ije/dyr080
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 021YU
UT WOS:000309922700011
PM 21593078
ER
PT J
AU Zhang, XL
Gao, YT
Yang, G
Li, HL
Cai, QY
Xiang, YB
Ji, BT
Franke, AA
Zheng, W
Shu, XO
AF Zhang, Xianglan
Gao, Yu-Tang
Yang, Gong
Li, Honglan
Cai, Qiuyin
Xiang, Yong-Bing
Ji, Bu-Tian
Franke, Adrian A.
Zheng, Wei
Shu, Xiao-Ou
TI Urinary isoflavonoids and risk of coronary heart disease
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE coronary disease; isoflavones; soy foods
ID VASCULAR ENDOTHELIAL FUNCTION; SOY PROTEIN; POSTMENOPAUSAL WOMEN;
METABOLIZING PHENOTYPES; CARDIOVASCULAR HEALTH; CONTROLLED-TRIAL;
BLOOD-PRESSURE; CHINESE WOMEN; CROSS-OVER; CONSUMPTION
AB Background Whether soy food consumption may protect against coronary heart disease (CHD) remains controversial. No previous study has used biomarkers of soy intake in assessing the relationship between soy consumption and CHD. Biomarkers that reflect both intake and metabolism may be more informative than self-reports of dietary intake.
Methods We examined associations of urinary isoflavonoids, a biomarker of soy or soy isoflavone intake, with risk of CHD in a case-control study nested within two prospective cohort studies of Chinese adults in Shanghai. Cases were defined as subjects with no history of CHD at baseline who developed incident CHD during follow-up. Control subjects were randomly selected from those who remained free of CHD and matched to cases by sex, age, date and time of sample collection and antibiotic use. Baseline urinary isoflavonoids (daidzein, genistein, glycitein, equol, O-desmethylangolensin, dihydrodaidzein and dihydrogenistein) were compared between cases (n = 377) and control subjects (n = 753). Conditional logistic regression was used to evaluate the associations.
Results Total urinary isoflavonoids were not associated with CHD in either women or men. However, urinary equol excretion showed a significant inverse association with CHD in women. The adjusted odds ratios (95% confidence intervals) for CHD across increasing quartiles of equol levels in women were 1 (reference), 0.61 (0.32, 1.15), 0.51 (0.26, 0.98) and 0.46 (0.24, 0.89) (P = 0.02 for trend).
Conclusions Our study suggests for the first time that equol, a bioactive metabolite of soy isoflavone daidzein, may be inversely associated with risk of CHD in women.
C1 [Zhang, Xianglan] Vanderbilt Univ, Med Ctr, Vanderbilt Epidemiol Ctr, IMPH,Dept Med,Sch Med, Nashville, TN 37203 USA.
[Gao, Yu-Tang; Li, Honglan; Xiang, Yong-Bing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Franke, Adrian A.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
RP Zhang, XL (reprint author), Vanderbilt Univ, Med Ctr, Vanderbilt Epidemiol Ctr, IMPH,Dept Med,Sch Med, 2525 W End Ave,Suite 600, Nashville, TN 37203 USA.
EM xianglan.zhang@vanderbilt.edu
FU US National Institutes of Health [R01HL079123, R37CA070867, R01CA082729,
P30 CA71789, S10 RR020890]
FX Sources of support: This work was supported by research grants from the
US National Institutes of Health [grant numbers R01HL079123,
R37CA070867, R01CA082729, P30 CA71789, and S10 RR020890]. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
NR 31
TC 11
Z9 11
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD OCT
PY 2012
VL 41
IS 5
BP 1367
EP 1375
DI 10.1093/ije/dys130
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 021YU
UT WOS:000309922700022
PM 22927214
ER
PT J
AU Brodie, B
Pokharel, Y
Garg, A
Kissling, G
Hansen, C
Milks, S
Cooper, M
McAlhany, C
Stuckey, T
AF Brodie, Bruce
Pokharel, Yashashwi
Garg, Ankit
Kissling, Grace
Hansen, Charles
Milks, Sally
Cooper, Michael
McAlhany, Christopher
Stuckey, Tom
TI Predictors of Early, Late, and Very Late Stent Thrombosis After Primary
Percutaneous Coronary Intervention With Bare-Metal and Drug-Eluting
Stents for ST-Segment Elevation Myocardial Infarction
SO JACC-CARDIOVASCULAR INTERVENTIONS
LA English
DT Article
DE predictors stent thrombosis; primary PCI; STEMI; stent thrombosis
ID RANDOMIZED CONTROLLED-TRIAL; FOLLOW-UP; CLINICAL-PRACTICE; ANGIOPLASTY;
OUTCOMES; MULTICENTER; CLOPIDOGREL; REGISTRY; RISK
AB Objectives The purpose of this study was to evaluate the frequency and predictors of stent thrombosis (ST) after stenting for ST-segment elevation myocardial infarction (STEMI).
Background Stent thrombosis remains a major concern with STEMI patients treated with primary percutaneous coronary intervention.
Methods Consecutive patients (N = 1,640) undergoing stenting for STEMI were prospectively enrolled in our database and followed for 1 to 15 years. Bare-metal stents were implanted from 1995 to 2002, and drug-eluting and bare-metal stents were implanted from 2003 to 2009. Stent thrombosis was defined as definite or probable.
Results Our population had a high risk profile, including a high incidence of Killip class III to IV (11.5%) and STEMI due to ST (10.2%). Stent thrombosis occurred in 124 patients, including 42 with early ST (0 to 30 days), 35 with late ST (31 days to 1 year), and 47 with very late ST (>1 year). The frequency of ST was 2.7% at 30 days, 5.2% at 1 year, and 8.3% at 5 years. Independent predictors of early or late ST were STEMI due to ST (hazard ratio [HR]: 4.38, 95% confidence interval [CI]: 2.27 to 8.45), small stent size (HR: 2.44, 95% CI: 1.49 to 4.00), Killip class III to IV (HR: 2.39, 95% CI: 1.30 to 4.40), and reperfusion time <= 2 h (HR: 2.09, 95% CI: 1.03 to 4.24). Drug-eluting stent was the only independent predictor of very late ST (HR: 3.73, 95% CI: 1.81 to 7.88).
Conclusions Stent thrombosis after primary percutaneous coronary intervention is relatively frequent and continues to increase out to 5 years. New strategies are needed to prevent ST in STEMI patients, and targeted therapies are needed in patients identified at highest risk. (J Am Coll Cardiol Intv 2012;5:1043-51) (c) 2012 by the American College of Cardiology Foundation
C1 [Brodie, Bruce; Pokharel, Yashashwi; Garg, Ankit; Hansen, Charles] LeBauer Cardiovasc Res Fdn, Moses H Cone Mem Hosp, Internal Med Residency Program, Greensboro, NC 27408 USA.
[Kissling, Grace] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
RP Brodie, B (reprint author), LeBauer Cardiovasc Res Fdn, Moses H Cone Mem Hosp, Internal Med Residency Program, 313 Meadowbrook Terrace, Greensboro, NC 27408 USA.
EM bbrodie89@gmail.com
FU LeBauer Charitable Research Foundation; Intramural Research Program of
the National Institutes of Health, National Institute of Environmental
Health Sciences [Z01ES045005]
FX From *The LeBauer Cardiovascular Research Foundation, Greensboro, North
Carolina; dagger Internal Medicine Residency Program, Moses H. Cone
Memorial Hospital, Greensboro, North Carolina; and the double dagger
National Institute of Environmental Health Sciences, Research Triangle
Park, North Carolina. This study was supported by an unrestricted grant
from the LeBauer Charitable Research Foundation and by the Intramural
Research Program of the National Institutes of Health, National
Institute of Environmental Health Sciences (Z01ES045005). Dr. Brodie has
served on the Speakers' Bureau for the Medicines Company and
Medrad/Possis. Dr. Stuckey has served as consultant to and on the
Speakers' Bureau and on the Advisory Board for Boston Scientific
Corporation. All other authors have reported that they have no
relationships relevant to the contents of this paper to disclose.
NR 22
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U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-8798
J9 JACC-CARDIOVASC INTE
JI JACC-Cardiovasc. Interv.
PD OCT
PY 2012
VL 5
IS 10
BP 1043
EP 1051
DI 10.1016/j.jcin.2012.06.013
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 025NY
UT WOS:000310197800010
PM 23078734
ER
PT J
AU Kang, L
Lustig, ME
Bonner, JS
Lee-Young, RS
Mayes, WH
James, FD
Lin, CT
Perry, CGR
Anderson, EJ
Neufer, PD
Wasserman, DH
AF Kang, Li
Lustig, Mary E.
Bonner, Jeffrey S.
Lee-Young, Robert S.
Mayes, Wesley H.
James, Freyja D.
Lin, Chien-Te
Perry, Christopher G. R.
Anderson, Ethan J.
Neufer, P. Darrell
Wasserman, David H.
TI Mitochondrial antioxidative capacity regulates muscle glucose uptake in
the conscious mouse: effect of exercise and diet
SO JOURNAL OF APPLIED PHYSIOLOGY
LA English
DT Article
DE superoxide dismutase; catalase; hydrogen peroxide; superoxide anion;
high-fat diet
ID MANGANESE SUPEROXIDE-DISMUTASE; ACTIVATED PROTEIN-KINASE;
SKELETAL-MUSCLE; HYDROGEN-PEROXIDE; OXIDATIVE STRESS;
INSULIN-RESISTANCE; REACTIVE OXYGEN; HEXOKINASE-II; IN-VIVO; ENDURANCE
CAPACITY
AB The objective of this study was to test the hypothesis that exercise-stimulated muscle glucose uptake (MGU) is augmented by increasing mitochondrial reactive oxygen species (mtROS) scavenging capacity. This hypothesis was tested in genetically altered mice fed chow or a high-fat (HF) diet that accelerates mtROS formation. Mice overexpressing SOD2 (sod2(Tg)), mitochondria-targeted catalase (mcat(Tg)), and combined SOD2 and mCAT (mtAO) were used to increase mtROS scavenging. mtROS was assessed by the H2O2 emitting potential (JH(2)O(2)) in muscle fibers. sod2(Tg) did not decrease JH(2)O(2) in chow-fed mice, but decreased JH(2)O(2) in HF-fed mice. mcat(Tg) and mtAO decreased JH(2)O(2) in both chow-and HF-fed mice. In parallel, the ratio of reduced to oxidized glutathione (GSH/GSSG) was unaltered in sod2(Tg) in chow-fed mice, but was increased in HF-fed sod2(Tg) and both chow-and HF-fed mcat(Tg) and mtAO. Nitrotyrosine, a marker of NO-dependent, reactive nitrogen species (RNS)-induced nitrative stress, was decreased in both chow-and HF-fed sod2(Tg), mcat(Tg), and mtAO mice. This effect was not changed with exercise. Kg, an index of MGU was assessed using 2-[C-14]-deoxyglucose during exercise. In chow-fed mice, sod2(Tg), mcat(Tg), and mtAO increased exercise Kg compared with wild types. Exercise Kg was also augmented in HF-fed sod2(Tg) and mcat(Tg) mice but unchanged in HF-fed mtAO mice. In conclusion, mtROS scavenging is a key regulator of exercise-mediated MGU and this regulation depends on nutritional state.
C1 [Kang, Li; Lustig, Mary E.; Bonner, Jeffrey S.; Lee-Young, Robert S.; Mayes, Wesley H.; James, Freyja D.; Wasserman, David H.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
[Kang, Li; Wasserman, David H.] Vanderbilt Univ, Mouse Metab Phenotyping Ctr, Nashville, TN USA.
[Lin, Chien-Te; Perry, Christopher G. R.; Anderson, Ethan J.; Neufer, P. Darrell] E Carolina Univ, E Carolina Diabet & Obes Inst, Greenville, NC USA.
[Lin, Chien-Te; Perry, Christopher G. R.; Anderson, Ethan J.; Neufer, P. Darrell] E Carolina Univ, Dept Physiol, Greenville, NC USA.
[Lin, Chien-Te; Perry, Christopher G. R.; Anderson, Ethan J.; Neufer, P. Darrell] E Carolina Univ, Dept Kinesiol, Greenville, NC USA.
RP Kang, L (reprint author), 823 Light Hall,2200 Pierce Ave, Nashville, TN 37232 USA.
EM li.kang@vanderbilt.edu
FU National Institutes of Health [DK-073488, DK-054902, DK-059637]
FX This work was supported by National Institutes of Health Grants
DK-073488 (to P. D. Neufer), DK-054902 (to D. H. Wasserman), and
DK-059637 (Mouse Metabolic Phenotyping Center; to D. H. Wasserman).
NR 64
TC 3
Z9 3
U1 1
U2 9
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 8750-7587
J9 J APPL PHYSIOL
JI J. Appl. Physiol.
PD OCT
PY 2012
VL 113
IS 8
BP 1173
EP 1183
DI 10.1152/japplphysiol.01344.2011
PG 11
WC Physiology; Sport Sciences
SC Physiology; Sport Sciences
GA 022RM
UT WOS:000309979600002
PM 22653994
ER
PT J
AU Carl, N
Hodoscek, M
Vehar, B
Konc, J
Brooks, BR
Janezic, D
AF Carl, Nejc
Hodoscek, Milan
Vehar, Blaz
Konc, Janez
Brooks, Bernard R.
Janezic, Dusanka
TI Correlating Protein Hot Spot Surface Analysis Using ProBiS with
Simulated Free Energies of Protein-Protein Interfacial Residues
SO JOURNAL OF CHEMICAL INFORMATION AND MODELING
LA English
DT Article
ID MOLECULAR-DYNAMICS SIMULATIONS; LOCAL STRUCTURAL ALIGNMENT;
BINDING-SITES PREDICTION; EMPIRICAL FORCE-FIELD; WEB SERVER;
THERMODYNAMIC INTEGRATION; LIGAND-BINDING; NUCLEIC-ACIDS; REGIONS;
CHARMM
AB A protocol was developed for the computational determination of the contribution of interfacial amino acid residues to the free energy of protein-protein binding. Thermodynamic integration, based on molecular dynamics simulation in CHARMM, was used to determine the free energy associated with single point mutations to glycine in a protein-protein interface. The hot spot amino acids found in this way were then correlated to structural similarity scores detected by the ProBiS algorithm for local structural alignment. We find that amino acids with high structural similarity scores contribute on average -3.19 kcal/mol to the free energy of protein-protein binding and are thus correlated with hot spot residues, while residues with low similarity scores contribute on average only -0.43 kcal/mol. This suggests that the local structural alignment method provides a good approximation of the contribution of a residue to the free energy of binding and is particularly useful for detection of hot spots in proteins with known structures but undetermined protein-protein complexes.
C1 [Carl, Nejc; Hodoscek, Milan; Vehar, Blaz; Konc, Janez; Janezic, Dusanka] Natl Inst Chem, SI-1000 Ljubljana, Slovenia.
[Brooks, Bernard R.] NHLBI, NIH, Lab Computat Biol, Rockville, MD 20852 USA.
RP Janezic, D (reprint author), Natl Inst Chem, Hajdrihova 19, SI-1000 Ljubljana, Slovenia.
EM dusa@cmm.ki.si
FU Ministry of Higher Education, Science, and Technology of Slovenia
[P1-0002]; Slovenian Research Agency
FX The authors express their thanks to Stefan Boresch for helpful
discussions that arose during the course of this work and Urban Bren for
helpful discussions and manuscript review. The financial support through
grant (P1-0002) of the Ministry of Higher Education, Science, and
Technology of Slovenia and the Slovenian Research Agency is
acknowledged.
NR 73
TC 2
Z9 2
U1 1
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9596
J9 J CHEM INF MODEL
JI J. Chem Inf. Model.
PD OCT
PY 2012
VL 52
IS 10
BP 2541
EP 2549
DI 10.1021/ci3003254
PG 9
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science,
Information Systems; Computer Science, Interdisciplinary Applications
SC Pharmacology & Pharmacy; Chemistry; Computer Science
GA 023OH
UT WOS:000310043800006
PM 23009716
ER
PT J
AU Nelson, MI
Gramer, MR
Vincent, AL
Holmes, EC
AF Nelson, Martha I.
Gramer, Marie R.
Vincent, Amy L.
Holmes, Edward C.
TI Global transmission of influenza viruses from humans to swine
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID PANDEMIC H1N1 2009; A VIRUSES; UNITED-STATES; PIGS; REASSORTMENT;
ORIGIN; ARGENTINA; OUTBREAK; FARM
AB To determine the extent to which influenza viruses jump between human and swine hosts, we undertook a large-scale phylogenetic analysis of pandemic A/H1N1/09 (H1N1pdm09) influenza virus genome sequence data. From this, we identified at least 49 human-to-swine transmission events that occurred globally during 2009-2011, thereby highlighting the ability of the H1N1pdm09 virus to transmit repeatedly from humans to swine, even following adaptive evolution in humans. Similarly, we identified at least 23 separate introductions of human seasonal (non-pandemic) H1 and H3 influenza viruses into swine globally since 1990. Overall, these results reveal the frequency with which swine are exposed to human influenza viruses, indicate that humans make a substantial contribution to the genetic diversity of influenza viruses in swine, and emphasize the need to improve biosecurity measures at the human swine interface, including influenza vaccination of swine workers.
C1 [Nelson, Martha I.; Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Gramer, Marie R.] Univ Minnesota, Vet Diagnost Lab, St Paul, MN 55108 USA.
[Vincent, Amy L.] USDA ARS, Virus & Prion Dis Res Unit, Natl Anim Dis Ctr, Ames, IA 50010 USA.
[Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
RP Nelson, MI (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM nelsonma@mail.nih.gov
OI Holmes, Edward/0000-0001-9596-3552
FU Office of Global Affairs at the Department of Health and Human Services
(DHHS)
FX This research was conducted within the context of the Multinational
Influenza Seasonal Mortality Study (MISMS), an ongoing international
collaborative effort to understand influenza epidemiology and evolution,
led by the Fogarty International Center, NIH, with funding from the
Office of Global Affairs at the Department of Health and Human Services
(DHHS).
NR 26
TC 56
Z9 58
U1 0
U2 17
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
J9 J GEN VIROL
JI J. Gen. Virol.
PD OCT
PY 2012
VL 93
BP 2195
EP 2203
DI 10.1099/vir.0.044974-0
PN 10
PG 9
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA 023OD
UT WOS:000310043400012
PM 22791604
ER
PT J
AU Kawayama, T
Okamoto, M
Imaoka, H
Kato, S
Young, HA
Hoshino, T
AF Kawayama, Tomotaka
Okamoto, Masaki
Imaoka, Haruki
Kato, Seiya
Young, Howard A.
Hoshino, Tomoaki
TI Interleukin-18 in Pulmonary Inflammatory Diseases
SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
LA English
DT Review
ID IDIOPATHIC INTERSTITIAL PNEUMONIAS; IFN-GAMMA PRODUCTION; ACUTE LUNG
INJURY; T-CELLS; LEGIONELLA-PNEUMOPHILA; ALLERGIC-ASTHMA; INNATE
IMMUNITY; POTENTIAL ROLE; CUTTING EDGE; IL-18
AB The proinflammatory cytokine interleukin (IL)-18 was originally discovered as an interferon-g-inducing factor in 1995. IL-18 is known to play an important role in Th1/Tc1 polarization and promoting the production of Th2 cytokines (e. g., IL-4, IL-5, IL-9, and IL-13) by T cells, NK cells, basophils, and mast cells. IL-18 can act as a cofactor for Th2 cell development and IgE production, and also plays an important role in the differentiation of Th17 cells. IL-18 is a key player in the pathogenesis of inflammatory diseases such as atopic dermatitis, rheumatoid arthritis, adult-onset Still's disease, Sjogren's syndrome, and inflammatory bowel diseases. Furthermore, many lines of evidence suggest that IL-18 plays a key role in the pathogenesis of pulmonary inflammatory diseases, including bronchial asthma and chronic obstructive pulmonary disease. Here, we review the pathological roles of IL-18 in pulmonary inflammatory diseases.
C1 [Kawayama, Tomotaka; Okamoto, Masaki; Imaoka, Haruki; Hoshino, Tomoaki] Kurume Univ, Div Respirol Neurol & Rheumatol, Dept Med 1, Sch Med, Kurume, Fukuoka 8300011, Japan.
[Kato, Seiya] Univ Ryukyus, Grad Sch, Div Pathol & Cell Biol, Okinawa, Japan.
[Kato, Seiya] Univ Ryukyus, Fac Med, Okinawa, Japan.
[Young, Howard A.] Frederick Natl Lab Canc Res, LEI, Frederick, MD USA.
RP Hoshino, T (reprint author), Kurume Univ, Div Respirol Neurol & Rheumatol, Dept Med 1, Sch Med, Kurume, Fukuoka 8300011, Japan.
EM hoshino@med.kurume-u.ac.jp
NR 76
TC 22
Z9 23
U1 0
U2 12
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1079-9907
J9 J INTERF CYTOK RES
JI J. Interferon Cytokine Res.
PD OCT
PY 2012
VL 32
IS 10
BP 443
EP 449
DI 10.1089/jir.2012.0029
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 022QE
UT WOS:000309974900001
PM 22900713
ER
PT J
AU Nolting, S
Garcia, E
Alusi, G
Giubellino, A
Pacak, K
Korbonits, M
Grossman, AB
AF Noelting, Svenja
Garcia, Edwin
Alusi, Ghassan
Giubellino, Alessio
Pacak, Karel
Korbonits, Marta
Grossman, Ashley B.
TI Combined blockade of signalling pathways shows marked anti-tumour
potential in phaeochromocytoma cell lines
SO JOURNAL OF MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID LOVASTATIN-INDUCED APOPTOSIS; MEDULLARY-THYROID CANCER; DUAL PI3K/MTOR
INHIBITOR; CARCINOID-TUMOR CELLS; GROWTH-FACTOR-I; MALIGNANT
PHEOCHROMOCYTOMA; PROSTATE-CANCER; KINASE-B; RAF-1 ACTIVATOR; SUPPRESSOR
GENE
AB Currently, there is no completely effective therapy available for metastatic phaeochromocytomas (PCCs) and paragangliomas. In this study, we explore new molecular targeted therapies for these tumours, using one more benign (mouse phaeochromocytoma cell (MPC)) and one more malignant (mouse tumour tissue (MTT)) mouse PCC cell line - both generated from heterozygous neurofibromin 1 knockout mice. Several PCC-promoting gene mutations have been associated with aberrant activation of PI3K/AKT, mTORC1 and RAS/RAF/ERK signalling. We therefore investigated different agents that interfere specifically with these pathways, including antagonism of the IGF1 receptor by NVP-AEW541. We found that NVP-AEW541 significantly reduced MPC and MTT cell viability at relatively high doses but led to a compensatory up-regulation of ERK and mTORC1 signalling at suboptimal doses while PI3K/AKT inhibition remained stable. We subsequently investigated the effect of the dual PI3K/mTORC1/2 inhibitor NVP-BEZ235, which led to a significant decrease of MPC and MTT cell viability at doses down to 50 nM but again increased ERK signalling. Accordingly, we next examined the combination of NVP-BEZ235 with the established agent lovastatin, as this has been described to inhibit ERK signalling. Lovastatin alone significantly reduced MPC and MTT cell viability at therapeutically relevant doses and inhibited both ERK and AKT signalling, but increased mTORC1/p70S6K signalling. Combination treatment with NVP-BEZ235 and lovastatin showed a significant additive effect in MPC and MTT cells and resulted in inhibition of both AKT and mTORC1/p70S6K signalling without ERK up-regulation. Simultaneous inhibition of PI3K/AKT, mTORC1/2 and ERK signalling suggests a novel therapeutic approach for malignant PCCs. Journal of Molecular Endocrinology (2012) 49, 79-96
C1 [Grossman, Ashley B.] Univ Oxford, Dept Endocrinol, Oxford Ctr Diabet Endocrinol & Metab, Churchill Hosp, Oxford OX3 7LE, England.
[Noelting, Svenja; Garcia, Edwin; Korbonits, Marta; Grossman, Ashley B.] Queen Mary Univ London, William Harvey Res Inst, Dept Endocrinol, Barts & London Sch Med, London, England.
[Alusi, Ghassan] Queen Mary Univ London, Barts & London Sch Med, Barts Canc Inst, London, England.
[Giubellino, Alessio; Pacak, Karel] NIH, Bethesda, MD 20892 USA.
RP Grossman, AB (reprint author), Univ Oxford, Dept Endocrinol, Oxford Ctr Diabet Endocrinol & Metab, Churchill Hosp, Oxford OX3 7LE, England.
EM ashley.grossman@ocdem.ox.ac.uk
OI Korbonits, Marta/0000-0002-4101-9432; Giubellino,
Alessio/0000-0002-5352-0662
FU German Research Foundation [NO925/1-1]; Novartis
FX This work was supported by the German Research Foundation (grant number
NO925/1-1).; Prof. A B G has received lecture fees and advisory board
honoraria from Novartis. Dr S N has received travel costs from Ipsen for
attending the ENEA Workshop on Aggressive Pituitary Tumours in Munich,
2011.
NR 80
TC 17
Z9 18
U1 0
U2 4
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0952-5041
J9 J MOL ENDOCRINOL
JI J. Mol. Endocrinol.
PD OCT
PY 2012
VL 49
IS 2
BP 79
EP 96
DI 10.1530/JME-12-0028
PG 18
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 020KB
UT WOS:000309806300009
PM 22715163
ER
PT J
AU Norlin, N
Hellberg, M
Filippov, A
Sousa, AA
Grobner, G
Leapman, RD
Almqvist, N
Antzutkin, ON
AF Norlin, Nils
Hellberg, Magnus
Filippov, Andrei
Sousa, Alioscka A.
Grobner, Gerhard
Leapman, Richard D.
Almqvist, Nils
Antzutkin, Oleg N.
TI Aggregation and fibril morphology of the Arctic mutation of Alzheimer's
A beta peptide by CD, TEM, STEM and in situ AFM
SO JOURNAL OF STRUCTURAL BIOLOGY
LA English
DT Article
DE Amyloid beta-peptide; Arctic mutation; Spherical aggregates;
Polymorphism of amyloid fibrils; AFM; TEM; STEM; Mass-per-length
measurements; Real time growth; CD; ThT assay
ID ATOMIC-FORCE MICROSCOPY; SOLID-STATE NMR; TRANSMISSION
ELECTRON-MICROSCOPY; RAPID CELLULAR DEGENERATION;
NUCLEAR-MAGNETIC-RESONANCE; AMYLOID ION CHANNELS; SHEET STRUCTURES;
PROTEIN 1-42; DISEASE; PROTOFIBRILS
AB Morphology of aggregation intermediates, polymorphism of amyloid fibrils and aggregation kinetics of the "Arctic" mutant of the Alzheimer's amyloid beta-peptide, A beta((1-40))(E22G), in a physiologically relevant Tris buffer (pH 7.4) were thoroughly explored in comparison with the human wild type Alzheimer's amyloid peptide, wt-A beta((1-40)), using both in situ atomic force and electron microscopy, circular dichroism and thioflavin T fluorescence assays. For arc-A beta((1-40)) at the end of the 'lag'-period of fibrillization an abrupt appearance of similar to 3 nm size 'spherical aggregates' with a homogeneous morphology, was identified. Then, the aggregation proceeds with a rapid growth of amyloid fibrils with a variety of morphologies, while the spherical aggregates eventually disappeared during in situ measurements. Arc-A beta((1-40)) was also shown to form fibrils at much lower concentrations than wt-A beta((1-40)): <= 2.5 mu M and 12.5 mu M, respectively. Moreover, at the same concentration, 50 mu M, the aggregation process proceeds more rapidly for arc-A beta((1-40)): the first amyloid fibrils were observed after Ca. 72 h from the onset of incubation as compared to approximately 7 days for wt-A beta((1-40)). Amyloid fibrils of arc-A beta((1-40)) exhibit a large variety of polymorphs, at least five, both coiled and non-coiled distinct fibril structures were recognized by AFM, while at least four types of arc-A beta((1-40)) fibrils were identified by TEM and STEM and their mass-per-length statistics were collected suggesting supramolecular structures with two, four and six beta-sheet laminae. Our results suggest a pathway of fibrillogenesis for full-length Alzheimer's peptides with small and structurally ordered transient spherical aggregates as on-pathway immediate precursors of amyloid fibrils. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Hellberg, Magnus; Almqvist, Nils] Lulea Univ Technol, Div Phys, SE-97187 Lulea, Sweden.
[Filippov, Andrei] Kazan VI Lenin State Univ, Dept Phys, Kazan 420008, Russia.
[Sousa, Alioscka A.; Leapman, Richard D.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA.
[Grobner, Gerhard] Umea Univ, Inst Chem, Dept Biol Chem, SE-90187 Lulea, Sweden.
[Antzutkin, Oleg N.] Univ Warwick, Dept Phys, Coventry CV4 7AL, W Midlands, England.
RP Almqvist, N (reprint author), Lulea Univ Technol, Div Phys, SE-97187 Lulea, Sweden.
EM Nils.Almqvist@ltu.se; O.N.Antzutkin@warwick.ac.uk
RI Filippov, Andrei/A-1053-2013
OI Filippov, Andrei/0000-0002-6810-1882
FU Swedish Research Council; Foundation in memory of J.C.; Seth M. Kempe
[JCK-2701, JCK-2905]; [SMK-2546]
FX We thank Dr. Goldsbury for useful technical discussions regarding
time-lapse imaging of fibril assembly and Dr. Mannequist for valuable
ideas in the design of the tapping mode system. This work was supported
by the Swedish Research Council (O.A., N.A. and G.G.) and from the
Foundation in memory of J.C. and Seth M. Kempe (Grant Nos. JCK-2701 and
JCK-2905, used for a stipend for A.F. a peptide synthesizer, HPLC and
chemicals) but also for AFM support (SMK-2546). Alzheimer's foundation
in Sweden is acknowledged for grants (2001, 2003, 2005 and in 2010) used
for a stipend (N.N.) and for purchase of chemicals and a vacuum pump.
Peptides were synthesized and purified by O.A. in the group of Tycko,
Laboratory of Chemical Physics, NIDDK, NIH, USA and also by A.F. at LTU,
Lulea, Sweden.
NR 85
TC 30
Z9 33
U1 5
U2 63
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1047-8477
J9 J STRUCT BIOL
JI J. Struct. Biol.
PD OCT
PY 2012
VL 180
IS 1
BP 174
EP 189
DI 10.1016/j.jsb.2012.06.010
PG 16
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 023PH
UT WOS:000310046400020
PM 22750418
ER
PT J
AU Schrack, JA
Simonsick, EM
Chaves, PH
Ferrucci, L
AF Schrack, Jennifer A.
Simonsick, Eleanor M.
Chaves, Paulo H. M.
Ferrucci, Luigi
TI The Role of Energetic Cost in the Age-Related Slowing of Gait Speed
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE energy expenditure; gait speed; physical function
ID HEALTHY OLDER-ADULTS; METABOLIC COST; ACTIVITY LEVEL; WALKING;
PREDICTOR; SURVIVAL; OUTCOMES; PEOPLE; FORCE; PACE
AB Objectives To determine whether slow gait represents a compensatory strategy to reduce the energetic cost of walking with age. Design Cross-sectional analysis. Setting Community-dwelling volunteers from the Baltimore Longitudinal Study of Aging (BLSA). Participants Four hundred twenty community-dwelling persons aged 32 to 96 (mean 68.1 +/- 12.5) who underwent a physical examination, physical function testing, and energy expenditure assessment. Measurements Energy expenditure per minute (mL/kg/min) and per meter (mL/kg/m) during 2.5 minutes of overground walking at customary speed and usual gait speed over 6 m (m/s) were examined. General linear regression models were used to assess the relationship between customary walking energy expenditure and usual gait speed, adjusted for potential confounders including smoking, medical diagnoses, walking-related pain, and balance difficulty. Results Usual gait speed was slower with increasing age after age 65. Energy expenditure per minute during customary walking averaged 13.0 +/- 2.8 mL/kg/min and was independent of age (rho < 0.01, P = .88). In contrast, energy expenditure per meter walked was progressively higher after age 65 (rho = 0.35, P < .001) and heightened after age 80 (r = 0.57, P < .001), mirroring the observed pattern of usual gait speed. This relationship remained significant after adjusting for multiple impairments and comorbidities. Conclusion These observations support the hypothesis that slower gait at older ages may reflect a compensatory action to offset the greater energetic cost of walking associated with aging and chronic conditions. Future studies should evaluate the specific mechanisms that contribute to this phenomenon as novel targets for clinical intervention.
C1 [Schrack, Jennifer A.; Simonsick, Eleanor M.; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21225 USA.
[Chaves, Paulo H. M.] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA.
[Schrack, Jennifer A.; Chaves, Paulo H. M.] Johns Hopkins Univ, Ctr Aging & Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Schrack, JA (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, 3001 S Hanover St, Baltimore, MD 21225 USA.
EM schrackja@mail.nih.gov
FU NIA, National Institutes of Health, Baltimore, Maryland
FX This research was supported by the Intramural Research Program of the
NIA, National Institutes of Health, Baltimore, Maryland. Data for these
analyses were obtained from the BLSA, a study performed by the NIA.
NR 30
TC 25
Z9 25
U1 3
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD OCT
PY 2012
VL 60
IS 10
BP 1811
EP 1816
DI 10.1111/j.1532-5415.2012.04153.x
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 019LF
UT WOS:000309740400003
PM 23035640
ER
PT J
AU Shahar, DR
Houston, DK
Hue, TF
Lee, JS
Sahyoun, NR
Tylavsky, FA
Geva, D
Vardi, H
Harris, TB
AF Shahar, Danit R.
Houston, Denise K.
Hue, Trisha F.
Lee, Jung-Sun
Sahyoun, Nadine R.
Tylavsky, Frances A.
Geva, Diklah
Vardi, Hillel
Harris, Tamara B.
CA Hlth Aging Body Composition Study
TI Adherence to Mediterranean Diet and Decline in Walking Speed over 8
Years in Community-Dwelling Older Adults
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE walking speed; elderly; Mediterranean diet; dietary assessment; function
ID HUMAN SKELETAL-MUSCLE; SUBSEQUENT DISABILITY; COGNITIVE DECLINE;
BODY-COMPOSITION; BLOOD-PRESSURE; GAIT SPEED; OLIVE OIL; WOMEN;
POPULATION; SURVIVAL
AB Objectives To determine the association between Mediterranean diet (MedDiet) score and 20-m walking speed over 8 years. Design Health, Aging and Body Composition Study (Health ABC) beginning in 1997/98. Setting Community. Participants Two thousand two hundred twenty-five well-functioning individuals aged 70 and older. Measurements Walking speed was assessed in relation to low, medium, and high adherence to the MedDiet (0-2, 3-5, 6-9 points, respectively). Results Individuals in the highest MedDiet adherence group were more likely to be male; less likely to smoke; and more likely to have lower body mass index, higher energy intake, and greater physical activity (P < .05). Usual and rapid 20-m walking speed were highest in the high MedDiet adherence group than in the other groups (high, 1.19 +/- 0.19 m/s; medium, 1.16 +/- 0.21 m/s; low, 1.15 +/- 0.19 m/s, P = .02, for usual speed; high, 1.65 +/- 0.30 m/s; medium, 1.59 +/- 0.32 m/s; low, 1.55 +/- 0.30 m/s, P = .001, for rapid speed). Over 8 years, usual and rapid 20-m walking speed declined in all MedDiet adherence groups. Higher MedDiet adherence was an independent predictor of less decline in usual 20-m walking speed (P = .049) in generalized estimating equations adjusted for age, race, sex, site, education, smoking, physical activity, energy intake, health status, depression and cognitive score. The effect decreased after adding total body fat percentage to the model (P = .13). Similar results were observed for MedDiet adherence and rapid 20-m walking speed; the association remained significant after adjustment for total body fat percentage (P = .01). The interaction between time and MedDiet adherence was not significant in any of the models. Conclusion Walking speed over 8 years was faster in those with higher MedDiet adherence at baseline. The differences remained significant over 8 years, suggesting a long-term effect of diet on mobility performance with aging.
C1 [Shahar, Danit R.; Geva, Diklah; Vardi, Hillel] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Epidemiol & Hlth Evaluat, S Daniel Int Ctr Hlth & Nutr, Negev, Israel.
[Houston, Denise K.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA.
[Hue, Trisha F.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Lee, Jung-Sun] Univ Georgia, Dept Foods & Nutr, Athens, GA 30602 USA.
[Sahyoun, Nadine R.] Univ Maryland, Dept Food Sci & Nutr, College Pk, MD 20742 USA.
[Tylavsky, Frances A.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Shahar, DR (reprint author), Ben Gurion Univ Negev, S Daniel Abraham Int Ctr Hlth & Nutr, Dept Epidemiol & Hlth Serv Evaluat, Fac Hlth Sci, POB 653, IL-84105 Beer Sheva, Israel.
EM dshahar@bgu.ac.il
RI Shahar, Danit/B-4280-2012; Sahyoun, Nadine/G-2608-2011
FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106]; NIA [RO1-AG028050]; National Institute of Nursing
Research [RO1-NR012459]; National Institutes of Health, NIA
FX This research was supported by National Institute on Aging (NIA)
Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; NIA Grant
RO1-AG028050, and National Institute of Nursing Research Grant
RO1-NR012459. This research was supported in part by the Intramural
Research Program of the National Institutes of Health, NIA.
NR 47
TC 17
Z9 17
U1 5
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD OCT
PY 2012
VL 60
IS 10
BP 1881
EP 1888
DI 10.1111/j.1532-5415.2012.04167.x
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 019LF
UT WOS:000309740400011
PM 23035758
ER
PT J
AU Adeyi, O
Alexander, G
Baiocchi, L
Balasubramanian, M
Batal, I
Bellamy, COC
Bhan, A
Bridges, N
Bucuvalas, J
Charlotte, F
Colvin, B
Czaja, A
Demetris, A
DeVera, M
El-Monayeri, MS
Feng, S
Ferrell, L
Fiel, MI
Fontes, P
Fung, J
Haga, H
Hart, J
Honsova, E
Hubscher, S
Wesam, I
Itoh, T
Jhala, N
Jungmann, P
Khettry, U
Koshiba, T
Lassman, C
Lerut, J
Ligato, S
Lunz, J
Mazariegos, G
McCaughan, G
McClelland, SA
Minervini, MI
Misdraji, J
Mohanakumar, T
Molne, J
Musat, A
Nalesnik, M
Nasser, I
Neil, D
Neuberger, J
Pappo, O
Petrovic, L
Randhawa, P
Reinholt, FP
Rubin, E
Ruiz, P
Sagol, O
Fueyo, AS
Sasatomi, E
Schiano, T
Sebagh, M
Shaked, A
Sharkey, FE
Shimizu, T
Sis, B
Smith, M
Sonzogni, A
Tchao, N
Thung, S
Tisone, G
Tsamandas, A
Wernerson, A
Wu, T
Yilmaz, F
AF Adeyi, Oyedele
Alexander, Graeme
Baiocchi, Leonardo
Balasubramanian, Manjula
Batal, Ibrahim
Bellamy, Chris O. C.
Bhan, Atul
Bridges, Nancy
Bucuvalas, John
Charlotte, Frederic
Colvin, Bob
Czaja, Albert
Demetris, Anthony
DeVera, Michael
El-Monayeri, Magda S.
Feng, Sandy
Ferrell, Linda
Fiel, Maria Isabel
Fontes, Paulo
Fung, John
Haga, Hironori
Hart, John
Honsova, Eva
Hubscher, Stefan
Wesam, Ismail
Itoh, Tomoo
Jhala, Nirag
Jungmann, Patricia
Khettry, Urmila
Koshiba, Takaaki
Lassman, Charles
Lerut, Jan
Ligato, Saverio
Lunz, John
Mazariegos, George
McCaughan, Geoff
McClelland, Sandra A.
Minervini, Marta I.
Misdraji, Joseph
Mohanakumar, Thalachallour
Molne, Johan
Musat, Alexandru
Nalesnik, Michael
Nasser, Imad
Neil, Desley
Neuberger, James
Pappo, Orit
Petrovic, Lydia
Randhawa, Parmjeet
Reinholt, Finn P.
Rubin, Erin
Ruiz, Phil
Sagol, Ozgul
Sanchez Fueyo, Alberto
Sasatomi, Eizaburo
Schiano, Thomas
Sebagh, Mylene
Shaked, Avi
Sharkey, Francis Edward
Shimizu, Tomokazu
Sis, Banu
Smith, Maxwell
Sonzogni, Aurelio
Tchao, Nadia
Thung, Swan
Tisone, Giuseppe
Tsamandas, Athanassios
Wernerson, Annika
Wu, Tong
Yilmaz, Funda
CA Banff Working Grp Liver Allograft
TI Importance of liver biopsy findings in immunosuppression management:
Biopsy monitoring and working criteria for patients with operational
tolerance
SO LIVER TRANSPLANTATION
LA English
DT Review
ID RECURRENT HEPATITIS-C; LONG-TERM OUTCOMES; NOVO AUTOIMMUNE HEPATITIS;
CHRONIC VIRAL-HEPATITIS; PLASMA-CELL HEPATITIS; REGULATORY T-CELLS;
TRANSPLANT RECIPIENTS; FOLLOW-UP; ALLOGRAFT-REJECTION; GRAFT FIBROSIS
AB Obstacles to morbidity-free long-term survival after liver transplantation (LT) include complications of immunosuppression (IS), recurrence of the original disease and malignancies, and unexplained chronic hepatitis and graft fibrosis. Many programs attempt to minimize chronic exposure to IS by reducing dosages and stopping steroids. A few programs have successfully weaned a highly select group of recipients from all IS without apparent adverse consequences, but long-term follow-up is limited. Patients subjected to adjustments in IS are usually followed by serial liver chemistry tests, which are relatively insensitive methods for detecting allograft damage. Protocol biopsy has largely been abandoned for hepatitis C virusnegative recipients, at least in part because of the inability to integrate routine histopathological findings into a rational clinical management algorithm. Recognizing a need to more precisely categorize and determine the clinical significance of findings in long-term biopsy samples, the Banff Working Group on Liver Allograft Pathology has reviewed the literature, pooled the experience of its members, and proposed working definitions for biopsy changes that (1) are conducive to lowering IS and are compatible with operational tolerance (OT) and (2) raise concern for closer follow-up and perhaps increased IS during or after IS weaning. The establishment of guidelines should help us to standardize analyses of the effects of various treatments and/or weaning protocols and more rigorously categorize patients who are assumed to show OT. Long-term follow-up using standardized criteria will help us to determine the consequences of lowering IS and to define and determine the incidence and robustness of OT in liver allografts. Liver Transpl 18:1154-1170, 2012. (c) 2012 AASLD.
C1 [Demetris, Anthony; Fontes, Paulo; Lunz, John; Mazariegos, George; McClelland, Sandra A.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA.
[Adeyi, Oyedele] Toronto Gen Hosp, Toronto, ON, Canada.
[Alexander, Graeme] Univ Cambridge, Cambridge CB2 1TN, England.
[Baiocchi, Leonardo] Univ Roma Tor Vergata, Rome, Italy.
[Balasubramanian, Manjula] Albert Einstein Med Ctr, Philadelphia, PA 19141 USA.
[Batal, Ibrahim] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Bellamy, Chris O. C.] Edinburgh Royal Infirm, Edinburgh, Midlothian, Scotland.
[Bhan, Atul; Colvin, Bob] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
[Bridges, Nancy] NIAID, Bethesda, MD 20892 USA.
[Bucuvalas, John] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Charlotte, Frederic] Hop La Pitie Salpetriere, Paris, France.
[Czaja, Albert] Mayo Clin, Coll Med, Rochester, MN 55905 USA.
[DeVera, Michael] Loma Linda Univ, Loma Linda, CA 92350 USA.
[Feng, Sandy; Ferrell, Linda] Univ Calif San Francisco, Ctr Med, San Francisco, CA 94143 USA.
[Fiel, Maria Isabel] Mt Sinai Sch Med, New York, NY USA.
[Fung, John] Cleveland Clin Fdn, Cleveland, OH USA.
[Haga, Hironori] Kyoto Univ Hosp, Kyoto, Japan.
[Hart, John] Univ Chicago, Ctr Med, Chicago, IL 60637 USA.
[Honsova, Eva] Inst Clin & Expt Med, Prague, Czech Republic.
[Hubscher, Stefan] Univ Birmingham, Birmingham B15 2TT, W Midlands, England.
[Wesam, Ismail] Bani Sweif Univ, Bani Suwayf, Egypt.
[Itoh, Tomoo] Hokkaido Univ Hosp, Sapporo, Hokkaido, Japan.
[Jhala, Nirag] Univ Alabama Birmingham, Birmingham, AL USA.
[Jungmann, Patricia] Univ Fed Pernambuco, Recife, PE, Brazil.
[Koshiba, Takaaki] Kyoto Univ, Kyoto 6068501, Japan.
[Lassman, Charles] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Ligato, Saverio] Hartford Hosp, Hartford, CT USA.
[McCaughan, Geoff] Univ Sydney, Royal Prince Alfred Hosp, Sydney, NSW 2006, Australia.
[Mohanakumar, Thalachallour] Washington Univ, St Louis, MO 63130 USA.
[Molne, Johan] Sahlgrens Univ Hosp, Gothenburg, Sweden.
[Musat, Alexandru] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Nasser, Imad] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cambridge, MA 02138 USA.
[Neil, Desley; Neuberger, James] Univ Hosp Birmingham, Birmingham, W Midlands, England.
[Pappo, Orit] Hadassah Med Ctr, Jerusalem, Israel.
[Petrovic, Lydia] Univ So Calif, Univ Hosp, Los Angeles, CA 90089 USA.
[Ruiz, Phil] Univ Miami, Sch Med, Coral Gables, FL 33124 USA.
[Reinholt, Finn P.] Univ Oslo, N-0316 Oslo, Norway.
[Reinholt, Finn P.] Oslo Univ Univ, Rikshosp, Oslo, Norway.
[Sagol, Ozgul] Dokuz Eylul Univ, TR-35210 Alsancak, Turkey.
[Sanchez Fueyo, Alberto] Hosp Clin Barcelona, Liver Transplant Unit, Barcelona, Spain.
[Schiano, Thomas; Thung, Swan] Mt Sinai Med Ctr, New York, NY USA.
[Sebagh, Mylene] Hop Paul Brousse, Villejuif, France.
[Shaked, Avi] Hosp Univ Penn, Philadelphia, PA 19104 USA.
[Sharkey, Francis Edward] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Shimizu, Tomokazu] Tokyo Womens Med Univ, Tokyo, Japan.
[Sis, Banu] Univ Alberta Hosp, Edmonton, AB, Canada.
[Sonzogni, Aurelio] Univ Pittsburgh, Med Ctr, Palermo, Italy.
[Tisone, Giuseppe] Univ Rome, Rome, Italy.
[Tsamandas, Athanassios] Univ Patras, Sch Med, GR-26110 Patras, Greece.
[Wernerson, Annika] Karolinska Univ Hosp, Stockholm, Sweden.
[Wu, Tong] Tulane Univ, Sch Med, New Orleans, LA 70118 USA.
[Yilmaz, Funda] Univ Ege, Izmir, Turkey.
RP Demetris, A (reprint author), Univ Pittsburgh, Med Ctr, 3459 5th Ave,UPMC Montefiore E741, Pittsburgh, PA 15213 USA.
EM demetrisaj@upmc.edu
RI Fung, John/A-2679-2012;
OI Wernerson, Annika/0000-0003-2792-0010; Neil, Desley/0000-0001-9800-6811
NR 123
TC 28
Z9 28
U1 1
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1527-6465
EI 1527-6473
J9 LIVER TRANSPLANT
JI Liver Transplant.
PD OCT
PY 2012
VL 18
IS 10
BP 1154
EP 1170
DI 10.1002/lt.23481
PG 17
WC Gastroenterology & Hepatology; Surgery; Transplantation
SC Gastroenterology & Hepatology; Surgery; Transplantation
GA 021WS
UT WOS:000309916700007
ER
PT J
AU Noinaj, N
Buchanan, SK
Cornelissen, CN
AF Noinaj, Nicholas
Buchanan, Susan K.
Cornelissen, Cynthia Nau
TI The transferrin-iron import system from pathogenic Neisseria species
SO MOLECULAR MICROBIOLOGY
LA English
DT Review
ID BINDING PROTEIN-B; RECEPTOR PROTEIN; STRUCTURAL BASIS; LIGAND-BINDING;
GONORRHOEAE; IDENTIFICATION; MENINGITIDIS; TONB; EXPRESSION; ANTIBODIES
AB Two pathogenic species within the genus Neisseria cause the diseases gonorrhoea and meningitis. While vaccines are available to protect against four N.?meningitidis serogroups, there is currently no commercial vaccine to protect against serogroup B or against N.?gonorrhoeae. Moreover, the available vaccines have significant limitations and with antibiotic resistance becoming an alarming issue, the search for effective vaccine targets to elicit long-lasting protection against Neisseria species is becoming more urgent. One strategy for vaccine development has targeted the neisserial iron import systems. Without iron, the Neisseriae cannot survive and, therefore, these iron import systems tend to be relatively well conserved and are promising vaccine targets, having the potential to offer broad protection against both gonococcal and meningococcal infections. These efforts have been boosted by recent reports of the crystal structures of the neisserial receptor proteins TbpA and TbpB, each solved in complex with human transferrin, an iron binding protein normally responsible for delivering iron to human cells. Here, we review the recent structural reports and put them into perspective with available functional studies in order to derive the mechanism(s) for how the pathogenic Neisseriae are able to hijack human iron transport systems for their own survival and pathogenesis.
C1 [Noinaj, Nicholas; Buchanan, Susan K.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Cornelissen, Cynthia Nau] Virginia Commonwealth Univ, Med Ctr, Dept Microbiol & Immunol, Richmond, VA 23298 USA.
RP Buchanan, SK (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
EM skbuchan@helix.nih.gov; cncornel@vcu.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health; U.S. Public Health Service from the
National Institute of Allergy and Infectious Diseases at the National
Institutes of Health [AI065555, AI084400]; SE STI Center from the
National Institute of Allergy and Infectious Diseases [U19 AI31496]
FX N.N. and S. K. B. are supported by the Intramural Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health. Funding was provided to C.N.C. by U.S.
Public Health Service grant numbers AI065555 and AI084400 from the
National Institute of Allergy and Infectious Diseases at the National
Institutes of Health. C.N.C. is also supported by the SE STI Center
grant (U19 AI31496) from the National Institute of Allergy and
Infectious Diseases.
NR 58
TC 21
Z9 22
U1 2
U2 26
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0950-382X
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD OCT
PY 2012
VL 86
IS 2
BP 246
EP 257
DI 10.1111/mmi.12002
PG 12
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 019RH
UT WOS:000309756500002
PM 22957710
ER
PT J
AU Kumar, P
Arora, K
Lloyd, JR
Lee, Y
Nair, V
Fischer, E
Boshoff, HIM
Barry, CE
AF Kumar, Pradeep
Arora, Kriti
Lloyd, John R., III
Lee, Y.
Nair, Vinod
Fischer, Elizabeth
Boshoff, Helena I. M.
Barry, Clifton E., III
TI Meropenem inhibits D,D-carboxypeptidase activity in Mycobacterium
tuberculosis
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID MULTIDRUG-RESISTANT TUBERCULOSIS; PENICILLIN-BINDING PROTEINS;
BETA-LACTAM RESISTANCE; ESCHERICHIA-COLI; ENTEROCOCCUS-FAECIUM;
DIAMINOPIMELIC ACID; CELL-WALL; PEPTIDOGLYCAN BIOSYNTHESIS;
NONREPLICATING PERSISTENCE; N-GLYCOLYLATION
AB Carbapenems such as meropenem are being investigated for their potential therapeutic utility against highly drug-resistant tuberculosis. These beta-lactams target the transpeptidases that introduce interpeptide cross-links into bacterial peptidoglycan thereby controlling rigidity of the bacterial envelope. Treatment of Mycobacterium tuberculosis (Mtb) with the beta-lactamase inhibitor clavulanate together with meropenem resulted in rapid, polar, cell lysis releasing cytoplasmic contents. In Mtb it has been previously demonstrated that 3-3 cross-linkages [involving two diaminopimelate (DAP) molecules] predominate over 4-3 cross-linkages (involving one DAP and one D-alanine) in stationary-phase cells. We purified and analysed peptidoglycan from Mtb and found that 3-3 cross-linkages predominate throughout all growth phases and the ratio of 4-3/3-3 linkages does not vary significantly under any growth condition. Meropenem treatment was accompanied by a dramatic accumulation of unlinked pentapeptide stems with no change in the tetrapeptide pools, suggesting that meropenem inhibits both a D,D-carboxypeptidase and an L,D-transpeptidase. We purified a candidate D,D-carboxypeptidase DacB2 and showed that meropenem indeed directly inhibits this enzyme by forming a stable adduct at the enzyme active site. These results suggest that the rapid lysis of meropenem-treated cells is the result of synergistically inhibiting the transpeptidases that introduce 3,3-cross-links while simultaneously limiting the pool of available substrates available for cross-linking.
C1 [Kumar, Pradeep; Arora, Kriti; Lee, Y.; Boshoff, Helena I. M.; Barry, Clifton E., III] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA.
[Lloyd, John R., III] NIDDK, Lab Bioorgan Chem, NIH, Bethesda, MD 20892 USA.
[Lee, Y.] Korea Res Inst Chem Technol, Ctr Metab Syndrome Therapeut, Bioorgan Sci Div, Taejon 305600, South Korea.
[Nair, Vinod; Fischer, Elizabeth] Rocky Mt Labs, Electron Microscopy Unit, Res Technol Branch, Hamilton, MT 59840 USA.
RP Barry, CE (reprint author), NIAID, TB Res Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM cbarry@mail.nih.gov
RI Barry, III, Clifton/H-3839-2012; Kumar, Pradeep/I-7989-2014
OI Kumar, Pradeep/0000-0003-0042-7525
FU Intramural Research Program of the NIAID, NIH
FX We would like to thank Michael Goodwin for technical assistance. We
would like to thank Chandan Gope for writing the software for cell
length measurements. This work was funded by the Intramural Research
Program of the NIAID, NIH.
NR 49
TC 44
Z9 44
U1 1
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0950-382X
EI 1365-2958
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD OCT
PY 2012
VL 86
IS 2
BP 367
EP 381
DI 10.1111/j.1365-2958.2012.08199.x
PG 15
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 019RH
UT WOS:000309756500010
PM 22906310
ER
PT J
AU Christner, M
Heinze, C
Busch, M
Franke, G
Hentschke, M
Duhring, SB
Buttner, H
Kotasinska, M
Wischnewski, V
Kroll, G
Buck, F
Molin, S
Otto, M
Rohde, H
AF Christner, Martin
Heinze, Constanze
Busch, Michael
Franke, Gefion
Hentschke, Moritz
Duhring, Sara Bayard
Buettner, Henning
Kotasinska, Marta
Wischnewski, Victoria
Kroll, Gesche
Buck, Friedrich
Molin, Soeren
Otto, Michael
Rohde, Holger
TI sarA negatively regulates Staphylococcus epidermidis biofilm formation
by modulating expression of 1?MDa extracellular matrix binding protein
and autolysis-dependent release of eDNA
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID POLYSACCHARIDE INTERCELLULAR ADHESIN; DNA RELEASE;
ENTEROCOCCUS-FAECALIS; AUREUS; ACCUMULATION; INFECTION; VIRULENCE;
MODEL; IDENTIFICATION; STRAINS
AB Biofilm formation is essential for Staphylococcus epidermidis pathogenicity in implant-associated infections. Nonetheless, large proportions of invasive Staphylococcus epidermidis isolates fail to form a biofilm in vitro. We here tested the hypothesis that this apparent paradox is related to the existence of superimposed regulatory systems suppressing a multicellular biofilm life style in vitro. Transposon mutagenesis of clinical significant but biofilm-negative S.?epidermidis 1585 was used to isolate a biofilm positive mutant carrying a Tn917 insertion in sarA, chief regulator of staphylococcal virulence. Genetic analysis revealed that inactivation of sarA induced biofilm formation via overexpression of the giant 1?MDa extracellular matrix binding protein (Embp), serving as an intercellular adhesin. In addition to Embp, increased extracellular DNA (eDNA) release significantly contributed to biofilm formation in mutant 1585?sarA. Increased eDNA amounts indirectly resulted from upregulation of metalloprotease SepA, leading to boosted processing of autolysin AtlE, in turn inducing augmented autolysis and release of eDNA. Hence, this study identifies sarA as a negative regulator of Embp- and eDNA-dependent biofilm formation. Given the importance of SarA as a positive regulator of polysaccharide mediated cell aggregation, the regulator enables S.?epidermidis to switch between mechanisms of biofilm formation, ensuring S.?epidermidis adaptation to hostile environments.
C1 [Christner, Martin; Heinze, Constanze; Busch, Michael; Franke, Gefion; Hentschke, Moritz; Buettner, Henning; Kotasinska, Marta; Wischnewski, Victoria; Kroll, Gesche; Rohde, Holger] Univ Med Ctr Hamburg Eppendorf, Inst Med Microbiol Virol & Hyg, D-20246 Hamburg, Germany.
[Buck, Friedrich] Univ Med Ctr Hamburg Eppendorf, Inst Clin Chem, D-20246 Hamburg, Germany.
[Duhring, Sara Bayard; Molin, Soeren] Tech Univ Denmark, Dept Syst Biol, Ctr Syst Microbiol, DK-2800 Lyngby, Denmark.
[Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
RP Rohde, H (reprint author), Univ Med Ctr Hamburg Eppendorf, Inst Med Microbiol Virol & Hyg, Martinistr 52, D-20246 Hamburg, Germany.
EM rohde@uke.uni-hamburg.de
OI Otto, Michael/0000-0002-2222-4115
FU Deutsche Forschungsgemeinschaft [Ro2413/3-1]; Bundesministerium fur
Bildung und Forschung (GenoMik-Transfer) [0315587C]
FX We thank Paul Fey for providing mutant 1457 Delta sarA and plasmid
pNF96. Phage A6C was kindly provided by V. T. Rosdahl, Statens Serum
Institute, Copenhagen, Denmark. This work was supported by grants of the
Deutsche Forschungsgemeinschaft (Ro2413/3-1, given to H. R.) and the
Bundesministerium fur Bildung und Forschung (GenoMik-Transfer, 0315587C,
given to H.R.).
NR 59
TC 18
Z9 18
U1 1
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0950-382X
EI 1365-2958
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD OCT
PY 2012
VL 86
IS 2
BP 394
EP 410
DI 10.1111/j.1365-2958.2012.08203.x
PG 17
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 019RH
UT WOS:000309756500012
PM 22957858
ER
PT J
AU Yepes, A
Schneider, J
Mielich, B
Koch, G
Garcia-Betancur, JC
Ramamurthi, KS
Vlamakis, H
Lopez, D
AF Yepes, Ana
Schneider, Johannes
Mielich, Benjamin
Koch, Gudrun
Garcia-Betancur, Juan-Carlos
Ramamurthi, Kumaran S.
Vlamakis, Hera
Lopez, Daniel
TI The biofilm formation defect of a Bacillus subtilis flotillin-defective
mutant involves the protease FtsH
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID SUBCELLULAR-LOCALIZATION; BACTERIAL-MEMBRANES; STATIONARY-PHASE;
SIGMA(W) REGULON; SPFH DOMAIN; GENES; SPORULATION; PROTEINS; MULTIPLE;
SIGNALS
AB Biofilm formation in Bacillus subtilis requires the differentiation of a subpopulation of cells responsible for the production of the extracellular matrix that structures the biofilm. Differentiation of matrix-producing cells depends, among other factors, on the FloT and YqfA proteins. These proteins are present exclusively in functional membrane microdomains of B.?subtilis and are homologous to the eukaryotic lipid raft-specific flotillin proteins. In the absence of FloT and YqfA, diverse proteins normally localized to the membrane microdomains of B.?subtilis are not functional. Here we show that the absence of FloT and YqfA reduces the level of the septal-localized protease FtsH. The flotillin homologues FloT and YqfA are occasionally present at the midcell in exponentially growing cells and the absence of FloT and YqfA negatively affects FtsH concentration. Biochemical experiments indicate a direct interaction between FloT/YqfA and FtsH. Moreover, FtsH is essential for the differentiation of matrix producers and hence, biofilm formation. This molecular trigger of biofilm formation may therefore be used as a target for the design of new biofilm inhibitors. Accordingly, we show that the small protein SpoVM, known to bind to and inhibit FtsH activity, inhibits biofilm formation in B.?subtilis and other distantly related bacteria.
C1 [Yepes, Ana; Schneider, Johannes; Mielich, Benjamin; Koch, Gudrun; Garcia-Betancur, Juan-Carlos; Lopez, Daniel] Univ Wurzburg, Res Ctr Infect Dis ZINF, D-97080 Wurzburg, Germany.
[Ramamurthi, Kumaran S.] NCI, Lab Mol Biol, NIH, Bethesda, MD 20892 USA.
[Vlamakis, Hera] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
RP Lopez, D (reprint author), Univ Wurzburg, Res Ctr Infect Dis ZINF, D-97080 Wurzburg, Germany.
EM daniel.lopez@uni-wuerzburg.de
RI Ramamurthi, Kumaran/P-3516-2015;
OI Schneider, Johannes/0000-0002-6028-9956
FU Young Investigator Program of the Research Center of Infectious Diseases
(ZINF) of the University of Wurzburg, Germany; German Research
Foundation DFG [LO 1804/2-1]; Schrodinger fellowship (FWF); Graduate
School of Life Sciences (GSLS) of the University of Wuerzburg;
Intramural Research Program of the NIH National Cancer Institute Center
for Cancer Research
FX We thank all members of the Institute of Molecular Infection Biology
(IMIB), especially Isa Westedt for technical assistance. We thank Prof.
Dr Thomas Wiegert (University of Bayreuth, Germany) for kindly providing
FtsH antibody and the strain harbouring the deletion ftsH::tet. This
work was funded by the Young Investigator Program of the Research Center
of Infectious Diseases (ZINF) of the University of Wurzburg, Germany and
the grant LO 1804/2-1 from The German Research Foundation DFG. G. K. is
recipient of Schrodinger fellowship (FWF). J.C.G.B. is recipient of PhD
fellowship from the Graduate School of Life Sciences (GSLS) of the
University of Wuerzburg. K. S. R. acknowledges funding from the
Intramural Research Program of the NIH National Cancer Institute Center
for Cancer Research.
NR 76
TC 25
Z9 25
U1 1
U2 23
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0950-382X
EI 1365-2958
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD OCT
PY 2012
VL 86
IS 2
BP 457
EP 471
DI 10.1111/j.1365-2958.2012.08205.x
PG 15
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 019RH
UT WOS:000309756500016
PM 22882210
ER
PT J
AU Nakajima, K
Wess, J
AF Nakajima, Ken-ichiro
Wess, Juergen
TI Design and Functional Characterization of a Novel, Arrestin-Biased
Designer G Protein-Coupled Receptor
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID 7-TRANSMEMBRANE RECEPTORS; INSULIN-SECRETION; ACTIVATION;
BETA-ARRESTIN2; IDENTIFICATION; RECRUITMENT; LIGAND
AB Mutational modification of distinct muscarinic receptor subtypes has yielded novel designer G protein-coupled receptors (GPCRs) that are unable to bind acetylcholine (ACh), the endogenous muscarinic receptor ligand, but can be efficiently activated by clozapine-N-oxide (CNO), an otherwise pharmacologically inert compound. These CNO-sensitive designer GPCRs [alternative name: designer receptors exclusively activated by designer drug (DREADDs)] have emerged as powerful new tools to dissect the in vivo roles of distinct G protein signaling pathways in specific cell types or tissues. As is the case with other GPCRs, CNO-activated DREADDs not only couple to heterotrimeric G proteins but can also recruit proteins of the arrestin family (arrestin-2 and -3). Accumulating evidence suggests that arrestins can act as scaffolding proteins to promote signaling through G protein-independent signaling pathways. To explore the physiological relevance of these arrestin-dependent signaling pathways, the availability of an arrestin-biased DREADD would be highly desirable. In this study, we describe the development of an M-3 muscarinic receptor-based DREADD [Rq(R165L)] that is no longer able to couple to G proteins but can recruit arrestins and promote extracellular signal-regulated kinase-1/2 phosphorylation in an arrestin-and CNO-dependent fashion. Moreover, CNO treatment of mouse insulinoma (MIN6) cells expressing the Rq(R165L) construct resulted in a robust, arrestin-dependent stimulation of insulin release, directly implicating arrestin signaling in the regulation of insulin secretion. This newly developed arrestin-biased DREADD represents an excellent novel tool to explore the physiological relevance of arrestin signaling pathways in distinct tissues and cell types.
C1 [Nakajima, Ken-ichiro; Wess, Juergen] NIDDKD, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Wess, J (reprint author), NIDDKD, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Room B1A-05,8 Ctr Dr,MSC 0810, Bethesda, MD 20892 USA.
EM jwess@helix.nih.gov
FU National Institutes of Health National Institute of Diabetes and
Digestive and Kidney Diseases
FX This work was supported by the Intramural Research program of the
National Institutes of Health National Institute of Diabetes and
Digestive and Kidney Diseases.
NR 24
TC 38
Z9 39
U1 3
U2 10
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD OCT
PY 2012
VL 82
IS 4
BP 575
EP 582
DI 10.1124/mol.112.080358
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 016HZ
UT WOS:000309509900003
PM 22821234
ER
PT J
AU Makia, NL
Amunom, I
Falkner, KC
Conklin, DJ
Surapureddi, S
Goldstein, JA
Prough, RA
AF Makia, N. L.
Amunom, I.
Falkner, K. C.
Conklin, D. J.
Surapureddi, S.
Goldstein, J. A.
Prough, R. A.
TI Activator Protein-1 Regulation of Murine Aldehyde Dehydrogenase 1a1
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID ANTIOXIDANT RESPONSE ELEMENT; GENE-EXPRESSION; OXIDATIVE STRESS;
RETINOIC ACID; OLIGONUCLEOTIDE MICROARRAY; KEAP1-KNOCKDOWN MICE;
SIGNAL-TRANSDUCTION; CONSENSUS SEQUENCE; C-FOS; IDENTIFICATION
AB Previously we demonstrated that aldehyde dehydrogenase (ALDH) 1a1 is the major ALDH expressed in mouse liver and is an effective catalyst in metabolism of lipid aldehydes. Quantitative real-time polymerase chain reaction analysis revealed a approximate to 2.5- to 3-fold induction of the hepatic ALDH1A1 mRNA in mice administered either acrolein (5 mg/kg acrolein p.o.) or butylated hydroxylanisole (BHA) (0.45% in the diet) and of cytosolic NAD(+)-dependent ALDH activity. We observed approximate to 2-fold increases in ALDH1A1 mRNA levels in both Nrf2(+/+) and Nrf2(-/-) mice treated with BHA compared with controls, suggesting that BHA-induced expression is independent of nuclear factor E2-related factor 2 (Nrf2). The levels of activator protein-1 (AP-1) mRNA and protein, as well as the amount of phosphorylated c-Jun were significantly increased in mouse liver or Hepa1c1c7 cells treated with either BHA or acrolein. With use of luciferase reporters containing the 5'-flanking sequence of Aldh1a1 (-1963/+27), overexpression of c-Jun resulted in an approximate to 4-fold induction in luciferase activity, suggesting that c-Jun transactivates the Aldh1a1 promoter as a homodimer and not as a c-Jun/c-Fos heterodimer. Promoter deletion and mutagenesis analyses demonstrated that the AP-1 site at position -758 and possibly -1069 relative to the transcription start site was responsible for c-Jun-mediated transactivation. Electrophoretic mobility shift assay analysis with antibodies against c-Jun and c-Fos showed that c-Jun binds to the proximal AP-1 site at position -758 but not at -1069. Recruitment of c-Jun to this proximal AP-1 site by BHA was confirmed by chromatin immunoprecipitation analysis, indicating that recruitment of c-Jun to the mouse Aldh1a1 gene promoter results in increased transcription. This mode of regulation of an ALDH has not been described before.
C1 [Makia, N. L.; Amunom, I.; Prough, R. A.] Univ Louisville, Sch Med, Dept Biochem & Mol Biol, Louisville, KY 40292 USA.
[Falkner, K. C.] Univ Louisville, Sch Med, Dept Med Gastroenterol Hepatol & Nutr, Louisville, KY 40292 USA.
[Conklin, D. J.] Univ Louisville, Sch Med, Dept Med Cardiovasc Med, Louisville, KY 40292 USA.
[Conklin, D. J.] Univ Louisville, Sch Med, Diabet & Obes Ctr, Louisville, KY 40292 USA.
[Surapureddi, S.; Goldstein, J. A.] NIEHS, Human Metab Grp, Res Triangle Pk, NC 27709 USA.
RP Prough, RA (reprint author), Univ Louisville, Sch Med, Dept Biochem & Mol Biol, Louisville, KY 40292 USA.
EM raprou01@louisville.edu
FU National Institutes of Health National Heart, Lung, and Blood Institute
[HL89380]; National Institutes of Health National Institute for
Environmental Health Sciences [ES11860]; Preston Pope Joyes Research
Endowment
FX This work was supported in part by the National Institutes of Health
National Heart, Lung, and Blood Institute [Grant HL89380] (to D.J.C.);
the National Institutes of Health National Institute for Environmental
Health Sciences [Grant ES11860]; and the Preston Pope Joyes Research
Endowment.
NR 42
TC 5
Z9 5
U1 0
U2 2
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD OCT
PY 2012
VL 82
IS 4
BP 601
EP 613
DI 10.1124/mol.112.078147
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 016HZ
UT WOS:000309509900006
PM 22740640
ER
PT J
AU Hallett, M
Iseki, K
AF Hallett, Mark
Iseki, Kazumi
TI Real and imaginary gait
SO MOVEMENT DISORDERS
LA English
DT Editorial Material
ID PARKINSONS-DISEASE; FUNCTIONAL MRI; MOTOR IMAGERY; PREMOTOR
C1 [Hallett, Mark; Iseki, Kazumi] NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA.
RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA.
EM hallettm@ninds.nih.gov
OI Hallett, Mark/0000-0002-3180-6811
FU Intramural NIH HHS [ZIA NS003031-05]
NR 11
TC 1
Z9 1
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD OCT
PY 2012
VL 27
IS 12
BP 1473
EP 1474
DI 10.1002/mds.25186
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 023VL
UT WOS:000310064800002
PM 23008184
ER
PT J
AU Elble, R
Comella, C
Fahn, S
Hallett, M
Jankovic, J
Juncos, JL
LeWitt, P
Lyons, K
Ondo, W
Pahwa, R
Sethi, K
Stover, N
Tarsy, D
Testa, C
Tintner, R
Watts, R
Zesiewicz, T
AF Elble, Rodger
Comella, Cynthia
Fahn, Stanley
Hallett, Mark
Jankovic, Joseph
Juncos, Jorge L.
LeWitt, Peter
Lyons, Kelly
Ondo, William
Pahwa, Rajesh
Sethi, Kapil
Stover, Natividad
Tarsy, Daniel
Testa, Claudia
Tintner, Ron
Watts, Ray
Zesiewicz, Theresa
TI Reliability of a new scale for essential tremor
SO MOVEMENT DISORDERS
LA English
DT Article
DE essential tremor; rating scale; reliability
ID RATING-SCALE
AB Background: The objective of this study was to determine the reliability of a new scale for the clinical assessment of essential tremor. The Essential Tremor Rating Assessment Scale contains 9 performance items that rate action tremor in the head, face, voice, limbs, and trunk from 0 to 4 in half-point intervals. Head and limb tremor ratings are defined by specific amplitude ranges in centimeters. Methods: Videos of 44 patients and 6 controls were rated by 10 specialists on 2 occasions 12 months apart. Inter- and intrarater reliability was assessed with a 2-way random-effects intraclass correlation, using an absolute agreement definition. Results: Inter- and intrarater intraclass correlations for head and upper-limb tremor ranged from 0.86 to 0.96, and intraclass correlations for total score were 0.94 and 0.96. The intraclass correlations for voice, face, trunk, and leg were less robust. Conclusions: This scale is an exceptionally reliable tool for the clinical assessment of essential tremor. (c) 2012 Movement Disorder Society
C1 [Elble, Rodger] So Illinois Univ, Sch Med, Dept Neurol, Springfield, IL 62794 USA.
[Comella, Cynthia] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Fahn, Stanley] Columbia Univ, Med Ctr, New York, NY USA.
[Hallett, Mark] NINDS, Bethesda, MD 20892 USA.
[Jankovic, Joseph] Baylor Coll Med, Houston, TX 77030 USA.
[Juncos, Jorge L.] Emory Univ, Atlanta, GA 30322 USA.
[LeWitt, Peter] Henry Ford Hlth Syst, Bloomfield, MI USA.
[Lyons, Kelly; Pahwa, Rajesh] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
[Ondo, William] Univ Texas Hlth Sci Ctr, Houston, TX USA.
[Sethi, Kapil] Georgia Hlth Sci Univ, Augusta, GA USA.
[Stover, Natividad; Watts, Ray] Univ Alabama Birmingham, Birmingham, AL USA.
[Tarsy, Daniel] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Testa, Claudia] Virginia Commonwealth Univ, Richmond, VA USA.
[Tintner, Ron] Methodist Hosp, Houston, TX 77030 USA.
[Zesiewicz, Theresa] Univ S Florida, Tampa, FL USA.
RP Elble, R (reprint author), So Illinois Univ, Sch Med, Dept Neurol, 751 N Rutledge,POB 19643, Springfield, IL 62794 USA.
EM relble@siumed.edu
FU GlaxoSmithKline
FX This study was supported by a grant from GlaxoSmithKline.
NR 18
TC 17
Z9 17
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD OCT
PY 2012
VL 27
IS 12
BP 1567
EP 1569
DI 10.1002/mds.25162
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 023VL
UT WOS:000310064800018
PM 23032792
ER
PT J
AU Shuch, B
Linehan, WM
AF Shuch, Brian
Linehan, W. Marston
TI KIDNEY CANCER Is incomplete renal ablation linked to tumour progression?
SO NATURE REVIEWS UROLOGY
LA English
DT Editorial Material
C1 [Shuch, Brian; Linehan, W. Marston] NCI, NIH, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Linehan, WM (reprint author), NCI, NIH, Urol Oncol Branch, Ctr Canc Res, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM wml@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4812
J9 NAT REV UROL
JI Nat. Rev. Urol.
PD OCT
PY 2012
VL 9
IS 10
BP 547
EP 548
DI 10.1038/nrurol.2012.174
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 022MQ
UT WOS:000309963900001
PM 22926423
ER
PT J
AU Natarajan, G
Pappas, A
Shankaran, S
Laptook, AR
Walsh, M
McDonald, SA
Ehrenkranz, RA
Tyson, JE
Goldberg, RN
Bara, R
Higgins, RD
Das, A
Munoz, B
AF Natarajan, Girija
Pappas, Athina
Shankaran, Seetha
Laptook, Abbot R.
Walsh, Michele
McDonald, Scott A.
Ehrenkranz, Richard A.
Tyson, Jon E.
Goldberg, Ronald N.
Bara, Rebecca
Higgins, Rosemary D.
Das, Abhik
Munoz, Breda
TI Effect of inborn vs. outborn delivery on neurodevelopmental outcomes in
infants with hypoxic-ischemic encephalopathy: secondary analyses of the
NICHD whole-body cooling trial
SO PEDIATRIC RESEARCH
LA English
DT Article
ID MODERATE HYPOTHERMIA; NEONATAL ENCEPHALOPATHY; HETEROGENEITY; NEWBORNS;
SAFETY; RISK
AB BACKGROUND: The effect of birth location on hypothermia-related outcomes has not been rigorously examined in the literature. In this study, we determined whether birth location had an impact on the benefits of whole-body cooling to 33.5 degrees C for 72h in term infants (n = 208) with hypoxic ischemic encephalopathy (HIE) who participated in the Neonatal Research Network (NRN) randomized controlled trial.
METHODS: Heterogeneity by birth location was examined with respect to cooling treatment for the 18-mo primary outcomes (death, moderate disability, severe disability) and secondary outcomes (death, components of disability), and in-hospital organ dysfunction. Logistic regression models were used to generate adjusted odds ratios.
RESULTS: Infants born at a location other than an NRN center (outborn) (n = 93) experienced significant delays in initiation of therapy (mean (SD): 5.5 (1.1) vs. 4.4 (1.2) h), lower baseline temperatures (36.6 (1.2) vs. 37.1 (0.9) degrees C), and more severe HIE (43 vs. 29%) than infants born in an NRN center (inborn) (n = 115). Maternal education <12 y (50 vs. 14%) and African-American ethnicity (43 vs. 25%) were more common in the inborn group. When adjusted for NRN center and HIE severity, there were no significant differences in 18-mo outcomes or in-hospital organ dysfunction between inborn and outborn infants.
CONCLUSION: Although limited by sample size and some differences in baseline characteristics, the study showed that birth location does not appear to modify the treatment effect of hypothermia after HIE.
C1 [Natarajan, Girija; Pappas, Athina; Shankaran, Seetha; Bara, Rebecca] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[Walsh, Michele] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[McDonald, Scott A.; Das, Abhik; Munoz, Breda] Res Triangle Int, Dept Pediat, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Tyson, Jon E.] Univ Texas Med Sch Houston, Dept Pediat, Houston, TX USA.
[Goldberg, Ronald N.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Pediat, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med,NIH, Bethesda, MD USA.
RP Natarajan, G (reprint author), Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
EM gnatara@med.wayne.edu
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD); Alpert Medical School of
Brown University; Women & Infants Hospital of Rhode Island [U10
HD27904]; Case Western Reserve University, Rainbow Babies & Children's
Hospital [U10 HD21364, M01 RR80]; Cincinnati Children's Hospital Medical
Center, University Hospital and Good Samaritan Hospital [U10 HD27853,
M01 RR8084]; Duke University, School of Medicine University Hospital,
Alamance Regional Medical Center; Durham Regional Hospital [U10 HD40492,
M01 RR30]; Emory University; Children's Healthcare of Atlanta; Grady
Memorial Hospital; Emory University Hospital Midtown [U10 HD27851, M01
RR39]; Indiana University; University Hospital; Methodist Hospital;
Riley Hospital for Children; Wishard Health Services [U10 HD27856, M01
RR750]; RTI International [U10 HD36790]; Stanford University and Lucile
Packard Children's Hospital [U10 HD27880, M01 RR70]; University of
Alabama at Birmingham Health System; Children's Hospital of Alabama [U10
HD34216, M01 RR32]; University of California San Diego Medical Center;
Sharp Mary Birch Hospital for Women and Newborns [U10 HD40461];
University of Miami Holtz Children's Hospital [U10 HD21397, M01
RR16587]; University of Rochester Medical Center Golisano Children's
Hospital [U10 HD40521, M01 RR44]; University of Texas Southwestern;
Medical Center at Dallas Parkland Health & Hospital System; Children's
Medical Center Dallas [U10 HD40689, M01 RR633]; University of Texas
Health Science Center at Houston, Medical School, Children's Memorial
Hermann Hospital; Lyndon Baines Johnson General Hospital/Harris County
Hospital District [U10 HD21373]; Wayne State University; Hutzel Women's
Hospital; Children's Hospital of Michigan [U10 HD21385]; Yale
University,Yale-New Haven Children's Hospital [U10 HD27871, UL1 RR24139,
GCRC MO1 RR125, M01 RR6022]
FX The National Institutes of Health and the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD)
provided grant support for the Neonatal Research Network's Whole-Body
Hypothermia Trial. Grant funding was provided by Alpert Medical School
of Brown University and Women & Infants Hospital of Rhode Island (U10
HD27904); Case Western Reserve University, Rainbow Babies & Children's
Hospital (U10 HD21364, M01 RR80); Cincinnati Children's Hospital Medical
Center, University Hospital and Good Samaritan Hospital (U10 HD27853,
M01 RR8084); Duke University, School of Medicine University Hospital,
Alamance Regional Medical Center, and Durham Regional Hospital (U10
HD40492, M01 RR30); Emory University, Children's Healthcare of Atlanta,
Grady Memorial Hospital, and Emory University Hospital Midtown (U10
HD27851, M01 RR39); Indiana University, University Hospital, Methodist
Hospital, Riley Hospital for Children, and Wishard Health Services (U10
HD27856, M01 RR750); RTI International (U10 HD36790); Stanford
University and Lucile Packard Children's Hospital (U10 HD27880, M01
RR70); University of Alabama at Birmingham Health System and Children's
Hospital of Alabama (U10 HD34216, M01 RR32); University of California
San Diego Medical Center and Sharp Mary Birch Hospital for Women and
Newborns (U10 HD40461); University of Miami Holtz Children's Hospital
(U10 HD21397, M01 RR16587); University of Rochester Medical Center
Golisano Children's Hospital (U10 HD40521, M01 RR44); University of
Texas Southwestern, Medical Center at Dallas Parkland Health & Hospital
System and Children's Medical Center Dallas (U10 HD40689, M01 RR633);
University of Texas Health Science Center at Houston, Medical School,
Children's Memorial Hermann Hospital, and Lyndon Baines Johnson General
Hospital/Harris County Hospital District (U10 HD21373); Wayne State
University, Hutzel Women's Hospital and Children's Hospital of Michigan
(U10 HD21385); and Yale University,Yale-New Haven Children's Hospital
(U10 HD27871, UL1 RR24139, GCRC MO1 RR125, M01 RR6022).
NR 18
TC 8
Z9 8
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0031-3998
J9 PEDIATR RES
JI Pediatr. Res.
PD OCT
PY 2012
VL 72
IS 4
BP 414
EP 419
DI 10.1038/pr.2012.103
PG 6
WC Pediatrics
SC Pediatrics
GA 020FQ
UT WOS:000309794800012
PM 22914450
ER
PT J
AU Lancaster, TS
Jefferson, SJ
Hunter, JC
Lopez, V
Van Eyk, JE
Lakatta, EG
Korzick, DH
AF Lancaster, T. S.
Jefferson, S. J.
Hunter, J. Craig
Lopez, Veronica
Van Eyk, J. E.
Lakatta, E. G.
Korzick, D. H.
TI Quantitative proteomic analysis reveals novel mitochondrial targets of
estrogen deficiency in the aged female rat heart
SO PHYSIOLOGICAL GENOMICS
LA English
DT Article
DE monoamine oxidase-A; respiration; ischemia; iTRAQ; cardioprotection
ID PERMEABILITY TRANSITION PORE; ISCHEMIA-REPERFUSION INJURY;
GLYCOGEN-SYNTHASE KINASE-3-BETA; PKC-EPSILON; OXIDATIVE STRESS; INDUCED
CARDIOPROTECTION; ANTIOXIDANT ENZYME; PROTEIN EXPRESSION; POSTISCHEMIC
HEART; SUPEROXIDE ANION
AB Lancaster TS, Jefferson SJ, Hunter JC, Lopez V, Van Eyk JE, Lakatta EG, Korzick DH. Quantitative proteomic analysis reveals novel mitochondrial targets of estrogen deficiency in the aged female rat heart. Physiol Genomics 44: 957-969, 2012. First published August 28, 2012; doi:10.1152/physiolgenomics.00184.2011.-The incidence of myocardial infarction rises sharply at menopause, implicating a potential role for estrogen (E-2) loss in age-related increases in ischemic injury. We aimed to identify quantitative changes to the cardiac mitochondrial proteome of aging females, based on the hypothesis that E-2 deficiency exacerbates age-dependent disruptions in mitochondrial proteins. Mitochondria isolated from left ventricles of adult (6 mo) and aged (24 mo) F344 ovary-intact or ovariectomized (OVX) rats were labeled with 8plex isobaric tags for relative and absolute quantification (iTRAQ; n = 5-6/group). Groups studied were adult, adult OVX, aged, and aged OVX. In vivo coronary artery ligation and in vitro mitochondrial respiration studies were also performed in a subset of rats. We identified 965 proteins across groups and significant directional changes in 67 proteins of aged and/or aged OVX; 32 proteins were unique to aged OVX. Notably, only six proteins were similarly altered in adult OVX (voltage-dependent ion channel 1, adenine nucleotide translocator 1, cytochrome c oxidase subunits VIIc and VIc, catalase, and myosin binding protein C). Proteins affected by aging were primarily related to cellular metabolism, oxidative stress, and cell death. The largest change occurred in monoamine oxidase-A (MAO-A), a source of oxidative stress. While acute MAO-A inhibition induced mild uncoupling in aged mitochondria, reductions in infarct size were not observed. Age-dependent alterations in mitochondrial signaling indicate a highly selective myocardial response to E-2 deficiency. The combined proteomic and functional approaches described here offer possibility of new protein targets for experimentation and therapeutic intervention in the aged female population.
C1 [Korzick, D. H.] Penn State Univ, Noll Lab, Dept Kinesiol, University Pk, PA 16802 USA.
[Korzick, D. H.] Penn State Univ, IGDP Physiol, University Pk, PA 16802 USA.
[Van Eyk, J. E.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Lakatta, E. G.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Korzick, DH (reprint author), Penn State Univ, Noll Lab, Dept Kinesiol, University Pk, PA 16802 USA.
EM dhk102@psu.edu
FU National Institutes of Health (NIH) [HL-091097, HL-091097-01A2S1,
AA-019403]; Intramural Research Program of the NIH, National Institute
on Aging
FX This work was supported by National Institutes of Health (NIH) Grants
HL-091097, HL-091097-01A2S1, and AA-019403 (to D. H. Korzick) and the
Intramural Research Program of the NIH, National Institute on Aging (E.
G. Lakatta).
NR 80
TC 15
Z9 15
U1 1
U2 14
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1094-8341
EI 1531-2267
J9 PHYSIOL GENOMICS
JI Physiol. Genomics
PD OCT
PY 2012
VL 44
IS 20
BP 957
EP 969
DI 10.1152/physiolgenomics.00184.2011
PG 13
WC Cell Biology; Genetics & Heredity; Physiology
SC Cell Biology; Genetics & Heredity; Physiology
GA 025TX
UT WOS:000310218700001
PM 22930739
ER
PT J
AU Ambatipudi, KS
Swatkoski, S
Moresco, JJ
Tu, PG
Coca, A
Anolik, JH
Gucek, M
Sanz, I
Yates, JR
Melvin, JE
AF Ambatipudi, Kiran S.
Swatkoski, Stephen
Moresco, James J.
Tu, Patricia G.
Coca, Andreea
Anolik, Jennifer H.
Gucek, Marjan
Sanz, Ignacio
Yates, John R., III
Melvin, James E.
TI Quantitative proteomics of parotid saliva in primary Sjogren's syndrome
SO PROTEOMICS
LA English
DT Article
DE Autoimmune; Biomarkers; Biomedicine; Label-free quantitation; Parotid
saliva; Sjogren's syndrome
ID PROTEIN IDENTIFICATION TECHNOLOGY; MASS-SPECTROMETRY;
RHEUMATOID-ARTHRITIS; SHOTGUN PROTEOMICS; SYSTEMIC-SCLEROSIS; YEAST
PROTEOME; T-CELLS; BIOMARKERS; GLAND; EXOSOMES
AB The diagnosis of primary Sjogren's syndrome (pSS) is difficult due to the lack of specific laboratory and clinical tests. As an initial step for the global discovery of changes in the abundance of parotid salivary proteins in pSS, a pooled sample was compared to that from healthy control subjects by multidimensional protein identification technology (MudPIT). A total of 1246 proteins were identified by MudPIT. The abundance of 477 of these proteins did not change, 529 were only detected in either the pSS or HC sample, while 206 of these proteins were significantly upregulated = twofold and 34 were downregulated = 0.5. Ingenuity Pathway Analyses of differentially expressed proteins identified by MudPIT resulted in the identification of 100 significant pathways. The same samples were quantified in parallel using RP MS. Fifty-eight of 71 proteins identified by RP overlapped with MudPIT results. Five proteins were further analyzed by targeted label-free quantification to confirm the similar relative differential expression observed by RP and MudPIT approaches. The present study supports the use of MS for global discovery and validation of marker proteins for improved and early diagnosis of pSS.
C1 [Ambatipudi, Kiran S.; Melvin, James E.] Natl Inst Dent & Craniofacial Res, Secretory Mech & Dysfunct Sect, NIH, Bethesda, MD 20892 USA.
[Swatkoski, Stephen; Gucek, Marjan] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA.
[Moresco, James J.; Tu, Patricia G.; Yates, John R., III] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA.
[Coca, Andreea; Anolik, Jennifer H.; Sanz, Ignacio] Univ Rochester, Med Ctr, Dept Med, Div Allergy Immunol & Rheumatol, Rochester, NY 14642 USA.
RP Melvin, JE (reprint author), Natl Inst Dent & Craniofacial Res, Secretory Mech & Dysfunct Sect, NIH, 10 Ctr Dr,MSC 1470, Bethesda, MD 20892 USA.
EM jyates@scripps.edu; james.melvin@nih.gov
OI Moresco, James/0000-0003-1178-1642
FU NIH [DE017585, U19-AI56390, P41 RR011823]
FX We gratefully acknowledge Mireya Gonzalez-Begne, Gene Watson, Bingwen
Lu, Robin Park, and Charlene Chung for assistance with samples and
discussions during the course of this study. This work was supported in
part by Intramural NIH programs, NIH grants DE017585 (I.S.), U19-AI56390
(I.S.), and P41 RR011823 (J.R.Y.).
NR 37
TC 12
Z9 12
U1 2
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1615-9853
J9 PROTEOMICS
JI Proteomics
PD OCT
PY 2012
VL 12
IS 19-20
SI SI
BP 3113
EP 3120
DI 10.1002/pmic.201200208
PG 8
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 023ZJ
UT WOS:000310076300020
PM 22888089
ER
PT J
AU Meyerowitz, BE
Christie, KM
Stanton, AL
Rowland, JH
Ganz, PA
AF Meyerowitz, Beth E.
Christie, Kysa M.
Stanton, Annette L.
Rowland, Julia H.
Ganz, Patricia A.
TI Men's Adjustment After Their Partners' Complete Treatment for Localized
Breast Cancer
SO PSYCHOLOGY OF MEN & MASCULINITY
LA English
DT Article
DE breast cancer; partners; psychological adjustment; cancer survivorship;
quality of life
ID QUALITY-OF-LIFE; PSYCHOLOGICAL DISTRESS; GENDER-DIFFERENCES;
HELP-SEEKING; COUPLES; WOMEN; MASCULINITY; CAREGIVERS; SPOUSES; STRESS
AB Each year, thousands of men are confronted with adjusting to the challenges presented when their partners are diagnosed with breast cancer. The months after completion of medical treatment may be unexpectedly difficult as a result of unrealistic expectations about a rapid return to life before cancer, especially for men who feel unprepared for their partners' transition from active treatment. We tested the hypotheses that men would report improved adjustment during this transition period, with men who felt well-prepared reporting better adjustment throughout. Participants were 164 male partners of women who had recently completed treatment for localized breast cancer and who had participated in the Moving Beyond Cancer clinical trial. Men completed questionnaires that assessed quality of life, mood, and cancer-related stress at approximately four and eight months after their partners finished primary treatment. In general, perceived preparedness interacted with time such that men who felt less well-prepared improved significantly over time whereas men who reported high preparedness experienced high levels of adjustment at both time points. Intrusive thoughts about cancer at the initial time point mediated the association between perceived preparedness and subsequent negative affect. These findings suggest that the patient's reentry period after treatment for breast cancer is a time of active adjustment for men who do not feel well-prepared for the challenges of this transition.
C1 [Meyerowitz, Beth E.; Christie, Kysa M.] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA.
[Stanton, Annette L.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA.
[Rowland, Julia H.] NCI, Bethesda, MD 20892 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA USA.
RP Meyerowitz, BE (reprint author), Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA.
EM meyerow@usc.edu
NR 29
TC 1
Z9 1
U1 0
U2 4
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 1524-9220
EI 1939-151X
J9 PSYCHOL MEN MASCULIN
JI Psychol. Men Masculinity
PD OCT
PY 2012
VL 13
IS 4
BP 400
EP 406
DI 10.1037/a0029245
PG 7
WC Psychology, Social
SC Psychology
GA 023NA
UT WOS:000310040500007
ER
PT J
AU Chung, JH
Manganiello, V
Dyck, JRB
AF Chung, Jay H.
Manganiello, Vincent
Dyck, Jason R. B.
TI Resveratrol as a calorie restriction mimetic: therapeutic implications
SO TRENDS IN CELL BIOLOGY
LA English
DT Review
DE PDE; AMPK; Sirt1; calorie restriction; diabetes
ID ACTIVATED PROTEIN-KINASE; SIRT1 TRANSGENIC MICE; LIFE-SPAN;
CAENORHABDITIS-ELEGANS; MITOCHONDRIAL-FUNCTION; SKELETAL-MUSCLE;
SACCHAROMYCES-CEREVISIAE; ISCHEMIA-REPERFUSION; METABOLIC-DISORDERS;
ENERGY HOMEOSTASIS
AB It is widely believed that calorie restriction (CR) can extend the lifespan of model organisms and protect against aging-related diseases. A potential CR mimetic is resveratrol, which may have beneficial effects against numerous diseases such as type 2 diabetes, cardiovascular diseases, and cancer in tissue culture and animal models. However, resveratrol in its current form is not ideal as therapy, because even at very high doses it has modest efficacy and many downstream effects. Identifying the cellular targets responsible for the effects of resveratrol and developing target-specific therapies will be helpful in increasing the efficacy of this drug without increasing its potential adverse effects. A recent discovery suggests that the metabolic effects of resveratrol may be mediated by inhibiting cAMP phosphodiesterases (PDEs), particularly PDE4. Here, we review the current literature on the metabolic and cardiovascular effects of resveratrol and attempt to shed light on the controversies surrounding its action.
C1 [Chung, Jay H.] NHLBI, Lab Obes & Aging Res, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Manganiello, Vincent] NHLBI, Cardiovasc Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Dyck, Jason R. B.] Univ Alberta, Dept Pediat, Mazankowski Alberta Heart Inst, Cardiovasc Res Ctr, Edmonton, AB T6G 2S2, Canada.
RP Chung, JH (reprint author), NHLBI, Lab Obes & Aging Res, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
EM chungj@nhlbi.nih.gov
FU Intramural Research Program; National Heart Lung and Blood Institute;
National Institutes of Health; Canadian Institutes of Health Research
FX This work was supported by the Intramural Research Program, the National
Heart Lung and Blood Institute, the National Institutes of Health, and
the Canadian Institutes of Health Research. We thank Dr Alexandra Brown
for helpful comments and manuscript preparation.
NR 97
TC 70
Z9 71
U1 2
U2 50
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0962-8924
J9 TRENDS CELL BIOL
JI Trends Cell Biol.
PD OCT
PY 2012
VL 22
IS 10
BP 546
EP 554
DI 10.1016/.tcb.2012.07.004
PG 9
WC Cell Biology
SC Cell Biology
GA 025KJ
UT WOS:000310187500006
PM 22885100
ER
PT J
AU Bu, LP
Fee, E
AF Bu, Liping
Fee, Elizabeth
TI Family Planning and Economic Development in CHINA
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
ID POLICY
C1 [Bu, Liping] Alma Coll, Dept Hist, Alma, MI 48801 USA.
[Fee, Elizabeth] NIH, Natl Lib Med, Bethesda, MD 20892 USA.
RP Bu, LP (reprint author), Alma Coll, Dept Hist, 614 W Super St, Alma, MI 48801 USA.
EM bulipi@alma.edu
NR 4
TC 0
Z9 0
U1 2
U2 4
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD OCT
PY 2012
VL 102
IS 10
BP 1858
EP 1859
DI 10.2105/AJPH.2012.300731
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 015GU
UT WOS:000309435200009
PM 22897553
ER
PT J
AU Burwen, DR
Sandhu, SK
MaCurdy, TE
Kelman, JA
Gibbs, JM
Garcia, B
Markatou, M
Forshee, RA
Izurieta, HS
Ball, R
AF Burwen, Dale R.
Sandhu, Sukhminder K.
MaCurdy, Thomas E.
Kelman, Jeffrey A.
Gibbs, Jonathan M.
Garcia, Bruno
Markatou, Marianthi
Forshee, Richard A.
Izurieta, Hector S.
Ball, Robert
CA Safety Surveillance Working Grp
TI Surveillance for Guillain-Barre Syndrome After Influenza Vaccination
Among the Medicare Population, 2009-2010
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID ADVERSE EVENTS; UNITED-STATES; 2009-JANUARY 2010; SAFETY; VACCINES;
ASSOCIATION; COVERAGE; RECEIPT; HUMANS; SYSTEM
AB Objectives. We implemented active surveillance for Guillain Barre syndrome (GBS) following seasonal or H1N1 influenza vaccination among the Medicare population during the 2009-2010 influenza season.
Methods. We used weekly Medicare claims data to monitor vaccinations and subsequent hospitalizations with principal diagnosis code for GBS within 42 days. Group sequential testing assessed whether the observed GBS rate exceeded a critical limit based on the expected rate from 5 previous years adjusted for claims delay. We evaluated the lag between date of service and date of claims availability and used it for adjustment.
Results. By July 30, 2010 (after 26 interim surveillance tests), 14.0 million seasonal and 3.3 million H1N1 vaccinations had accrued. Taking into account claims delay appropriately lowered the critical limit during early monitoring. The observed GBS rate was below the critical limit throughout the surveillance.
Conclusions. Medicare data contributed rapid safety monitoring among millions of 2009-2010 influenza vaccine recipients. Adjustment for claims delay facilitates early detection of potential safety issues. Although limited by lack of medical record review to confirm cases, this claims-based surveillance did not indicate a statistically significant elevated GBS rate following seasonal or H1N1 influenza vaccination. (Am J Public Health. 2012;102:1921-1927. doi:10.2105/AJPH.2011.300510)
C1 [Burwen, Dale R.; Sandhu, Sukhminder K.; Forshee, Richard A.; Izurieta, Hector S.; Ball, Robert] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Markatou, Marianthi] IBM Corp, TJ Watson Res Ctr, Hawthorne, NY USA.
[MaCurdy, Thomas E.; Gibbs, Jonathan M.; Garcia, Bruno] Acumen LLC, Burlingame, CA USA.
[MaCurdy, Thomas E.] Stanford Univ, Stanford, CA 94305 USA.
[Kelman, Jeffrey A.] Ctr Medicare & Medicaid Serv CMS, Ctr Medicare, Baltimore, MD USA.
RP Burwen, DR (reprint author), NIH, 6701 Rockledge Dr,Room 9186,Rockledge 2,MSC 7913, Bethesda, MD 20892 USA.
EM dale.burwen@nih.gov
FU FDA; CMS; National Vaccine Program Office, US Department of Health and
Human Services
FX This work was funded by the FDA, CMS, and National Vaccine Program
Office, US Department of Health and Human Services.
NR 41
TC 21
Z9 21
U1 0
U2 2
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD OCT
PY 2012
VL 102
IS 10
BP 1921
EP 1927
DI 10.2105/AJPH.2011.300510
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 015GU
UT WOS:000309435200020
PM 22970693
ER
PT J
AU Zhang, DP
Iyer, LM
Aravind, L
AF Zhang, Dapeng
Iyer, Lakshminarayan M.
Aravind, L.
TI Bacterial GRAS domain proteins throw new light on gibberellic acid
response mechanisms
SO BIOINFORMATICS
LA English
DT Article
ID ARABIDOPSIS-THALIANA; NATURAL-HISTORY; FAMILY; ROOT; METHYLTRANSFERASE;
TRANSCRIPTION; REGULATOR; DATABASE; REVEALS; MUTANT
AB Gibberellic acids (GAs) are key plant hormones, regulating various aspects of growth and development, which have been at the center of the 'green revolution'. GRAS family proteins, the primary players in GA signaling pathways, remain poorly understood. Using sequence-profile searches, structural comparisons and phylogenetic analysis, we establish that the GRAS family first emerged in bacteria and belongs to the Rossmann fold methyltransferase superfamily. All bacterial and a subset of plant GRAS proteins are likely to function as small-molecule methylases. The remaining plant versions have lost one or more AdoMet (SAM)-binding residues while preserving their substrate-binding residues. We predict that GRAS proteins might either modify or bind small molecules such as GAs or their derivatives.
C1 [Zhang, Dapeng; Iyer, Lakshminarayan M.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM aravind@ncbi.nlm.nih.gov
FU Intramural funds of the National Library of Medicine, National
Institutes of Health, USA
FX Intramural funds of the National Library of Medicine, National
Institutes of Health, USA.
NR 24
TC 19
Z9 22
U1 1
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD OCT 1
PY 2012
VL 28
IS 19
BP 2407
EP 2411
DI 10.1093/bioinformatics/bts464
PG 5
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 018UA
UT WOS:000309687500001
PM 22829623
ER
PT J
AU Grant, CW
Duclos, SK
Moran-Paul, CM
Yahalom, B
Tirabassi, RS
Arreaza-Rubin, G
Spain, LM
Guberski, DL
AF Grant, Christian W.
Duclos, Shane K.
Moran-Paul, Catherine M.
Yahalom, Barak
Tirabassi, Rebecca S.
Arreaza-Rubin, Guillermo
Spain, Lisa M.
Guberski, Dennis L.
TI Development of Standardized Insulin Treatment Protocols for Spontaneous
Rodent Models of Type 1 Diabetes
SO COMPARATIVE MEDICINE
LA English
DT Article
ID BETA-CELL REGENERATION; NOD MICE; COMBINATION THERAPY; BB RAT; MOUSE;
GLUCOSE; AUTOIMMUNITY; TOLERANCE; EXENDIN-4; REVERSAL
AB Standardized protocols for maintaining near-normal glycemic levels in diabetic rodent models for testing therapeutic agents to treat disease are unavailable. We developed protocols for 2 common models of spontaneous type 1 diabetes, the BioBreeding diabetes-prone (BBDP) rat and nonobese diabetic (NOD) mouse. Insulin formulation, dose level, timing of dose administration, and delivery method were examined and adjusted so that glycemic levels remained within a normal range and fluctuation throughout feeding and resting cycles was minimized. Protamine zinc formulations provided the longest activity, regardless of the source of insulin. Glycemic control with few fluctuations was achieved in diabetic BBDP rats through twice-daily administration of protamine zinc insulin, and results were similar regardless of whether BBDP rats were acutely or chronically diabetic at initiation of treatment. In contrast, glycemic control could not be attained in NOD mice through administration of insulin twice daily. However, glycemic control was achieved in mice through daily administration of 0.25 U insulin through osmotic pumps. Whereas twice-daily injections of protamine zinc insulin provided glycemic control with only minor fluctuations in BBDP rats, mice required continuous delivery of insulin to prevent wide glycemic excursions. Use of these standard protocols likely will aid in the testing of agents to prevent or reverse diabetes.
C1 [Grant, Christian W.; Duclos, Shane K.; Moran-Paul, Catherine M.; Yahalom, Barak; Tirabassi, Rebecca S.; Guberski, Dennis L.] Biomed Res Models, Worcester, MA USA.
[Arreaza-Rubin, Guillermo; Spain, Lisa M.] NIDDK, NIH, Bethesda, MD USA.
RP Guberski, DL (reprint author), Biomed Res Models, Worcester, MA USA.
EM dguberski@biomere.com
FU NIDDK [N01-DK-6-2909]
FX This work was supported by NIDDK contract N01-DK-6-2909. We would like
to thank members of our scientific advisory board for their assistance
with this ongoing program.
NR 38
TC 6
Z9 8
U1 0
U2 5
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1532-0820
J9 COMPARATIVE MED
JI Comparative Med.
PD OCT
PY 2012
VL 62
IS 5
BP 381
EP 390
PG 10
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 020GN
UT WOS:000309797100004
PM 23114041
ER
PT J
AU Boekelheide, K
Blumberg, B
Chapin, RE
Cote, I
Graziano, JH
Janesick, A
Lane, R
Lillycrop, K
Myatt, L
States, JC
Thayer, KA
Waalkes, MP
Rogers, JM
AF Boekelheide, Kim
Blumberg, Bruce
Chapin, Robert E.
Cote, Ila
Graziano, Joseph H.
Janesick, Amanda
Lane, Robert
Lillycrop, Karen
Myatt, Leslie
States, J. Christopher
Thayer, Kristina A.
Waalkes, Michael P.
Rogers, John M.
TI Predicting Later-Life Outcomes of Early-Life Exposures
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Review
DE arsenic; development; epigenetics; exposure; fetal; malnutrition;
obesogen; PPAR
ID INTRAUTERINE GROWTH RESTRICTION; ENDOCRINE DISRUPTING CHEMICALS;
MATERNAL PROTEIN RESTRICTION; FETAL ORIGINS HYPOTHESIS; LONG-TERM
CONSEQUENCES; CORONARY-HEART-DISEASE; HIGH BLOOD-PRESSURE; PRENATAL
EXPOSURE; DNA METHYLATION; DUTCH FAMINE
AB BACKGROUND: In utero exposure of the fetus to a stressor can lead to disease in later life. Epigenetic mechanisms are likely mediators of later-life expression of early-life events.
OBJECTIVES: We examined the current state of understanding of later-life diseases resulting from early-life exposures in order to identify in utero and postnatal indicators of later-life diseases, develop an agenda for future research, and consider the risk assessment implications of this emerging knowledge.
METHODS: This review was developed based on our participation in a National Research Council workshop titled "Use of in Utero and Postnatal Indicators to Predict Health Outcomes Later in Life: State of the Science and Research Recommendations." We used a case study approach to highlight the later-life consequences of early-life malnutrition and arsenic exposure.
DISCUSSION: The environmental sensitivity of the epigenome is viewed as an adaptive mechanism by which the developing organism adjusts its metabolic and homeostatic systems to suit the anticipated extrauterine environment. Inappropriate adaptation may produce a mismatch resulting in subsequent increased susceptibility to disease. A nutritional mismatch between the prenatal and postnatal environments, or early-life obesogen exposure, may explain at least some of the recent rapid increases in the rates of obesity, type 2 diabetes, and cardiovascular diseases. Early-life arsenic exposure is also associated with later-life diseases, including cardiovascular disease and cancer.
CONCLUSIONS: With mounting evidence connecting early-life exposures and later-life disease, new strategies are needed to incorporate this emerging knowledge into health protective practices.
C1 [Boekelheide, Kim] Brown Univ, Dept Pathol & Lab Med, Div Biol & Med, Providence, RI 02912 USA.
[Blumberg, Bruce; Janesick, Amanda] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA.
[Blumberg, Bruce; Janesick, Amanda] Univ Calif Irvine, Dept Pharmaceut Sci, Irvine, CA USA.
[Chapin, Robert E.] Pfizer Global Res & Dev, Dev & Reprod Toxicol Ctr Expertise Drug Safety Re, Groton, CT USA.
[Cote, Ila] US EPA, Off Res & Dev, Natl Ctr Environm Assessment, Washington, DC 20460 USA.
[Graziano, Joseph H.] Columbia Univ, Dept Environm Hlth Sci, Mailman Sch Publ Hlth, New York, NY USA.
[Lane, Robert] Univ Utah, Sch Med, Dev Origins Hlth Labs, Div Neonatol,Dept Pediat, Salt Lake City, UT USA.
[Lillycrop, Karen] Univ Southampton, Ctr Biol Sci, Inst Dev Sci, Southampton, Hants, England.
[Myatt, Leslie] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA.
[States, J. Christopher] Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA.
[Thayer, Kristina A.; Waalkes, Michael P.] NIEHS, Div Natl Toxicol Program, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Rogers, John M.] US EPA, Tox Assessment Div, Natl Hlth Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
RP Boekelheide, K (reprint author), Brown Univ, Dept Pathol & Lab Med, Div Biol & Med, Box G-E5, Providence, RI 02912 USA.
EM kim_boekelheide@brown.edu
OI Chapin, Robert/0000-0002-5997-1261
FU National Institutes of Health [P20ES018169]; U.S. Environmental
Protection Agency (EPA) [RD-83459401-1]
FX Publication was supported by a grant from the National Institutes of
Health (P20ES018169) and the U.S. Environmental Protection Agency (EPA)
(RD-83459401-1) to the Brown University Formative Center for the
Evaluation of Environmental Impacts on Fetal Development.
NR 137
TC 56
Z9 57
U1 3
U2 77
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD OCT
PY 2012
VL 120
IS 10
BP 1353
EP 1361
DI 10.1289/ehp.1204934
PG 9
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 018US
UT WOS:000309692600015
PM 22672778
ER
PT J
AU Joubert, BR
Haberg, SE
Nilsen, RM
Wang, XT
Vollset, SE
Murphy, SK
Huang, Z
Hoyo, C
Midttun, O
Cupul-Uicab, LA
Ueland, PM
Wu, MC
Nystad, W
Bell, DA
Peddada, SD
London, SJ
AF Joubert, Bonnie R.
Haberg, Siri E.
Nilsen, Roy M.
Wang, Xuting
Vollset, Stein E.
Murphy, Susan K.
Huang, Zhiqing
Hoyo, Cathrine
Midttun, Oivind
Cupul-Uicab, Lea A.
Ueland, Per M.
Wu, Michael C.
Nystad, Wenche
Bell, Douglas A.
Peddada, Shyamal D.
London, Stephanie J.
TI 450K Epigenome-Wide Scan Identifies Differential DNA Methylation in
Newborns Related to Maternal Smoking during Pregnancy
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE epigenetics; epigenome-wide; in utero; maternal smoking; methylation
ID ARYL-HYDROCARBON RECEPTOR; CIGARETTE-SMOKING; NORWEGIAN MOTHER;
GENE-REGULATION; TOBACCO-SMOKE; CHILD COHORT; HUMAN GENOME; EXPOSURE;
WOMEN; SUPPLEMENTATION
AB BACKGROUND: Epigenetic modifications, such as DNA methylation, due to in utero exposures may play a critical role in early programming for childhood and adult illness. Maternal smoking is a major risk factor for multiple adverse health outcomes in children, but the underlying mechanisms are unclear.
OBJECTIVE: We investigated epigenome-wide methylation in cord blood of newborns in relation to maternal smoking during pregnancy.
METHODS: We examined maternal plasma cotinine (an objective biomarker of smoking) measured during pregnancy in relation to DNA methylation at 473,844 CpG sites (CpGs) in 1,062 newborn cord blood samples from the Norwegian Mother and Child Cohort Study (MoBa) using the Infinium HumanMethylation450 Bead Chip (450K).
RESULTS: We found differential DNA methylation at epigenome-wide statistical significance (p-value < 1.06 x 10(-7)) for 26 CpGs mapped to 10 genes. We replicated findings for CpGs in AHRR, CYP1A1, and GFI1 at strict Bonferroni-corrected statistical significance in a U.S. birth cohort. AHRR and CYP1A1 play a key role in the aryl hydrocarbon receptor signaling pathway, which mediates the detoxification of the components of tobacco smoke. GFI1 is involved in diverse developmental processes but has not previously been implicated in responses to tobacco smoke.
CONCLUSIONS: We identified a set of genes with methylation changes present at birth in children whose mothers smoked during pregnancy. This is the first study of differential methylation across the genome in relation to maternal smoking during pregnancy using the 450K platform. Our findings implicate epigenetic mechanisms in the pathogenesis of the adverse health outcomes associated with this important in utero exposure.
C1 [Joubert, Bonnie R.; Wang, Xuting; Cupul-Uicab, Lea A.; Bell, Douglas A.; Peddada, Shyamal D.; London, Stephanie J.] NIEHS, Div Intramural Res, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Haberg, Siri E.; Vollset, Stein E.; Nystad, Wenche] Norwegian Inst Publ Hlth, Oslo, Norway.
[Nilsen, Roy M.] Haukeland Hosp, N-5021 Bergen, Norway.
[Vollset, Stein E.; Ueland, Per M.] Univ Bergen, Bergen, Norway.
[Murphy, Susan K.; Huang, Zhiqing; Hoyo, Cathrine] Duke Univ, Sch Med, Durham, NC USA.
[Midttun, Oivind] Bevital AS, Bergen, Norway.
[Wu, Michael C.] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
RP London, SJ (reprint author), 111 TW Alexander Dr,Rall Bldg,A306, Res Triangle Pk, NC 27709 USA.
EM london2@niehs.nih.gov
RI Ueland, Per/C-7340-2013; CUPUL UICAB, LEA/C-8699-2014;
OI CUPUL UICAB, LEA/0000-0001-6190-4474; Murphy, Susan/0000-0001-8298-7272;
Wang, Xuting/0000-0001-6781-8008; London, Stephanie/0000-0003-4911-5290;
Wu, Michael C./0000-0002-3357-6570
FU Intramural Research Program of the National Institutes of Health (NIH),
NIEHS [Z01-ES-49019]; Norwegian Ministry of Health and the Ministry of
Education and Research, NIH/NIEHS [NO-ES-75558]; NIH/NINDS [1 UO1 NS
047537-01]; Norwegian Research Council/FUGE [151918/S10]; NIH
[R21ES01497, R01 ES016772, R01 DK085173, P30ES011961]; Duke
Comprehensive Cancer Center
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health (NIH), NIEHS (Z01-ES-49019). The
Norwegian Mother and Child Cohort Study is supported by the Norwegian
Ministry of Health and the Ministry of Education and Research, NIH/NIEHS
(contract NO-ES-75558), NIH/NINDS (grant 1 UO1 NS 047537-01), and the
Norwegian Research Council/FUGE (grant 151918/S10). The Newborn
Epigenetics STudy is supported by NIH grants R21ES01497, R01 ES016772,
R01 DK085173, and P30ES011961 and by the Duke Comprehensive Cancer
Center.
NR 41
TC 233
Z9 237
U1 4
U2 60
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD OCT
PY 2012
VL 120
IS 10
BP 1425
EP 1431
DI 10.1289/ehp.1205412
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 018US
UT WOS:000309692600025
PM 22851337
ER
PT J
AU Hoffman, K
Adgent, M
Goldman, BD
Sjodin, A
Daniels, JL
AF Hoffman, Kate
Adgent, Margaret
Goldman, Barbara Davis
Sjoedin, Andreas
Daniels, Julie L.
TI Lactational Exposure to Polybrominated Diphenyl Ethers and Its Relation
to Social and Emotional Development among Toddlers
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE neurodevelopment; polybrominated diphenyl ethers (PBDEs); social and
emotional development
ID POLYCHLORINATED-BIPHENYLS; POSTNATAL EXPOSURE; FLAME RETARDANTS;
BREAST-MILK; HOUSE-DUST; PBDE-99; SAMPLES; BLOOD; MICE
AB BACKGROUND: Polybrominated diphenyl ethers (PBDEs) have been widely used as flame retardants and are ubiquitous environmental contaminants. PBDEs have been linked to adverse neurodevelopment in animals and humans.
OBJECTIVES: We investigated the association between breast milk PBDE levels and social and emotional development in toddlers.
METHODS: The Pregnancy Infection and Nutrition (PIN) and PIN Babies studies followed a cohort of North Carolina pregnant women and their children through 36 months of age. Breast milk samples obtained at 3 months postpartum were analyzed for PBDEs. The Infant Toddler Social and Emotional Assessment (ITSEA) was completed by mothers when children were approximately 30 months of age (n = 222). We assessed the relationship between breast milk concentrations of five PBDE congeners-BDEs 28, 47, 99, 100, and 153-and children's social and emotional development, adjusting for other factors.
RESULTS: A small, imprecise, yet consistent positive association was apparent between BDEs 47, 99, and 100 and increased externalizing behaviors, specifically activity/impulsivity behaviors. Externalizing domain T-scores ranged from 30 to 87 with a mean of 47.8. Compared with those with BDE-47 concentrations below the median, adjusted externalizing behavior domain scores were 1.6 [95% confidence interval (CI): -1.2, 4.4] and 2.8 (95% CI -0.1, 5.7) points higher for children born to women with breast milk concentrations in the 3rd and 4th quartiles, respectively. PBDEs were not associated with other social and emotional developmental domains.
CONCLUSIONS: Our results, although imprecise, suggest a subtle association between early-life PBDE exposure and increased activity/impulsivity behaviors in early childhood. Confirmation of these results is needed in other longitudinal studies.
C1 [Daniels, Julie L.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Adgent, Margaret] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Goldman, Barbara Davis] Univ N Carolina, Frank Porter Graham Child Dev Inst, Chapel Hill, NC 27599 USA.
[Goldman, Barbara Davis] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA.
[Sjoedin, Andreas] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA USA.
RP Daniels, JL (reprint author), Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, McGavran Greenberg Hall,CB 7435, Chapel Hill, NC 27599 USA.
EM juliedaniels@unc.edu
RI Sjodin, Andreas/F-2464-2010
FU U.S. Environmental Protection Agency [RD832736]; National Institute of
Environmental Health Sciences (NIEHS) [P30ES10126]; NIEHS Environmental
Biostatistics Training Program [T32ES007018]; Intramural Research
Program of the National Institutes of Health, NIEHS
FX This research was supported by grants from the U.S. Environmental
Protection Agency (RD832736) and the National Institute of Environmental
Health Sciences (NIEHS; P30ES10126). The work of K.H. was supported by
the NIEHS Environmental Biostatistics Training Program (T32ES007018).
The work of M.A. on this project was supported [in part] by the
Intramural Research Program of the National Institutes of Health, NIEHS.
NR 29
TC 39
Z9 40
U1 3
U2 30
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD OCT
PY 2012
VL 120
IS 10
BP 1438
EP 1442
DI 10.1289/ehp.1205100
PG 5
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 018US
UT WOS:000309692600027
PM 22814209
ER
PT J
AU Camargo, M
Rivera, D
Moreno, L
Lidral, AC
Harper, U
Jones, M
Solomon, BD
Roessler, E
Velez, JI
Martinez, AF
Chandrasekharappa, SC
Arcos-Burgos, M
AF Camargo, Mauricio
Rivera, Dora
Moreno, Lina
Lidral, Andrew C.
Harper, Ursula
Jones, Marypat
Solomon, Benjamin D.
Roessler, Erich
Velez, Jorge I.
Martinez, Ariel F.
Chandrasekharappa, Settara C.
Arcos-Burgos, Mauricio
TI GWAS reveals new recessive loci associated with non-syndromic facial
clefting
SO EUROPEAN JOURNAL OF MEDICAL GENETICS
LA English
DT Article
DE Non-syndromic clefting; Facial; GWAS; Recessive loci; B3GAT1; CSMD1
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PRIMARY SJOGRENS-SYNDROME;
GENOME-WIDE ASSOCIATION; IDIOPATHIC EPILEPSY; NECK CARCINOGENESIS;
COMPLEX SEGREGATION; GENETIC ISOLATE; CANDIDATE GENE; EARLY-ONSET; LIP
AB We have applied a GWAS to 40 consanguineous families segregating cases of non-syndromic cleft lip with or without cleft palate (NS CL/P) (a total of 160 affected and unaffected individuals) in order to trace potential recessive loci that confer susceptibility to this common facial malformation. Pedigree-based association test (PBAT) analyses reported nominal evidence of association and linkage over SNP markers located at 11q25 (rs4937877, P = 2.7 x 10(-6)), 19p12 (rs4324267, P = 1.6 x 10(-5)), 5q14.1 (rs4588572, P-value = 3.36 x 10(-5)), and 15q21.1 (rs4774497, P = 1.08 x 10(-4)). Using the Versatile Gene-Based Association Study to complement the PBAT results, we found clusters of markers located at chromosomes 19p12, 11q25, and 8p23.2 overcome the threshold for GWAS significance (P < 1 x 10(-7)). From this study, new recessive loci implicated in NS CL/P include: B3GAT1, GLB1L2, ZNF431, ZNF714, and CSMD1, even though the functional association with the genesis of NS CL/P remains to be elucidated. These results emphasize the importance of using homogeneous populations, phenotypes, and family structures for GWAS combined with gene-based association analyses, and should encourage. other researchers to evaluate these genes on independent patient samples affected by NS CL/P. (C) 2012 Elsevier Masson SAS. All rights reserved.
C1 [Arcos-Burgos, Mauricio] Australian Natl Univ, John Curtin Sch Med Res, Grp Translat Gen, Dept Translat Med, Canberra, ACT 0200, Australia.
[Camargo, Mauricio; Rivera, Dora] Univ Antioquia, Populat Genet & Mutacarcinogenesis Grp, Medellin, Colombia.
[Moreno, Lina; Lidral, Andrew C.] Univ Iowa, Coll Dent, Dept Orthodont, Iowa City, IA 52242 USA.
[Moreno, Lina] Univ Iowa, Coll Dent, Dows Inst Dent Res, Iowa City, IA 52242 USA.
[Harper, Ursula; Jones, Marypat; Chandrasekharappa, Settara C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Solomon, Benjamin D.; Roessler, Erich; Velez, Jorge I.; Martinez, Ariel F.; Arcos-Burgos, Mauricio] NHGRI, Neurodev Lab, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Arcos-Burgos, M (reprint author), Australian Natl Univ, John Curtin Sch Med Res, Grp Translat Gen, Dept Translat Med, Bldg 131,Garran Rd, Canberra, ACT 0200, Australia.
EM Mauricio.Arcos-Burgos@anu.edu.au
FU COLCIENCIAS [1115-408-20519]; Programa Sostenibilidad Universidad de
Antioquia, Colombia; Division of Intramural Research, National Human
Genome Research Institute, National Institutes of Health, USA
FX The authors would like to extend their deepest gratitude to all the
patients and families from Antioquia, Colombia, who took part in our
ongoing CL/CP program. This research was supported by COLCIENCIAS (Grant
1115-408-20519), Programa Sostenibilidad Universidad de Antioquia,
Colombia, and in part by the Division of Intramural Research, National
Human Genome Research Institute, National Institutes of Health, USA.
NR 50
TC 6
Z9 6
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1769-7212
J9 EUR J MED GENET
JI Eur. J. Med. Genet.
PD OCT
PY 2012
VL 55
IS 10
BP 510
EP 514
DI 10.1016/j.ejmg.2012.06.005
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA 019MI
UT WOS:000309743500002
PM 22750566
ER
PT J
AU Kapogiannis, D
Kisser, J
Davatzikos, C
Ferrucci, L
Metter, J
Resnick, SM
AF Kapogiannis, Dimitrios
Kisser, Jason
Davatzikos, Christos
Ferrucci, Luigi
Metter, Jeffrey
Resnick, Susan M.
TI Alcohol consumption and premotor corpus callosum in older adults
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Alcohol; corpus callosum; premotor; white matter
ID MARCHIAFAVA-BIGNAMI-DISEASE; VOXEL-BASED MORPHOMETRY; SEX-DIFFERENCES;
BRAIN VOLUMES; THIAMINE-DEFICIENCY; COGNITIVE FUNCTIONS; WHITE-MATTER;
DEMENTIA; DRINKING; RISK
AB Heavy alcohol consumption is toxic to the brain, especially to the frontal white matter (WM), but whether lesser amounts of alcohol negatively impact the brain WM is unclear. In this study, we examined the relationship between self-reported alcohol consumption and regional WM and grey matter (GM) volume in fifty-six men and thirty-seven women (70 + - 7 years) cognitively intact participants of the Baltimore Longitudinal Study of Aging (BLSA) with no history of alcohol abuse. We used regional analysis of volumes examined in normalized space (RAVENS) maps methodology for WM and GM segmentation and normalization followed by voxel based morphometry (VBM) implemented in SPM8 to examine the cross-sectional association between alcohol consumption and regional WM (and, separately, GM) volume controlling for age, sex, smoking, blood pressure and dietary thiamine intake. WM VBM revealed that in men, but not in women, higher alcohol consumption was associated with lower volume in premotor frontal corpus callosum. This finding suggests that even moderate amounts of alcohol may be detrimental to corpus callosum and white matter integrity. Published by Elsevier B.V.
C1 [Kapogiannis, Dimitrios; Kisser, Jason; Ferrucci, Luigi; Metter, Jeffrey] NIA, NIH, Clin Res Branch, Baltimore, MD 21225 USA.
[Resnick, Susan M.] NIA, NIH, Lab Behav Neurosci, Baltimore, MD 21225 USA.
[Davatzikos, Christos] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
RP Kapogiannis, D (reprint author), NIA, NIH, Clin Res Branch, 3001 S Hanover St, Baltimore, MD 21225 USA.
EM kapogiannisd@mail.nih.gov
FU NIH/NIA; [N01-AG-3-2124]
FX This research was supported in part by the Intramural Research Program
of the NIH/NIA and in part by N01-AG-3-2124. The study was conducted as
part of official duty for U.S. Government employees DK, JK, JM, LF and
SMR. The present manuscript underwent clearance for publication by NIA.
NR 60
TC 8
Z9 8
U1 2
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD OCT
PY 2012
VL 22
IS 10
BP 704
EP 710
DI 10.1016/j.euroneuro.2012.02.003
PG 7
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 020AQ
UT WOS:000309781200003
PM 22401959
ER
PT J
AU de Azua, IR
Nakajima, KI
Rossi, M
Cui, YH
Jou, W
Gavrilova, O
Wess, J
AF de Azua, Inigo Ruiz
Nakajima, Ken-ichiro
Rossi, Mario
Cui, Yinghong
Jou, William
Gavrilova, Oksana
Wess, Juergen
TI Spinophilin as a novel regulator of M-3 muscarinic receptor-mediated
insulin release in vitro and in vivo
SO FASEB JOURNAL
LA English
DT Article
DE G-protein-coupled receptors; knockout mice; receptor regulation; signal
transduction
ID PROTEIN-COUPLED-RECEPTORS; RESONANCE ENERGY-TRANSFER; PANCREATIC
BETA-CELLS; GLUCAGON-LIKE PEPTIDE-1; ACETYLCHOLINE-RECEPTORS;
7-TRANSMEMBRANE RECEPTORS; DENDRITIC SPINES; MICE; ACTIVATION; SECRETION
AB Spinophilin (SPL), a multidomain scaffolding protein known to modulate the activity of different G-protein-coupled receptors, regulates various central nervous system (CNS) functions. However, little is known about the role of SPL expressed in peripheral cell types including pancreatic beta cells. In this study, we examined the ability of SPL to modulate the activity of beta -cell M-3 muscarinic acetylcholine receptors (M3Rs), which play an important role in facilitating insulin release and maintaining normal blood glucose levels. We demonstrated, by using both in vitro and in vivo approaches (mouse insulinoma cells and SPL-deficient mice), that SPL is a potent negative regulator of M3R-mediated signaling and insulin release. Additional biochemical and biophysical studies, including the use of bioluminescence resonance energy transfer technology, suggested that SPL is able to recruit regulator of G-protein signaling 4 (RGS4) to the M3R signaling complex in an agonist-dependent fashion. Since RGS4 is a member of the RGS family of proteins that act to reduce the lifetime of activated G proteins, these findings support the concept that the inhibitory effects of SPL on M3R activity are mediated by RGS4. These data suggest that SPL or other G-protein-coupled receptor-associated proteins may serve as novel targets for drug therapy aimed at improving beta -cell function for the treatment of type 2 diabetes.-Ruiz de Azua, I., Nakajima, K.-I., Rossi, M., Cui, Y., Jou, W., Gavrilova, O., Wess, J. Spinophilin as a novel regulator of M-3 muscarinic receptor-mediated insulin release in vitro and in vivo. FASEB J. 26, 4275-4286 (2012). www.fasebj.org
C1 [Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Jou, William; Gavrilova, Oksana] NIDDK, Mouse Metab Core Facil, Bethesda, MD 20892 USA.
RP Wess, J (reprint author), NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-05,8 Ctr Dr,MSC 0810, Bethesda, MD 20892 USA.
EM jwess@helix.nih.gov
FU U.S. National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK)
FX This research was supported by the Intramural Research Program of the
U.S. National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK). The authors thank Dr. Sara McMillin (NIDDK) and Drs. Diaz
Gimenez and Vsevolod Gurevich (Vanderbilt University, Nashville, TN,
USA) for their help setting up the BRET experiments. Dr. Paul Greengard
(Rockefeller University, New York, NY, USA) generously provided the
SPL-/- mice. Finally, the authors thank Drs. Patrick B. Allen
(Yale University, New Haven, CT, USA) and Diaz Gimenez and Vsevolod
Gurevich (Vanderbilt University), and Qin Wang (University of Alabama,
Birmingham, AL, USA) for providing important reagents and plasmids used
in this study. The authors declare no conflicts of interest.
NR 42
TC 7
Z9 7
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD OCT
PY 2012
VL 26
IS 10
BP 4275
EP 4286
DI 10.1096/fj.12-204644
PG 12
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 018YM
UT WOS:000309704000032
ER
PT J
AU Huang, FL
Huang, KP
AF Huang, F. L.
Huang, K. -P.
TI Methylphenidate improves the behavioral and cognitive deficits of
neurogranin knockout mice
SO GENES BRAIN AND BEHAVIOR
LA English
DT Article
DE Cognitive deficit; environmental enrichment; methylphenidate;
neurogranin knockout mice
ID TERMINAL DELETION DISORDER; NEURAL STEM-CELLS; NULL MUTANT MICE;
RECEPTOR; RAT; CALMODULIN; KINASE; MEMORY; HYPERACTIVITY; RECOGNITION
AB Neurogranin (Ng), a brain-specific calmodulin-binding protein, is expressed highly in hippocampus, and is important for cognitive function. Deletion of the Ng gene from mice caused attenuation of signal reaction cascade in hippocampus, impairments in learning and memory and high frequency stimulation-induced long-term potentiation (LTP). Environmental enrichment alone failed to improve cognitive function. In this study, behavioral testing revealed that Ng knockout (NgKO) mice were both hyperactive and socially withdrawn. Methylphenidate (MPH) was given to mice while they were also kept under an enrichment condition. MPH treatment reduced the hyperactivity of NgKO mice tested in both the open field and forced swim chamber. MPH improved their social abilities such that mice recognized and interacted better with novel subjects. The cognitive memories of MPH-treated mutants were improved in both water maze and contextual fear conditioning tests. High frequency stimulation-induced LTP of NgKO mice was also improved by MPH. The present treatment regimen, however, did not fully reverse the deficits of the mutant mice. In contrast, MPH exerted only a minimal effect on the wild type mice. At the cellular level, MPH increased the number of glial fibrillary acidic protein-positive cells in hippocampus, particularly within the dentate gyrus of NgKO mice. Therefore it will be of interest to determine the nature of MPH-mediated astrocyte activation and how it may modulate behavior in future studies. Taken together these NgKO mice may be useful for the development of better drug treatment to improve cognitive and behavioral impairments.
C1 [Huang, F. L.; Huang, K. -P.] NICHHD, Program Dev Neurobiol, NIH, Bethesda, MD 20892 USA.
RP Huang, FL (reprint author), NICHHD, Program Dev Neurobiol, NIH, 49 Convent Dr,MSC 4570, Bethesda, MD 20892 USA.
EM fhuang@mail.nih.gov; huangk@mail.nih.gov
FU National Institute of Child Health and Human Development, National
Institutes of Health
FX This work was supported by the Intramural Research Program of National
Institute of Child Health and Human Development, National Institutes of
Health. The authors like to thank Daniel Abebe, James Ofori, Bahafta
Behre and Dennis Costellon for their helps in the behavioral test and
animal welfare including maintenance of enrichment environment and drug
injection. We also like to thank Dr. Chris McBain, Program Chief of
Developmental Neurobiology, NICHD, for his critical reading and
suggestion regarding the manuscript. The authors have no conflict of
interest to declare.
NR 34
TC 5
Z9 6
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1601-1848
J9 GENES BRAIN BEHAV
JI Genes Brain Behav.
PD OCT
PY 2012
VL 11
IS 7
BP 794
EP 805
DI 10.1111/j.1601-183X.2012.00825.x
PG 12
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 019QE
UT WOS:000309753600005
PM 22809330
ER
PT J
AU Selby, JV
Fleurence, R
Lauer, M
Schneeweiss, S
AF Selby, Joe V.
Fleurence, Rachael
Lauer, Michael
Schneeweiss, Sebastian
TI Reviewing Hypothetical Migraine Studies Using Funding Criteria From The
Patient-Centered Outcomes Research Institute
SO HEALTH AFFAIRS
LA English
DT Review
AB What role can rigorous observational comparative effectiveness studies play in guiding clinical decision making? What criteria should be used in determining whether the results of such studies should be communicated to clinicians and to patients? We address these questions by considering two hypothetical observational studies in patients with migraine against the backdrop of the review criteria drawn up by the Patient-Centered Outcomes Research Institute (PCORI). These criteria emphasize that patient-centered comparative effectiveness research should exhibit relevance to patients, have great potential to affect practice and improve outcomes, and be conducted using rigorous analytic methods. We conclude that these hypothetical studies would be unlikely to have been funded or communicated by PCORI, and we offer suggestions for improving their relevance and analytic approaches. We also conclude that high-quality observational studies can effectively complement findings from randomized trials, and that communicating their results to patients and clinicians is warranted.
C1 [Selby, Joe V.; Fleurence, Rachael] PCORI, Washington, DC USA.
[Lauer, Michael] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Schneeweiss, Sebastian] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Schneeweiss, Sebastian] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA.
RP Selby, JV (reprint author), PCORI, Washington, DC USA.
EM jselby@pcori.org
RI Schneeweiss, Sebastian/C-2125-2013
FU National Pharmaceutical Council
FX This article grew out of a May 9, 2012, roundtable hosted by Health
Affairs and sponsored by the National Pharmaceutical Council on issues
surrounding the communication of comparative effectiveness research
results.
NR 16
TC 9
Z9 9
U1 0
U2 6
PU PROJECT HOPE
PI BETHESDA
PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA
SN 0278-2715
J9 HEALTH AFFAIR
JI Health Aff.
PD OCT
PY 2012
VL 31
IS 10
BP 2193
EP 2199
DI 10.1377/hlthaff.2012.0774
PG 7
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 020MU
UT WOS:000309815900007
PM 23048096
ER
PT J
AU Arora, NK
AF Arora, Neeraj K.
TI A Complex Patient Or Complex Illnesses?
SO HEALTH AFFAIRS
LA English
DT Letter
C1 NCI, Bethesda, MD 20892 USA.
RP Arora, NK (reprint author), NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PROJECT HOPE
PI BETHESDA
PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA
SN 0278-2715
J9 HEALTH AFFAIR
JI Health Aff.
PD OCT
PY 2012
VL 31
IS 10
DI 10.1377/hlthaff.2012.0937
PG 1
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 020MU
UT WOS:000309815900034
ER
PT J
AU Bell, LN
Wang, J
Muralidharan, S
Chalasani, S
Fullenkamp, AM
Wilson, LA
Sanyal, AJ
Kowdley, KV
Neuschwander-Tetri, BA
Brunt, EM
McCullough, AJ
Bass, NM
Diehl, AM
Unalp-Arida, A
Chalasani, N
AF Bell, Lauren N.
Wang, Jiangxia
Muralidharan, Sriya
Chalasani, Sadhana
Fullenkamp, Allison M.
Wilson, Laura A.
Sanyal, Arun J.
Kowdley, Kris V.
Neuschwander-Tetri, Brent A.
Brunt, Elizabeth M.
McCullough, Arthur J.
Bass, Nathan M.
Diehl, Anna Mae
Unalp-Arida, Aynur
Chalasani, Naga
CA Nonalcoholic Steatohepatitis
TI Relationship between adipose tissue insulin resistance and liver
histology in nonalcoholic steatohepatitis: A pioglitazone versus vitamin
E versus placebo for the treatment of nondiabetic patients with
nonalcoholic steatohepatitis trial follow-up study
SO HEPATOLOGY
LA English
DT Letter
ID DISEASE; MECHANISMS; CIRRHOSIS; DESIGN; FAT
AB The PIVENS (Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis [NASH]) trial demonstrated that pioglitazone and vitamin E improved liver histology to varying degrees, but the mechanisms are unknown. We conducted a study to examine the changes in adipose tissue insulin resistance (Adipo-IR) during the PIVENS trial and its relationship to histological endpoints. Adipo-IR (fasting nonesterified fatty acids [NEFAs] x fasting insulin) was calculated at baseline and after 16 and 96 weeks of therapy. Compared to placebo, the baseline Adipo-IR was not different in either the vitamin E group (P = 0.34) or the pioglitazone group (P = 0.29). Baseline Adipo-IR was significantly associated with fibrosis score (P = 0.02), but not with other histological features or nonalcoholic fatty liver disease (NAFLD) activity score (NAS). After 16 weeks, compared to placebo, the pioglitazone group had a significant reduction in Adipo-IR (-15.7 versus -1.91; P = 0.02), but this effect did not persist at 96 weeks (-3.25 versus -4.28; P = 0.31). Compared to placebo, Adipo-IR in the vitamin E group did not change significantly either after 16 weeks (P = 0.70) or after 96 weeks (P = 0.85). Change in Adipo-IR at week 16 was not associated with changes in any histological parameters at week 96, but improvement in Adipo-IR at week 96 was significantly associated with improvement in ballooning (P = 0.03), fibrosis (P = 0.004), and NAS (P = 0.01). Conclusion: Vitamin E improved liver histology independent of changes in Adipo-IR, and pioglitazone treatment acutely improved Adipo-IR, but this was not sustained. Changes in Adipo-IR were associated with changes in liver histology, including fibrosis. (HEPATOLOGY 2012)
C1 [Bell, Lauren N.; Muralidharan, Sriya; Chalasani, Sadhana; Fullenkamp, Allison M.; Chalasani, Naga] Indiana Univ, Div Gastroenterol Hepatol, Indianapolis, IN 46204 USA.
[Wang, Jiangxia; Wilson, Laura A.; Unalp-Arida, Aynur] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Sanyal, Arun J.] Virginia Commonwealth Univ, Richmond, VA USA.
[Kowdley, Kris V.] Virginia Mason Med Ctr, Seattle, WA 98101 USA.
[Neuschwander-Tetri, Brent A.] St Louis Univ, Sch Med, St Louis, MO USA.
[Brunt, Elizabeth M.] Washington Univ, Sch Med, St Louis, MO USA.
[McCullough, Arthur J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Bass, Nathan M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Diehl, Anna Mae] Duke Univ, Sch Med, Durham, NC USA.
[Nonalcoholic Steatohepatitis] NIDDKD, Bethesda, MD 20892 USA.
RP Chalasani, N (reprint author), Indiana Univ Sch Med, Div Gastroenterol Hepatol, 1050 Wishard Blvd,RG 4100, Indianapolis, IN 46202 USA.
EM nchalasa@iupui.edu
RI Vaughn, Ivana/B-6138-2016
OI Vaughn, Ivana/0000-0002-7201-0289
FU NCATS NIH HHS [UL1 TR000454, UL1 TR000439]; NCRR NIH HHS [UL1RR024128,
M01RR000827, M01RR000065, UL1RR024989, UL1RR024131, UL1 RR024128, M01
RR000065, M01RR000750, UL1 RR025014, M01 RR000750, UL1 RR024989,
UL1RR025014, UL1 RR024131, M01 RR000827]; NIDDK NIH HHS [U01 DK061728,
U01 DK061730, U01DK61737, U01DK61734, U01 DK061738, U01DK61718, K24
DK072101, U01DK61731, U01 DK061737, U01 DK061734, U01DK61738,
U01DK61730, U01 DK061731, U01 DK061718, U01DK61732, U01DK61713, U01
DK061732, U01DK61728, U01 DK061713]
NR 15
TC 29
Z9 31
U1 0
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2012
VL 56
IS 4
BP 1311
EP 1318
DI 10.1002/hep.25805
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 018PJ
UT WOS:000309673500015
PM 22532269
ER
PT J
AU Stauffer, JK
Scarzello, AJ
Jiang, Q
Wiltrout, RH
AF Stauffer, Jimmy K.
Scarzello, Anthony J.
Jiang, Qun
Wiltrout, Robert H.
TI Chronic inflammation, immune escape, and oncogenesis in the liver: A
unique neighborhood for novel intersections
SO HEPATOLOGY
LA English
DT Review
ID HEPATOCELLULAR-CARCINOMA PATIENTS; HEPATITIS-C INFECTION; REGULATORY
T-CELLS; SUPPRESSOR-CELLS; KAPPA-B; CANCER; CARCINOGENESIS; SENESCENCE;
ORGAN; PD-1
AB Sustained hepatic inflammation, driven by alcohol consumption, nonalcoholic fatty liver disease, and/or chronic viral hepatitis (hepatitis B and C), results in damage to parenchyma, oxidative stress, and compensatory regeneration/proliferation. There is substantial evidence linking these inflammation-associated events with the increased incidence of hepatocellular carcinogenesis. Although acute liver inflammation can play a vital and beneficial role in response to liver damage or acute infection, the effects of chronic liver inflammation, including liver fibrosis and cirrhosis, are sufficient in a fraction of individuals to initiate the process of transformation and the development of hepatocellular carcinoma. This review highlights immune-dependent mechanisms that may be associated with hepatocellular oncogenesis, including critical transformative events/pathways in the context of chronic inflammation and subverted tolerogenesis. (HEPATOLOGY 2012)
C1 [Stauffer, Jimmy K.; Scarzello, Anthony J.; Jiang, Qun; Wiltrout, Robert H.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
RP Wiltrout, RH (reprint author), NCI, Canc & Inflammat Program, Bldg 428,Rm 48A, Frederick, MD 21702 USA.
EM wiltrour@mail.nih.gov
RI Jiang, Qun/A-1358-2014
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX Funded in whole or in part with federal funds from the National Cancer
Institute, National Institutes of Health, Contract No.
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government.
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PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2012
VL 56
IS 4
BP 1567
EP 1574
DI 10.1002/hep.25674
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 018PJ
UT WOS:000309673500040
PM 22378061
ER
PT J
AU Berger, VW
AF Berger, Vance W.
TI Internal validity and the risk of bias: a case for a comprehensive
review
SO JOURNAL OF ANESTHESIA
LA English
DT Letter
DE Allocation Concealment; Biases; Masking; Randomized Trials
C1 [Berger, Vance W.] NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
[Berger, Vance W.] UMBC, Bethesda, MD 20892 USA.
RP Berger, VW (reprint author), NCI, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA.
EM vance917@gmail.com
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PU SPRINGER JAPAN KK
PI TOKYO
PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065,
JAPAN
SN 0913-8668
J9 J ANESTH
JI J. Anesth.
PD OCT
PY 2012
VL 26
IS 5
BP 802
EP 803
DI 10.1007/s00540-012-1420-8
PG 2
WC Anesthesiology
SC Anesthesiology
GA 021CI
UT WOS:000309862500030
PM 22653407
ER
PT J
AU Ilani, N
Roth, MY
Amory, JK
Swerdloff, RS
Dart, C
Page, ST
Bremner, WJ
Sitruk-Ware, R
Kumar, N
Blithe, DL
Wang, C
AF Ilani, Niloufar
Roth, Mara Y.
Amory, John K.
Swerdloff, Ronald S.
Dart, Clint
Page, Stephanie T.
Bremner, William J.
Sitruk-Ware, Regine
Kumar, Narender
Blithe, Diana L.
Wang, Christina
TI A New Combination of Testosterone and Nestorone Transdermal Gels for
Male Hormonal Contraception
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID DEPOT MEDROXYPROGESTERONE ACETATE; NORETHISTERONE ENANTHATE; HYPOGONADAL
MEN; CHINESE MEN; INJECTABLE TESTOSTERONE; ORAL LEVONORGESTREL; INDUCED
AZOOSPERMIA; CLINICAL-TRIAL; SPERMATOGENESIS; SUPPRESSION
AB Context: Combinations of testosterone (T) and nestorone (NES; a nonandrogenic progestin) transdermal gels may suppress spermatogenesis and prove appealing to men for contraception.
Objective: The objective of the study was to determine the effectiveness of T gel alone or combined with NES gel in suppressing spermatogenesis.
Design and Setting: This was a randomized, double-blind, comparator clinical trial conducted at two academic medical centers.
Participants: Ninety-nine healthy male volunteers participated in the study.
Interventions: Volunteers were randomized to one of three treatment groups applying daily transdermal gels (group 1: T gel 10 g + NES 0 mg/placebo gel; group 2: T gel 10 g + NES gel 8 mg; group 3: T gel 10 g + NES gel 12 mg).
Main Outcome Variable: The main outcome variable of the study was the percentage of men whose sperm concentration was suppressed to 1 million/ml or less by 20-24 wk of treatment.
Results: Efficacy data analyses were performed on 56 subjects who adhered to the protocol and completed at least 20 wk of treatment. The percentage of men whose sperm concentration was 1 million/ml or less was significantly higher for T + NES 8 mg (89%, P < 0.0001) and T + NES 12 mg (88%, P = 0.0002) compared with T + NES 0 mg group (23%). The median serum total and free T concentrations in all groups were maintained within the adult male range throughout the treatment period. Adverse effects were minimal in all groups.
Conclusion: A combination of daily NES + T gels suppressed sperm concentration to 1 million/ml or less in 88.5% of men, with minimal adverse effects, and may be further studied as a male transdermal hormonal contraceptive. (J Clin Endocrinol Metab 97: 3476-3486, 2012)
C1 [Wang, Christina] Univ Calif Los Angeles, Clin & Translat Sci Inst, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.
[Ilani, Niloufar; Swerdloff, Ronald S.; Wang, Christina] Harbor Univ Calif Los Angeles, Med Ctr, Dept Med, Div Endocrinol, Torrance, CA 90509 USA.
[Roth, Mara Y.; Amory, John K.; Page, Stephanie T.; Bremner, William J.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Dart, Clint] Hlth Decis, Durham, NC 27713 USA.
[Swerdloff, Ronald S.; Kumar, Narender] Populat Council, Ctr Biomed Res, New York, NY 10065 USA.
[Blithe, Diana L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Contracept & Reprod Hlth Branch, NIH, Bethesda, MD 20852 USA.
RP Wang, C (reprint author), Univ Calif Los Angeles, Clin & Translat Sci Inst, Los Angeles Biomed Res Inst, 1000 W Carson St, Torrance, CA 90509 USA.
EM wang@labiomed.org
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [HHSN275200403369I, HHSN2751008060044U]; Population
Council; Endocrinology, Metabolism, and Nutrition Training Grant [NIH
T32 DK007571]; General Clinical Research Center Grant [MO1 NIH RR00425];
University of California, Los Angeles, Clinical and Translational
Science Institute Grant at Harbor-University of California, Los Angeles,
Medical Center [NIH 1UL1-RR033176]; Los Angeles Biomedical Research
Institute; NICHD [HHSN27520040337, 5K12HD053984]; Center for Research in
Reproduction and Contraception Grant [NIH U54 HD 04245]
FX This work was supported by Eunice Kennedy Shriver National Institute of
Child Health and Human Development (NICHD) Contracts HHSN275200403369I
and HHSN2751008060044U and the Population Council. The Los Angeles
Center was supported by the Endocrinology, Metabolism, and Nutrition
Training Grant NIH T32 DK007571, and the General Clinical Research
Center Grant MO1 NIH RR00425 and the University of California, Los
Angeles, Clinical and Translational Science Institute Grant NIH
1UL1-RR033176 at Harbor-University of California, Los Angeles, Medical
Center and Los Angeles Biomedical Research Institute. The Seattle center
was supported by Contract HHSN27520040337 from the NICHD, the Center for
Research in Reproduction and Contraception Grant NIH U54 HD 04245
(NICHD), and NICHD Grant 5K12HD053984.
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SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD OCT 1
PY 2012
VL 97
IS 10
BP 3476
EP 3486
DI 10.1210/jc.2012-1384
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 018MH
UT WOS:000309664400041
PM 22791756
ER
PT J
AU Giallauria, F
Milaneschi, Y
Tanaka, T
Maggio, M
Canepa, M
Elango, P
Vigorito, C
Lakatta, EG
Ferrucci, L
Strait, J
AF Giallauria, Francesco
Milaneschi, Yuri
Tanaka, Toshiko
Maggio, Marcello
Canepa, Marco
Elango, Palchamy
Vigorito, Carlo
Lakatta, Edward G.
Ferrucci, Luigi
Strait, James
TI Arterial Stiffness and Vitamin D Levels: the Baltimore Longitudinal
Study of Aging
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID PULSE-WAVE VELOCITY; RENIN-ANGIOTENSIN SYSTEM; ALL-CAUSE MORTALITY;
D-BINDING PROTEIN; 25-HYDROXYVITAMIN D; 1,25-DIHYDROXYVITAMIN D-3;
CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; KNOCKOUT MICE; OLDER-ADULTS
AB Context: The importance of vitamin D for bone health has long been acknowledged. Recent evidence suggests that vitamin D can also play a role in reducing the risk of several other diseases, including cardiovascular disease.
Objective: The aim of this study is to test the hypothesis that 25-hydroxyvitamin D (25-OH D) is an independent cross-sectional correlate of central arterial stiffness in a normative aging study population.
Design and Settings: We conducted a cross-sectional analysis.
Subjects: We studied 1228 healthy volunteers (50% males; age, 70 +/- 12 yr) of the Baltimore Longitudinal Study of Aging.
Main Outcome Measures: We measured carotid-femoral pulse wave velocity (PWV) and 25-OH D levels.
Results: We found a significant inverse association between PWV and 25-OHD levels (adjusted r(2) = 0.27; beta = -0.43; P = 0.001). After adjusting for age, gender, ethnicity, season of blood draw, estimated glomerular filtration rate, physical activity level, cardiovascular risk factors score (smoking, visceral obesity, hypercholesterolemia, hypertension, and diabetes), calcium/vitamin D supplementation, serum calcium, and PTH levels, the association between PWV and 25-OHD levels was only slightly reduced and remained statistically significant (adjusted r(2) = 0.34; beta = -0.34; P = 0.04).
Conclusions: Vitamin D levels are inversely associated with increased arterial stiffness in a normative aging population, irrespective of traditional risk factor burden. Further research is needed to understand the mechanism of this association and to test the hypothesis that vitamin D supplementation can reduce arterial stiffness. (J Clin Endocrinol Metab 97: 3717-3723, 2012)
C1 [Giallauria, Francesco; Milaneschi, Yuri; Tanaka, Toshiko; Elango, Palchamy; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21225 USA.
[Giallauria, Francesco; Vigorito, Carlo] Univ Naples Federico II, Dept Clin Med Cardiovasc & Immunol Sci, I-80131 Naples, Italy.
[Milaneschi, Yuri] VU Univ Med Ctr GGZ InGeest, Dept Psychiat, NL-1081 HZ Amsterdam, Netherlands.
[Maggio, Marcello] Univ Parma, Sect Geriatr, Dept Internal Med & Biomed Sci, I-43100 Parma, Italy.
[Canepa, Marco; Lakatta, Edward G.; Strait, James] NIA, Lab Cardiovasc Sci, Baltimore, MD 21225 USA.
RP Giallauria, F (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, 3001 S Hanover St, Baltimore, MD 21225 USA.
EM giallauriaf@mail.nih.gov
RI Giallauria, Francesco/B-5681-2013
OI Giallauria, Francesco/0000-0003-4119-9397
FU Intramural Research Program of the National Institutes of Health,
National Institute on Aging; "Programma di Scambi Internazionali con
Universita ed Istituti di Ricerca Stranieri per la Mobilta di Breve
Durata di Docenti, Ricercatori e Studiosi" of the University of Naples
"Federico II"
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute on Aging; and in part
by the "Programma di Scambi Internazionali con Universita ed Istituti di
Ricerca Stranieri per la Mobilta di Breve Durata di Docenti, Ricercatori
e Studiosi" of the University of Naples "Federico II."
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SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD OCT 1
PY 2012
VL 97
IS 10
BP 3717
EP 3723
DI 10.1210/jc.2012-1584
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 018MH
UT WOS:000309664400069
PM 22767638
ER
PT J
AU Matthews, CE
Fortner, RT
Xu, X
Hankinson, SE
Eliassen, AH
Ziegler, RG
AF Matthews, Charles E.
Fortner, Renee T.
Xu, Xia
Hankinson, Susan E.
Eliassen, A. Heather
Ziegler, Regina G.
TI Association between Physical Activity and Urinary Estrogens and Estrogen
Metabolites in Premenopausal Women
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; BREAST-CANCER; POSTMENOPAUSAL WOMEN;
EUMENORRHEIC WOMEN; MENSTRUAL FUNCTION; EXERCISING WOMEN; BONE-DENSITY;
RISK; HORMONE; REPRODUCIBILITY
AB Objective: The objective of the study was to evaluate in premenopausal women the relationships of physically active and sedentary behaviors reported for adulthood and adolescence with a comprehensive profile of estrogen metabolism.
Methodology: Fifteen estrogens and estrogen metabolites (jointly termed EM) were measured using liquid chromatography-tandem mass spectrometry in luteal phase urines from 603 premenopausal women in the Nurses' Health Study II. Geometric means of individual EM, metabolic pathway groups, and pathway ratios were examined by level of exposure after adjustment for age, body mass index, alcohol intake, menstrual cycle length, and sample collection timing.
Results: High overall physical activity in adulthood (42+ metabolic equivalent h/wk vs. <3 metabolic equivalent h/wk) was associated with a 15% lower level of urinary estradiol (P-trend = 0.03) and 15% lower level of 16-hydroxylation pathway EM (P-trend = 0.03). Levels of 2- and 4-hydroxylation pathway EM did not differ significantly by physical activity. High overall activity was also positively associated with four ratios: 2-pathway EM to parent estrogens (P-trend = 0.05), 2-pathway catechols to parent estrogens (P-trend = 0.03), 2-pathway catechols to methylated 2-pathway catechols (P-trend < 0.01), and 2-hydroxyestrone to 16 alpha-hydroxyestrone (P-trend = 0.01). Similar patterns of association were noted for walking and vigorous physical activity, but there was little evidence of associations with sedentary behaviors or activity during adolescence.
Conclusions: High levels of physical activity were associated with lower levels of parent estrogens and 16-hydroxylation pathway EM and preferential metabolism to 2-pathway catechols. The results of our analysis, the largest, most comprehensive examination of physical activity and estrogen metabolism to date, may be useful in future studies investigating the etiology of diseases linked to both physical activity and endogenous estrogen. (J Clin Endocrinol Metab 97: 3724-3733, 2012)
C1 [Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Ziegler, Regina G.] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Fortner, Renee T.; Hankinson, Susan E.; Eliassen, A. Heather] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Fortner, Renee T.; Hankinson, Susan E.; Eliassen, A. Heather] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Xu, Xia] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Hankinson, Susan E.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
RP Matthews, CE (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 3028, Bethesda, MD 20892 USA.
EM charles.matthews2@nih.gov
RI matthews, Charles/E-8073-2015;
OI matthews, Charles/0000-0001-8037-3103; Fortner,
Renee/0000-0002-1426-8505
FU National Cancer Institute (NCI) [CA67262, CA50385]; Intramural Research
Program of the NCI Division of Cancer Epidemiology and Genetics; NCI
[HHSN261200800001E]; [T32 CA09001]
FX This work was supported by Research Grants CA67262 and CA50385 from the
National Cancer Institute (NCI) and the Intramural Research Program of
the NCI Division of Cancer Epidemiology and Genetics and with federal
funds of the NCI awarded under Contract HHSN261200800001E (to
SAIC-Frederick). R. T. F. is supported, in part, by Grant T32 CA09001.
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SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD OCT 1
PY 2012
VL 97
IS 10
BP 3724
EP 3733
DI 10.1210/jc.2012-1732
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 018MH
UT WOS:000309664400070
PM 22855335
ER
PT J
AU Kaess, BM
Enserro, DM
McManus, DD
Xanthakis, V
Chen, MH
Sullivan, LM
Ingram, C
O'Donnell, CJ
Keaney, JF
Vasan, RS
Glazer, NL
AF Kaess, Bernhard M.
Enserro, Danielle M.
McManus, David D.
Xanthakis, Vanessa
Chen, Ming-Huei
Sullivan, Lisa M.
Ingram, Cheryl
O'Donnell, Christoper J.
Keaney, John F.
Vasan, Ramachandran S.
Glazer, Nicole L.
TI Cardiometabolic Correlates and Heritability of Fetuin-A, Retinol-Binding
Protein 4, and Fatty-Acid Binding Protein 4 in the Framingham Heart
Study
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID INSULIN-RESISTANCE; METABOLIC SYNDROME; RETINOL-BINDING-PROTEIN-4;
SERUM; ASSOCIATION; BIOMARKER; OBESITY; RISK; NULL; MICE
AB Context: Fetuin-A, retinol-binding protein 4 (RBP4), and fatty-acid binding protein 4 (FABP4) are novel biomarkers that may link adiposity to insulin resistance and the metabolic syndrome (MetSyn).
Objective: The aim of this study was to investigate the correlates of these three adiposity biomarkers in a large community-based sample.
Design, Setting, Participants, and Outcomes: Serum concentrations of fetuin-A, RBP4, and FABP4 were assayed in 3658 participants of the Third Generation Framingham Heart Study cohort (mean age 40 yr, 54% women). We used multivariable regression to cross-sectionally relate biomarkers to insulin resistance, cardiovascular risk factors, and the MetSyn. The genetic contribution to inter-individual variation in biomarker levels was assessed using variance-components analysis.
Results: All three biomarkers exhibited sexual dimorphisms (levels higher in women for fetuin-A and FABP4 but greater in men for RBP4) and were associated positively with insulin resistance assessed using the homeostasis model, with high-sensitivity C-reactive protein, and with prevalent MetSyn (P < 0.01 for all). The biomarkers showed distinct patterns of association with metabolic risk factors. RBP4 levels were correlated with body mass index only in unadjusted but not in adjusted models. None of the biomarkers were associated with prevalent diabetes in multivariable models. Circulating fetuin-A, RBP4, and FABP4 levels showed modest heritability, ranging from 15-44% (all P < 0.0001).
Conclusions: In our large young- to middle-aged community-based sample, we observed that circulating levels of fetuin-A, RBP4, and FABP4 are associated with insulin resistance and with distinct components of MetSyn consistent with the multifactorial pathogenesis of metabolic dysregulation. (J Clin Endocrinol Metab 97: E1943-E1947, 2012)
C1 [Glazer, Nicole L.] Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA.
[Kaess, Bernhard M.; O'Donnell, Christoper J.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Kaess, Bernhard M.] Univ Hosp Regensburg, Klin & Poliklin Innere Med 2, D-93042 Regensburg, Germany.
[McManus, David D.; Ingram, Cheryl; Keaney, John F.] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA.
[Enserro, Danielle M.; Xanthakis, Vanessa; Sullivan, Lisa M.; Glazer, Nicole L.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA.
[O'Donnell, Christoper J.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Glazer, NL (reprint author), Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, 801 Massachusetts Ave, Boston, MA 02118 USA.
EM nlglazer@bu.edu
OI Ramachandran, Vasan/0000-0001-7357-5970; Sullivan,
Lisa/0000-0003-0726-7149
FU National Institutes of Health [NO1-HC 25195, R01-DK-080739-01]
FX This work was supported through National Institutes of Health contract
NO1-HC 25195 and R01-DK-080739-01 (to R.S.V.).
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PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD OCT 1
PY 2012
VL 97
IS 10
BP E1943
EP E1947
DI 10.1210/jc.2012-1458
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 018MH
UT WOS:000309664400015
PM 22855337
ER
PT J
AU Mumford, SL
Steiner, AZ
Pollack, AZ
Perkins, NJ
Filiberto, AC
Albert, PS
Mattison, DR
Wactawski-Wende, J
Schisterman, EF
AF Mumford, Sunni L.
Steiner, Anne Z.
Pollack, Anna Z.
Perkins, Neil J.
Filiberto, Amanda C.
Albert, Paul S.
Mattison, Donald R.
Wactawski-Wende, Jean
Schisterman, Enrique F.
TI The Utility of Menstrual Cycle Length as an Indicator of Cumulative
Hormonal Exposure
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID BREAST-CANCER; RISK; WOMEN; PHASES; PATTERNS; BIOCYCLE; LONG
AB Context: Associations between menstrual cycle length and chronic diseases are hypothesized to be due to differences in underlying hormonal patterns.
Objective: The aim of the study was to evaluate the association between menstrual cycle length and the hormonal profile and anovulation.
Design and Setting: We conducted a prospective cohort study at the University at Buffalo from 2005 to 2007.
Participants: We recruited 259 healthy, regularly menstruating women aged 18-44 yr.
Main Outcome Measures: Cycle length was observed for up to two cycles. Serum estradiol, progesterone, LH, and FSH were measured up to eight times per cycle for up to two cycles.
Results: Women with short cycles (<26 d) had higher FSH concentrations during menses and in the late luteal phase, higher follicular estradiol concentrations, and lower LH concentrations across the cycle. Among women with longer cycles (>35 d), estradiol and LH peaks occurred on average about 3 d later, and FSH peaks about 1 d later compared to women with normal-length cycles. Both short and long cycles, compared with normal-length cycles, had an increased probability of anovulation. In general, per-cycle exposure to hormones was less in short cycles based on the area under the curve, although over time the cumulative exposure to estradiol would be greater for women with short cycles.
Conclusions: Short ovulatory cycles were associated with higher follicular phase estradiol, an earlier rise in FSH, and an increased risk of anovulation. These results suggest that menstrual cycle length may be a relevant indicator of estradiol exposure and risk of anovulation among regularly cycling women. (J Clin Endocrinol Metab 97: E1871-E1879, 2012)
C1 [Mumford, Sunni L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA.
[Steiner, Anne Z.] Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC 27599 USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA.
RP Mumford, SL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,7B03, Rockville, MD 20852 USA.
EM mumfords@mail.nih.gov
RI Mattison, Donald/L-4661-2013;
OI Mattison, Donald/0000-0001-5623-0874; Perkins, Neil/0000-0002-6802-4733;
Pollack, Anna/0000-0002-4313-3298; Schisterman,
Enrique/0000-0003-3757-641X
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health [HSN275200403394C]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health (Contract #
HSN275200403394C).
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SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD OCT 1
PY 2012
VL 97
IS 10
BP E1871
EP E1879
DI 10.1210/jc.2012-1350
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 018MH
UT WOS:000309664400006
PM 22837188
ER
PT J
AU Sun, MN
Guo, XJ
Qian, XL
Wang, HB
Yang, CY
Brinkman, KL
Serrano-Gonzalez, M
Jope, RS
Zhou, BH
Engler, DA
Zhan, M
Wong, STC
Fu, L
Xu, B
AF Sun, Mianen
Guo, Xiaojing
Qian, Xiaolong
Wang, Haibo
Yang, Chunying
Brinkman, Kathryn L.
Serrano-Gonzalez, Monica
Jope, Richard S.
Zhou, Binhua
Engler, David A.
Zhan, Ming
Wong, Stephen T. C.
Fu, Li
Xu, Bo
TI Activation of the ATM-Snail pathway promotes breast cancer metastasis
SO JOURNAL OF MOLECULAR CELL BIOLOGY
LA English
DT Article
DE ATM; snail; metastasis
ID EPITHELIAL-MESENCHYMAL TRANSITION; DNA-DAMAGE RESPONSE; SHOCK-PROTEIN
90; TUMOR PROGRESSION; E-CADHERIN; ATAXIA-TELANGIECTASIA; INDUCED
APOPTOSIS; REPRESSOR SNAIL; PHOSPHORYLATION; EXPRESSION
AB The DNA damage response (DDR) is critical for the maintenance of genetic stability and serves as an anti-cancer barrier during early tumorigenesis. However, the role of the DDR in tumor progression and metastasis is less known. Here, we demonstrate that the ATM kinase, one of the critical DDR elements, is hyperactive in late stage breast tumor tissues with lymph-node metastasis and this hyperactivity correlates with elevated expression of the epithelialmesenchymal transition marker, Snail. At the molecular level, we demonstrate that ATM regulates Snail stabilization by phosphorylation on Serine-100. Using mass spectrometry, we identified HSP90 as a critical binding protein of Snail in response to DNA damage. HSP90 binds to and stabilizes phosphorylated Snail. We further provide in vitro and in vivo evidence that activation of ATM-mediated Snail phosphorylation promotes tumor invasion and metastasis. Finally, we demonstrate that Snail Serine-100 phosphorylation is elevated in breast cancer tissues with lymph-node metastasis, indicating clinical significance of the ATM-Snail pathway. Together, our findings provide strong evidence that the ATM-Snail pathway promotes tumor metastasis, highlighting a previously undescribed role of the DDR in tumor invasion and metastasis.
C1 [Sun, Mianen; Guo, Xiaojing; Wang, Haibo; Yang, Chunying; Brinkman, Kathryn L.; Serrano-Gonzalez, Monica; Xu, Bo] Methodist Hosp Res Inst, Dept Radiat Oncol, Houston, TX 77030 USA.
[Guo, Xiaojing; Qian, Xiaolong; Fu, Li] Tianjin Med Univ Canc Inst & Hosp, Dept Breast Canc Pathol, Tianjin 300060, Peoples R China.
[Guo, Xiaojing; Qian, Xiaolong; Fu, Li] Tianjin Med Univ Canc Inst & Hosp, Res Lab, Key Lab Breast Canc Breast Canc Prevent & Therapy, Tianjin 300060, Peoples R China.
[Jope, Richard S.] Univ Alabama Birmingham, Dept Cell Biol, Birmingham, AL 35294 USA.
[Zhou, Binhua] Univ Kentucky, Dept Biochem, Lexington, KY 40506 USA.
[Engler, David A.] Methodist Hosp Res Inst, Prote Programmat Core, Houston, TX 77030 USA.
[Zhan, Ming; Wong, Stephen T. C.] Methodist Hosp Res Inst, Dept Syst Med & Bioengn, Houston, TX 77030 USA.
[Zhan, Ming; Wong, Stephen T. C.; Xu, Bo] NCI Ctr Modeling Canc Dev, Houston, TX 77030 USA.
RP Xu, B (reprint author), Methodist Hosp Res Inst, Dept Radiat Oncol, Houston, TX 77030 USA.
EM fuli@tmu.edu.cn; boxu2002@yahoo.com
RI Wang, Haibo/H-3151-2012
FU NIH [R01CA133093, R01ES016354, R21NS061748]; Oshman Foundation
[U54CA149169, R01CA125454]; National Natural Science Foundation of China
[30930038]; Program for Changjiang Scholars and Innovative Research Team
[IRT0743]; National 973 Program of China [2009CB521700]
FX This work was supported by NIH grants R01CA133093, R01ES016354,
R21NS061748 and Oshman Foundation to B. X., U54CA149169 to S. W.,
R01CA125454 to B.Z., and National Natural Science Foundation of China
(grant no. 30930038), Program for Changjiang Scholars and Innovative
Research Team (grant no. IRT0743), and the National 973 Program of China
(grant no. 2009CB521700) to L.F.
NR 43
TC 29
Z9 30
U1 3
U2 18
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1674-2788
J9 J MOL CELL BIOL
JI J. Mol. Cell Biol.
PD OCT
PY 2012
VL 4
IS 5
BP 304
EP 315
DI 10.1093/jmcb/mjs048
PG 12
WC Cell Biology
SC Cell Biology
GA 018ZP
UT WOS:000309707000005
PM 22923499
ER
PT J
AU Wires, ES
Alvarez, D
Dobrowolski, C
Wang, Y
Morales, M
Karn, J
Harvey, BK
AF Wires, Emily S.
Alvarez, David
Dobrowolski, Curtis
Wang, Yun
Morales, Marisela
Karn, Jonathan
Harvey, Brandon K.
TI Methamphetamine activates nuclear factor kappa-light-chain-enhancer of
activated B cells (NF-kappa B) and induces human immunodeficiency virus
(HIV) transcription in human microglial cells
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Article
DE HIV; Microglia; Methamphetamine; NF-kappa B (NF-kappa B); Nuclear
translocation
ID DNA-BINDING ACTIVITY; HUMAN FETAL MICROGLIA; INDUCED NEUROTOXICITY;
PROTEIN TAT; PRODUCTIVE INFECTION; NEURONAL INJURY; BRAIN; APOPTOSIS;
STRIATUM; DOPAMINE
AB Human immunodeficiency virus (HIV) primarily infects glial cells in the central nervous system (CNS). Recent evidence suggests that HIV-infected individuals who abuse drugs such as methamphetamine (METH) have higher viral loads and experience more severe neurological complications than HIV-infected individuals who do not abuse drugs. The aim of this study was to determine the effect of METH on HIV expression from the HIV long terminal repeat (LTR) promoter and on an HIV integrated provirus in microglial cells, the primary host cells for HIV in the CNS. Primary human microglial cells immortalized with SV40 T antigen (CHME-5 cells) were cotransfected with an HIV LTR reporter and the HIV Tat gene, a key regulator of viral replication and gene expression, and exposed to METH. Our results demonstrate that METH treatment induced LTR activation, an effect potentiated in the presence of Tat. We also found that METH increased the nuclear translocation of the nuclear factor kappa B (NF-kappa B), a key cellular transcriptional regulator of the LTR promoter, and the activity of an NF-kappa B-specific reporter plasmid in CHME-5 cells. The presence of a dominant-negative regulator of NF-kappa B blocked METH-related activation of the HIV LTR. Furthermore, treatment of HIV-latently infected CHME-5 (CHME-5/HIV) cells with METH induced HIV expression and nuclear translocation of the p65 subunit of NF-kappa B. These results suggest that METH can stimulate HIV gene expression in microglia cells through activation of the NF-kappa B signaling pathway. This mechanism may outline the initial biochemical events leading to the observed increased neurodegeneration in HIV-positive individuals who use METH.
C1 [Wires, Emily S.; Wang, Yun; Morales, Marisela; Harvey, Brandon K.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Alvarez, David; Dobrowolski, Curtis; Karn, Jonathan] Case Western Reserve Univ, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA.
RP Harvey, BK (reprint author), NIDA, Intramural Res Program, NIH, Suite 200,Room 06A729,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM bharvey@mail.nih.gov
FU Intramural Research Program at the National Institute on Drug Abuse;
[DP1 DA028869]
FX The following reagents were obtained through the AIDS Research and
Reference Program, Division of AIDS, NIAID, NIH: pCTatBL43.CS and
pETatBL43.CS from Dr. Udaylumar Ranga. This work was supported by the
Intramural Research Program at the National Institute on Drug Abuse and
DP1 DA028869 to JK.
NR 45
TC 25
Z9 25
U1 3
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-0284
J9 J NEUROVIROL
JI J. Neurovirol.
PD OCT
PY 2012
VL 18
IS 5
BP 400
EP 410
DI 10.1007/s13365-012-0103-4
PG 11
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA 018LQ
UT WOS:000309662500006
PM 22618514
ER
PT J
AU Vegosen, L
Davis, MF
Silbergeld, E
Breysse, PN
Agnew, J
Gray, G
Freeman, LB
Kamel, F
AF Vegosen, Leora
Davis, Meghan F.
Silbergeld, Ellen
Breysse, Patrick N.
Agnew, Jacqueline
Gray, Gregory
Freeman, Laura Beane
Kamel, Freya
TI Neurologic Symptoms Associated With Cattle Farming in the Agricultural
Health Study
SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID GUILLAIN-BARRE-SYNDROME; ACUTE FLACCID PARALYSIS; CAMPYLOBACTER-JEJUNI;
MOLECULAR MIMICRY; ANTIMICROBIAL RESISTANCE; UNITED-STATES;
RISK-FACTORS; THERMOPHILIC CAMPYLOBACTER; DAIRY-CATTLE; PREVALENCE
AB Objective: Infection with Campylobacter jejuni, a bacterium carried by poultry and livestock, is the most frequently identified antecedent to the autoimmune neurologic condition Guillain-Barre Syndrome. We used Agricultural Health Study data to assess whether cattle farming was associated with prevalence of neurologic symptoms. Methods: Prevalence of self-reported symptoms in cattle farmers (n = 8878) was compared with farmers who did not work with animals (n = 7462), using multivariate regression. Results: Prevalence of numbness and weakness were increased for beef and dairy farmers compared with the reference group (P < 0.0001). Of cattle farmers, 48% did not report raising other animal species, and prevalence of numbness and weakness were also increased in this subgroup compared with the reference group (P < 0.02). Conclusions: Occupational exposure to cattle was associated with increased prevalence of self-reported symptoms associated with peripheral neuropathy.
C1 [Vegosen, Leora; Davis, Meghan F.; Silbergeld, Ellen; Breysse, Patrick N.; Agnew, Jacqueline] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA.
[Gray, Gregory] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Environm & Global Hlth, Gainesville, FL USA.
[Freeman, Laura Beane] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Kamel, Freya] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Vegosen, L (reprint author), 615 N Wolfe St,Room W7034G, Baltimore, MD 21205 USA.
EM lvegosen@jhsph.edu
RI Davis, Meghan/C-1494-2013; Beane Freeman, Laura/C-4468-2015;
OI Davis, Meghan/0000-0002-3475-4578; Beane Freeman,
Laura/0000-0003-1294-4124; Kamel, Freya/0000-0001-5052-6615
FU National Institutes of Health; National Institute of Environmental
Health Sciences [Z01-ES049030]; National Cancer Institute
[Z01-CP010119]; National Institute for Occupational Safety and Health
(NIOSH) Education and Research Center for Occupational Safety and Health
at the Johns Hopkins Bloomberg School of Public Health [T42OH008428];
Johns Hopkins Center for a Livable Future Innovation Grant; Hopkins
Sommer Scholarship; Kruse Award; NIAID; DoD
FX This work was supported in part by the intramural research program of
the National Institutes of Health, the National Institute of
Environmental Health Sciences (Z01-ES049030) and National Cancer
Institute (Z01-CP010119), the National Institute for Occupational Safety
and Health (NIOSH) Education and Research Center for Occupational Safety
and Health at the Johns Hopkins Bloomberg School of Public Health
#T42OH008428, the Johns Hopkins Center for a Livable Future Innovation
Grant, Hopkins Sommer Scholarship, Kruse Award, NIAID, and DoD.
NR 45
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Z9 1
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1076-2752
J9 J OCCUP ENVIRON MED
JI J. Occup. Environ. Med.
PD OCT
PY 2012
VL 54
IS 10
BP 1253
EP 1258
DI 10.1097/JOM.0b013e31825a2574
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 020FK
UT WOS:000309794200014
PM 22975665
ER
PT J
AU Yaroch, AL
Tooze, J
Thompson, FE
Blanck, HM
Thompson, OM
Colon-Ramos, U
Shaikh, AR
McNutt, S
Nebeling, LC
AF Yaroch, Amy L.
Tooze, Janet
Thompson, Frances E.
Blanck, Heidi M.
Thompson, Olivia M.
Colon-Ramos, Uriyoan
Shaikh, Abdul R.
McNutt, Susanne
Nebeling, Linda C.
TI Evaluation of Three Short Dietary Instruments to Assess Fruit and
Vegetable Intake: The National Cancer Institute's Food Attitudes and
Behaviors Survey
SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS
LA English
DT Article
DE Fruits and vegetables; Screener; Validity; Reliability
ID FREQUENCY QUESTIONNAIRE; SERUM CAROTENOIDS; BIOMARKERS; PERFORMANCE;
CONSUMPTION; ENERGY; ADULTS
AB Background Fruit and vegetable (F/V) intake assessment tools that are valid, reliable, brief, and easy to administer and code are vital to the field of public health nutrition.
Objective To evaluate three short F/V intake screeners (ie, a 2-item serving tool, a 2-item cup tool, and a 16-item F/V intake screener) among adults using multiple 24-hour dietary recalls (24-hour recalls) as the reference instrument and evaluate test-retest reliability of the screeners across a 2- to 3-week time period.
Design Validity and reliability study.
Participants/setting Two hundred forty-four adults for the validity study and 335 adults for test-retest reliability.
Statistical analyses performed Median values for F/V intakes were calculated for the screeners and 24-hour recalls. The Wilcoxon signed rank test was used to compare screeners with the 24-hour recalls. Deattenuated Pearson correlations were reported for validity and intraclass correlation coefficient used for reliability.
Results The estimated median daily servings/cups of F/V for the 2-item serving screener was lower, for the 2-item cup screener was equivalent for then but higher for women, and for the 16-item F/V intake screener were about the same when compared with 24-hour recall values. The deattenuated correlations comparing the 24-hour recalls with the screeners were positive but weak for the 2-item serving screener, and were positive and moderate in strength for the 2-item cup and 16-item F/V intake screeners. The test-retest intraclass correlation coefficients were all positive and fairly strong for all of the screeners.
Conclusions Although dietary screeners offer a more cost-effective, less burdensome way to obtain gross estimates to rank individuals with regard to F/V intake, these methods are not recommended for assessing precise intake levels. J Acad Nutr Diet. 2012;112:1570-1577.
C1 [Yaroch, Amy L.] Gretchen Swanson Ctr Nutr, Omaha, NE 68105 USA.
[Tooze, Janet] Wake Forest Univ, Dept Biostat Studies, Winston Salem, NC 27109 USA.
[Thompson, Frances E.; Shaikh, Abdul R.; Nebeling, Linda C.] NCI, Rockville, MD USA.
[Blanck, Heidi M.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Thompson, Olivia M.] Coll Charleston, Dept Hlth & Human Performance, Charleston, SC 29401 USA.
[Colon-Ramos, Uriyoan] George Washington Univ, Dept Global Hlth, Sch Publ Hlth & Hlth Serv, Washington, DC USA.
[McNutt, Susanne] Westat Corp, Rockville, MD USA.
RP Yaroch, AL (reprint author), Gretchen Swanson Ctr Nutr, 505 Durham Res Plaza, Omaha, NE 68105 USA.
EM ayaroch@centerfornutrition.org
FU Division of Cancer Control and Population Sciences at the National
Cancer Institute
FX This project was supported through the Division of Cancer Control and
Population Sciences at the National Cancer Institute. The findings and
conclusions in this article are those of the authors and do not
necessarily represent the official position of the National Cancer
Institute or the Centers for Disease Control and Prevention.
NR 25
TC 25
Z9 25
U1 3
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2212-2672
J9 J ACAD NUTR DIET
JI J. Acad. Nutr. Diet.
PD OCT
PY 2012
VL 112
IS 10
BP 1570
EP 1577
DI 10.1016/j.jand.2012.06.002
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 017CB
UT WOS:000309566600009
PM 23017567
ER
PT J
AU Kovalchik, SA
Pfeifer, RM
AF Kovalchik, Stephanie A.
Pfeifer, Ruth M.
TI Re: Assessment of Impact of Outmigration on Incidence of Second Primary
Neoplasms in Childhood Cancer Survivors Estimated From SEER Data
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
C1 [Kovalchik, Stephanie A.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
RP Kovalchik, SA (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 8047, Rockville, MD 20852 USA.
EM kovalchiksa@mail.nih.gov
FU Intramural NIH HHS; NCI NIH HHS [U24 CA55727]
NR 7
TC 2
Z9 2
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD OCT
PY 2012
VL 104
IS 19
BP 1517
EP 1518
DI 10.1093/jnci/djs360
PG 2
WC Oncology
SC Oncology
GA 018MZ
UT WOS:000309666300013
PM 22914782
ER
PT J
AU Nagel, JD
Rudick, J
AF Nagel, Joan Davis
Rudick, Joyce
TI Ninth Annual NIH Interdisciplinary Women's Health Research Symposium
November 15, 2012 Introduction
SO JOURNAL OF WOMENS HEALTH
LA English
DT Editorial Material
C1 [Nagel, Joan Davis; Rudick, Joyce] NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA.
RP Rudick, J (reprint author), NIH, Off Res Womens Hlth, 6707 Democracy Blvd,Suite 400, Bethesda, MD 20892 USA.
EM ORWH-Research@od.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
J9 J WOMENS HEALTH
JI J. Womens Health
PD OCT
PY 2012
VL 21
IS 10
BP 986
EP 987
PG 2
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA 018JF
UT WOS:000309655600001
ER
PT J
AU Bakkum-Gamez, JN
Chien, J
Clayton, AC
Halling, KC
Cliby, WA
Dowdy, SC
Kipp, BR
Famuyide, A
Mariani, A
Oberg, AL
Wentzensen, N
Sherman, M
Podratz, KC
Shridhar, V
AF Bakkum-Gamez, Jamie N.
Chien, Jeremy
Clayton, Amy C.
Halling, Kevin C.
Cliby, William A.
Dowdy, Sean C.
Kipp, Benjamin R.
Famuyide, Abimbola
Mariani, Andrea
Oberg, Ann L.
Wentzensen, Nicolas
Sherman, Mark
Podratz, Karl C.
Shridhar, Viji
TI Development of Biomarkers in Endometrial Cancer and Its Precursor
Lesions
SO JOURNAL OF WOMENS HEALTH
LA English
DT Meeting Abstract
C1 [Bakkum-Gamez, Jamie N.; Cliby, William A.; Dowdy, Sean C.; Mariani, Andrea; Podratz, Karl C.] Mayo Clin, Div Gynecol Surg, Rochester, MN 55905 USA.
[Chien, Jeremy; Shridhar, Viji] Mayo Clin, Div Expt Pathol, Rochester, MN 55905 USA.
[Clayton, Amy C.; Halling, Kevin C.; Kipp, Benjamin R.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
[Famuyide, Abimbola] Mayo Clin, Div Med Gynecol, Rochester, MN 55905 USA.
[Oberg, Ann L.] Mayo Clin, Div Biomed Stat & Informat Canc Ctr Stat, Rochester, MN 55905 USA.
[Wentzensen, Nicolas; Sherman, Mark] NIH, Hormonal & Reprod Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
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U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
J9 J WOMENS HEALTH
JI J. Womens Health
PD OCT
PY 2012
VL 21
IS 10
BP 1004
EP 1004
PG 1
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA 018JF
UT WOS:000309655600061
ER
PT J
AU Thoma, ME
Hediger, ML
Sundaram, R
Stanford, JB
Peterson, CM
Croughan, MS
Chen, Z
Louis, GMB
AF Thoma, Marie E.
Hediger, Mary L.
Sundaram, Rajeshwari
Stanford, Joseph B.
Peterson, C. Matthew
Croughan, Mary S.
Chen, Zhen
Louis, Germaine M. Buck
CA ENDO Study Working Grp
TI Comparing Apples and Pears: Women's Perceptions of Their Body Size and
Shape
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID FAT DISTRIBUTION; WAIST CIRCUMFERENCE; MASS INDEX; ANTHROPOMETRIC
MEASUREMENTS; SELF-MEASUREMENT; BREAST SIZE; HIP RATIO; ENDOMETRIOSIS;
ASSOCIATION; DISEASE
AB Background: Obesity is a growing public health problem among reproductive-aged women, with consequences for chronic disease risk and reproductive and obstetric morbidities. Evidence also suggests that body shape (i.e., regional fat distribution) may be independently associated with risk, yet it is not known if women adequately perceive their shape. This study aimed to assess the validity of self-reported body size and shape figure drawings when compared to anthropometric measures among reproductive-aged women.
Methods: Self-reported body size was ascertained using the Stunkard nine-level figures and self-reported body shape using stylized pear, hourglass, rectangle, and apple figures. Anthropometry was performed by trained researchers. Body size and body mass index (BMI) were compared using Spearman's correlation coefficient. Fat distribution indicators were compared across body shapes for nonobese and obese women using analysis of variance (ANOVA) and Fisher's exact test. Percent agreement and kappa statistics were computed for apple and pear body shapes.
Results: The 131 women studied were primarily Caucasian (81%), aged 32 years, with a mean BMI of 27.1 kg/m(2) (range 16.6-52.8 kg/m(2)). The correlation between body size and BMI was 0.85 (p<0.001). Among nonobese women, waist-to-hip ratios (WHR) were 0.75, 0.75, 0.80, and 0.82 for pear, hourglass, rectangle, and apple, respectively (p<0.001). Comparing apples and pears, the percent agreement (kappa) for WHR >= 0.80 was 83% (0.55).
Conclusions: Self-reported size and shape were consistent with anthropometric measures commonly used to assess obesity and fat distribution, respectively. Self-reported body shape may be a useful proxy measure in addition to body size in large-scale surveys.
C1 [Thoma, Marie E.; Hediger, Mary L.; Sundaram, Rajeshwari; Chen, Zhen; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA.
[Stanford, Joseph B.] Univ Utah, Dept Family & Prevent Med, Salt Lake City, UT USA.
[Peterson, C. Matthew] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
[Croughan, Mary S.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA.
[Croughan, Mary S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP Thoma, ME (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,Room 7B03, Bethesda, MD 20892 USA.
EM thomame@mail.nih.gov
OI Sundaram, Rajeshwari/0000-0002-6918-5002; Buck Louis,
Germaine/0000-0002-1774-4490
FU Intramural Research Program, Eunice Kennedy Shriver National Institute
of Child Health and Human Development, National Institutes of Health
[NO1-DK-6-3428, NO1-DK-6-3427, 10001406-02]
FX This work was funded by the Intramural Research Program, Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
National Institutes of Health (contracts NO1-DK-6-3428, NO1-DK-6-3427,
10001406-02). Results from this study were presented at the Annual
Meeting of the American Society for Reproductive Medicine in October
2011.
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U2 17
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
J9 J WOMENS HEALTH
JI J. Womens Health
PD OCT
PY 2012
VL 21
IS 10
BP 1074
EP 1081
DI 10.1089/jwh.2012.3634
PG 8
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA 018JF
UT WOS:000309655600091
PM 22873752
ER
PT J
AU Bradley, A
Anastassiadis, K
Ayadi, A
Battey, JF
Bell, C
Birling, MC
Bottomley, J
Brown, SD
Burger, A
Bult, CJ
Bushell, W
Collins, FS
Desaintes, C
Doe, B
Economides, A
Eppig, JT
Finnell, RH
Fletcher, C
Fray, M
Frendewey, D
Friedel, RH
Grosveld, FG
Hansen, J
Herault, Y
Hicks, G
Horlein, A
Houghton, R
de Angelis, MH
Huylebroeck, D
Iyer, V
de Jong, PJ
Kadin, JA
Kaloff, C
Kennedy, K
Koutsourakis, M
Lloyd, KCK
Marschall, S
Mason, J
McKerlie, C
McLeod, MP
von Melchner, H
Moore, M
Mujica, AO
Nagy, A
Nefedov, M
Nutter, LM
Pavlovic, G
Peterson, JL
Pollock, J
Ramirez-Solis, R
Rancourt, DE
Raspa, M
Remacle, JE
Ringwald, M
Rosen, B
Rosenthal, N
Rossant, J
Noppinger, PR
Ryder, E
Schick, JZ
Schnutgen, F
Schofield, P
Seisenberger, C
Selloum, M
Simpson, EM
Skarnes, WC
Smedley, D
Stanford, WL
Stewart, AF
Stone, K
Swan, K
Tadepally, H
Teboul, L
Tocchini-Valentini, GP
Valenzuela, D
West, AP
Yamamura, K
Yoshinaga, Y
Wurst, W
AF Bradley, Allan
Anastassiadis, Konstantinos
Ayadi, Abdelkader
Battey, James F.
Bell, Cindy
Birling, Marie-Christine
Bottomley, Joanna
Brown, Steve D.
Buerger, Antje
Bult, Carol J.
Bushell, Wendy
Collins, Francis S.
Desaintes, Christian
Doe, Brendan
Economides, Aris
Eppig, Janan T.
Finnell, Richard H.
Fletcher, Colin
Fray, Martin
Frendewey, David
Friedel, Roland H.
Grosveld, Frank G.
Hansen, Jens
Herault, Yann
Hicks, Geoffrey
Hoerlein, Andreas
Houghton, Richard
de Angelis, Martin Hrabe
Huylebroeck, Danny
Iyer, Vivek
de Jong, Pieter J.
Kadin, James A.
Kaloff, Cornelia
Kennedy, Karen
Koutsourakis, Manousos
Lloyd, K. C. Kent
Marschall, Susan
Mason, Jeremy
McKerlie, Colin
McLeod, Michael P.
von Melchner, Harald
Moore, Mark
Mujica, Alejandro O.
Nagy, Andras
Nefedov, Mikhail
Nutter, Lauryl M.
Pavlovic, Guillaume
Peterson, Jane L.
Pollock, Jonathan
Ramirez-Solis, Ramiro
Rancourt, Derrick E.
Raspa, Marcello
Remacle, Jacques E.
Ringwald, Martin
Rosen, Barry
Rosenthal, Nadia
Rossant, Janet
Noppinger, Patricia Ruiz
Ryder, Ed
Schick, Joel Zupicich
Schnuetgen, Frank
Schofield, Paul
Seisenberger, Claudia
Selloum, Mohammed
Simpson, Elizabeth M.
Skarnes, William C.
Smedley, Damian
Stanford, William L.
Stewart, A. Francis
Stone, Kevin
Swan, Kate
Tadepally, Hamsa
Teboul, Lydia
Tocchini-Valentini, Glauco P.
Valenzuela, David
West, Anthony P.
Yamamura, Ken-ichi
Yoshinaga, Yuko
Wurst, Wolfgang
TI The mammalian gene function resource: the international knockout mouse
consortium
SO MAMMALIAN GENOME
LA English
DT Article
ID EMBRYONIC STEM-CELLS; GENOME
AB In 2007, the International Knockout Mouse Consortium (IKMC) made the ambitious promise to generate mutations in virtually every protein-coding gene of the mouse genome in a concerted worldwide action. Now, 5 years later, the IKMC members have developed high-throughput gene trapping and, in particular, gene-targeting pipelines and generated more than 17,400 mutant murine embryonic stem (ES) cell clones and more than 1,700 mutant mouse strains, most of them conditional. A common IKMC web portal (www.knockoutmouse.org) has been established, allowing easy access to this unparalleled biological resource. The IKMC materials considerably enhance functional gene annotation of the mammalian genome and will have a major impact on future biomedical research.
C1 [Bradley, Allan; Bottomley, Joanna; Bushell, Wendy; Houghton, Richard; Iyer, Vivek; Kennedy, Karen; Koutsourakis, Manousos; Mujica, Alejandro O.; Ramirez-Solis, Ramiro; Rosen, Barry; Ryder, Ed; Skarnes, William C.; Smedley, Damian; West, Anthony P.] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
[Anastassiadis, Konstantinos; Stewart, A. Francis] Tech Univ Dresden, Biotechnol Ctr BIOTEC, D-01307 Dresden, Germany.
[Ayadi, Abdelkader; Birling, Marie-Christine; Herault, Yann; Pavlovic, Guillaume; Selloum, Mohammed] Inst Clin Souris, F-67404 Illkirch Graffenstaden, France.
[Ayadi, Abdelkader; Birling, Marie-Christine; Herault, Yann; Pavlovic, Guillaume; Selloum, Mohammed] Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France.
[Battey, James F.; Collins, Francis S.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA.
[Bell, Cindy; Swan, Kate] Genome Canada, Ottawa, ON K2P 1P1, Canada.
[Brown, Steve D.; Fray, Martin; Teboul, Lydia] MRC Harwell, Mammalian Genet Unit, Didcot OX11 0RD, Oxon, England.
[Buerger, Antje; Friedel, Roland H.; Hansen, Jens; Hoerlein, Andreas; Kaloff, Cornelia; Schick, Joel Zupicich; Seisenberger, Claudia; Wurst, Wolfgang] Tech Univ Munich, Helmholtz Zentrum Munchen, Inst Dev Genet, D-85764 Neuherberg, Germany.
[Bult, Carol J.; Eppig, Janan T.; Kadin, James A.; Mason, Jeremy; Ringwald, Martin; Stone, Kevin; Tadepally, Hamsa] Jackson Lab, Bar Harbor, ME 04609 USA.
[Desaintes, Christian; Remacle, Jacques E.] DG Res & Innovat, European Commiss, B-1049 Brussels, Belgium.
[Doe, Brendan; Raspa, Marcello; Tocchini-Valentini, Glauco P.] CNR, Ist Biol Cellulare, I-00015 Rome, Italy.
[Economides, Aris; Frendewey, David; Mujica, Alejandro O.; Valenzuela, David] Regeneron Pharmaceut Inc, Velocigene Div, Tarrytown, NY 10591 USA.
[Finnell, Richard H.; McLeod, Michael P.] Texas A&M Inst Genom Med, College Stn, TX 77843 USA.
[Finnell, Richard H.] Univ Texas Austin, Austin, TX 78712 USA.
[Fletcher, Colin; Moore, Mark; Peterson, Jane L.] NIH, Bethesda, MD 20205 USA.
[Friedel, Roland H.] Mt Sinai Hosp, Icahn Med Inst, New York, NY 10029 USA.
[Grosveld, Frank G.] Erasmus MC, Dept Cell Biol, Ctr Biomed Genet, NL-3015 GE Rotterdam, Netherlands.
[Hicks, Geoffrey] Univ Manitoba, Manitoba Inst Cell Biol, Winnipeg, MB R3E OV9, Canada.
[de Angelis, Martin Hrabe; Marschall, Susan] Helmholtz Zentrum Munchen, Inst Expt Genet, D-85764 Neuherberg, Germany.
[Huylebroeck, Danny] Univ Leuven KU Leuven, Dept Dev & Regenerat, Fac Med, B-3000 Louvain, Belgium.
[de Jong, Pieter J.; Nefedov, Mikhail; Yoshinaga, Yuko] CHORI, Oakland, CA 94609 USA.
[Lloyd, K. C. Kent] Univ Calif Davis, Sch Vet Med, Mouse Biol Program, Davis, CA 95616 USA.
[McKerlie, Colin; Nutter, Lauryl M.; Rossant, Janet] Hosp Sick Children, SickKids Fdn, Res Inst, Toronto, ON M5G 2L3, Canada.
[von Melchner, Harald; Schnuetgen, Frank] Univ Frankfurt Med Sch, Dept Mol Haematol, D-60590 Frankfurt, Germany.
[Nagy, Andras] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Pollock, Jonathan] NIDA, Div Basic Neurosci & Res, Bethesda, MD 20892 USA.
[Rancourt, Derrick E.] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 1N4, Canada.
[Rosenthal, Nadia] EMBL, I-00015 Rome, Italy.
[Noppinger, Patricia Ruiz] Charite, Dept Vertebrate Genom, Ctr Cardiovasc Res, D-10115 Berlin, Germany.
[Schofield, Paul] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England.
[Simpson, Elizabeth M.] Univ British Columbia, Child & Family Res Inst, Dept Med Genet, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 4H4, Canada.
[Smedley, Damian] EBI, Cambridge CB10 1ST, England.
[Stanford, William L.] Ottawa Hosp Res Inst, Ottawa, ON K1N 6N5, Canada.
[Yamamura, Ken-ichi] Kumamoto Univ, Inst Resource Dev & Anal, Div Dev Genet, Ctr Anim Resources & Dev, Kumamoto 8600811, Japan.
[Wurst, Wolfgang] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Wurst, Wolfgang] Deutsch Zentrum Neurodegenerat Erkrankungen eV DZ, D-80336 Munich, Germany.
RP Bradley, A (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1HH, England.
EM abradley@sanger.ac.uk; wurst@helmholtz-muenchen.de
RI Pavlovic, Guillaume/C-9907-2013; Nagy, Andras/G-6465-2013; raspa,
marcello/M-6455-2014; Rosenthal, Nadia/H-4012-2013; Ruiz Noppinger,
Patricia/D-6418-2014; Anastassiadis, Konstantinos/A-8944-2010; Stewart,
A. Francis/E-7789-2010; Hansen, Jens/E-8791-2015; Rosenthal,
Nadia/O-7009-2015; Hrabe de Angelis, Martin/F-5531-2012; Herault,
Yann/B-5500-2012
OI Stanford, William/0000-0002-5813-8016; Huylebroeck,
Danny/0000-0003-4862-1079; Economides, Aris/0000-0002-6508-8942;
Friedel, Roland/0000-0002-7513-3604; Birling,
Marie-Christine/0000-0002-3372-8108; Rosenthal,
Nadia/0000-0002-7599-7365; /0000-0002-2796-5123; Pavlovic,
Guillaume/0000-0001-9122-4592; Frendewey, David/0000-0003-2305-3490;
raspa, marcello/0000-0002-3437-2430; Ruiz Noppinger,
Patricia/0000-0001-5617-8965; Anastassiadis,
Konstantinos/0000-0002-9814-0559; Hrabe de Angelis,
Martin/0000-0002-7898-2353; Herault, Yann/0000-0001-7049-6900
FU European Commission (EC) [LSHG-CT-2005-018931, Health-F4-2010-261492];
National Institutes of Health (NIH); Genome Canada; State of Texas
FX The authors thank the European Commission (EC, LSHG-CT-2005-018931,
Health-F4-2010-261492), the National Institutes of Health (NIH), Genome
Canada, and the State of Texas for funding.
NR 10
TC 93
Z9 94
U1 1
U2 16
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0938-8990
J9 MAMM GENOME
JI Mamm. Genome
PD OCT
PY 2012
VL 23
IS 9-10
SI SI
BP 580
EP 586
DI 10.1007/s00335-012-9422-2
PG 7
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 016TU
UT WOS:000309543200010
PM 22968824
ER
PT J
AU Laughlin, MR
Lloyd, KCK
Cline, GW
Wasserman, DH
AF Laughlin, Maren R.
Lloyd, K. C. Kent
Cline, Gary W.
Wasserman, David H.
TI NIH Mouse Metabolic Phenotyping Centers: the power of centralized
phenotyping
SO MAMMALIAN GENOME
LA English
DT Article
ID VENTRICULAR-FUNCTION; GLUCOSE-HOMEOSTASIS; IN-VIVO; MICE; STRAINS;
OBESITY
AB The Mouse Metabolic Phenotyping Centers (MMPCs) were founded in 2001 by the National Institutes of Health (NIH) to advance biomedical research by providing the scientific community with standardized, high-quality phenotyping services for mouse models of diabetes, obesity, and their complications. The intent is to allow researchers to take optimum advantage of the many new mouse models produced in labs and in high-throughput public efforts. The six MMPCs are located at universities around the country and perform complex metabolic tests in intact mice and hormone and analyte assays in tissues on a fee-for-service basis. Testing is subsidized by the NIH in order to reduce the barriers for mouse researchers. Although data derived from these tests belong to the researcher submitting mice or tissues, these data are archived after publication in a public database run by the MMPC Coordinating and Bioinformatics Unit. It is hoped that data from experiments performed in many mouse models of metabolic diseases, using standard protocols, will be useful in understanding the nature of these complex disorders. The current areas of expertise include energy balance and body composition, insulin action and secretion, whole-body and tissue carbohydrate and lipid metabolism, cardiovascular and renal function, and metabolic pathway kinetics. In addition to providing services, the MMPC staff provides expertise and advice to researchers, and works to develop and refine test protocols to best meet the community's needs in light of current scientific developments. Test technology is disseminated by publications and through annual courses.
C1 [Laughlin, Maren R.] NIDDKD, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA.
[Lloyd, K. C. Kent] Univ Calif Davis, Ctr Comparat Med, Sch Vet Med, Mouse Biol Program, Davis, CA 95616 USA.
[Cline, Gary W.] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06510 USA.
[Wasserman, David H.] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA.
[Wasserman, David H.] Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37212 USA.
RP Laughlin, MR (reprint author), NIDDKD, Div Diabet Endocrinol & Metab Dis, NIH, 6707 Democracy Blvd,Rm 787,MSC 5460, Bethesda, MD 20892 USA.
EM maren.laughlin@nih.gov
FU U24 Grants [DK059630, DK059632, DK059635, DK59637, DK076126, DK076169,
DK076174, DK092993, DK093000]
FX The MMPCs are supported by U24 Grants DK059630, DK059632, DK059635,
DK59637, DK076126, DK076169, DK076174, DK092993, and DK093000.
NR 16
TC 7
Z9 7
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0938-8990
J9 MAMM GENOME
JI Mamm. Genome
PD OCT
PY 2012
VL 23
IS 9-10
SI SI
BP 623
EP 631
DI 10.1007/s00335-012-9425-z
PG 9
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 016TU
UT WOS:000309543200014
PM 22940748
ER
PT J
AU Brown, SDM
Moore, MW
AF Brown, Steve D. M.
Moore, Mark W.
TI The International Mouse Phenotyping Consortium: past and future
perspectives on mouse phenotyping
SO MAMMALIAN GENOME
LA English
DT Article
ID FUNCTIONAL ANNOTATION; RESOURCE; GENOME; EUROPHENOME; MICROSCOPY;
MORPHOLOGY; EMPRESS
AB Determining the function of all mammalian genes remains a major challenge for the biomedical science community in the 21st century. The goal of the International Mouse Phenotyping Consortium (IMPC) over the next 10 years is to undertake broad-based phenotyping of 20,000 mouse genes, providing an unprecedented insight into mammalian gene function. This short article explores the drivers for large-scale mouse phenotyping and provides an overview of the aims and processes involved in IMPC mouse production and phenotyping.
C1 [Brown, Steve D. M.] MRC Harwell, MRC Mammalian Genet Unit, Didcot OX11 0RD, Oxon, England.
[Moore, Mark W.] NHGRI, Int Mouse Phenotyping Consortium, NIH, Bethesda, MD 20892 USA.
RP Brown, SDM (reprint author), MRC Harwell, MRC Mammalian Genet Unit, Didcot OX11 0RD, Oxon, England.
EM s.brown@har.mrc.ac.uk
FU Medical Research Council [MC_U142684172, MC_U142684175]; NHGRI NIH HHS
[U54 HG006348]; NIH HHS [U42 OD011174]
NR 18
TC 90
Z9 90
U1 1
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0938-8990
J9 MAMM GENOME
JI Mamm. Genome
PD OCT
PY 2012
VL 23
IS 9-10
SI SI
BP 632
EP 640
DI 10.1007/s00335-012-9427-x
PG 9
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 016TU
UT WOS:000309543200015
PM 22940749
ER
PT J
AU Weyemi, U
Dupuy, C
AF Weyemi, Urbain
Dupuy, Corinne
TI The emerging role of ROS-generating NADPH oxidase NOX4 in DNA-damage
responses
SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH
LA English
DT Article
DE NADPH oxidases; NOX4; Reactive oxygen species (ROS); DNA damage; Genomic
instability; Oxidative stress; Inflammation; Cancer
ID SMOOTH-MUSCLE-CELLS; REACTIVE OXYGEN; HYDROGEN-PEROXIDE; CRITICAL
MEDIATOR; OXIDATIVE STRESS; NOX/DUOX FAMILY; NAD(P)H OXIDASE;
PLASMA-MEMBRANE; DUAL OXIDASE; CLONING
AB The human genome is continuously exposed to such potentially deleterious agents as the highly reactive molecules known as reactive oxygen species (ROS). ROS include superoxide anions (O-2(-)) and hydrogen peroxide (H2O2). Over the last decade, the ROS-generating NADPH oxidases (NOXs) have been recognized as one of the main sources of ROS production in numerous human cell types. In addition to regulating normal physiological redox-dependent processes, the NOXs are involved in cellular oxidative stress. In contrast to the other NOXs, the NADPH oxidase NOX4 exists in the immediate environment of the nucleus. There is accumulating evidence for the involvement of NOX4-derived ROS in genomic instability as well as in cancer and other inflammation-related diseases. We recently showed that NOX4 plays a critical role in oncogenic Ras-induced DNA damage. Here we reflect upon the growing awareness of NOX4, review its role in inducing genomic instability, and call attention to its possible role in nuclear redox-sensitive mechanisms underlying DNA-damage signaling and repair. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Dupuy, Corinne] Univ Paris Sud, Inst Gustave Roussy, CNRS, UMR 8200, F-94805 Villejuif, France.
[Weyemi, Urbain] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA.
RP Dupuy, C (reprint author), Univ Paris Sud, Inst Gustave Roussy, CNRS, UMR 8200, 114 Rue Edouard Vaillant, F-94805 Villejuif, France.
EM dupuy@igr.fr
RI Weyemi, Urbain/E-2083-2016
NR 45
TC 33
Z9 34
U1 0
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5742
J9 MUTAT RES-REV MUTAT
JI Mutat. Res.-Rev. Mutat. Res.
PD OCT-DEC
PY 2012
VL 751
IS 2
BP 77
EP 81
DI 10.1016/j.mrrev.2012.04.002
PG 5
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 017UW
UT WOS:000309617500001
PM 22580379
ER
PT J
AU Izzotti, A
Cartiglia, C
Steele, VE
De Flora, S
AF Izzotti, Alberto
Cartiglia, Cristina
Steele, Vernon E.
De Flora, Silvio
TI MicroRNAs as targets for dietary and pharmacological inhibitors of
mutagenesis and carcinogenesis
SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH
LA English
DT Review
DE MicroRNA; Chemoprevention; Dietary agents; Pharmacological agents
ID DNA-DAMAGE RESPONSE; PANCREATIC-CANCER CELLS; CIGARETTE-SMOKE;
PROSTATE-CANCER; DOWN-REGULATION; EXPRESSION PROFILES; GENE-EXPRESSION;
RETINOIC ACID; BREAST-CANCER; UP-REGULATION
AB MicroRNAs (miRNAs) have been implicated in many biological processes, cancer, and other diseases. In addition, miRNAs are dysregulated following exposure to toxic and genotoxic agents. Here we review studies evaluating modulation of miRNAs by dietary and pharmacological agents, which could potentially be exploited for inhibition of mutagenesis and carcinogenesis. This review covers natural agents, including vitamins, oligoelements, polyphenols, isoflavones, indoles, isothiocyanates, phospholipids, saponins, anthraquinones and polyunsaturated fatty acids, and synthetic agents, including thiols, nuclear receptor agonists, histone deacetylase inhibitors, antiinflammatory drugs, and selective estrogen receptor modulators. As many as 145 miRNAs, involved in the control of a variety of carcinogenesis mechanisms, were modulated by these agents, either individually or in combination. Most studies used cancer cells in vitro with the goal of modifying their phenotype by changing miRNA expression profiles. In vivo studies evaluated regulation of miRNAs by chemopreventive agents in organs of mice and rats, either untreated or exposed to carcinogens, with the objective of evaluating their safety and efficacy. The tissue specificity of miRNAs could be exploited for the chemoprevention of site-specific cancers, and the study of polymorphic miRNAs is expected to predict the individual response to chemopreventive agents as a tool for developing new prevention strategies. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Izzotti, Alberto; Cartiglia, Cristina; De Flora, Silvio] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy.
[Steele, Vernon E.] NCI, Bethesda, MD 20892 USA.
RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy.
EM sdf@unige.it
OI izzotti, alberto/0000-0002-8588-0347
FU U.S. National Cancer Institute (NCI) [NO1-CN53301]; Associazione
Italiana per la Ricerca sul Cancro (AIRC) [8909]
FX This work was supported by the U.S. National Cancer Institute (NCI,
contract NO1-CN53301) and by the Associazione Italiana per la Ricerca
sul Cancro (AIRC, grant no. 8909). We thank Dr. Patrizio Arrigo
(National Research Council, Genoa, Italy) for providing 3D Dicer
structures.
NR 121
TC 23
Z9 23
U1 0
U2 21
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5742
J9 MUTAT RES-REV MUTAT
JI Mutat. Res.-Rev. Mutat. Res.
PD OCT-DEC
PY 2012
VL 751
IS 2
BP 287
EP 303
DI 10.1016/j.mrrev.2012.05.004
PG 17
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 017UW
UT WOS:000309617500006
PM 22683846
ER
PT J
AU Rocha, CT
Kesari, A
Punetha, J
Bonnemann, C
Hoffman, E
AF Rocha, C. Tesi
Kesari, A.
Punetha, J.
Bonnemann, C.
Hoffman, E.
TI Next-generation sequencing approach for muscular dystrophy diagnosis:
Advantages and pitfalls of new diagnostic technology
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 17th International Congress of the World-Muscle-Society (WMS)
CY OCT 09-13, 2012
CL Perth, AUSTRALIA
SP World Muscle Soc (WMS)
C1 [Rocha, C. Tesi; Kesari, A.; Punetha, J.; Hoffman, E.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Bonnemann, C.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2012
VL 22
IS 9-10
BP 807
EP 807
DI 10.1016/j.nmd.2012.06.021
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 024IT
UT WOS:000310103600012
ER
PT J
AU Donkervoort, S
Medne, L
Schindler, A
Pappa, MB
Bonnemann, CG
AF Donkervoort, S.
Medne, L.
Schindler, A.
Pappa, M. B.
Bonnemann, C. G.
TI Ethical, social, legal implications of clinical and research genetic
testing in the neuromuscular setting: A case study approach
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 17th International Congress of the World-Muscle-Society (WMS)
CY OCT 09-13, 2012
CL Perth, AUSTRALIA
SP World Muscle Soc (WMS)
C1 [Donkervoort, S.; Schindler, A.; Bonnemann, C. G.] NINDS, NIH, Neurogenet Branch, Bethesda, MD 20892 USA.
[Medne, L.] Childrens Hosp Philadelphia, Dept Neurol, Philadelphia, PA 19104 USA.
[Pappa, M. B.] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2012
VL 22
IS 9-10
BP 808
EP 808
DI 10.1016/j.nmd.2012.06.023
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 024IT
UT WOS:000310103600014
ER
PT J
AU Cho, A
Malicdan, MC
Nonaka, I
Hayashi, YK
Nishino, I
Noguchi, S
AF Cho, A.
Malicdan, M. C.
Nonaka, I.
Hayashi, Y. K.
Nishino, I.
Noguchi, S.
TI Muscle atrophy in the GNE myopathy mouse model is associated with
oxidative stress
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 17th International Congress of the World-Muscle-Society (WMS)
CY OCT 09-13, 2012
CL Perth, AUSTRALIA
SP World Muscle Soc (WMS)
C1 [Cho, A.; Nonaka, I.; Hayashi, Y. K.; Nishino, I.; Noguchi, S.] Natl Ctr Neurol & Psychiat, Tokyo, Japan.
[Malicdan, M. C.] NIH, Bethesda, MD 20892 USA.
RI Malicdan, May Christine/F-2806-2013
NR 0
TC 1
Z9 1
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2012
VL 22
IS 9-10
BP 816
EP 816
DI 10.1016/j.nmd.2012.06.049
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 024IT
UT WOS:000310103600040
ER
PT J
AU Dastgir, J
Donkervoort, S
Meilleur, K
Wheeler, P
Laing, NG
Bonnemann, CG
AF Dastgir, J.
Donkervoort, S.
Meilleur, K.
Wheeler, P.
Laing, N. G.
Bonnemann, C. G.
TI MYH7 gene mutation related myopathies of skeletal and cardiac muscle
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 17th International Congress of the World-Muscle-Society (WMS)
CY OCT 09-13, 2012
CL Perth, AUSTRALIA
SP World Muscle Soc (WMS)
C1 [Dastgir, J.; Donkervoort, S.; Meilleur, K.; Bonnemann, C. G.] NINDS, NIH, Neurogenet Branch, Bethesda, MD 20892 USA.
[Wheeler, P.] Nemours Childrens Clin, Div Genet, Orlando, FL USA.
[Laing, N. G.] Univ Western Australia, Med Res Ctr, Nedlands, WA 6009, Australia.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2012
VL 22
IS 9-10
BP 817
EP 817
DI 10.1016/j.nmd.2012.06.053
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 024IT
UT WOS:000310103600044
ER
PT J
AU Rocha, CT
Taylor, M
Chang, T
Reyes, C
Winder, T
Moore, S
Bonnemann, C
Nelson, K
AF Rocha, C. Tesi
Taylor, M.
Chang, T.
Reyes, C.
Winder, T.
Moore, S.
Bonnemann, C.
Nelson, K.
TI Novel homozygous stop mutation in alphaB crystallin: Expanding the
phenotype
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 17th International Congress of the World-Muscle-Society (WMS)
CY OCT 09-13, 2012
CL Perth, AUSTRALIA
SP World Muscle Soc (WMS)
C1 [Rocha, C. Tesi; Taylor, M.; Chang, T.; Reyes, C.; Nelson, K.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Winder, T.] Prevent Genet, Marshfield, WI USA.
[Moore, S.] Univ Iowa, Iowa City, IA USA.
[Bonnemann, C.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2012
VL 22
IS 9-10
BP 821
EP 821
DI 10.1016/j.nmd.2012.06.066
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 024IT
UT WOS:000310103600055
ER
PT J
AU Yavuz, AO
Goldfarb, L
Tuncer, O
Dursun, M
Olive, M
Deymeer, F
Parman, Y
Tuncay, R
Serdaroglu-Oflazer, P
AF Yavuz, A. Ozturk
Goldfarb, L.
Tuncer, O.
Dursun, M.
Olive, M.
Deymeer, F.
Parman, Y.
Tuncay, R.
Serdaroglu-Oflazer, P.
TI Muscle MRI in a filaminopathy family: Involvement of paraspinals is
earlier and more severe than of thigh muscles
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 17th International Congress of the World-Muscle-Society (WMS)
CY OCT 09-13, 2012
CL Perth, AUSTRALIA
SP World Muscle Soc (WMS)
C1 [Yavuz, A. Ozturk] Istanbul Gaziosmanpasa Hosp, Istanbul, Turkey.
[Goldfarb, L.] NIH, Clin Neurogenet Unit, Bethesda, MD 20892 USA.
[Tuncer, O.] Bilim Univ, Fac Med, Istanbul, Turkey.
[Dursun, M.; Deymeer, F.; Parman, Y.; Tuncay, R.; Serdaroglu-Oflazer, P.] Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey.
[Olive, M.] IDIBELL Hosp Univ Bellvitge, Inst Neuropatol, Barcelona, Spain.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2012
VL 22
IS 9-10
BP 821
EP 822
DI 10.1016/j.nmd.2012.06.068
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 024IT
UT WOS:000310103600057
ER
PT J
AU Dastgir, J
Bharucha-Goebel, D
Medne, L
Donkervoort, S
Meilleur, K
Bonnemann, CG
AF Dastgir, J.
Bharucha-Goebel, D.
Medne, L.
Donkervoort, S.
Meilleur, K.
Bonnemann, C. G.
TI Muscle ultrasound as a consistent imaging marker for RYR1 related
myopathies
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 17th International Congress of the World-Muscle-Society (WMS)
CY OCT 09-13, 2012
CL Perth, AUSTRALIA
SP World Muscle Soc (WMS)
C1 [Dastgir, J.; Donkervoort, S.; Meilleur, K.; Bonnemann, C. G.] NINDS, NIH, Neurogenet Branch, Bethesda, MD 20892 USA.
[Bharucha-Goebel, D.; Medne, L.] Childrens Hosp Philadelphia, Dept Neurol, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2012
VL 22
IS 9-10
BP 824
EP 824
DI 10.1016/j.nmd.2012.06.078
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 024IT
UT WOS:000310103600067
ER
PT J
AU Butterfield, RJ
Bonnemann, C
Weiss, RB
AF Butterfield, R. J.
Bonnemann, C.
Weiss, R. B.
TI Transcriptome profiling identifies key regulators of molecular
pathogenesis in collagen VI myopathies
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 17th International Congress of the World-Muscle-Society (WMS)
CY OCT 09-13, 2012
CL Perth, AUSTRALIA
SP World Muscle Soc (WMS)
C1 [Butterfield, R. J.; Weiss, R. B.] Univ Utah, Salt Lake City, UT USA.
[Bonnemann, C.] Natl Inst Neurol Disorders & Stroke, NIH, Neuromuscular & Neurogenet Disorders Childhood Se, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2012
VL 22
IS 9-10
BP 828
EP 828
DI 10.1016/j.nmd.2012.06.090
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 024IT
UT WOS:000310103600079
ER
PT J
AU Donkervoort, S
Hu, Y
Dastgir, J
Meilleur, K
Zou, Y
Foley, AR
Harper, A
Bonnemann, CG
AF Donkervoort, S.
Hu, Y.
Dastgir, J.
Meilleur, K.
Zou, Y.
Foley, A. R.
Harper, A.
Bonnemann, C. G.
TI Possible mutation dependent mechanisms for intra-familial variation of
severity in Collagen VI-Related Myopathies (COL6-RM)
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 17th International Congress of the World-Muscle-Society (WMS)
CY OCT 09-13, 2012
CL Perth, AUSTRALIA
SP World Muscle Soc (WMS)
C1 [Donkervoort, S.; Hu, Y.; Dastgir, J.; Meilleur, K.; Zou, Y.; Bonnemann, C. G.] NINDS, NIH, Neurogenet Branch, Bethesda, MD 20892 USA.
[Foley, A. R.] UCL, Inst Child Hlth, London, England.
[Foley, A. R.] Great Ormond St Hosp Sick Children, London WC1N 3JH, England.
[Harper, A.] Jeff Gordon Childrens Hosp, Levine Childrens Hosp, Charlotte, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2012
VL 22
IS 9-10
BP 829
EP 829
DI 10.1016/j.nmd.2012.06.092
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 024IT
UT WOS:000310103600081
ER
PT J
AU Donkervoort, S
Tesi-Rocha, C
Schreiber, A
Schindler, A
Leach, ME
Zurcher, V
Hu, Y
Mankodi, A
Friedman, NR
Bonnemann, CG
AF Donkervoort, S.
Tesi-Rocha, C.
Schreiber, A.
Schindler, A.
Leach, M. E.
Zurcher, V.
Hu, Y.
Mankodi, A.
Friedman, N. R.
Bonnemann, C. G.
TI 'Double Trouble': Diagnostic challenges in DMD in patients with an
additional hereditary skeletal dysplasia
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 17th International Congress of the World-Muscle-Society (WMS)
CY OCT 09-13, 2012
CL Perth, AUSTRALIA
SP World Muscle Soc (WMS)
C1 [Donkervoort, S.; Schindler, A.; Hu, Y.; Mankodi, A.; Bonnemann, C. G.] NINDS, NIH, Neurogenet Branch, Bethesda, MD 20892 USA.
[Tesi-Rocha, C.; Leach, M. E.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Schreiber, A.; Zurcher, V.] Cleveland Clin, Genom Med Inst, Cleveland, OH 44106 USA.
[Friedman, N. R.] Cleveland Clin, Ctr Pediat Neurol, Cleveland, OH 44106 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2012
VL 22
IS 9-10
BP 836
EP 837
DI 10.1016/j.nmd.2012.06.116
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 024IT
UT WOS:000310103600105
ER
PT J
AU Bonnemann, CG
AF Boennemann, C. G.
TI Congenital myopathies: Blurring the boundaries, sharpening the focus
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 17th International Congress of the World-Muscle-Society (WMS)
CY OCT 09-13, 2012
CL Perth, AUSTRALIA
SP World Muscle Soc (WMS)
C1 [Boennemann, C. G.] NINDS, NIH, Neuromuscular & Neurogenet Disorders Childhood Se, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2012
VL 22
IS 9-10
BP 838
EP 838
DI 10.1016/j.nmd.2012.06.121
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 024IT
UT WOS:000310103600110
ER
PT J
AU Chauveau, C
Bonnemann, C
Alexandrovich, A
Kho, AL
Julien, C
Foley, R
Vihola, A
Udd, B
Samuels, ME
Gautel, M
Ferreiro, A
AF Chauveau, C.
Boennemann, C.
Alexandrovich, A.
Kho, A. L.
Julien, C.
Foley, R.
Vihola, A.
Udd, B.
Samuels, M. E.
Gautel, M.
Ferreiro, A.
TI Ventricular noncompaction with arthrogryposis due to TTN compound
heterozygosity leading to loss of functional TTN kinase domain
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 17th International Congress of the World-Muscle-Society (WMS)
CY OCT 09-13, 2012
CL Perth, AUSTRALIA
SP World Muscle Soc (WMS)
C1 [Chauveau, C.; Julien, C.; Ferreiro, A.] UPMC, INSERM, GH Pitie Salpetriere, Grp Myol,UMR787, Paris, France.
[Boennemann, C.; Foley, R.] NIH, Bethesda, MD 20892 USA.
[Alexandrovich, A.; Kho, A. L.; Gautel, M.] Kings Coll London, Div Cardiovasc, London WC2R 2LS, England.
[Alexandrovich, A.; Kho, A. L.; Gautel, M.] Kings Coll London, Randall Div Cell & Mol Biophys, London WC2R 2LS, England.
[Vihola, A.; Udd, B.] Univ Helsinki, Folkhalsan Inst Genet, Helsinki, Finland.
[Vihola, A.; Udd, B.] Univ Helsinki, Dept Med Genet, Haartman Inst, Helsinki, Finland.
[Samuels, M. E.] Univ Montreal, Ctr Rech, CHU Ste Justine, Montreal, PQ, Canada.
RI Kho, Ay Lin/M-4214-2013; Ferreiro, Ana/F-5371-2011
OI Kho, Ay Lin/0000-0002-9753-2091;
NR 0
TC 0
Z9 0
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2012
VL 22
IS 9-10
BP 840
EP 840
DI 10.1016/j.nmd.2012.06.127
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 024IT
UT WOS:000310103600116
ER
PT J
AU Yonekawa, T
Malicdan, MC
Nonaka, I
Hayashi, YK
Mine, T
Yamamoto, T
Nishino, I
Noguchi, S
AF Yonekawa, T.
Malicdan, M. C.
Nonaka, I.
Hayashi, Y. K.
Mine, T.
Yamamoto, T.
Nishino, I.
Noguchi, S.
TI Sialyllactose reversed myopathic phenotype in symptomatic GNE myopathy
model mice
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 17th International Congress of the World-Muscle-Society (WMS)
CY OCT 09-13, 2012
CL Perth, AUSTRALIA
SP World Muscle Soc (WMS)
C1 [Nonaka, I.; Hayashi, Y. K.; Nishino, I.; Noguchi, S.] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Neuromuscular Res, Tokyo, Japan.
[Malicdan, M. C.] NHGRI, NIH, Med Genet Branch, Bethesda, MD 20892 USA.
[Mine, T.; Yamamoto, T.] Japan Tobacco Inc, Glycotechnol Business Unit, Tokyo, Japan.
RI Malicdan, May Christine/F-2806-2013
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2012
VL 22
IS 9-10
BP 849
EP 849
DI 10.1016/j.nmd.2012.06.155
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 024IT
UT WOS:000310103600144
ER
PT J
AU Noguchi, S
Ogawa, M
Malicdan, MC
Nishino, I
AF Noguchi, S.
Ogawa, M.
Malicdan, M. C.
Nishino, I.
TI Allele-specific knockdown to mutant mRNA retrieves cellular function in
fibroblasts with point-mutated Ullrich CMD
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 17th International Congress of the World-Muscle-Society (WMS)
CY OCT 09-13, 2012
CL Perth, AUSTRALIA
SP World Muscle Soc (WMS)
C1 [Noguchi, S.; Ogawa, M.; Nishino, I.] NCNP, Natl Inst Neurosci, Tokyo, Japan.
[Malicdan, M. C.] NHGRI, NIH, Med Genet Branch, Bethesda, MD 20892 USA.
RI Malicdan, May Christine/F-2806-2013
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2012
VL 22
IS 9-10
BP 867
EP 867
DI 10.1016/j.nmd.2012.06.215
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 024IT
UT WOS:000310103600204
ER
PT J
AU Meilleur, KG
Pierson, TM
Jain, M
Donkervoort, S
Markello, T
Wolfe, L
Accardi, J
Adams, D
Sincan, M
Fuentes-Fajardo, K
Cherukuri, PF
Cruz, P
Bajraktari, I
Lehky, T
Teer, JK
Mullikin, JC
Gahl, WA
Boerkoel, CF
Tifft, CJ
Bonnemann, CG
AF Meilleur, K. G.
Pierson, T. M.
Jain, M.
Donkervoort, S.
Markello, T.
Wolfe, L.
Accardi, J.
Adams, D.
Sincan, M.
Fuentes-Fajardo, K.
Cherukuri, P. F.
Cruz, P.
Bajraktari, I.
Lehky, T.
Teer, J. K.
Mullikin, J. C.
Gahl, W. A.
Boerkoel, C. F.
Tifft, C. J.
Bonnemann, C. G.
TI Two sibs with early onset myopathy with areflexia, respiratory distress,
and dysphagia (EMARDD) due to homozygous exon 7 deletion in MEGF10
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 17th International Congress of the World-Muscle-Society (WMS)
CY OCT 09-13, 2012
CL Perth, AUSTRALIA
SP World Muscle Soc (WMS)
C1 [Meilleur, K. G.; Pierson, T. M.; Donkervoort, S.; Bajraktari, I.; Lehky, T.; Bonnemann, C. G.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Markello, T.; Wolfe, L.; Accardi, J.; Adams, D.; Sincan, M.; Fuentes-Fajardo, K.; Cherukuri, P. F.; Teer, J. K.; Gahl, W. A.; Boerkoel, C. F.; Tifft, C. J.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Cruz, P.; Mullikin, J. C.] NIH, NIH Intramural Sequencing Ctr, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2012
VL 22
IS 9-10
BP 870
EP 871
DI 10.1016/j.nmd.2012.06.225
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 024IT
UT WOS:000310103600214
ER
PT J
AU Collins, J
Vandyke, R
Fenchel, M
McCallum, M
Volker, S
Foley, AR
Muntoni, F
Stehling, F
Schara, U
Rutkowski, A
Deconinck, N
Sawnani, H
Bonnemann, CG
Amin, R
AF Collins, J.
Vandyke, R.
Fenchel, M.
McCallum, M.
Volker, S.
Foley, A. R.
Muntoni, F.
Stehling, F.
Schara, U.
Rutkowski, A.
Deconinck, N.
Sawnani, H.
Bonnemann, C. G.
Amin, R.
TI Percent predicted forced vital capacity is a viable outcome measure in
Laminin alpha 2-Deficient congenital muscular dystrophy
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 17th International Congress of the World-Muscle-Society (WMS)
CY OCT 09-13, 2012
CL Perth, AUSTRALIA
SP World Muscle Soc (WMS)
C1 [Collins, J.; Vandyke, R.; Fenchel, M.; Sawnani, H.; Amin, R.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[McCallum, M.; Volker, S.] Inst Med Genet, Newcastle Upon Tyne, Tyne & Wear, England.
[Foley, A. R.; Muntoni, F.] Inst Child Hlth, Dubowitz Neuromuscular Ctr, London, England.
[Stehling, F.] Univ Hosp Essen, Essen, Germany.
[Schara, U.] Univ Essen Gesamthsch, Essen, Germany.
[Rutkowski, A.] Cure CMD, Los Angeles, CA USA.
[Rutkowski, A.] Kaiser SCPMG, Los Angeles, CA USA.
[Deconinck, N.] Univ Hosp Ghent, Ghent, Belgium.
[Deconinck, N.] Univ Libre Brussels, Hop Univ Enfants Reine Fabiola, Brussels, Belgium.
[Bonnemann, C. G.] NIH, Bethesda, MD 20892 USA.
RI Szczesniak, Rhonda/M-4446-2015
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2012
VL 22
IS 9-10
BP 893
EP 894
DI 10.1016/j.nmd.2012.06.298
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 024IT
UT WOS:000310103600287
ER
PT J
AU Meilleur, KG
Jain, M
Kim, E
Hynan, L
Shieh, CY
Waite, M
Duong, T
Glanzman, A
Main, M
Rose, K
McGuire, M
Bendixen, R
Foley, R
Donkervoort, S
Schindler, A
Kokkinis, A
Hartnett, EJ
Leach, M
Dastgir, J
North, K
Muntoni, F
Rutkowski, A
Bonnemann, CG
AF Meilleur, K. G.
Jain, M.
Kim, E.
Hynan, L.
Shieh, C. Y.
Waite, M.
Duong, T.
Glanzman, A.
Main, M.
Rose, K.
McGuire, M.
Bendixen, R.
Foley, R.
Donkervoort, S.
Schindler, A.
Kokkinis, A.
Hartnett, E. J.
Leach, M.
Dastgir, J.
North, K.
Muntoni, F.
Rutkowski, A.
Bonnemann, C. G.
TI Clinical outcome measures in Collagen 6 (COL6) and Laminin alpha
2(LAMA2) related congenital muscular dystrophy
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 17th International Congress of the World-Muscle-Society (WMS)
CY OCT 09-13, 2012
CL Perth, AUSTRALIA
SP World Muscle Soc (WMS)
C1 [Meilleur, K. G.; Jain, M.; Shieh, C. Y.; Waite, M.; Donkervoort, S.; Schindler, A.; Kokkinis, A.; Hartnett, E. J.; Dastgir, J.; Bonnemann, C. G.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Kim, E.] CureCMD, San Francisco, CA USA.
[Hynan, L.] Dallas Childrens Med Ctr, Dallas, TX USA.
[Duong, T.; Leach, M.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Glanzman, A.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Main, M.; Foley, R.; Muntoni, F.] UCL, London, England.
[Rose, K.; North, K.] Insitute Neurosci & Muscle Res, Westmead, NSW, Australia.
[McGuire, M.] Cincinatti Childrens Hosp, Cincinnati, OH USA.
[Bendixen, R.] Univ Florida, Gainesville, FL USA.
[Rutkowski, A.] Kaiser Permanente, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2012
VL 22
IS 9-10
BP 893
EP 893
DI 10.1016/j.nmd.2012.06.296
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 024IT
UT WOS:000310103600285
ER
PT J
AU Leach, ME
Collins, J
Bonnemann, CG
AF Leach, M. E.
Collins, J.
Bonnemann, C. G.
TI Reported incidence of orthopedic and cardiopulmonary complications in
patients with congenital muscle disease
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT 17th International Congress of the World-Muscle-Society (WMS)
CY OCT 09-13, 2012
CL Perth, AUSTRALIA
SP World Muscle Soc (WMS)
C1 [Leach, M. E.] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA.
[Collins, J.] Cincinnati Childrens Hosp Med Ctr, Div Neurol, Cincinnati, OH USA.
[Bonnemann, C. G.] NINDS, NIH, Neurogenet Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD OCT
PY 2012
VL 22
IS 9-10
BP 895
EP 895
DI 10.1016/j.nmd.2012.06.303
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 024IT
UT WOS:000310103600292
ER
PT J
AU Tsai, WXL
Forbes, JG
Wang, K
AF Tsai, Wanxia Li
Forbes, Jeffrey G.
Wang, Kuan
TI Engineering of an elastic scaffolding polyprotein based on an
SH3-binding intrinsically disordered titin PEVK module
SO PROTEIN EXPRESSION AND PURIFICATION
LA English
DT Article
DE Tandem repeat biopolymer; Functionalized elastomer
ID SPIDER DRAGLINE SILK; TETRACYSTEINE-TAGGED PROTEINS; CONTROLLED
DRUG-DELIVERY; HIGH-LEVEL EXPRESSION; POLYPROLINE-II HELIX; CODON USAGE
BIAS; ESCHERICHIA-COLI; PICHIA-PASTORIS; MASS-SPECTROMETRY;
GENE-EXPRESSION
AB Titin is a large elastic protein found in muscle that maintains the elasticity and structural integrity of the sarcomere. The PEVK region of titin is intrinsically disordered, highly elastic and serves as a hub to bind signaling proteins. Systematic investigation of the structure and affinity profile of the PEVK region will provide important information about the functions of titin. Since PEVK is highly heterogeneous due to extensive differential splicing from more than one hundred exons, we engineered and expressed polyproteins that consist of a defined number of identical single exon modules. These customized polyproteins reduce heterogeneity, amplify interactions of less dominant modules, and most importantly, provide tags for atomic force microscopy and allow more readily interpretable data from single-molecule techniques.
Expression and purification of recombinant polyprotein with repeat regions presented many technical challenges: recombination events in tandem repeats of identical DNA sequences exacerbated by high GC content, toxicity of polymer plasmid and expressed protein to the bacteria; early truncation of proteins expressed with different numbers of modules; and extreme sensitivity to proteolysis. We have investigated a number of in vitro and in vivo bacterial and yeast expression systems, as well as baculoviral systems as potential solutions to these problems. We successfully expressed and purified in gram quantities a polyprotein derived from human titin exon 172 using Pichia pastoris yeast. This study provides valuable insights into the technical challenges regarding the engineering and purification of a tandem repeat sequence of an intrinsically disordered biopolymer. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Tsai, Wanxia Li; Forbes, Jeffrey G.; Wang, Kuan] NIAMS, Muscle Prote & Nanotechnol Sect, Muscle Biol Lab, NIH,DHHS, Bethesda, MD 20892 USA.
RP Wang, K (reprint author), Acad Sinica, Inst Chem, 128 Acad Rd,Sec 2, Taipei 115, Taiwan.
EM liwan@mail.nih.gov; jgf@twicinc.com; Wangk@gate.sinica.edu.tw
FU Intramural NIH HHS [Z99 AR999999]
NR 102
TC 2
Z9 2
U1 1
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-5928
EI 1096-0279
J9 PROTEIN EXPRES PURIF
JI Protein Expr. Purif.
PD OCT
PY 2012
VL 85
IS 2
BP 187
EP 199
DI 10.1016/j.pep.2012.08.003
PG 13
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 020CP
UT WOS:000309786600005
PM 22910563
ER
PT J
AU Sakata, R
Kleinerman, RA
Mabuchi, K
Stovall, M
Smith, SA
Weathers, R
Wactawski-Wende, J
Cookfair, DL
Boice, JD
Inskip, PD
AF Sakata, Ritsu
Kleinerman, Ruth A.
Mabuchi, Kiyohiko
Stovall, Marilyn
Smith, Susan A.
Weathers, Rita
Wactawski-Wende, Jean
Cookfair, Diane L.
Boice, John D., Jr.
Inskip, Peter D.
TI Cancer Mortality Following Radiotherapy for Benign Gynecologic Disorders
SO RADIATION RESEARCH
LA English
DT Article
ID ATOMIC-BOMB SURVIVORS; BREAST-CANCER; PELVIC RADIOTHERAPY;
MULTIPLE-MYELOMA; CERVICAL-CANCER; UTERINE CORPUS; LEUKEMIA RISK;
RADIATION; COHORT; LYMPHOMA
AB The purpose of this study is to quantify cancer mortality in relationship to organ-specific radiation dose among women irradiated for benign gynecologic disorders. Included in this study are 12,955 women treated for benign gynecologic disorders at hospitals in the Northeastern U.S. between 1925 and 1965; 9,770 women treated by radiation and 3,186 women treated by other methods. The average age at treatment was 45.9 years (range, 13-88 years), and the average follow-up period was 30.1 years (maximum, 69.9 years). Radiation doses to organs and active bone marrow were reconstructed by medical physicists using original radiotherapy records. The highest doses were received by the uterine cervix (median, 120 Gy) and uterine corpus (median, 34 Gy), followed by the bladder, rectum and colon (median, 1.7-7.2 Gy), with other abdominal organs receiving median doses <= 1 Gy and organs in the chest and head receiving doses <0.1 Gy. Standardized mortality rate ratios relative to the general U.S. population were calculated. Radiation-related risks were estimated in internal analyses using Poisson regression models. Mortality was significantly elevated among irradiated women for cancers of the uterine corpus, ovary, bladder, rectum, colon and brain, as well as for leukemia (exclusive of chronic lymphocytic leukemia) but not for cancer of the cervix, Hodgkin or non-Hodgkin lymphoma, multiple myeloma, or chronic lymphocytic leukemia. Evidence of a dose-response was seen for cancers of the ovary [excess relative risk (ERR) = 0.31/Gy, P < 0.001], bladder (ERR = 0.21/Gy, P = 0.02) and rectum (ERR = 0.23/Gy, P = 0.05) and suggested for colon (ERR = 0.09/Gy, P = 0.10), but not for cancers of the uterine corpus or brain nor for non-chronic lymphocytic leukemia. Relative risks of mortality due to cancers of the stomach, pancreas, liver and kidney were close to 1.0, with no evidence of dose-response over the range of 0-1.5 Gy. Breast cancer was not significantly associated with dose to the breast or ovary. Mortality due to cancers of heavily irradiated organs remained elevated up to 40 years after irradiation. Significantly elevated radiation-related risk was seen for cancers of organs proximal to the radiation source or fields (bladder, rectum and ovary), as well as for non-chronic lymphocytic leukemia. Our results corroborate those from previous studies that suggest that cells of the uterine cervix and lymphopoietic system are relatively resistant to the carcinogenic effects of radiation. Studies of women irradiated for benign gynecologic disorders, together with studies of women treated with higher doses of radiation for uterine cancers, provide quantitative information on cancer risks associated with a broad range of pelvic radiation exposures. (C) 2012 by Radiation Research Society
C1 [Sakata, Ritsu] Radiat Effects Res Fdn, Dept Epidemiol, Minami Ku, Hiroshima 7320815, Japan.
[Sakata, Ritsu; Kleinerman, Ruth A.; Mabuchi, Kiyohiko] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Stovall, Marilyn; Smith, Susan A.; Weathers, Rita] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA.
[Wactawski-Wende, Jean; Inskip, Peter D.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
[Cookfair, Diane L.] SUNY Buffalo, Sch Med, Dept Neurol, Buffalo, NY 14260 USA.
[Boice, John D., Jr.] Vanderbilt Univ, Sch Med, Dept Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA.
[Boice, John D., Jr.] Int Epidemiol Inst, Rockville, MD USA.
RP Sakata, R (reprint author), Radiat Effects Res Fdn, Dept Epidemiol, Minami Ku, 5-2 Hijiyama Pk, Hiroshima 7320815, Japan.
EM rsakata@rerf.or.jp
OI Kleinerman, Ruth/0000-0001-7415-2478
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health; Japanese Ministry of Health, Labour and
Welfare (MHLW); U.S. Department of Energy (DOE) [DE-HS0000031]
FX This study was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health. We are grateful for the substantial
contributions made by Dr. Joseph K. Wagoner (deceased) in developing
cohorts of women treated for benign gynecological disease in Connecticut
and Massachusetts, and by Drs. Richard R. Monson and George B. Hutchison
who, when at the Harvard School of Public Health, provided valuable
guidance and advice during the early years of study development and
conduct. We are also grateful for the support provided to Dr. Ritsu
Sakata by the Radiation Effects Research Foundation while she was a
Visiting Scientist at the National Cancer Institute. The Radiation
Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan, is a
private, non-profit foundation funded by the Japanese Ministry of
Health, Labour and Welfare (MHLW) and the U.S. Department of Energy
(DOE), the latter in part through DOE Award DE-HS0000031 to the National
Academy of Sciences. The views of the authors do not necessarily reflect
those of the two governments.
NR 40
TC 2
Z9 2
U1 0
U2 3
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
J9 RADIAT RES
JI Radiat. Res.
PD OCT
PY 2012
VL 178
IS 4
BP 266
EP 279
DI 10.1667/RR2845.1
PG 14
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 020EE
UT WOS:000309791000003
PM 22856888
ER
PT J
AU Johnson, CH
Patterson, AD
Krausz, KW
Kalinich, JF
Tyburski, JB
Kang, DW
Luecke, H
Gonzalez, FJ
Blakely, WF
Idle, JR
AF Johnson, Caroline H.
Patterson, Andrew D.
Krausz, Kristopher W.
Kalinich, John F.
Tyburski, John B.
Kang, Dong Wook
Luecke, Hans
Gonzalez, Frank J.
Blakely, William F.
Idle, Jeffrey R.
TI Radiation Metabolomics. 5. Identification of Urinary Biomarkers of
Ionizing Radiation Exposure in Nonhuman Primates by Mass
Spectrometry-Based Metabolomics
SO RADIATION RESEARCH
LA English
DT Article
ID GAMMA-IRRADIATED RATS; IN-VIVO; INDUCED DEAMINATION; MESSENGER-RNA;
STRESS GENES; METABOLISM; CYTOSINE; DAMAGE; ACID; DNA
AB Mass spectrometry-based metabolomics has previously demonstrated utility for identifying biomarkers of ionizing radiation exposure in cellular, mouse and rat in vivo radiation models. To provide a valuable link from small laboratory rodents to humans, gamma-radiation-induced urinary biomarkers were investigated using a nonhuman primate total-body-irradiation model. Mass spectrometry-based metabolomics approaches were applied to determine whether biomarkers could be identified, as well as the previously discovered rodent biomarkers of gamma radiation. Ultra-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry analysis was carried out on a time course of clean-catch urine samples collected from nonhuman primates (n = 6 per cohort) exposed to sham, 1.0, 3.5, 6.5 or 8.5 Gy doses of Co-60 gamma ray (similar to 0.55 Gy/min) ionizing radiation. By multivariate data analysis, 13 biomarkers of radiation were discovered: N-acetyltaurine, isethionic acid, taurine, xanthine, hypoxanthine, uric acid, creatine, creatinine, tyrosol sulfate, 3-hydroxytyrosol sulfate, tyramine sulfate, N-acetylserotonin sulfate, and adipic acid. N-Acetyltaurine, isethionic acid, and taurine had previously been identified in rats, and taurine and xanthine in mice after ionizing radiation exposure. Mass spectrometry-based metabolomics has thus successfully revealed and verified urinary biomarkers of ionizing radiation exposure in the nonhuman primate for the first time, which indicates possible mechanisms for ionizing radiation injury. (C) 2012 by Radiation Research Society
C1 [Idle, Jeffrey R.] Univ Bern, Dept Clin Res, Hepatol Res Grp, CH-3010 Bern, Switzerland.
[Johnson, Caroline H.; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Patterson, Andrew D.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Patterson, Andrew D.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
[Kalinich, John F.; Blakely, William F.] Uniformed Serv Univ Hlth Sci, Armed Forces Radiobiol Res Inst, Bethesda, MD 20814 USA.
[Tyburski, John B.] Georgetown Univ, Med Ctr, Dept Biochem & Mol & Cellular Biol, Washington, DC 20007 USA.
[Kang, Dong Wook; Luecke, Hans] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Idle, JR (reprint author), Univ Bern, Dept Clin Res, Hepatol Res Grp, CH-3010 Bern, Switzerland.
EM jeff.idle@ikp.unibe.ch
RI Patterson, Andrew/G-3852-2012;
OI Patterson, Andrew/0000-0003-2073-0070; Idle, Jeff/0000-0002-6143-1520
FU National Cancer Institute Intramural Research Program; National
Institutes of Health/National Institute of Allergy and Infectious
Diseases (NIH/NIAID) [U19 AI067773-06/]
FX This work was supported by the National Cancer Institute Intramural
Research Program and also performed as part of the Columbia University
Center for Medical Countermeasures against Radiation (P.I.: Dr. David J.
Brenner), funded by National Institutes of Health/National Institute of
Allergy and Infectious Diseases (NIH/NIAID), grant U19 AI067773-06/07.
AFRRI also supported this research under AFRRI work units RBB4AR and
RAB4AU. The authors gratefully acknowledge Dr. Terry C. Pellmar (Silver
Spring, MD) for her efforts to enable these studies, the assistance of
veterinarian, Dr. Jennifer Mitchell, and her colleagues in AFRRI's
Veterinary Science Department. Radiation exposure and dosimetry support
from AFRRI's dosimetrist, Dr. Vitaly Nagy and his colleagues at AFRRI's
Radiation Science Department. The author (WFB) credits and appreciates
the professional assistance in the rhesus macaque radiation model from
Drs. Natalia I. Ossetrova, Gregory I. King, and Arifur Rahman and
technical support from David J. Sandgren, HM2 Sergio Gallego, Katya
Kranopolsky, and Yvonne Eudy. Views presented in this manuscript are
those of the authors. No endorsement by the Department of Defense has
been given or should be inferred.
NR 34
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U1 1
U2 17
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
J9 RADIAT RES
JI Radiat. Res.
PD OCT
PY 2012
VL 178
IS 4
BP 328
EP 340
DI 10.1667/RR2950.1
PG 13
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 020EE
UT WOS:000309791000010
PM 22954391
ER
PT J
AU Veiga, LHS
Lubin, JH
Anderson, H
de Vathaire, F
Tucker, M
Bhatti, P
Schneider, A
Johansson, R
Inskip, P
Kleinerman, R
Shore, R
Pottern, L
Holmberg, E
Hawkins, MM
Adams, MJ
Sadetzki, S
Lundell, M
Sakata, R
Damber, L
Neta, G
Ron, E
AF Veiga, Lene H. S.
Lubin, Jay H.
Anderson, Harald
de Vathaire, Florent
Tucker, Margaret
Bhatti, Parveen
Schneider, Arthur
Johansson, Robert
Inskip, Peter
Kleinerman, Ruth
Shore, Roy
Pottern, Linda
Holmberg, Erik
Hawkins, Michael M.
Adams, M. Jacob
Sadetzki, Siegal
Lundell, Marie
Sakata, Ritsu
Damber, Lena
Neta, Gila
Ron, Elaine
TI A Pooled Analysis of Thyroid Cancer Incidence Following Radiotherapy for
Childhood Cancer
SO RADIATION RESEARCH
LA English
DT Article
ID IONIZING-RADIATION; DETECTION LIMITS; UNITED-STATES; SURVIVORS; RISK;
EXPOSURE; TUMORS; TRENDS
AB Childhood cancer five-year survival now exceeds 70-80%. Childhood exposure to radiation is a known thyroid carcinogen; however, data are limited for the evaluation of radiation dose-response at high doses, modifiers of the dose-response relationship and joint effects of radiotherapy and chemotherapy. To address these issues, we pooled two cohort and two nested case-control studies of childhood cancer survivors including 16,757 patients, with 187 developing primary thyroid cancer. Relative risks (RR) with 95% confidence intervals (CI) for thyroid cancer by treatment with alkylating agents, anthracyclines or bleomycin were 3.25 (0.9-14.9), 4.5 (1.4-17.8) and 3.2 (0.8-10.4), respectively, in patients without radiotherapy, and declined with greater radiation dose (RR trends, P = 0.02, 0.12 and 0.01, respectively). Radiation dose-related RRs increased approximately linearly for <10 Gy, leveled off at 10-15-fold for 10-30 Gy and then declined, but remained elevated for doses >50 Gy. The fitted RR at 10 Gy was 13.7 (95% CI: 8.0-24.0). Dose-related excess RRs increased with decreasing age at exposure (P < 0.01), but did not vary with attained age or time-since-exposure, remaining elevated 25+ years after exposure. Gender and number of treatments did not modify radiation effects. Thyroid cancer risks remained elevated many decades following radiotherapy, highlighting the need for continued follow up of childhood cancer survivors. (C) 2012 by Radiation Research Society
C1 [Veiga, Lene H. S.; Lubin, Jay H.; Tucker, Margaret; Inskip, Peter; Kleinerman, Ruth; Neta, Gila; Ron, Elaine] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Veiga, Lene H. S.] Brazilian Nucl Energy Commiss, Institbte Radiat Protect & Dosimetry, Rio De Janeiro, Brazil.
[Anderson, Harald] Univ Lund Hosp, Dept Canc Epidemiol, S-22185 Lund, Sweden.
[de Vathaire, Florent] Inst Gustave Roussy, Natl Inst Hlth & Med Res, Canc Epidemiol Res Unit, Villejuif, France.
[Bhatti, Parveen] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA.
[Schneider, Arthur] Univ Illinois, Coll Med, Sect Endocrinol Diabet & Metab, Chicago, IL USA.
[Johansson, Robert] Univ Hosp Umea, Dept Oncol, Umea, Sweden.
[Shore, Roy; Sakata, Ritsu] Radiat Effects Res Fdn, Hiroshima, Japan.
[Pottern, Linda] US PHS, Bethesda, MD USA.
[Holmberg, Erik] Sahlgrens Univ Hosp, Ctr Oncol, Gothenburg, Sweden.
[Holmberg, Erik] Sahlgrens Univ Hosp, Dept Oncol & Radiat Phys, Gothenburg, Sweden.
[Hawkins, Michael M.] Univ Birmingham, Dept Publ Hlth & Epidemiol, Ctr Childhood Canc Survivor Studies, Birmingham, W Midlands, England.
[Adams, M. Jacob] Univ Rochester, Sch Med & Dent, Dept Community & Prevent Med, Div Epidemiol, Rochester, NY USA.
[Sadetzki, Siegal] Tel Aviv Univ, Chaim Sheba Med Ctr, Gertner Inst, Canc & Radiat Epidemiol Unit, IL-69978 Tel Aviv, Israel.
[Sadetzki, Siegal] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
[Lundell, Marie] Karolinska Univ Hosp, Dept Med Phys, Stockholm, Sweden.
[Lundell, Marie] Karolinska Inst, Stockholm, Sweden.
[Damber, Lena] Umea Univ, Dept Radiat Sci, Umea, Sweden.
RP Lubin, JH (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd, Bethesda, MD 20892 USA.
EM lubinj@mail.nih.uov
RI Tucker, Margaret/B-4297-2015; de Vathaire, Florent/L-2983-2016;
OI Kleinerman, Ruth/0000-0001-7415-2478; Holmberg,
Erik/0000-0001-5107-4550; Adams, Michael Jacob/0000-0002-3245-5793
FU U.S. National Institutes of Health, National Cancer Institute, Division
of Cancer Epidemiology and Genetics; National Cancer Institute [U24
CA55727]; Children's Cancer Research Fund; Lance Armstrong Foundation
[147149]
FX This study was supported by the Intramural Research Program of the U.S.
National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics. The Childhood Cancer Survivor Study
was funded by the National Cancer Institute grant U24 CA55727, the
Children's Cancer Research Fund, the Lance Armstrong Foundation grant
147149 and the Intramural Research Program of the NIH, National Cancer
Institute, Division of Cancer Epidemiology and Genetics. We would also
like to acknowledge members of the Nordic Countries Childhood Cancer
Survivor Study Group, who have contributed to the Nordic Countries
Childhood Cancer Survivor Study, including: H. Hertz, J. Olsen
(Denmark); G. Jonmundsson, H. Tulinius (Iceland); M. Lanning, R. Sankila
(Finland); H. Dollner, F. Langmark (Norway); and H. Anderson, S.
Garwicz, T. Moller, G. Svahn-Tapper (Sweden). We particularly wish to
recognize the contribution of our late colleague, Dr. Elaine Ron, who
initiated and guided this pooling project and whose collegiality
suffused all aspects of this effort.
NR 28
TC 28
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U1 0
U2 7
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
J9 RADIAT RES
JI Radiat. Res.
PD OCT
PY 2012
VL 178
IS 4
BP 365
EP 376
DI 10.1667/RR2889.1
PG 12
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 020EE
UT WOS:000309791000013
PM 22857014
ER
PT J
AU Saade, GR
Spong, CY
AF Saade, George R.
Spong, Catherine Y.
TI Introduction
SO SEMINARS IN PERINATOLOGY
LA English
DT Editorial Material
C1 [Saade, George R.] Univ Texas Med Branch, Dept Obstet Gynecol, Soc Maternal Fetal Med, Galveston, TX 77005 USA.
[Spong, Catherine Y.] NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
RP Saade, GR (reprint author), Univ Texas Med Branch, Dept Obstet Gynecol, Soc Maternal Fetal Med, 301 Univ Blvd, Galveston, TX 77005 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0146-0005
J9 SEMIN PERINATOL
JI Semin. Perinatol.
PD OCT
PY 2012
VL 36
IS 5
BP 307
EP 307
DI 10.1053/j.semperi.2012.04.029
PG 1
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 017ZE
UT WOS:000309628900001
PM 23009960
ER
PT J
AU Boyle, A
Reddy, UM
AF Boyle, Annelee
Reddy, Uma M.
TI Epidemiology of Cesarean Delivery: The Scope of the Problem
SO SEMINARS IN PERINATOLOGY
LA English
DT Review
DE primary cesarean delivery; epidemiology; indications
ID RATES; SINGLETON; PATTERNS; SECTION; BIRTH; LABOR; TERM
AB Approximately one-third of births in the United States are via cesarean delivery (CD). The rate of CD has increased dramatically since the 1990s, reaching a peak of 32.9% in 2009. The increase can be seen among women of all ages and race/ethnicities, in every state, and across all gestational ages. The primary CD rate has increased from 14.5% in 1996 to 23.4% in 2007. Because the primary CD rate has increased and the rate of trial of labor after CD has decreased, the primary cesarean rate has become a major driver in the total CD rate. Also contributing to the high CD rate is an increase in somewhat subjective indications, such as fetal distress or nonreassuring fetal tracing and failure to progress leading to performance of CD in the latent phase of labor. Addressing these factors as well as focusing on the use of elective induction and management of early labor in the particular subgroup of nulliparous women at term, with singleton fetuses in vertex presentation may have a significant impact on the total CD rate. Semin Perinatol 36:308-314 Published by Elsevier Inc.
C1 [Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA.
[Boyle, Annelee] Washington Hosp Ctr, Div Maternal Fetal Med, Dept Obstet & Gynecol, Washington, DC 20010 USA.
RP Reddy, UM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, 6100 Execut Blvd,Room 4B03F, Bethesda, MD 20892 USA.
EM reddyu@mail.nih.gov
NR 22
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U1 1
U2 7
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0146-0005
J9 SEMIN PERINATOL
JI Semin. Perinatol.
PD OCT
PY 2012
VL 36
IS 5
BP 308
EP 314
DI 10.1053/j.semperi.2012.04.012
PG 7
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 017ZE
UT WOS:000309628900002
PM 23009961
ER
PT J
AU Kastrinsky, DB
Kumar, P
Marriner, GA
Barry, CE
AF Kastrinsky, David B.
Kumar, Pradeep
Marriner, Gwendolyn A.
Barry, Clifton E., III
TI A Convergent Synthesis of Chiral Diaminopimelic Acid Derived Substrates
for Mycobacterial L, D-Transpeptidases
SO SYNTHESIS-STUTTGART
LA English
DT Article
DE tuberculosis; Mtb L, D-transpeptidases; diaminopimelic acid; Goodman's
reagent; olefin cross-metathesis
ID BETA-LACTAM ANTIBIOTICS; PROTECTED MESO-2,6-DIAMINOPIMELIC ACID; OLEFIN
CROSS-METATHESIS; CELL WALL BIOSYNTHESIS; ASYMMETRIC-SYNTHESIS;
AMINO-ACIDS; STEREOSELECTIVE-SYNTHESIS; PEPTIDOGLYCAN; TUBERCULOSIS;
PATHWAY
AB Amidated and deamidated chiral DAP-D-Ala analogues were prepared by olefin cross-metathesis of 12 with modified D-allylglycines using Grubbs' 2nd generation catalyst. Hydrogenation and deprotection of these precursors provided four chiral (2S, 6R)-DAP-D-alanine derivatives that were examined as substrates for Mtb L, D-transpeptidases in a C-14-D-Ala exchange reaction.
C1 [Kastrinsky, David B.; Kumar, Pradeep; Marriner, Gwendolyn A.; Barry, Clifton E., III] NIAID, NIH, TB Res Sect, Bethesda, MD 20892 USA.
RP Kastrinsky, DB (reprint author), NIAID, NIH, TB Res Sect, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM cbarry@mail.nih.gov
RI Barry, III, Clifton/H-3839-2012
FU Intramural Program of the National Institutes of Health, National
Institute of Allergy and Infectious Diseases (NIAID)
FX This work was funded by the Intramural Program of the National
Institutes of Health, National Institute of Allergy and Infectious
Diseases (NIAID). We gratefully acknowledge Dr. Noel Whittaker of the
National Institutes of Diabetes, Digestive and Kidney Diseases (NIDDK)
for high resolution mass spectrometry analysis.
NR 50
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U1 0
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PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0039-7881
EI 1437-210X
J9 SYNTHESIS-STUTTGART
JI Synthesis
PD OCT
PY 2012
VL 44
IS 19
BP 3043
EP 3048
DI 10.1055/s-0032-1316774
PG 6
WC Chemistry, Organic
SC Chemistry
GA 020LZ
UT WOS:000309812200011
ER
PT J
AU Patel, D
Kebebew, E
AF Patel, Dhaval
Kebebew, Electron
TI Pros and Cons of Robotic Transaxillary Thyroidectomy
SO THYROID
LA English
DT Editorial Material
ID VIDEO-ASSISTED THYROIDECTOMY; SURGERY; EXPERIENCE
C1 [Patel, Dhaval; Kebebew, Electron] NCI, Endocrine Oncol Branch, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, 10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
OI Patel, Dhaval/0000-0002-5744-568X
NR 18
TC 9
Z9 9
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
J9 THYROID
JI Thyroid
PD OCT
PY 2012
VL 22
IS 10
BP 984
EP 985
DI 10.1089/thy.2012.2210.ed
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 017QS
UT WOS:000309606200002
PM 23025539
ER
PT J
AU Loukinov, D
Pugacheva, E
Robinson, S
Rivero-Hinojosa, S
Lobanenkov, V
AF Loukinov, D.
Pugacheva, E.
Robinson, S.
Rivero-Hinojosa, S.
Lobanenkov, V.
TI Functions of CTCF and its testis specific paralog BORIS revealed by
analysis of knockout mice and ChIP-seq data
SO TUMOR BIOLOGY
LA English
DT Meeting Abstract
CT 40th Congress of the International-Society-of-Oncology-and-Biomarkers
CY OCT 13-17, 2012
CL Jerusalem, ISRAEL
SP Int Soc Oncol & Biomarkers
C1 [Loukinov, D.; Pugacheva, E.; Robinson, S.; Rivero-Hinojosa, S.; Lobanenkov, V.] NIAID, Mol Pathol Sect, Immunogenet Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1010-4283
J9 TUMOR BIOL
JI Tumor Biol.
PD OCT
PY 2012
VL 33
SU 1
BP 104
EP 104
PG 1
WC Oncology
SC Oncology
GA 016VM
UT WOS:000309547800165
ER
PT J
AU Hallengard, D
Applequist, SE
Nystrom, S
Maltais, AK
Marovich, M
Moss, B
Earl, P
Nihlmark, K
Wahren, B
Brave, A
AF Hallengard, David
Applequist, Steven E.
Nystrom, Sanna
Maltais, Anna-Karin
Marovich, Mary
Moss, Bernard
Earl, Patricia
Nihlmark, Kopek
Wahren, Britta
Brave, Andreas
TI Immunization with Multiple Vaccine Modalities Induce Strong HIV-Specific
Cellular and Humoral Immune Responses
SO VIRAL IMMUNOLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD8(+) T-CELL; GP120 PROTEIN;
DOUBLE-BLIND; DNA; IMMUNOGENICITY; PRIME; ELECTROPORATION; CHALLENGE;
ANTIBODY
AB Heterologous priming and boosting with antigens expressed by DNA, viral vectors, or as proteins, are experimental strategies to induce strong immune responses against infectious diseases and cancer. In a preclinical study we compared the ability of recombinant modified vaccinia Ankara encoding HIV antigens (MVA-CMDR), and/or recombinant gp140C (rgp140C), to boost responses induced by a multigene/multisubtype HIV DNA vaccine delivered by electroporation (EP). Homologous DNA immunizations augmented by EP stimulated strong cellular immune responses. Still stronger cellular immune responses were observed after DNA priming and MVA-CMDR boosting, which was superior to all other immunization schedules tested in terms of antigen-specific IFN-gamma, IL-2, and bifunctional IFN-g and IL-2 responses. For HIV Env-specific antibody responses, mice receiving repeated rgp140C immunizations, and mice boosted with rgp140C, elicited the highest binding titers and the highest numbers of antibody-secreting B cells. When considering both cellular and humoral immune responses, a combination of DNA, MVA-CMDR, and rgp140C immunizations induced the overall most potent immune responses and the highest avidity of HIV Env-specific antibodies. These data emphasize the importance of including multiple vaccine modalities that can stimulate both T and B cells, and thus elicit strong and balanced immune responses. The present HIV vaccine combination holds promise for further evaluation in clinical trials.
C1 [Hallengard, David; Wahren, Britta; Brave, Andreas] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden.
[Applequist, Steven E.; Nystrom, Sanna] Karolinska Inst, Ctr Infect Med, Huddinge, Sweden.
[Maltais, Anna-Karin] Cyto Pulse Sci Inc, Solna, Sweden.
[Marovich, Mary] Walter Reed Army Inst Res, US Mil HIV Res Program, Rockville, MD USA.
[Moss, Bernard; Earl, Patricia] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Nihlmark, Kopek] Mabtech AB, Nacka Strand, Sweden.
RP Hallengard, D (reprint author), Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Nobels Vag 16, S-17177 Stockholm, Sweden.
EM david.hallengard@ki.se
FU EU [LSHP-CT-2006-037611, Health-F3-2008-201433]
FX We thank the EU programs EUROPRISE (LSHP-CT-2006-037611) and NGIN
(Health-F3-2008-201433) for funding, and Polymun Scientific for
supplying the gp140C protein vaccine candidate.
NR 46
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U1 0
U2 4
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0882-8245
J9 VIRAL IMMUNOL
JI Viral Immunol.
PD OCT
PY 2012
VL 25
IS 5
BP 423
EP 432
DI 10.1089/vim.2012.0046
PG 10
WC Immunology; Virology
SC Immunology; Virology
GA 018JX
UT WOS:000309657500010
PM 23035853
ER
PT J
AU Mousa, AA
Cappello, RE
Estrada-Gutierrez, G
Shukla, J
Romero, R
Strauss, JF
Walsh, SW
AF Mousa, Ahmad A.
Cappello, Renato E.
Estrada-Gutierrez, Guadalupe
Shukla, Juhi
Romero, Roberto
Strauss, Jerome F., III
Walsh, Scott W.
TI Preeclampsia Is Associated with Alterations in DNA Methylation of Genes
Involved in Collagen Metabolism
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID MATRIX METALLOPROTEINASE-2; OXIDATIVE STRESS; EXPRESSION; CLEAVAGE;
DISEASE; WOMEN; VASOCONSTRICTION; ENDOTHELIN-1; ACTIVATION; MECHANISMS
AB Maternal vascular dysfunction is a hallmark of preeclampsia. A recently described vascular phenotype of preeclampsia involves increased expression of matrix metalloproteinase-1 (MMP-1) in endothelial cells, vascular smooth muscle, and infiltrating neutrophils. In contrast, the expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) and collagen type la 1 is either reduced or not changed in the vessels, suggesting an imbalance in vessel collagen degradation and synthesis in preeclampsia. In the present study, we explored the possible contribution of DNA methylation to the altered expression of genes involved in collagen metabolism. We assayed the differences in DNA methylation in omental arteries from normal pregnant and preeclamptic women, and determined whether reduced DNA methylation increases the expression of MMP-1 in cultured vascular smooth muscle cells and a neutrophil-like cell line, HL-60. Several MMP genes, including MMP1 and MMP8, were significantly less methylated in preeclamptic omental arteries, whereas TIMP and COL genes either were significantly more methylated or had no significant change in their DNA methylation status compared with normal pregnancy. Experimentally induced DNA hypomethylation increased MMP-1 expression in cultured vascular smooth muscle cells and MMP-1 cells. Our findings suggest that epigenetic regulation contributes to the imbalance in genes involved in collagen metabolism in blood vessels of preeclamptic women. (Am J Pathol 2012, 181:1455-1463; http://dx.doi.org/10.1016/j.ajpath.2012.06.019)
C1 [Walsh, Scott W.] Virginia Commonwealth Univ, Med Ctr, Dept Obstet & Gynecol, Richmond, VA 23298 USA.
[Mousa, Ahmad A.; Walsh, Scott W.] Virginia Commonwealth Univ, Dept Physiol & Biophys, Richmond, VA 23298 USA.
[Estrada-Gutierrez, Guadalupe] Natl Inst Perinatol, Dept Infect, Mexico City, DF, Mexico.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perintol Res Branch, US Dept HHS, Bethesda, MD USA.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perintol Res Branch, US Dept HHS, Detroit, MI USA.
RP Walsh, SW (reprint author), Virginia Commonwealth Univ, Med Ctr, Dept Obstet & Gynecol, 1101 E Marshall St,POB 980034, Richmond, VA 23298 USA.
EM swwalsh@vcu.edu
FU National Heart, Lung, and Blood Institute [RO1 HL069851]; National
Center on Minority Health and Health Disparities [P60 MD002256];
Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, Department of Health and Human Services [N01
HD-2-3342]; NIH Fogarty grant [1D43 TW007692]; NIH-National Cancer
Institute Cancer Center Support Grant [P30 CA016059]; National Center
for Advancing Translational Sciences (CTSA) [UL1TR000058]
FX Supported, in part, by grants from the National Heart, Lung, and Blood
Institute (RO1 HL069851 to S.W.W.); the National Center on Minority
Health and Health Disparities (P60 MD002256 to J.F.S.); the Perinatology
Research Branch, Division of Intramural Research, Eunice Kennedy Shriver
National Institute of Child Health and Human Development, NIH,
Department of Health and Human Services (N01 HD-2-3342 to J.F.S.); and
NIH Fogarty grant (1D43 TW007692 to G.E.-G.). DNA sequencing and
methylation analysis were performed at the Virginia Commonwealth
University Nucleic Acids Research Facility core laboratory, which is
supported, in part, by funding from NIH-National Cancer Institute Cancer
Center Support Grant (P30 CA016059), and the National Center for
Advancing Translational Sciences (CTSA award No. UL1TR000058).
NR 28
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U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD OCT
PY 2012
VL 181
IS 4
BP 1455
EP 1463
DI 10.1016/j.ajpath.2012.06.019
PG 9
WC Pathology
SC Pathology
GA 017DK
UT WOS:000309570100035
PM 22863954
ER
PT J
AU Douglass, J
Gunaratne, R
Bradford, D
Saeed, F
Hoffert, JD
Steinbach, PJ
Knepper, MA
Pisitkun, T
AF Douglass, Jacqueline
Gunaratne, Ruwan
Bradford, Davis
Saeed, Fahad
Hoffert, Jason D.
Steinbach, Peter J.
Knepper, Mark A.
Pisitkun, Trairak
TI Identifying protein kinase target preferences using mass spectrometry
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE protein kinase A; Sgk1; SPAK; Wnk1; glycogen synthase kinase
ID COLLECTING DUCT CELLS; PHOSPHORYLATION MOTIFS; SIGNALING PATHWAYS;
CATALYTIC SUBUNIT; SEQUENCE LOGOS; DYNAMICS; SITES; SPECIFICITY;
CONTAINS; NETWORKS
AB Douglass J, Gunaratne R, Bradford D, Saeed F, Hoffert JD, Steinbach PJ, Knepper MA, Pisitkun T. Identifying protein kinase target preferences using mass spectrometry. Am J Physiol Cell Physiol 303: C715-C727, 2012. First published June 20, 2012; doi:10.1152/ajpcell.00166.2012.-A general question in molecular physiology is how to identify candidate protein kinases corresponding to a known or hypothetical phosphorylation site in a protein of interest. It is generally recognized that the amino acid sequence surrounding the phosphorylation site provides information that is relevant to identification of the cognate protein kinase. Here, we present a mass spectrometry-based method for profiling the target specificity of a given protein kinase as well as a computational tool for the calculation and visualization of the target preferences. The mass spectrometry-based method identifies sites phosphorylated in response to in vitro incubation of protein mixtures with active recombinant protein kinases followed by standard phosphoproteomic methodologies. The computational tool, called "PhosphoLogo," uses an information-theoretic algorithm to calculate position-specific amino acid preferences and anti-preferences from the mass-spectrometry data (http://helixweb.nih.gov/PhosphoLogo/). The method was tested using protein kinase A (catalytic subunit alpha), revealing the well-known preference for basic amino acids in positions -2 and -3 relative to the phosphorylated amino acid. It also provides evidence for a preference for amino acids with a branched aliphatic side chain in position +1, a finding compatible with known crystal structures of protein kinase A. The method was also employed to profile target preferences and anti-preferences for 15 additional protein kinases with potential roles in regulation of epithelial transport: CK2, p38, AKT1, SGK1, PKC delta, CaMK2 delta, DAPK1, MAPKAPK2, PKD3, PIM1, OSR1, STK39/SPAK, GSK3 beta, Wnk1, and Wnk4.
C1 [Douglass, Jacqueline; Gunaratne, Ruwan; Bradford, Davis; Saeed, Fahad; Hoffert, Jason D.; Knepper, Mark A.; Pisitkun, Trairak] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA.
[Steinbach, Peter J.] NIH, Ctr Mol Modeling, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Knepper, MA (reprint author), NHLBI, Epithelial Syst Biol Lab, NIH, Bldg 10,Rm 6N307,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA.
EM knepperm@nhlbi.nih.gov
RI Saeed, Fahad/D-1545-2013;
OI Pisitkun, Trairak/0000-0001-6677-2271
FU National Heart, Lung and Blood Institute [ZO1-HL001285]; Center for
Information Technology [CT000265-16]
FX A portion of the data in this paper was presented as part of the Davson
Lecture of the American Physiological Society at the Experimental
Biology 2012 Meeting in San Diego, California. We thank Guanghui Wang of
the National Heart, Lung, and Blood Institute Proteomics Core Facility
(Marjan Gucek, Director) for assistance with the mass spectrometry.
Steven Shaw provided valuable early advice regarding protein kinase
specificities. Thomas Schneider provided advice on construction of the
sequence logo algorithm. Chou-Long Huang provided reagents and advice on
Wnk1 and Wnk4 kinases. The study was carried out in the intramural
program of the National Heart, Lung and Blood Institute (Project
ZO1-HL001285, M. A. Knepper) and the Center for Information Technology
(Project CT000265-16, P. J. Steinbach).
NR 40
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Z9 21
U1 0
U2 11
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD OCT
PY 2012
VL 303
IS 7
BP C715
EP C727
DI 10.1152/ajpcell.00166.2012
PG 13
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 016NY
UT WOS:000309527100004
PM 22723110
ER
PT J
AU Soares, HD
Potter, WZ
Pickering, E
Kuhn, M
Immermann, FW
Shera, DM
Ferm, M
Dean, RA
Simon, AJ
Swenson, F
Siuciak, JA
Kaplow, J
Thambisetty, M
Zagouras, P
Koroshetz, WJ
Wan, HI
Trojanowski, JQ
Shaw, LM
AF Soares, Holly D.
Potter, William Z.
Pickering, Eve
Kuhn, Max
Immermann, Frederick W.
Shera, David M.
Ferm, Mats
Dean, Robert A.
Simon, Adam J.
Swenson, Frank
Siuciak, Judith A.
Kaplow, June
Thambisetty, Madhav
Zagouras, Panayiotis
Koroshetz, Walter J.
Wan, Hong I.
Trojanowski, John Q.
Shaw, Leslie M.
CA Biomarkers Consortium Alzheimers
TI Plasma Biomarkers Associated With the Apolipoprotein E Genotype and
Alzheimer Disease
SO ARCHIVES OF NEUROLOGY
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; DIAGNOSTIC GUIDELINES; NATRIURETIC PEPTIDE;
NATIONAL INSTITUTE; DEMENTIA; RECOMMENDATIONS; WORKGROUPS; CORTISOL;
BLOOD; APOE
AB Background: A blood-based test that could be used as a screen for Alzheimer disease (AD) may enable early intervention and better access to treatment.
Objective: To apply a multiplex immunoassay panel to identify plasma biomarkers of AD using plasma samples from the Alzheimer's Disease Neuroimaging Initiative cohort.
Design: Cohort study.
Setting: The Biomarkers Consortium Alzheimer's Disease Plasma Proteomics Project.
Participants: Plasma samples at baseline and at 1 year were analyzed from 396 (345 at 1 year) patients with mild cognitive impairment, 112 (97 at 1 year) patients with AD, and 58 (54 at 1 year) healthy control subjects.
Main Outcome Measures: Multivariate and univariate statistical analyses were used to examine differences across diagnostic groups and relative to the apolipoprotein E (ApoE) genotype.
Results: Increased levels of eotaxin 3, pancreatic polypeptide, and N-terminal protein B-type brain natriuretic peptide were observed in patients, confirming similar changes reported in cerebrospinal fluid samples of patients with AD and MCI. Increases in tenascin C levels and decreases in IgM and ApoE levels were also observed. All participants with Apo epsilon 3/epsilon 4 or epsilon 4/epsilon 4 alleles showed a distinct biochemical profile characterized by low C-reactive protein and ApoE levels and by high cortisol, interleukin 13, apolipoprotein B, and gamma interferon levels. The use of plasma biomarkers improved specificity in differentiating patients with AD from controls, and ApoE plasma levels were lowest in patients whose mild cognitive impairment had progressed to dementia.
Conclusions: Plasma biomarker results confirm cerebrospinal fluid studies reporting increased levels of pancreatic polypeptide and N-terminal protein B-type brain natriuretic peptide in patients with AD and mild cognitive impairment. Incorporation of plasma biomarkers yielded high sensitivity with improved specificity, supporting their usefulness as a screening tool. The ApoE genotype was associated with a unique biochemical profile irrespective of diagnosis, highlighting the importance of genotype on blood protein profiles.
C1 [Soares, Holly D.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA.
[Pickering, Eve; Kuhn, Max; Swenson, Frank; Zagouras, Panayiotis] Pfizer Worldwide Res & Dev, Groton, CT USA.
[Thambisetty, Madhav] NIA, Lab Behav Neurosci, Clin Res Branch, Intramural Res Program, Baltimore, MD 21224 USA.
[Koroshetz, Walter J.] NINDS, Div Extramural Res, Bethesda, MD 20892 USA.
[Immermann, Frederick W.] Pfizer Worldwide Res & Dev, Pearl River, NY USA.
[Shera, David M.] Merck Res Labs, Whitehouse Stn, NJ USA.
[Kaplow, June] Eisai Med Res, Woodcliff Lake, NJ USA.
[Ferm, Mats] AstraZeneca Res & Dev, Cent Nervous Syst & Pain Innovat Med, Sodertalje, Sweden.
[Dean, Robert A.] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Simon, Adam J.] AJ Simon Enterprises LLC, Yardley, England.
[Trojanowski, John Q.; Shaw, Leslie M.] Univ Penn, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Trojanowski, John Q.; Shaw, Leslie M.] Univ Penn, Perelman Sch Med, Inst Aging, Philadelphia, PA 19104 USA.
[Wan, Hong I.] Pfizer Worldwide Res & Dev, Biotherapeut Clin Programs, San Francisco, CA USA.
RP Soares, HD (reprint author), Bristol Myers Squibb Co, 5 Res Pkwy, Wallingford, CT 06492 USA.
EM Holly.soares@bms.com
RI Kowall, Neil/G-6364-2012; Preda, Adrian /K-8889-2013; Saykin,
Andrew/A-1318-2007; Siuciak, Judith/K-2759-2016
OI Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438;
Saykin, Andrew/0000-0002-1376-8532; Siuciak, Judith/0000-0002-3945-3555
FU Foundation for the National Institutes of Health; National Institute on
Aging [U01 AG024904]; National Institute of Biomedical Imaging and
Bioengineering of the National Institutes of Health; The Canadian
Institutes of Health Research; National Institutes of Health [P30
AG010129, K01 AG030514]; The Dana Foundation
FX Dr Soares reported owning shares in Bristol-Myers Squibb. Mr Immermann
and Dr Wan reported owning shares in Pfizer Inc. Dr Simon reported
serving as an independent biomarker consultant. Data collection and
sharing for this study represent the work of the Biomarkers Consortium
Project "Use of Targeted Multiplex Proteomic Strategies to Identify
Plasma-Based Biomarkers in Alzheimer's Disease." This project was
submitted to the Biomarkers Consortium Neuroscience Steering Committee
by a subgroup of the ADNI Private Partner Scientific Board for execution
and was managed by a Biomarkers Consortium Project Team that includes
members from academia, government, and the pharmaceutical industry.
Funding for this project was provided through an overage of funds raised
by the Foundation for the National Institutes of Health for the ADNI
partnership. The entire data set described in the present study, along
with the Biomarkers Consortium plasma proteomics project team data
primer and statistical analysis plan, are available on the ADNI website
(http://adni.loni.ucla.edu).; The ADNI study is funded by grant U01
AG024904 from the National Institute on Aging and the National Institute
of Biomedical Imaging and Bioengineering of the National Institutes of
Health and through generous contributions from the following: Abbott,
Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Amorfix
Life Sciences Ltd, AstraZeneca, Bayer HealthCare, BioClinica Inc, Biogen
Idec Inc, BristolMyers Squibb, Eisai Inc, Elan Pharmaceuticals Inc, Eli
Lilly and Company, F. Hoffmann-La Roche Ltd and its affiliated company
Genentech Inc, GE Healthcare, Innogenetics, NV, Janssen Alzheimer
Immunotherapy Research& Development, LLC, Johnson & Johnson
Pharmaceutical Research & Development LLC, Medpace Inc, Merck & Co Inc,
Meso Scale Diagnostics LLC, Novartis Pharmaceuticals Corporation, Pfizer
Inc, Servier, Synarc Inc, and Takeda Pharmaceutical Company. The
Canadian Institutes of Health Research is providing funds to support
ADNI clinical sites in Canada. Private sector contributions are
facilitated by the Foundation for the National Institutes of Health
(www.fnih.org). The grantee organization is the Northern California
Institute for Research and Education, and the study is coordinated by
the Alzheimer's Disease Cooperative Study at the University of
California, San Diego. The ADNI data are disseminated by the Laboratory
for Neuro Imaging at the University of California, Los Angeles. This
research was also supported by grants P30 AG010129 and K01 AG030514 from
the National Institutes of Health and by The Dana Foundation.
NR 38
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U1 2
U2 21
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9942
J9 ARCH NEUROL-CHICAGO
JI Arch. Neurol.
PD OCT
PY 2012
VL 69
IS 10
BP 1310
EP 1317
DI 10.1001/archneurol.2012.1070
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 016TC
UT WOS:000309541400010
PM 22801723
ER
PT J
AU Javaid, MK
Kiran, A
Guermazi, A
Kwoh, CK
Zaim, S
Carbone, L
Harris, T
McCulloch, CE
Arden, NK
Lane, NE
Felson, D
Nevitt, M
AF Javaid, M. K.
Kiran, A.
Guermazi, A.
Kwoh, C. K.
Zaim, S.
Carbone, L.
Harris, T.
McCulloch, C. E.
Arden, N. K.
Lane, N. E.
Felson, D.
Nevitt, M.
TI Individual magnetic resonance imaging and radiographic features of knee
osteoarthritis in subjects with unilateral knee pain: The health, aging,
and body composition study
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID BONE-MARROW LESIONS; BIOCHEMICAL MARKERS; HAND OSTEOARTHRITIS;
PROGRESSION; JOINT; MRI; ASSOCIATION; COMMUNITY; COHORT; ATTRITION
AB Objective Strong associations between radiographic features of knee osteoarthritis (OA) and pain have been demonstrated in persons with unilateral knee symptoms. This study was undertaken to compare radiographic and magnetic resonance imaging (MRI) features of knee OA and assess their ability to discriminate between painful and nonpainful knees in persons with unilateral symptoms. Methods The study population included 283 individuals ages 7079 years with unilateral knee pain who were enrolled in the Health, Aging, and Body Composition Study, a study of weight-related diseases and mobility. Radiographs of both knees were read for Kellgren/Lawrence (K/L) grade and individual radiographic features, and 1.5T MRIs were assessed using the Whole-Organ Magnetic Resonance Imaging Score. The association between structural features and pain was assessed using a within-person casecontrol design and conditional logistic regression. Receiver operating characteristic (ROC) analysis was then used to test the discriminatory performance of structural features. Results In conditional logistic analyses, knee pain was significantly associated with both radiographic features (any joint space narrowing grade =1) (odds ratio 3.20 [95% confidence interval 1.795.71]) and MRI features (any cartilage defect scored =2) (odds ratio 3.67 [95% confidence interval 1.499.04]). However, in most subjects, MRI revealed osteophytes and cartilage and bone marrow lesions in both knees, and using ROC analysis, no individual structural feature discriminated well between painful and nonpainful knees. The best-performing MRI feature (synovitis/effusion) was not significantly more informative than K/L grade =2 (P = 0.42). Conclusion In persons with unilateral knee pain, MRI and radiographic features were associated with knee pain, confirming that structural abnormalities in the knee have an important role in the etiology of pain. However, no single MRI or radiographic finding performed well in discriminating between painful and nonpainful knees. Further work is needed to examine how structural and nonstructural factors influence knee pain.
C1 [Javaid, M. K.] Univ Oxford, Botnar Res Ctr, NIHR Musculoskeletal BRU, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford OX3 7LD, England.
[Guermazi, A.; Felson, D.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Kwoh, C. K.] Univ Pittsburgh, Pittsburgh, PA USA.
[Zaim, S.] Synarc, San Francisco, CA USA.
[Carbone, L.] Univ Tennessee, Memphis, TN USA.
[Harris, T.] NIA, NIH, Bethesda, MD 20892 USA.
[McCulloch, C. E.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Lane, N. E.] Univ Calif Davis, Davis, CA 95616 USA.
RP Javaid, MK (reprint author), Univ Oxford, Botnar Res Ctr, NIHR Musculoskeletal BRU, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Windmill Rd, Oxford OX3 7LD, England.
EM kassim.javaid@ndorms.ox.ac.uk
OI Felson, David/0000-0002-2668-2447
FU NIH (National Institute on Aging) [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, R01-AG-028050]; NIH (National Institute of Nursing
Research) [R01-NR-012459]; NIHR Musculoskeletal Biomedical Research
Unit, University of Oxford; Arthritis Research UK; Merck Serono;
Genzyme; AstraZeneca; Stryker; Novartis
FX Supported by the NIH (National Institute on Aging contracts
N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106, National Institute on
Aging grant R01-AG-028050, and National Institute of Nursing Research
grant R01-NR-012459). Dr. Javaid's work was supported in part by the
NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, and
by Arthritis Research UK (traveling fellowship).; Dr. Guermazi has
received consulting fees, speaking fees, and/or honoraria from Merck
Serono, Genzyme, and AstraZeneca (less than $10,000 each) and from
Stryker (more than $10,000); he is president of and owns stock or stock
options in Boston Imaging Core Lab. Dr. Kwoh has received consulting
fees, speaking fees, and/or honoraria from Novartis (less than $10,000).
NR 32
TC 17
Z9 17
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD OCT
PY 2012
VL 64
IS 10
BP 3246
EP 3255
DI 10.1002/art.34594
PG 10
WC Rheumatology
SC Rheumatology
GA 014VE
UT WOS:000309403000023
PM 22736267
ER
PT J
AU Ruppert, SM
Li, WQ
Zhang, G
Carlson, AL
Limaye, A
Durum, SK
Khaled, AR
AF Ruppert, Shannon M.
Li, Wenqing
Zhang, Ge
Carlson, Adina L.
Limaye, Arati
Durum, Scott K.
Khaled, Annette R.
TI The major isoforms of Bim contribute to distinct biological activities
that govern the processes of autophagy and apoptosis in interleukin-7
dependent lymphocytes
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Article
DE Bcl-2; Cytokine; Lysosome; Fluorescence; Acidification; Dynein
ID FAMILY-MEMBER BIM; RECEPTOR-DEFICIENT MICE; CYTOCHROME-C RELEASE; T-CELL
SURVIVAL; BCL-2 FAMILY; REGULATES BIM; PROTEIN BIM; PROAPOPTOTIC
ACTIVITY; BH3-ONLY PROTEINS; INTRACELLULAR PH
AB Bim is a BH3-only member of the Bcl-2 family that enables the death of T-cells. Partial rescue of cytokine-deprived T-cells occurs when Bim and the receptor for the T-cell growth factor, interleukin-7, are deleted, implicating Bim as a possible target of interleukin-7-mediated signaling. Alternative splicing yields three major isoforms: BimEL, BimL and BimS. To study the effect of Him deficiency and define the function of the major isoforms, Him-containing and Bim-deficient T-cells, dependent on interleukin-7 for growth, were used. Loss of total Bim in interleukin-7-deprived T-cells resulted in delayed apoptosis. However, loss of Him also impeded the later degradative phase of autophagy. p62, an autophagy-adaptor protein which is normally degraded, accumulated in Bim deficient cells. To explain this. BimL was found to support acidification of lysosomes that later may associate with autophagic vesicles. Key findings showed that inhibition of lysosomal acidification accelerated death upon interleukin-7 withdrawal only in Bim-containing T-cells. intereukin-7 dependent T-cells lacking Bim were less sensitive to inhibition of lysosomal acidification. BimL co-immunoprecipitated with dynein and Lamp1-containing vesicles, indicating BimL could be an adaptor for dynein to facilitate loading of lysosomes. In Him deficient T-cells, lysosome-tracking probes revealed vesicles of less acidic pH. Over-expression of BimL restored acidic vesicles in Bim deficient T-cells, while other isoforms, BimEL and BimS, promoted intrinsic cell death. These results reveal a novel role for BimL in lysosomal positioning that may be required for the formation of degradative autolysosomes. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Ruppert, Shannon M.; Zhang, Ge; Carlson, Adina L.; Limaye, Arati; Khaled, Annette R.] Univ Cent Florida, Coll Med, Burnett Sch Biomed Sci, Orlando, FL 32827 USA.
[Li, Wenqing; Durum, Scott K.] NCI, Frederick, MD 21702 USA.
RP Khaled, AR (reprint author), Univ Cent Florida, Coll Med, Burnett Sch Biomed Sci, 6900 Lake Nona Blvd, Orlando, FL 32827 USA.
EM annette.khaled@ucf.edu
FU NIH/NCI from the National Institutes of Health (NIH) [CA109524RO1]
FX This study was supported by an NIH/NCI grant CA109524RO1 (Khaled) from
the National Institutes of Health (NIH).
NR 89
TC 8
Z9 8
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD OCT
PY 2012
VL 1823
IS 10
BP 1877
EP 1893
DI 10.1016/j.bbamcr.2012.06.017
PG 17
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 016CG
UT WOS:000309494300023
PM 22728771
ER
PT J
AU Lee, JH
Oh, H
Baxa, U
Raghavan, SR
Blumenthal, R
AF Lee, Jae-Ho
Oh, Hyuntaek
Baxa, Ulrich
Raghavan, Srinivasa R.
Blumenthal, Robert
TI Biopolymer-Connected Liposome Networks as Injectable Biomaterials
Capable of Sustained Local Drug Delivery
SO BIOMACROMOLECULES
LA English
DT Article
ID GELS; RELEASE; HYDROGELS; SYSTEMS; STABILITY
AB Biopolymers bearing hydrophobic side-chains, such as hydrophobically modified chitosan (hmC), can connect liposomes into a gel network via hydrophobic interactions. In this paper, we show that such liposome gels possess an attractive combination of properties for certain drug delivery applications. Their shear-thinning property allows these gels to be injected at a particular site, while their gel-like nature at rest ensures that the material will remain localized at that site. Moreover, drugs can be encapsulated in the interior of the liposomes and delivered at the local site for an extended period of time. The presence of two transport resistances - from the liposomal bilayer and the gel network is shown to be responsible for the sustained release; in turn, disruption of the liposomes both weakens the gel and causes a faster release. We have monitored release kinetics from liposome gels of a cationic anticancer drug doxorubicin (Dox) encapsulated in liposomes. Sustained release of Dox from these gels and the concomitant cytotoxic effect could be observed for over a week.
C1 [Lee, Jae-Ho; Blumenthal, Robert] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
[Oh, Hyuntaek; Raghavan, Srinivasa R.] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA.
[Baxa, Ulrich] SAIC Frederick, Electron Microscopy Lab, Adv Technol Program, Frederick, MD 21702 USA.
RP Lee, JH (reprint author), NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
EM leejaeho@mail.nih.gov
FU National Cancer Institute, Center for Cancer Research
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, Center for Cancer Research. We thank Dr. Anu
Puri for her sincere discussions and Dr. Hee-Young Lee for support with
the rheological studies.
NR 31
TC 17
Z9 17
U1 1
U2 43
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1525-7797
J9 BIOMACROMOLECULES
JI Biomacromolecules
PD OCT
PY 2012
VL 13
IS 10
BP 3388
EP 3394
DI 10.1021/bm301143d
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science
SC Biochemistry & Molecular Biology; Chemistry; Polymer Science
GA 016AC
UT WOS:000309488600039
PM 22970880
ER
PT J
AU Shiels, MS
Engels, EA
AF Shiels, Meredith S.
Engels, Eric A.
TI Increased risk of histologically defined cancer subtypes in human
immunodeficiency virus-infected individuals
SO CANCER
LA English
DT Article
DE human immunodeficiency virus; immunosuppression; infection; cancer
ID EPSTEIN-BARR-VIRUS; GERM-CELL TUMORS; TRANSPLANT RECIPIENTS;
HIV-INFECTION; UNITED-STATES; LUNG-CANCER; AIDS; CARCINOMA; PEOPLE;
ASSOCIATION
AB BACKGROUND: Malignancies that occur in excess among human immunodeficiency virus (HIV)-infected individuals may be caused by immunosuppression or infections. Because histologically defined cancer subtypes have not been systematically evaluated, their risk was assessed among people with acquired immunodeficiency syndrome (AIDS). METHODS: Analyses included 569,268 people with AIDS from the HIV/AIDS Cancer Match Study, a linkage of 15 US population-based HIV/AIDS and cancer registries during 1980 to 2007. Standardized incidence ratios (SIRs) were estimated to compare cancer risk in people with AIDS to the general population overall, and stratified by age, calendar period (a proxy of changing HIV therapies), and time since onset of AIDS (a proxy of immunosuppression). RESULTS: Sixteen individual cancer histologies or histology groupings manifested significantly elevated SIRs. Risks were most elevated for adult T cell leukemia/lymphoma (SIR = 11.3), neoplasms of histiocytes and accessory lymphoid cells (SIR = 10.7), giant cell carcinoma (SIR = 7.51), and leukemia not otherwise specified (SIR = 6.69). SIRs ranged from 1.4 to 4.6 for spindle cell carcinoma, bronchioloalveolar adenocarcinoma, adnexal and skin appendage neoplasms, sarcoma not otherwise specified, spindle cell sarcoma, leiomyosarcoma, mesothelioma, germ cell tumors, plasma cell tumors, immunoproliferative diseases, acute lymphocytic leukemia, and myeloid leukemias. For several of these cancer subtypes, significant declines in SIRs were observed across calendar periods (consistent with decreasing risk with improved HIV therapies) or increase in SIRs with time since onset of AIDS (ie, prolonged immunosuppression). CONCLUSIONS: The elevated risk of certain cancer subtypes in people with AIDS may point to an etiologic role of immunosuppression or infection. Future studies are needed to further investigate these associations and evaluate candidate infectious agents. Cancer 2012. (c) 2012 American Cancer Society.
C1 [Shiels, Meredith S.; Engels, Eric A.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
RP Shiels, MS (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7059, Rockville, MD 20892 USA.
EM shielsms@mail.nih.gov
FU National Cancer Institute
FX This study was funded by the Intramural Research Program of the National
Cancer Institute.
NR 34
TC 10
Z9 11
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD OCT 1
PY 2012
VL 118
IS 19
BP 4869
EP 4876
DI 10.1002/cncr.27454
PG 8
WC Oncology
SC Oncology
GA 008BK
UT WOS:000308931900029
PM 22359254
ER
PT J
AU Taplin, SH
Yabroff, KR
Zapka, J
AF Taplin, Stephen H.
Yabroff, K. Robin
Zapka, Jane
TI A Multilevel Research Perspective on Cancer Care Delivery: The Example
of Follow-Up to An Abnormal Mammogram
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID RANDOMIZED-CONTROLLED-TRIAL; LOW-INCOME WOMEN; PATIENT NAVIGATION;
BREAST-CANCER; HEALTH-CARE; QUALITY; INTERVENTIONS; COMMUNICATION;
TIMELINESS; EXPERIENCE
AB In 1999, researchers and policy makers recognized the challenge of creating an integrated patient-centered cancer care process across the many types of care from risk assessment through end of life. More than a decade later, there has been limited progress toward that goal even though the standard reductionist approach to health services and medical research has resulted in major advances in tests, procedures, and individualized patient approaches to care. In this commentary, we propose that considering an entire care process within its multilevel context may increase progress toward an integrated experience and improvements in the quality of care. As an illustrative case, wedescribe the multilevel context of care delivery for the process of follow-up to an abnormal screening mammogram. By taking a multilevel perspective on this process, we identify a rich set of options for intervening and improving follow-up to abnormalities and, therefore, outcomes of screening. We propose that taking this multilevel perspective when designing interventions may improve the quality of cancer care in an effective and sustainable way. Cancer Epidemiol Biomarkers Prev; 21(10); 1709-15. (c) 2012 AACR.
C1 [Taplin, Stephen H.; Yabroff, K. Robin] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Zapka, Jane] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA.
RP Taplin, SH (reprint author), NCI, 6130 Execut Blvd,MSC 7344,EPN 4005, Rockville, MD 20852 USA.
EM taplins@mail.nih.gov
OI Yabroff, K. Robin/0000-0003-0644-5572
FU Intramural NIH HHS [Z99 CA999999]
NR 45
TC 12
Z9 12
U1 0
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD OCT
PY 2012
VL 21
IS 10
BP 1709
EP 1715
DI 10.1158/1055-9965.EPI-12-0265
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 017FS
UT WOS:000309576100013
PM 22911332
ER
PT J
AU Banegas, MP
Puschel, K
Martinez-Gutierrez, J
Anderson, JC
Thompson, B
AF Banegas, Matthew P.
Pueschel, Klaus
Martinez-Gutierrez, Javiera
Anderson, Jennifer C.
Thompson, Beti
TI Perceived and Objective Breast Cancer Risk Assessment in Chilean Women
Living in an Underserved Area
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID PRIMARY-CARE; PREDICTORS; KNOWLEDGE; ACCURACY; MEDICINE; BARRIERS; TRIAL
AB Background: Breast cancer is the most frequently diagnosed malignancy among Chilean women and an increasingly significant public health threat. This study assessed the accuracy of breast cancer risk perception among underserved, Chilean women.
Methods: Women aged 50 to 70 years, with no mammogram during the last 2 years, were randomly selected from a community clinic registry in Santiago, Chile (n = 500). Perceived risk was measured using three methods: absolute risk, comparative risk, and numerical risk. Risk comprehension was measured by comparing women's perceived and objective risk estimates. Multivariate logistic regression was used to assess overestimation of perceived risk.
Results: Women at high risk of breast cancer were more likely than average risk women to perceive themselves at high or higher risk, using absolute and comparative risk approaches (P < 0.001). The majority of participants (67%) overestimated their breast cancer risk, on the basis of risk comprehension; although, participants achieved higher accuracy with comparative risk (40%) and absolute risk (31.6%) methods. [Age, breast cancer knowledge and Breast Cancer Risk Assessment Tool (BCRAT) 5-year risk were significantly associated (P < 0.01) with accuracy of perceived risk].
Conclusion: Chilean women residing in an underserved community may not accurately assess their breast cancer risk, although risk perception and level of accuracy differed between perceived risk measures. Comparative and absolute risk methods may better reflect women's interpretation and accuracy of risk perception.
Impact: Improving our understanding of Chilean women's perceptions of developing breast cancer may lead to the development of culturally relevant efforts to reduce the breast cancer burden in this population. Cancer Epidemiol Biomarkers Prev; 21(10); 1716-21. (c) 2012 AACR.
C1 [Banegas, Matthew P.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA.
[Banegas, Matthew P.; Martinez-Gutierrez, Javiera; Anderson, Jennifer C.; Thompson, Beti] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Pueschel, Klaus; Martinez-Gutierrez, Javiera] Pontificia Univ Catolica Chile, Dept Family Med, Sch Med, Santiago, Chile.
[Banegas, Matthew P.; Martinez-Gutierrez, Javiera; Thompson, Beti] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA.
RP Banegas, MP (reprint author), NCI, Canc Prevent Fellowship Program, Canc Prevent Div, 6120 Execut Blvd,Room 150E,MSC 7105, Bethesda, MD 20892 USA.
EM banegasmp@mail.nih.gov
FU NIH, National Cancer Institute, Center for Population Health and Health
Disparities [5 P50 CA148143]; Fogarty International Center [RO3
TW007900]
FX This research was supported, in part, by the NIH, National Cancer
Institute, Center for Population Health and Health Disparities (Grant
number: 5 P50 CA148143) and the Fogarty International Center (Grant
number: RO3 TW007900).
NR 24
TC 4
Z9 4
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD OCT
PY 2012
VL 21
IS 10
BP 1716
EP 1721
DI 10.1158/1055-9965.EPI-12-0242
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 017FS
UT WOS:000309576100014
PM 22837144
ER
PT J
AU Cui, Y
Cai, QY
Qu, SM
Chow, WH
Wen, WQ
Xiang, YB
Wu, J
Rothman, N
Yang, G
Shu, XO
Gao, YT
Zheng, W
AF Cui, Yong
Cai, Qiuyin
Qu, Shimian
Chow, Wong-Ho
Wen, Wanqing
Xiang, Yong-Bing
Wu, Jie
Rothman, Nathaniel
Yang, Gong
Shu, Xiao-Ou
Gao, Yu-Tang
Zheng, Wei
TI Association of Leukocyte Telomere Length with Colorectal Cancer Risk:
Nested Case-Control Findings from the Shanghai Women's Health Study
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID PREDISPOSITION FACTOR; CELL SENESCENCE; BLOOD-CELLS; DYSFUNCTION;
CARCINOMA; LONGER; SURVIVAL; SHORTER; DISEASE; AGE
AB Background: Telomeres are specialized chromatin structures essential for maintenance of chromosomal integrity and stability. Abnormal alteration of telomere length has been linked to several cancers; however, epidemiologic evidence about the association of telomere length with colorectal cancer risk has been conflicting.
Methods: We conducted a nested case-control study to evaluate the association between telomere length and colorectal cancer risk using peripheral blood samples collected before cancer diagnosis. The study included 441 women with incident colorectal cancer and 549 matched controls. Monochrome multiplex quantitative PCR was applied to measure relative telomere length. Multiple logistic regressions were used to derive adjusted OR with 95% confidence intervals (CI) as the measure of association between telomere length and subsequent colorectal cancer risk.
Results: A U-shaped association was observed between telomere length and colorectal cancer risk (test for nonlinearity P 0.0112). Women with telomere length in the third quintile (40th-60th percentiles) had the lowest risk of colorectal cancer, and the risks were elevated with a shorter or longer telomere length. This Ushaped association did not statistically differ for colon cancer and rectum cancer.Conclusions and Impact: Our prospective study revealed a U-shaped association between telomere length in peripheral blood cells and colorectal cancer risk. Our findings provide strong evidence that both very short and very long telomeres are associated with increased risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 21(10); 1807-13. (c) 2012 AACR.
C1 [Cui, Yong; Cai, Qiuyin; Qu, Shimian; Wen, Wanqing; Wu, Jie; Yang, Gong; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Med Ctr, Div Epidemiol, Dept Med, Nashville, TN 37203 USA.
Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Chow, Wong-Ho; Rothman, Nathaniel] NCI, Occupat Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
[Xiang, Yong-Bing; Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
RP Zheng, W (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, 2525 W End Ave,8th Floor, Nashville, TN 37203 USA.
EM wei.zheng@vanderbilt.edu
FU Vanderbilt-Ingram Cancer Center [P30 CA68485]; NIH grant [R37 CA 070867]
FX The authors wish to thank Ms. Regina Courtney for her excellent
laboratory assistance in sample handling and preparation. Sample
preparations and telomere length assays were conducted at the Survey and
Biospecimen Shared Resource, which is supported in part by the
Vanderbilt-Ingram Cancer Center (P30 CA68485).; Funding support for this
work was provided by NIH grant (R37 CA 070867).
NR 35
TC 24
Z9 24
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD OCT
PY 2012
VL 21
IS 10
BP 1807
EP 1813
DI 10.1158/1055-9965.EPI-12-0657
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 017FS
UT WOS:000309576100025
PM 22911335
ER
PT J
AU Kristal, AR
Till, C
Tangen, CM
Goodman, PJ
Neuhouser, ML
Stanczyk, FZ
Chu, LW
Patel, SK
Thompson, IM
Reichardt, JK
Hoque, A
Platz, EA
Figg, WD
Van Bokhoven, A
Lippman, SM
Hsing, AW
AF Kristal, Alan R.
Till, Cathee
Tangen, Catherine M.
Goodman, Phyllis J.
Neuhouser, Marian L.
Stanczyk, Frank Z.
Chu, Lisa W.
Patel, Sherfaraz K.
Thompson, Ian M.
Reichardt, Juergen K.
Hoque, Ashraful
Platz, Elizabeth A.
Figg, William D.
Van Bokhoven, Adrie
Lippman, Scott M.
Hsing, Ann W.
TI Associations of Serum Sex Steroid Hormone and 5 alpha-Androstane-3
alpha, 17 beta-Diol Glucuronide Concentrations with Prostate Cancer Risk
Among Men Treated with Finasteride
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID FREE TESTOSTERONE; MODELING APPROACH; PREVENTION TRIAL; HYPERPLASIA;
DUTASTERIDE; SENSITIVITY; EXPERIENCE; BIAS
AB Background: Finasteride, an inhibitor of 5 alpha-reductase (type II), lowers intraprostatic dihydrotestosterone (DHT), which is reflected in serum as reduced 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (3 alpha-dG). It also modestly increases serum testosterone (T), estrone (E-1), and estradiol (E-2). In this altered hormonal milieu, it is unknown whether serum concentrations of these hormones are associated with prostate cancer risk.
Methods: In this nested case-control study of men in the finasteride arm of the Prostate Cancer Prevention Trial, sex steroid hormones and sex hormone binding globulin were measured at baseline and approximately 3-year posttreatment in 553 prostate cancer cases and 694 controls.
Results: Median posttreatment changes in concentrations of 3a-dG, T, E1, and E-2 were -73.8%, +10.1%, +11.2%, and +7.5% (all P < 0.001), respectively. Neither the pre- nor posttreatment concentrations of 3a-dG, nor its change, were associated with risk. Pretreatment, high concentrations of E1 and low concentrations of T were associated with increased cancer risk [ OR; 95% confidence interval (CI) quartile 4 vs. 1: 1.38 (0.99-1.93) P-trend = 0.03; 0.64 (0.43-0.93) P-trend = 0.07, respectively]. Posttreatment, high concentrations of both E1 and E2 were associated with increased cancer risk [ OR; 95% CI quartile 4 vs. 1: 1.54 (1.09-2.17) Ptrend 0.03; 1.49 (1.07-2.07) P-trend = 0.02, respectively].
Conclusions: Among finasteride-treated men, concentrations of 3a-dG were not associated with total or Gleason grades 2 to 6, 7 to 10, or 8 to 10 cancer. High serum estrogens may increase cancer risk when intraprostatic DHT is pharmacologically lowered.
Impact: Low posttreatment serum estrogens may identify men more likely to benefit from use of finasteride to prevent prostate cancer. Cancer Epidemiol Biomarkers Prev; 21(10); 1823-32. (c) 2012 AACR.
C1 [Kristal, Alan R.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Kristal, Alan R.; Neuhouser, Marian L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Stanczyk, Frank Z.; Patel, Sherfaraz K.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA.
[Chu, Lisa W.] NCI, Div Canc Epidemiol, Bethesda, MD 20892 USA.
[Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA.
[Hoque, Ashraful] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA.
[Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Figg, William D.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Van Bokhoven, Adrie] Univ Colorado, Dept Pathol, Denver, CO USA.
[Lippman, Scott M.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
[Reichardt, Juergen K.] James Cook Univ, Fac Med Hlth & Mol Sci, Brisbane, Qld, Australia.
RP Kristal, AR (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Div Publ Hlth Sci, 1100 Fairview Ave N,Mail Stop M4-B402,POB 19024, Seattle, WA 98109 USA.
EM akristal@fhcrc.org
RI Figg Sr, William/M-2411-2016;
OI Kristal, Alan/0000-0002-7329-1617
FU National Cancer Institute [P01-CA108964]; Intramural Research Program of
the U.S. NIH, National Cancer Institute, Division of Cancer Epidemiology
and Genetics [P30-CA054174]; Cancer Center Support Grant for the Cancer
Therapy and Research Center at the University of Texas Health Science
Center at San Antonio [P30 CA015704-36]; Cancer Center Support Grant for
the Seattle Cancer Consortium, Seattle, WA
FX This work was funded by the following: P01-CA108964 from the National
Cancer Institute; Intramural Research Program of the U.S. NIH, National
Cancer Institute, Division of Cancer Epidemiology and Genetics;
P30-CA054174, the Cancer Center Support Grant for the Cancer Therapy and
Research Center at the University of Texas Health Science Center at San
Antonio; and P30 CA015704-36, the Cancer Center Support Grant for the
Seattle Cancer Consortium, Seattle, WA.
NR 22
TC 6
Z9 6
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD OCT
PY 2012
VL 21
IS 10
BP 1823
EP 1832
DI 10.1158/1055-9965.EPI-12-0695
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 017FS
UT WOS:000309576100027
PM 22879203
ER
PT J
AU Zheng, L
Enewold, L
Zahm, SH
Shriver, CD
Zhou, J
Marrogi, A
McGlynn, KA
Zhu, KM
AF Zheng, Li
Enewold, Lindsey
Zahm, Shelia H.
Shriver, Craig D.
Zhou, Jing
Marrogi, Aizen
McGlynn, Katherine A.
Zhu, Kangmin
TI Lung Cancer Survival among Black and White Patients in an Equal Access
Health System
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID AFRICAN-AMERICAN PATIENTS; LEUKEMIA GROUP-B; RACIAL DISPARITIES;
BREAST-CANCER; SOCIOECONOMIC-STATUS; LARGE COHORT; STAGE; DIAGNOSIS;
OUTCOMES; RACE
AB Background: Racial disparities in lung cancer outcomes have been observed in the general population. However, it is unclear whether survival differences persist when patients have equal access to health care. Our objective was to determine if lung cancer survival differed among black and white patients in the U.S. Military Health System (MHS), an equal access health care system.
Methods: The study subjects were 10,181 black and white patients identified through the Department of Defense's Automated Central Tumor Registry, who were 20 years old or more and diagnosed with lung cancer between 1990 and 2003. Racial differences in all-cause survival were examined using the Kaplan-Meier method and Cox proportional hazards regression models stratified by histology. For comparison, survival rates in the general population were calculated using Surveillance Epidemiology and End Results-9 data.
Results: Analyses included 9,154 white and 1,027 black patients: 1,834 small cell lung cancers, 3,876 adenocarcinomas, 2,741 squamous cell carcinomas, and 1,730 large cell carcinomas. Although more favorable crude survival was observed among black patients than white patients with small cell lung cancer (P = 0.04), survival was similar between the two groups after covariate adjustment. Racial differences in survival were nonsignificant for adenocarcinomas, squamous cell carcinomas, and large cell carcinomas. Survival rates appeared to be better in the MHS than in the general population.
Conclusions and Impact: All-cause survival was similar among black and white lung cancer patients in the MHS. Providing equal access to health care may eliminate racial disparities in lung cancer survival while improving the outcome of all cases. Cancer Epidemiol Biomarkers Prev; 21(10); 1841-7. (c) 2012 AACR.
C1 [Zhu, Kangmin] US Mil Canc Inst, Program Epidemiol, Rockville, MD 20852 USA.
[Zahm, Shelia H.; McGlynn, Katherine A.] NCI, Bethesda, MD 20892 USA.
[Shriver, Craig D.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
[Shriver, Craig D.; Zhu, Kangmin] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Marrogi, Aizen] Walter Reed Army Inst Res, Silver Spring, MD USA.
RP Zhu, KM (reprint author), US Mil Canc Inst, Program Epidemiol, 11300 Rockville Pike,Suite 1215, Rockville, MD 20852 USA.
EM kzhu@usuhs.mil
RI Zahm, Shelia/B-5025-2015
FU United States Military Cancer Institute via the Uniformed Services
University of the Health Sciences under the Henry M. Jackson Foundation
for the Advancement of Military Medicine
FX This research was supported by the United States Military Cancer
Institute via the Uniformed Services University of the Health Sciences
under the auspices of the Henry M. Jackson Foundation for the
Advancement of Military Medicine. The authors thank the Armed Forces
Institute of Pathology for providing the ACTUR data; Dr. Hongyu Wu for
her help in computer programming; and Dr. Sally Bushhouse of Minnesota
Cancer Surveillance System for providing the useful MN-PATRL document.
NR 29
TC 13
Z9 13
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD OCT
PY 2012
VL 21
IS 10
BP 1841
EP 1847
DI 10.1158/1055-9965.EPI-12-0560
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 017FS
UT WOS:000309576100029
PM 22899731
ER
PT J
AU Engel, LS
Orlow, I
Sima, CS
Satagopan, J
Mujumdar, U
Roy, P
Yoo, S
Sandler, DP
Alavanja, MC
AF Engel, Lawrence S.
Orlow, Irene
Sima, Camelia S.
Satagopan, Jaya
Mujumdar, Urvi
Roy, Pampa
Yoo, Sarah
Sandler, Dale P.
Alavanja, Michael C.
TI Vitamin D Receptor Gene Haplotypes and Polymorphisms and Risk of Breast
Cancer: A Nested Case-Control Study
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID FRENCH E3N COHORT; AGRICULTURAL HEALTH; SUN EXPOSURE; WOMEN; POPULATION;
ASSOCIATION; MORTALITY; RADIATION; DIETARY; ANTICANCER
AB Background: Observational and experimental studies suggest that vitamin D may influence breast cancer etiology. Most known effects of vitaminDare mediated via the vitamin D receptor (VDR). Few polymorphisms in the VDR gene have been well studied in relation to breast cancer risk and results have been inconsistent.
Methods: We investigated VDR polymorphisms and haplotypes in relation to breast cancer risk by genotyping 26 single nucleotide polymorphisms (SNP) that (i) had known/suspected impact on VDR function, (ii) were tagging SNPs for the three VDR haplotype blocks among whites, or (iii) were previously associated with breast cancer risk. We estimated odds ratios (OR) and 95% confidence intervals (CI) in relation to breast cancer risk among 270 incident cases and 554 matched controls within the Agricultural Health Study cohort.
Results: In individual SNP analyses, homozygous carriers of the minor allele for rs2544038 had significantly increased breast cancer risk (OR - 1.5; 95% CI: 1.0-2.5) and homozygous carriers of the minor allele for rs11168287 had significantly decreased risk (OR 0.6; 95% CI: 0.4-1.0). Carriers of the minor allele for rs2239181 exhibited marginally significant association with risk (OR = 1.4; 95% CI: 0.9-2.0). Haplotype analyses revealed three haplotype groups (blocks "A," "B," and "C"). Haplotype GTCATTTCCTA in block B was significantly associated with reduced risk (OR 0.5; 95% CI: 0.3-0.9).
Conclusions: These results suggest that variation in VDR may be associated with breast cancer risk.
Impact: Our findings may help guide future research needed to define the role of vitamin D in breast cancer prevention. Cancer Epidemiol Biomarkers Prev; 21(10); 1856-67. (c) 2012 AACR.
C1 [Engel, Lawrence S.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Sandler, Dale P.] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Orlow, Irene; Sima, Camelia S.; Satagopan, Jaya; Mujumdar, Urvi; Roy, Pampa; Yoo, Sarah] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Alavanja, Michael C.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Engel, LS (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
EM Larry.Engel@unc.edu
OI Satagopan, Jaya/0000-0001-7102-5633; Sandler, Dale/0000-0002-6776-0018;
Orlow, Irene/0000-0001-6234-6961; Engel, Lawrence/0000-0001-9268-4830
FU American Cancer Society [RSG-06-016-01-CNE]; NIH (Intramural Research
Program of the National Institute of Environmental Health Sciences)
[Z01-ES049030]; NIH (Intramural Research Program of the National Cancer
Institute) [Z01-CP010119]
FX This work was supported by American Cancer Society (RSG-06-016-01-CNE to
L.S. Engel); NIH (Intramural Research Program of the National Institute
of Environmental Health Sciences, Z01-ES049030; Intramural Research
Program of the National Cancer Institute, Z01-CP010119).
NR 68
TC 22
Z9 23
U1 0
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD OCT
PY 2012
VL 21
IS 10
BP 1856
EP 1867
DI 10.1158/1055-9965.EPI-12-0551
PG 12
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 017FS
UT WOS:000309576100031
PM 22892281
ER
PT J
AU Yin, ZY
Menendez, D
Resnick, MA
French, JE
Janardhan, KS
Jetten, AM
AF Yin, Zhengyu
Menendez, Daniel
Resnick, Michael A.
French, John E.
Janardhan, Kyathanahalli S.
Jetten, Anton M.
TI RAP80 Is Critical in Maintaining Genomic Stability and Suppressing Tumor
Development
SO CANCER RESEARCH
LA English
DT Article
ID DNA-DAMAGE RESPONSE; BREAST-CANCER SUSCEPTIBILITY; IONIZING-RADIATION;
IN-VIVO; MAMMARY TUMORIGENESIS; PROTEIN MODIFICATIONS; CHROMATIN
RESPONSE; TARGETS BRCA1; HISTONE H2AX; MICE LACKING
AB The ubiquitin interaction motif-containing protein RAP80 was recently found to play a key role in DNA damage response (DDR) signaling by facilitating the translocation of several DDR mediators, including BRCA1, to ionizing irradiation (IR)-induced foci. In this study, we examine the effect of the loss of RAP80 on genomic stability and the susceptibility to cancer development in RAP80 null (RAP80(-/-)) mice. RAP80(-/-) mice are viable and did not exhibit any apparent developmental defects. Mouse embryonic fibroblasts (MEF) derived from RAP80(-/-) mice underwent premature senescence compared with wild-type (WT) MEFs, were more sensitive to IR, and exhibited a higher level of spontaneous and IR-induced genomic instability. RAP80(-/-) thymocytes were more sensitive to IR-induced cell death than WT thymocytes. RAP80(-/-) mice were more susceptible to spontaneous lymphoma development and the development of 7,12-dimethylbenz(a)anthracene-induced mammary gland tumors. Moreover, the loss of RAP80 accelerated tumor formation in both p53(-/-) and p53(+/-) mice. Our data indicate that RAP80-deficiency promotes genomic instability and causes an increase in cancer risk consistent with the concept that RAP80 exhibits a tumor suppressor function. Cancer Res; 72(19); 5080-90. (C)2012 AACR.
C1 [Jetten, Anton M.] Natl Inst Environm Sci, NIH, Lab Resp Biol, Res Triangle Pk, NC 27709 USA.
[Menendez, Daniel; Resnick, Michael A.] Natl Inst Environm Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
[French, John E.] Natl Inst Environm Sci, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Janardhan, Kyathanahalli S.] NIH, Integrated Lab Syst Inc, Res Triangle Pk, NC USA.
RP Jetten, AM (reprint author), Natl Inst Environm Sci, NIH, Lab Resp Biol, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM jetten@niehs.nih.gov
OI Jetten, Anton/0000-0003-0954-4445
FU Intramural Research Program of the National Institute of Environmental
Health Sciences, NIH [Z01-ES-101586, Z01-ES065079]
FX This research was supported by the Intramural Research Program of the
National Institute of Environmental Health Sciences, NIH (Z01-ES-101586
to A. M. Jetten and Z01-ES065079 to M. A. Resnick).
NR 47
TC 15
Z9 15
U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2012
VL 72
IS 19
BP 5080
EP 5090
DI 10.1158/0008-5472.CAN-12-1484
PG 11
WC Oncology
SC Oncology
GA 016LY
UT WOS:000309521200022
PM 22896338
ER
PT J
AU Iwai, A
Bourboulia, D
Mollapour, M
Jensen-Taubman, S
Lee, S
Donnelly, AC
Yoshida, S
Miyajima, N
Tsutsumi, S
Smith, AK
Sun, D
Wu, XL
Blagg, BS
Trepel, JB
Stetler-Stevenson, WG
Neckers, L
AF Iwai, Aki
Bourboulia, Dimitra
Mollapour, Mehdi
Jensen-Taubman, Sandra
Lee, Sunmin
Donnelly, Alison C.
Yoshida, Soichiro
Miyajima, Naoto
Tsutsumi, Shinji
Smith, Armine K.
Sun, David
Wu, Xiaolin
Blagg, Brian S.
Trepel, Jane B.
Stetler-Stevenson, William G.
Neckers, Len
TI Combined inhibition of Wee1 and Hsp90 activates intrinsic apoptosis in
cancer cells
SO CELL CYCLE
LA English
DT Article
DE Wee1; heat shock protein 90; apoptosis; cancer; molecular targeted
anticancer drugs
ID SURVIVIN; PHOSPHORYLATION; TARGET; GROWTH; CHEMOTHERAPY; COMPLEXES;
CYCLE
AB Heat shock protein 90 (Hsp90) is an essential, evolutionarily conserved molecular chaperone. Cancer cells rely on Hsp90 to chaperone mutated and/or activated oncoproteins, and its involvement in numerous signaling pathways makes it an attractive target for drug development. Surprisingly, however, the impact of Hsp90 inhibitors on cancer cells is frequently cytostatic in nature, and efforts to enhance the antitumor activity of Hsp90 inhibitors in the clinic remain a significant challenge. In agreement with previous data obtained using Wee1 siRNA, we show that dual pharmacologic inhibition of Wee1 tyrosine kinase and Hsp90 causes cancer cells to undergo apoptosis in vitro and in vivo. Gene expression profiling revealed that induction of the intrinsic apoptotic pathway by this drug combination coincided with transcriptional downregulation of Survivin and Wee1, an outcome not seen in cells treated separately with either agent. At the translational level, expression of these two proteins, as well as activated Akt, was completely abrogated. These data support the hypothesis that Wee1 inhibition sensitizes cancer cells to Hsp90 inhibitors; they establish combined Wee1/Hsp90 inhibition as a novel therapeutic strategy; and they provide a mechanistic rationale for enhancing the proapoptotic activity of Hsp90 inhibitors.
C1 [Iwai, Aki; Mollapour, Mehdi; Yoshida, Soichiro; Miyajima, Naoto; Tsutsumi, Shinji; Smith, Armine K.; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Bourboulia, Dimitra; Jensen-Taubman, Sandra; Stetler-Stevenson, William G.] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Lee, Sunmin; Trepel, Jane B.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Donnelly, Alison C.; Blagg, Brian S.] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA.
[Sun, David; Wu, Xiaolin] NCI, Lab Mol Technol, SAIC Frederick, Frederick, MD 21701 USA.
RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM neckers@nih.gov
RI Stetler-Stevenson, William/H-6956-2012
OI Stetler-Stevenson, William/0000-0002-5500-5808
FU National Cancer Institute, Center for Cancer Research
FX We are grateful to Dr. J.D. Robertson for Jurkat cell lines and Ms.
Catherine Wells for assistance with tumor xenograft studies. This work
was supported by funds from the Intramural Research Program of the
National Cancer Institute, Center for Cancer Research.
NR 27
TC 11
Z9 11
U1 0
U2 7
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD OCT 1
PY 2012
VL 11
IS 19
BP 3649
EP 3655
DI 10.4161/cc.21926
PG 7
WC Cell Biology
SC Cell Biology
GA 016JE
UT WOS:000309513300023
PM 22935698
ER
PT J
AU Martins, D
Agodoa, L
Norris, KC
AF Martins, David
Agodoa, Lawrence
Norris, Keith C.
TI Hypertensive chronic kidney disease in African Americans: Strategies for
improving care
SO CLEVELAND CLINIC JOURNAL OF MEDICINE
LA English
DT Article
ID BLOOD-PRESSURE CONTROL; STAGE RENAL-DISEASE; RISK; DISPARITIES;
CONSENSUS; NEPHROPATHY; ASSOCIATION; COMMITTEE; BLACKS; UPDATE
AB African Americans have a disproportionate burden of chronic kidney disease (CKD), which tends to have an earlier onset and a more rapid progression in this population. Many of the factors responsible for the rapid progression of CKD in African Americans are detectable by screening and are modifiable with prompt therapy.
C1 [Martins, David; Norris, Keith C.] Charles R Drew Univ, Clin Res Ctr, Lynwood, CA USA.
[Agodoa, Lawrence] NIDDKD, Off Minor Hlth Res Coordinat, Bethesda, MD 20892 USA.
[Agodoa, Lawrence] NIDDK, Chron Kidney Dis Program, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA.
[Agodoa, Lawrence] NIDDK, End Stage Renal Dis Program, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA.
RP Norris, KC (reprint author), Charles R Drew Univ Med & Sci, 1731 E 120th St, Los Angeles, CA 90059 USA.
EM keithnorris@cdrewu.edu
FU NIH [RR026138, MD000182]
FX Support for this paper was provided in part by NIH grants RR026138 and
MD000182.
NR 34
TC 6
Z9 7
U1 0
U2 1
PU CLEVELAND CLINIC
PI CLEVELAND
PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA
SN 0891-1150
J9 CLEV CLIN J MED
JI Clevel. Clin. J. Med.
PD OCT
PY 2012
VL 79
IS 10
BP 726
EP 734
DI 10.3949/ccjm.79a.11109
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 017VJ
UT WOS:000309619000009
PM 23027732
ER
PT J
AU Poston, B
Kukke, SN
Paine, RW
Francis, S
Hallett, M
AF Poston, Brach
Kukke, Sahana N.
Paine, Rainer W.
Francis, Sophia
Hallett, Mark
TI Cortical silent period duration and its implications for surround
inhibition of a hand muscle
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE facilitation; human; inhibition; motor cortex; transcranial magnetic
stimulation
ID TRANSCRANIAL MAGNETIC STIMULATION; END-POINT ACCURACY; HUMAN MOTOR
CORTEX; PARKINSONS-DISEASE; BRAIN-STIMULATION; INTRACORTICAL INHIBITION;
ISOMETRIC CONTRACTIONS; MOVEMENT INITIATION; WRITERS CRAMP; OLD ADULTS
AB Surround inhibition is a neural mechanism that assists in the focusing of excitatory drive to muscles responsible for a given movement (agonist muscles) by suppressing unwanted activity in muscles not relevant to the movement (surround muscles). The purpose of the study was to determine the contribution of ?-aminobutyric acidB receptor-mediated intracortical inhibition, as assessed by the cortical silent period (CSP), to the generation of surround inhibition in the motor system. Eight healthy adults (five women and three men, 29.8 +/- 9 years) performed isometric contractions with the abductor digiti minimi (ADM) muscle in separate conditions with and without an index finger flexion movement. The ADM motor evoked potential amplitude and CSP duration elicited by transcranial magnetic stimulation were compared between a control condition in which the ADM was activated independently and during conditions involving three phases (pre-motor, phasic, and tonic) of the index finger flexion movement. The motor evoked potential amplitude of the ADM was greater during the control condition compared with the phasic condition. Thus, the presence of surround inhibition was confirmed in the present study. Most critically, the CSP duration of the ADM decreased during the phasic stage of finger flexion compared with the control condition, which indicated a reduction of this type of intracortical inhibition during the phasic condition. These findings indicate that ?-aminobutyric acidB receptor-mediated intracortical inhibition, as measured by the duration of the CSP, does not contribute to the generation of surround inhibition in hand muscles.
C1 [Poston, Brach; Kukke, Sahana N.; Paine, Rainer W.; Francis, Sophia; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM hallettm@ninds.nih.gov
FU NINDS
FX This work was supported by the NINDS intramural research program. The
authors would like to thank Tianxia Wu for assistance with the
statistical analysis.
NR 56
TC 7
Z9 7
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-816X
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD OCT
PY 2012
VL 36
IS 7
BP 2964
EP 2971
DI 10.1111/j.1460-9568.2012.08212.x
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 015QI
UT WOS:000309460600011
PM 22775302
ER
PT J
AU Konova, AB
Moeller, SJ
Tomasi, D
Parvaz, MA
Alia-Klein, N
Volkow, ND
Goldstein, RZ
AF Konova, Anna B.
Moeller, Scott J.
Tomasi, Dardo
Parvaz, Muhammad A.
Alia-Klein, Nelly
Volkow, Nora D.
Goldstein, Rita Z.
TI Structural and behavioral correlates of abnormal encoding of money value
in the sensorimotor striatum in cocaine addiction
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE fMRI; reward; sensorimotor striatum; ventromedial prefrontal cortex;
voxel-based morphometry
ID MEDIAL ORBITOFRONTAL CORTEX; VOXEL-BASED MORPHOMETRY; PREFRONTAL CORTEX;
DORSAL STRIATUM; DRUG-ADDICTION; NEURAL SYSTEMS; GRAY-MATTER;
DORSOLATERAL STRIATUM; INTERTEMPORAL CHOICE; SYNAPTIC PLASTICITY
AB Abnormalities in frontostriatal systems are thought to be central to the pathophysiology of addiction, and may underlie the maladaptive processing of the highly generalizable reinforcer, money. Although abnormal frontostriatal structure and function have been observed in individuals addicted to cocaine, it is less clear how individual variability in brain structure is associated with brain function to influence behavior. Our objective was to examine frontostriatal structure and neural processing of money value in chronic cocaine users and closely matched healthy controls. A reward task that manipulated different levels of money was used to isolate neural activity associated with money value. Gray matter volume measures were used to assess frontostriatal structure. Our results indicated that cocaine users had an abnormal money value signal in the sensorimotor striatum (right putamen/globus pallidus) that was negatively associated with accuracy adjustments to money and was more pronounced in individuals with more severe use. In parallel, group differences were also observed in both the function and gray matter volume of the ventromedial prefrontal cortex; in the cocaine users, the former was directly associated with response to money in the striatum. These results provide strong evidence for abnormalities in the neural mechanisms of valuation in addiction and link these functional abnormalities with deficits in brain structure. In addition, as value signals represent acquired associations, their abnormal processing in the sensorimotor striatum, a region centrally implicated in habit formation, could signal disadvantageous associative learning in cocaine addiction.
C1 [Konova, Anna B.; Moeller, Scott J.; Tomasi, Dardo; Parvaz, Muhammad A.; Alia-Klein, Nelly; Goldstein, Rita Z.] Brookhaven Natl Lab, Upton, NY 11973 USA.
[Konova, Anna B.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA.
[Tomasi, Dardo; Volkow, Nora D.] Natl Inst Alcohol & Alcoholism, Bethesda, MD USA.
[Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA.
RP Goldstein, RZ (reprint author), Brookhaven Natl Lab, Upton, NY 11973 USA.
EM rgoldstein@bnl.gov
RI Tomasi, Dardo/J-2127-2015; Moeller, Scott/L-5549-2016;
OI Moeller, Scott/0000-0002-4449-0844; Parvaz, Muhammad/0000-0002-2671-2327
FU National Institute on Drug Abuse [1R01DA023579]; General Clinical
Research Center [5-MO1-RR-10710]; Brookhaven Science Associates, LLC
[DE-AC02-98CHI-886]; U.S. Department of Energy
FX This work was supported by grants from the National Institute on Drug
Abuse (grant no. 1R01DA023579 to R.Z.G.) and General Clinical Research
Center (grant no. 5-MO1-RR-10710). This article has been authored by
Brookhaven Science Associates, LLC under Contract no. DE-AC02-98CHI-886
with the U.S. Department of Energy. The United States Government
retains, and the publisher, by accepting the article for publication,
acknowledges, a world-wide license to publish or reproduce the published
form of this manuscript, or allow others to do so, for the United States
Government purposes.
NR 71
TC 20
Z9 20
U1 2
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-816X
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD OCT
PY 2012
VL 36
IS 7
BP 2979
EP 2988
DI 10.1111/j.1460-9568.2012.08211.x
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 015QI
UT WOS:000309460600013
PM 22775285
ER
PT J
AU Caine, SB
Thomsen, M
Barrett, AC
Collins, GT
Grundt, P
Newman, AH
Butler, P
Xu, M
AF Caine, S. Barak
Thomsen, Morgane
Barrett, Andrew C.
Collins, Gregory T.
Grundt, Peter
Newman, Amy Hauck
Butler, Paul
Xu, Ming
TI Cocaine Self-Administration in Dopamine D-3 Receptor Knockout Mice
SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE cocaine; dopamine receptors; knockout mice; progressive ratio;
food-maintained behavior
ID CONDITIONED PLACE PREFERENCE; DISCRIMINATIVE-STIMULUS; SEEKING BEHAVIOR;
D3 RECEPTOR; RHESUS-MONKEYS; MUTANT MICE; INDUCED REINSTATEMENT;
SELECTIVE ANTAGONIST; LOCOMOTOR-ACTIVITY; AGONIST 7-OH-DPAT
AB The dopamine D-3 receptor has received attention over the last two decades as a target for medications development for substance abuse disorders. Results have remained mixed. Despite emergence of more D-3-selective ligands, possible attribution of observed effects to D-2 receptors remains a concern. Knockout mice may help shed light on mechanisms. Here we evaluated the effect of constitutive D-3 receptor inactivation ("knockout") on the reinforcing effects of cocaine. We tested D-3 wild-type (WT), heterozygous (D-3(+/-)), and knockout (D-3(-/-)), mice in acquisition and maintenance of intravenous self-administration across a broad range of cocaine doses, using a fixed ratio (FR) 1 and a progressive ratio (PR) schedule of reinforcement, along with parallel food-reinforced studies. Generally, D-3(-/-) mice showed cocaine self-administration comparable to WT controls across assays. Moderate and nonsignificant trends toward lesser reinforcing effects of a low cocaine dose (0.32 mg/kg) were apparent in acquisition and PR studies, consistent with the idea that the D-3 receptor may play a subtle role in the reinforcing effects of low cocaine doses under low FR conditions. However, those effects with cocaine self-administration were more subtle than the lower responding of D-3 knockout mice observed with food-maintained behavior. In addition, the D-3 antagonist PG01037 failed to affect cocaine self-administration under an FR 1 schedule in WT mice. The present data do not support a necessary role for the D-3 receptor in the direct reinforcing effects of cocaine.
C1 [Caine, S. Barak; Thomsen, Morgane; Barrett, Andrew C.; Collins, Gregory T.] Harvard Univ, McLean Hosp, Alcohol & Drug Abuse Res Ctr, Sch Med, Belmont, MA 02478 USA.
[Grundt, Peter; Newman, Amy Hauck] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA.
[Butler, Paul] Pfizer Worldwide R&D, Sandwich, Kent, England.
[Xu, Ming] Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA.
RP Caine, SB (reprint author), Harvard Univ, McLean Hosp, Alcohol & Drug Abuse Res Ctr, Sch Med, 115 Mill St, Belmont, MA 02478 USA.
EM barak@mclean.harvard.edu
RI Collins, Gregory/K-3125-2012
FU NIDA/NIH [DA12142, DA02472, DA17323, DA025088]; NIDA-Intramural Research
Program; NIH/NIDA [K99DA027825]
FX This work was supported by NIDA/NIH Grants DA12142 (to S. Barak Caine),
DA02472 (to S. Barak Caine, Andrew C. Barrett, Gregory T. Collins),
DA17323 (to Ming Xu). DA025088 (to Ming Xu) and the NIDA-Intramural
Research Program (to Amy Hauck Newman). In addition, Morgane Thomsen was
supported by NIH/NIDA Grant K99DA027825 while preparing this article. We
thank Jennifer Dohrmann, Joon Y. Boon, Jill Berkowitz, Kate Woodard, and
Melissa Gale for expert technical assistance.
NR 75
TC 17
Z9 17
U1 0
U2 11
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 1064-1297
J9 EXP CLIN PSYCHOPHARM
JI Exp. Clin. Psychopharmacol.
PD OCT
PY 2012
VL 20
IS 5
BP 352
EP 363
DI 10.1037/a0029135
PG 12
WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy;
Psychiatry
SC Psychology; Pharmacology & Pharmacy; Psychiatry
GA 015GS
UT WOS:000309435000002
PM 22867038
ER
PT J
AU Shurtleff, AC
Nguyen, TL
Kingery, DA
Bavari, S
AF Shurtleff, Amy C.
Nguyen, Tam L.
Kingery, David A.
Bavari, Sina
TI Therapeutics for filovirus infection: traditional approaches and
progress towards in silico drug design
SO EXPERT OPINION ON DRUG DISCOVERY
LA English
DT Review
DE ebolavirus; filovirus; glycoprotein; library screening; marburgvirus;
protein interactions; rational drug design; small molecule; structure;
structure-based drug design; viral entry mechanism; viral hemorrhagic
fever
ID EBOLA-VIRUS GLYCOPROTEIN; MATRIX PROTEIN VP40; MARBURG
HEMORRHAGIC-FEVER; NIEMANN-PICK C1; CHOLESTEROL ABSORPTION INHIBITORS;
SMALL-MOLECULE INHIBITORS; DOUBLE-STRANDED-RNA; PRELIMINARY-X-RAY;
CYNOMOLGUS MACAQUES; NUCLEOCAPSID PROTEINS
AB Introduction: Ebolaviruses and marburgviruses cause severe and often lethal human hemorrhagic fevers. As no FDA-approved therapeutics are available for these infections, efforts to discover new therapeutics are important, especially because these pathogens are considered biothreats and emerging infectious diseases. All methods for discovering new therapeutics should be considered, including compound library screening in vitro against virus and in silico structure-based drug design, where possible, if sufficient biochemical and structural information is available.
Areas covered: This review covers the structure and function of filovirus proteins, as they have been reported to date, as well as some of the current antiviral screening approaches. The authors discuss key studies mapping small-molecule modulators that were found through library and in silico screens to potential sites on viral proteins or host proteins involved in virus trafficking and pathogenesis. A description of ebolavirus and marburgvirus diseases and available animal models is also presented.
Expert opinion: To discover novel therapeutics with potent efficacy using sophisticated computational methods, more high-resolution crystal structures of filovirus proteins and more details about the protein functions and host interaction will be required. Current compound screening efforts are finding active antiviral compounds, but an emphasis on discovery research to investigate protein structures and functions enabling in silico drug design would provide another avenue for finding antiviral molecules. Additionally, targeting of protein-protein interactions may be a future avenue for drug discovery since disrupting catalytic sites may not be possible for all proteins.
C1 [Shurtleff, Amy C.; Kingery, David A.; Bavari, Sina] USA, Med Res Inst Infect Dis, Integrated Toxicol Div, Frederick, MD 21702 USA.
[Nguyen, Tam L.] NCI, Target Struct Based Drug Discovery Grp, SAIC Frederick, Frederick, MD 21702 USA.
RP Shurtleff, AC (reprint author), USA, Med Res Inst Infect Dis, Integrated Toxicol Div, 1425 Porter St, Frederick, MD 21702 USA.
EM amy.c.shurtleff.ctr@us.army.mil
FU Defense Threat Reduction Agency; Transformational Medical Technologies
FX This paper was sponsored by the Defense Threat Reduction Agency and
Transformational Medical Technologies. The authors declare no other
conflicts of interest.
NR 196
TC 5
Z9 5
U1 0
U2 21
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1746-0441
EI 1746-045X
J9 EXPERT OPIN DRUG DIS
JI Expert. Opin. Drug Discov.
PD OCT
PY 2012
VL 7
IS 10
BP 935
EP 954
DI 10.1517/17460441.2012.714364
PG 20
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 015QK
UT WOS:000309460800005
PM 22873527
ER
PT J
AU Clausen, AR
Girandon, L
Ali, A
Knecht, W
Rozpedowska, E
Sandrini, MPB
Andreasson, E
Munch-Petersen, B
Piskur, J
AF Clausen, Anders R.
Girandon, Lenart
Ali, Ashfaq
Knecht, Wolfgang
Rozpedowska, Elzbieta
Sandrini, Michael P. B.
Andreasson, Erik
Munch-Petersen, Birgitte
Piskur, Jure
TI Two thymidine kinases and one multisubstrate deoxyribonucleoside kinase
salvage DNA precursors in Arabidopsis thaliana
SO FEBS JOURNAL
LA English
DT Article
DE Arabidopsis; deoxyribonucleoside kinase; gene duplication; nucleoside
nucleotide metabolism; thymidine kinase
ID CELL-CYCLE; SUBSTRATE-SPECIFICITY; DEOXYCYTIDINE KINASE; ENZYME;
DEGRADATION; BIOSYNTHESIS; DEFICIENT; PATHWAY; STRESS; PURINE
AB Deoxyribonucleotides are the building blocks of DNA and can be synthesized via de novo and salvage pathways. Deoxyribonucleoside kinases (EC 2.7.1.145) salvage deoxyribonucleosides by transfer of a phosphate group to the 5' of a deoxyribonucleoside. This salvage pathway is well characterized in mammals, but in contrast, little is known about how plants salvage deoxyribonucleosides. We show that during salvage, deoxyribonucleosides can be phosphorylated by extracts of Arabidopsis thaliana into corresponding monophosphate compounds with an unexpected preference for purines over pyrimidines. Deoxyribonucleoside kinase activities were present in all tissues during all growth stages. In the A. thaliana genome, we identified two types of genes that could encode enzymes which are involved in the salvage of deoxyribonucleosides. Thymidine kinase activity was encoded by two thymidine kinase 1 (EC 2.7.1.21)-like genes (AtTK1a and AtTK1b). Deoxyadenosine, deoxyguanosine and deoxycytidine kinase activities were encoded by a single AtdNK gene. T-DNA insertion lines of AtTK1a and AtTK1b mutant genes had normal growth, although AtTK1a AtTK1b double mutants died at an early stage, which indicates that AtTK1a and AtTK1b catalyze redundant reactions. The results obtained in the present study suggest a crucial role for the salvage of thymidine during early plant development. Database Sequence data from the present study have been deposited in the EMBL database/GenBank under accession numbers: AT3G07800.1 (AtTK1a), At5G23070.1 (AtTK1b) and AT1G72040.1 (AtdNK).
C1 [Clausen, Anders R.; Girandon, Lenart; Ali, Ashfaq; Rozpedowska, Elzbieta; Sandrini, Michael P. B.; Andreasson, Erik; Piskur, Jure] Lund Univ, Dept Cell & Organism Biol, S-22100 Lund, Sweden.
[Knecht, Wolfgang; Sandrini, Michael P. B.; Piskur, Jure] Tech Univ Denmark, BioCtr DTU, DK-2800 Lyngby, Denmark.
[Munch-Petersen, Birgitte] Roskilde Univ, Dept Sci Syst & Models, Roskilde, Denmark.
RP Clausen, AR (reprint author), NIEHS, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM clausenar@niehs.nih.gov
RI Clausen, Anders R./I-7229-2012;
OI Clausen, Anders Ranegaard/0000-0002-5069-0930
FU Swedish Research Council (VR); Cancerfonden (Sweden); Wenner-Gren
Foundation; Crafoord Foundation; Sorensen Foundation; Fysiografen; Jubi
Kinase ApS
FX The authors acknowledge funding from Swedish Research Council (VR),
Cancerfonden (Sweden), Wenner-Gren Foundation, Crafoord Foundation,
Sorensen Foundation, Fysiografen and Jubi Kinase ApS.
NR 38
TC 11
Z9 12
U1 1
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD OCT
PY 2012
VL 279
IS 20
BP 3889
EP 3897
DI 10.1111/j.1742-4658.2012.08747.x
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 015LL
UT WOS:000309447400010
PM 22897443
ER
PT J
AU Chason, RJ
McLain, AC
Sundaram, R
Chen, Z
Segars, JH
Pyper, C
Louis, GMB
AF Chason, Rebecca J.
McLain, Alexander C.
Sundaram, Rajeshwari
Chen, Zhen
Segars, James H.
Pyper, Cecilia
Louis, Germaine M. Buck
TI Preconception stress and the secondary sex ratio: a prospective cohort
study
SO FERTILITY AND STERILITY
LA English
DT Article
DE Fecundity; secondary sex ratio; stress; salivary cortisol; salivary
alpha-amylase; preconception
ID SALIVARY ALPHA-AMYLASE; TERRORIST ATTACKS; KOBE EARTHQUAKE; SEPTEMBER
11; CORTISOL; BIRTH; POPULATION; CONCEPTION; DISORDERS; DECLINE
AB Objective: To study the association between salivary stress biomarkers and the secondary sex ratio.
Design: Prospective, longitudinal cohort study.
Setting: Community setting in the United Kingdom.
Patient(s): On discontinuation of contraception for purposes of becoming pregnant, 338 women aged 18-40 years with complete data (90%) were followed until pregnant or up to six menstrual cycles.
Intervention(s): None.
Main Outcome Measure(s): Secondary sex ratio.
Result(s): Human chorionic gonadotropin pregnancies were detected in 207 (61%) women of whom 130 (63%) delivered singleton infants with available gender data. The adjusted odds ratio for a male birth was decreased for women in the highest quartile (AOR = 0.26; 95% confidence interval = 0.09, 0.74) of salivary cortisol relative to women in the lowest quartile during cycle 1. An inverse relation was observed between a-amylase and the 2 degrees sex ratio, though not statistically significant.
Conclusion(s): Our findings are consistent with a reversal in the 2 degrees sex ratio with increasing preconception salivary cortisol concentrations. This relation suggests that activation of the hypothalamus-pituitary-adrenal axis may have implications in sex allocation and requires further study. (Fertil Steril (R) 2012;98:937-41. (C)2012 by American Society for Reproductive Medicine.)
C1 [Chason, Rebecca J.; Segars, James H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[McLain, Alexander C.; Sundaram, Rajeshwari; Chen, Zhen; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA.
[Pyper, Cecilia] Univ Oxford, Natl Perinatal Epidemiol Unit, Oxford, England.
RP Chason, RJ (reprint author), NICHD, Reprod Biol & Med Branch, NIH, 10 Ctr Dr,BG 10 CRC,Rm 1E-3140, Bethesda, MD 20892 USA.
EM rebecca.chason@nih.gov
OI McLain, Alexander/0000-0002-5475-0670; Sundaram,
Rajeshwari/0000-0002-6918-5002; Buck Louis, Germaine/0000-0002-1774-4490
FU Eunice Kennedy Shriver National Institute of Child Health & Human
Development; U.K. National Health Service; DLM Charitable Trust
FX Supported in part by the intramural program of the Eunice Kennedy
Shriver National Institute of Child Health & Human Development and
grants from the U.K. National Health Service and the DLM Charitable
Trust.
NR 36
TC 7
Z9 7
U1 1
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD OCT
PY 2012
VL 98
IS 4
BP 937
EP 941
DI 10.1016/j.fertnstert.2012.06.037
PG 5
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 016XP
UT WOS:000309553500035
PM 22884014
ER
PT J
AU Keehn, J
Holwell, E
Abdul-Karim, R
Chin, LJ
Leu, CS
Sauer, MV
Klitzman, R
AF Keehn, Jason
Holwell, Eve
Abdul-Karim, Ruqayyah
Chin, Lisa Judy
Leu, Cheng-Shiun
Sauer, Mark V.
Klitzman, Robert
TI Recruiting egg donors online: an analysis of in vitro fertilization
clinic and agency websites' adherence to American Society for
Reproductive Medicine guidelines
SO FERTILITY AND STERILITY
LA English
DT Article
DE Egg donor agency; financial compensation of oocyte donors; egg donor
compensation; commodification of egg donors; ethics; gamete donation
ID OOCYTE DONORS; DONATION; INTERNET; DECADES
AB Objective: To examine compliance with ethical guidelines of the American Society for Reproductive Medicine (ASRM) regarding trait-based payment variation, presentation of risks, and minimum recruitment age.
Design: In June 2010, we systematically examined 207 websites, of which 102 were egg donor agency or IVF clinic websites that both recruited online and displayed compensation amounts.
Setting: The Internet.
Patient(s): None.
Intervention(s): Not applicable.
Main Outcome Measure(s): Mention of increased payment for particular donor traits, recruitment age less than 21 years, noting risks to donors.
Result(s): Of the 102 sites, considerable numbers were noncompliant with ASRM's guidelines that prohibit varying compensation based on a donor's traits (34%), and recommend an age of 21 years or older (41%), and presentation of risks alongside compensation (56%). Trait-based payment variation was associated with being an agency rather than a clinic, location in the West, not being endorsed by ASRM or Society of Assisted Reproductive Technology (SART), and referring to ASRM's guidelines about compensation. Of sites mentioning traits, prior donation success was the most commonly paid for trait (64%).
Conclusion(s): Our data, the first to systematically analyze agency and clinic websites reveal that many do not follow ASRM's guidelines. These data have critical implications for policy, practice, and research, suggesting needs for consideration of possible changes in guidelines, and/or improvements in compliance and monitoring by ASRM or others. (Fertil Steril (R) 2012;98:995-1000. (C)2012 by American Society for Reproductive Medicine.)
C1 [Klitzman, Robert] Columbia Univ, Dept Clin Psychiat, Masters Bioeth Program, New York, NY 10032 USA.
[Holwell, Eve] Columbia Univ, Postbaccalaureate Premed Program, New York, NY 10032 USA.
[Abdul-Karim, Ruqayyah] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
[Chin, Lisa Judy] New York State Psychiat Inst & Hosp, HIV Ctr Clin & Behav Studies, New York, NY 10032 USA.
[Leu, Cheng-Shiun; Klitzman, Robert] Columbia Univ Mailman Sch Publ Hlth, New York, NY USA.
[Sauer, Mark V.; Klitzman, Robert] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
RP Klitzman, R (reprint author), Columbia Univ, Dept Clin Psychiat, Masters Bioeth Program, 1051 Riverside Dr 15, New York, NY 10032 USA.
EM rlk2@columbia.edu
FU NHGRI NIH HHS [P20 HG005535, R01 HG002431]
NR 19
TC 17
Z9 17
U1 1
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD OCT
PY 2012
VL 98
IS 4
BP 995
EP 1000
DI 10.1016/j.fertnstert.2012.06.052
PG 6
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 016XP
UT WOS:000309553500044
PM 22840240
ER
PT J
AU Boudreau, HE
Casterline, BW
Rada, B
Korzeniowska, A
Leto, TL
AF Boudreau, Howard E.
Casterline, Benjamin W.
Rada, Balazs
Korzeniowska, Agnieszka
Leto, Thomas L.
TI Nox4 involvement in TGF-beta and SMAD3-driven induction of the
epithelial-to-mesenchymal transition and migration of breast epithelial
cells
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE NADPH oxidase 4 (Nox4); Cell migration; TGF-beta signaling;
Epithelial-to-mesenchymal transition (EMT)
ID SMOOTH-MUSCLE-CELLS; OXYGEN SPECIES PRODUCTION; NAD(P)H OXIDASE;
ENDOTHELIAL-CELLS; OXIDATIVE STRESS; GROWTH-FACTOR; FIBRONECTIN
EXPRESSION; SIGNAL-TRANSDUCTION; TUMOR PROGRESSION; REDOX REGULATION
AB The epithelial-to-mesenchymal transition (EMT) is the development of increased cell plasticity that occurs normally during wound healing and embryonic development and can be coopted for cancer invasion and metastasis. TGF-beta induces EMT but the mechanism is unclear. Our studies suggest that Nox4, a member of the NADPH oxidase (Nox) family, is a source of reactive oxygen species (ROS) affecting cell migration and fibronectin expression, an EMT marker, in normal and metastatic breast epithelial cells. We found that TGF-beta induces Nox4 expression (mRNA and protein) and ROS generation in normal (MCF10A) and metastatic (MDA-MB-231) human breast epithelial cells. Conversely, cells expressing a dominant-negative form of Nox4 or Nox4-targeted shRNA showed significantly lower ROS production on TGF-beta treatment. Expression of a constitutively active TGF-beta receptor type I significantly increased Nox4 promoter activity, mRNA and protein expression, and ROS generation. Nox4 transcriptional regulation by TGF-beta was SMAD3 dependent based on the effect of constitutively active SMAD3 increasing Nox4 promoter activity, whereas dominant-negative SMAD3 or SIS3, a SMAD3-specific inhibitor, had the opposite effect. Furthermore, Nox4 knockdown, dominant-negative Nox4 or SMAD3, or SIS3 blunted TGF-beta induced wound healing and cell migration, whereas cell proliferation was not affected. Our experiments further indicate that Nox4 plays a role in TGF-beta regulation of fibronectin mRNA expression, based on the effects of dominant-negative Nox4 in reducing fibronectin mRNA in TGF-beta-treated MDA-MB-231 and MCF10A cells. Collectively, these data indicate that Nox4 contributes to NADPH oxiclase-dependent ROS production that may be critical for the progression of the EMT in breast epithelial cells, and thereby has therapeutic implications. Published by Elsevier Inc.
C1 [Boudreau, Howard E.; Casterline, Benjamin W.; Rada, Balazs; Korzeniowska, Agnieszka; Leto, Thomas L.] NIAID, Lab Host Def, NIH, Rockville, MD USA.
RP Leto, TL (reprint author), NIAID, Lab Host Def, NIH, 12441 Parklawn Dr, Rockville, MD USA.
EM tleto@nih.gov
OI Casterline, Benjamin/0000-0002-9937-5691
FU NIH, National Institute of Allergy and Infectious Diseases
[ZO1-AI-000614]
FX This work was supported by funds from the Intramural Research Program of
the NIH, National Institute of Allergy and Infectious Diseases
(ZO1-AI-000614). The authors declared no conflict of interest.
NR 55
TC 64
Z9 66
U1 1
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD OCT 1
PY 2012
VL 53
IS 7
BP 1489
EP 1499
DI 10.1016/j.freeradbiomed.2012.06.016
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 017FK
UT WOS:000309575300012
PM 22728268
ER
PT J
AU Ganini, D
Canistro, D
Jang, JJ
Stadler, K
Mason, RP
Kadiiska, MB
AF Ganini, Douglas
Canistro, Donatella
Jang, JinJie
Stadler, Krisztian
Mason, Ronald P.
Kadiiska, Maria B.
TI Ceruloplasmin (ferroxidase) oxidizes hydroxylamine probes: Deceptive
implications for free radical detection
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Ceruloplasmin; Free radicals; Electron spin and paramagnetic resonance;
Spin probes
ID ELECTRON-SPIN-RESONANCE; CRYSTALLINE HUMAN FERROXIDASE; SENSITIVE
PLASMA-PROTEINS; FERROUS ION OXIDATION; ACUTE-PHASE REACTANT; SERUM
CERULOPLASMIN; REACTIVE OXYGEN; OXIDASE ACTIVITY; MYOCARDIAL-INFARCTION;
EXTRACELLULAR-SUPEROXIDE
AB Ceruloplasmin (ferroxidase) is a copper-binding protein known to promote Fe2+ oxidation in plasma of mammals. In addition to its classical ferroxidase activity, ceruloplasmin is known to catalyze the oxidation of various substrates, such as amines and catechols. Assays based on cyclic hydroxylamine oxidation are used to quantify and detect free radicals in biological samples ex vivo and in vitro. We show here that human ceruloplasmin promotes the oxidation of the cyclic hydroxylamine 1-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine hydrochloride (CPH) and related probes in Chelex-treated phosphate buffer and rat serum. The reaction is suppressed by the metal chelators DTPA. EDTA, and desferal, whereas heparin and bathocuproine have no effect. Catalase or superoxide dismutase additions do not interfere with the CPH-oxidation yield, demonstrating that oxygen-derived free radicals are not involved in the CPH oxidation mediated by ceruloplasmin. Plasma samples immunodepleted of ceruloplasmin have lower levels of CPH oxidation, which confirms the role of ceruloplasmin (ferroxidase) as a biological oxidizing agent of cyclic hydroxylamines. In conclusion, we show that the ferroxidase activity of ceruloplasmin is a possible biological source of artifacts in the cyclic hydroxylamine-oxidation assay used for reactive oxygen species detection and quantification. Published by Elsevier Inc.
C1 [Ganini, Douglas; Jang, JinJie; Mason, Ronald P.; Kadiiska, Maria B.] NIEHS, Free Radical Metab Sect, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Canistro, Donatella] Univ Bologna, Dept Pharmacol, Mol Toxicol Unit, I-40126 Bologna, Italy.
[Stadler, Krisztian] Louisiana State Univ, Pennington Biomed Res Ctr, Oxidat Stress & Dis Lab, Baton Rouge, LA 70808 USA.
RP Kadiiska, MB (reprint author), NIEHS, Free Radical Metab Sect, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM kadiiska@niehs.nih.gov
FU NIH/NIEHS
FX The authors acknowledge Dr. Kalina Ranguelova and Dr. Olivier M.
Lardinois for helpful discussions and Ms. Jean Corbett, Dr. Ann Motten,
and Ms. Mary Mason for their valuable assistance in the preparation of
the manuscript. This work was supported by the intramural Research
Program of the NIH/NIEHS.
NR 67
TC 8
Z9 10
U1 2
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD OCT 1
PY 2012
VL 53
IS 7
BP 1514
EP 1521
DI 10.1016/j.freeradbiomed.2012.07.013
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 017FK
UT WOS:000309575300014
PM 22824865
ER
PT J
AU Reid, RJ
McBride, CM
Alford, SH
Price, C
Baxevanis, AD
Brody, LC
Larson, EB
AF Reid, Robert J.
McBride, Colleen M.
Alford, Sharon Hensley
Price, Cristofer
Baxevanis, Andreas D.
Brody, Lawrence C.
Larson, Eric B.
TI Association between health-service use and multiplex genetic testing
SO GENETICS IN MEDICINE
LA English
DT Article
DE delivery of health care; genetic counseling; genetic susceptibility;
genetic testing
ID BONE-MINERAL DENSITY; PERSONAL GENOME; CONFOUNDER-SELECTION; RISK;
POLYMORPHISM; METAANALYSIS; MEDICINE; FRACTURE; DISEASE; VARIANT
AB Purpose: The objective of this work was to examine whether offers of multiplex genetic testing increase health-care utilization among healthy patients aged 25-40 years. The identification of genetic variants associated with common disease is accelerating rapidly. "Multiplex tests" that give individuals feedback on large panels of genetic variants have proliferated. Availability of these test results may prompt consumers to use more health-care services.
Methods: A total of 1,599 continuously insured adults aged 25-40 years were surveyed and offered a multiplex genetic susceptibility test for eight common health conditions. Health-care utilization from automated records was compared in 12-month pre- and post-test periods among persons who completed a baseline survey only (68.7%), those who visited a study website but opted not to test (17.8%), and those who chose the multiplex genetic susceptibility test (13.6%).
Results: In the pretest period, persons choosing genetic testing used an average of 1.02 physician visits per quarter as compared with 0.93 and 0.82 for the baseline-only and Web-only groups, respectively (P < 0.05). There were no statistically significant differences by group in the pretest use of any common medical tests or procedures associated with four common health conditions. When changes in physician and medical test/procedure use in the posttest period were compared among the groups, no statistically significant differences were observed for any utilization category.
Conclusions: Persons offered and completing multiplex genetic susceptibility testing used more physician visits before testing, but testing was not associated with subsequent changes in use. This study supports the supposition that multiplex genetic testing offers can be provided directly to the patients in such a way that use of health services is not inappropriately increased.
C1 [Reid, Robert J.; Larson, Eric B.] Seattle Biomed Res Inst, Grp Hlth, Seattle, WA 98109 USA.
[McBride, Colleen M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Alford, Sharon Hensley] Henry Ford Hosp, Detroit, MI 48202 USA.
[Price, Cristofer] ABT Associates Inc, Bethesda, MD USA.
[Baxevanis, Andreas D.; Brody, Lawrence C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Reid, RJ (reprint author), Seattle Biomed Res Inst, Grp Hlth, 4 Nickerson St, Seattle, WA 98109 USA.
EM reid.rj@ghc.org
FU Intramural Research Program of the National Human Genome Research
Institute (NHGRI), National Institutes of Health (NIH); National Cancer
Institute [U19 CA 079689]; NIH [HHSN268200782096C]
FX Robert Reid had full access to all of the data in the study and takes
responsibility for the integrity of the data and the accuracy of the
data analysis. This work was supported by the Intramural Research
Program of the National Human Genome Research Institute (NHGRI),
National Institutes of Health (NIH). The research was also made possible
by collaboration with the Cancer Research Network funded by the National
Cancer Institute (U19 CA 079689). Additional resources were provided by
the Group Health Research Institute (GHRI) and Henry Ford Hospital
(HFH). Genotyping services were provided by the Center for Inherited
Disease Research, which is fully funded through a federal contract from
the NIH to The Johns Hopkins University (HHSN268200782096C). We are
indebted to G. Gibney, D. Kanney, M. Fredriksen, D. Leja, and C. Wade at
NHGRI; S. Anteau, H. Kromei, E. Hasiec, N. Maddy, and K. Wells at HFH,
and C. Wiese, and R. Pardee at GHRI for their assistance. We also
acknowledge A. Parsad and R. Subramanian from Abt Associates, who
assisted with the statistical analyses. Finally, we extend our deepest
thanks to all of the HFHS study participants.
NR 36
TC 22
Z9 22
U1 1
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD OCT
PY 2012
VL 14
IS 10
BP 852
EP 859
DI 10.1038/gim.2012.52
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 018FQ
UT WOS:000309645900004
PM 22595941
ER
PT J
AU El-Kassar, N
Flomerfelt, FA
Choudhury, B
Hugar, LA
Chua, KS
Kapoor, V
Lucas, PJ
Gress, RE
AF El-Kassar, Nahed
Flomerfelt, Francis A.
Choudhury, Baishakhi
Hugar, Lee A.
Chua, Kevin S.
Kapoor, Veena
Lucas, Philip J.
Gress, Ronald E.
TI High levels of IL-7 cause dysregulation of thymocyte development
SO INTERNATIONAL IMMUNOLOGY
LA English
DT Article
DE CD127; IL-7; IL-7R; Notch-1; thymus
ID COMMON LYMPHOID PROGENITORS; CELL LINEAGE COMMITMENT; MOUSE BONE-MARROW;
T-CELL; IN-VIVO; NOTCH LIGANDS; FATE DECISION; THYMIC-B;
DIFFERENTIATION; EXPRESSION
AB IL-7 signaling is required for thymocyte development and its loss has a severe deleterious effect on thymus function. Thymocytestromal cell interactions and other mechanisms tightly regulate IL-7 expression. We show that disruption of that regulation by over-expression of IL-7 inhibits T-cell development and promotes extensive B-cell lymphopoiesis in the thymus. Our data reveal that high levels of IL-7 negate Notch-1 function in thymocytes found in IL-7 transgenic mice and in co-culture with OP9-DL1 cells. While high levels of IL-7R are present on thymocytes, increased suppressor of cytokine signaling-1 expression blunts IL-7 downstream signaling, resulting in hypo-phosphorylation of proteins in the PI3K-Akt pathway. Consequently, GSK3 remains active and inhibits Notch-1 signaling as observed by decreased Hes-1 and Deltex expression in thymic progenitors. This is the first demonstration that high levels of IL-7 antagonize Notch-1 signaling and suggest that IL-7 may affect T- versus B-lineage choice in the thymus.
C1 [El-Kassar, Nahed; Flomerfelt, Francis A.; Choudhury, Baishakhi; Hugar, Lee A.; Chua, Kevin S.; Kapoor, Veena; Lucas, Philip J.; Gress, Ronald E.] NCI, Expt Immunol & Transplantat Branch, CRC, Bethesda, MD 20892 USA.
RP El-Kassar, N (reprint author), Agcy Healthcare Res & Qual, 540 Gaither Rd, Rockville, MD 20850 USA.
EM nahed.elkassar@ahrq.hhs.gov
FU National Cancer Institute at the National Institutes of Health
(Bethesda, MD USA)
FX The Intramural Research Program of the National Cancer Institute at the
National Institutes of Health (Bethesda, MD USA) provided funding for
these studies that were performed solely at the NCI.
NR 41
TC 4
Z9 5
U1 1
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0953-8178
J9 INT IMMUNOL
JI Int. Immunol.
PD OCT
PY 2012
VL 24
IS 10
BP 661
EP +
DI 10.1093/intimm/dxs067
PG 11
WC Immunology
SC Immunology
GA 015QG
UT WOS:000309460400001
PM 22899673
ER
PT J
AU Gordon, LB
Cao, K
Collins, FS
AF Gordon, Leslie B.
Cao, Kan
Collins, Francis S.
TI Progeria: Translational insights from cell biology
SO JOURNAL OF CELL BIOLOGY
LA English
DT Editorial Material
ID HUTCHINSON-GILFORD-PROGERIA; MOUSE MODEL; LAMIN; DISEASE; PROGRESSION;
PHENOTYPE; PREVENTS; DEFECTS; MITOSIS
AB Cell biologists love to think outside the box, pursuing many surprising twists and unexpected turns in their quest to unravel the mysteries of how cells work. But can cell biologists think outside the bench? We are certain that they can, and clearly some already do. To encourage more cell biologists to venture into the realm of translational research on a regular basis, we would like to share a handful of the many lessons that we have learned in our effort to develop experimental treatments for Hutchinson-Gilford progeria syndrome (HGPS), an endeavor that many view as a "poster child" for how basic cell biology can be translated to the clinic.
C1 [Collins, Francis S.] NIH, Bethesda, MD 20892 USA.
[Gordon, Leslie B.] Progeria Res Fdn, Peabody, MA 01961 USA.
[Gordon, Leslie B.] Brown Univ, Alpert Med Sch, Dept Pediat, Providence, RI 02903 USA.
[Gordon, Leslie B.] Hasbro Childrens Hosp, Providence, RI 02903 USA.
[Cao, Kan] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA.
[Gordon, Leslie B.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Gordon, Leslie B.] Boston Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA.
RP Collins, FS (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM collinsf@mail.nih.gov
FU Intramural NIH HHS; NIA NIH HHS [R00 AG029761, R00AG029761]
NR 34
TC 19
Z9 19
U1 0
U2 11
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD OCT 1
PY 2012
VL 199
IS 1
BP 9
EP 13
DI 10.1083/jcb.201207072
PG 5
WC Cell Biology
SC Cell Biology
GA 016NB
UT WOS:000309524500004
PM 23027899
ER
PT J
AU Duan, R
Jin, P
Luo, FB
Zhang, GF
Anderson, N
Chen, EH
AF Duan, Rui
Jin, Peng
Luo, Fengbao
Zhang, Guofeng
Anderson, Nathan
Chen, Elizabeth H.
TI Group I PAKs function downstream of Rac to promote podosome invasion
during myoblast fusion in vivo
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID BREAST-CANCER CELLS; DROSOPHILA-MELANOGASTER; P21-ACTIVATED KINASES;
DORSAL CLOSURE; IMMUNOGLOBULIN SUPERFAMILY; CYTOSKELETAL ORGANIZATION;
ACTIN CYTOSKELETON; MUSCLE DEVELOPMENT; LEADING-EDGE; BLOWN-FUSE
AB The p21-activated kinases (PAKs) play essential roles in diverse cellular processes and are required for cell proliferation, apoptosis, polarity establishment, migration, and cell shape changes. Here, we have identified a novel function for the group I PAKs in cell-cell fusion. We show that the two Drosophila group I PAKs, DPak3 and DPak1, have partially redundant functions in myoblast fusion in vivo, with DPak3 playing a major role. DPak3 is enriched at the site of fusion colocalizing with the F-actin focus within a podosome-like structure (PLS), and promotes actin filament assembly during PLS invasion. Although the small GTPase Rac is involved in DPak3 activation and recruitment to the PLS, the kinase activity of DPak3 is required for effective PLS invasion. We propose a model whereby group I PAKs act downstream of Rac to organize the actin filaments within the PLS into a dense focus, which in turn promotes PLS invasion and fusion pore initiation during myoblast fusion.
C1 [Duan, Rui; Jin, Peng; Luo, Fengbao; Anderson, Nathan; Chen, Elizabeth H.] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA.
[Zhang, Guofeng] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA.
RP Chen, EH (reprint author), Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA.
EM echen@jhmi.edu
FU National Institutes of Health [R01AR053173]
FX This work was supported by a grant from the National Institutes of
Health to E. H. Chen (R01AR053173). P. Jin was a predoctoral fellow and
R. Duan is a postdoctoral fellow of the American Heart Association.
NR 75
TC 25
Z9 25
U1 0
U2 6
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD OCT 1
PY 2012
VL 199
IS 1
BP 169
EP 185
DI 10.1083/jcb.201204065
PG 17
WC Cell Biology
SC Cell Biology
GA 016NB
UT WOS:000309524500017
PM 23007650
ER
PT J
AU Rosta, E
Warshel, A
AF Rosta, Edina
Warshel, Arieh
TI Origin of Linear Free Energy Relationships: Exploring the Nature of the
Off-Diagonal Coupling Elements in S(N)2 Reactions
SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION
LA English
DT Article
ID ELECTRON-TRANSFER REACTIONS; DENSITY-FUNCTIONAL THEORY; PROTON-TRANSFER
REACTIONS; QUANTUM-MECHANICAL CORRECTIONS; TRANSFER MATRIX-ELEMENTS;
VALENCE-BOND; AQUEOUS-SOLUTION; COMPUTER-SIMULATIONS;
CARBONIC-ANHYDRASE; BIOLOGICAL-SYSTEMS
AB Understanding the relationship between the adiabatic free energy profiles of chemical reactions and. the underlining diabatic states is central to the description of chemical reactivity. The diabatic states form the theoretical basis of linear free energy relationships (LFERs) and thus play a major role in physical organic chemistry and related fields. However, the theoretical justification for some of the implicit LFER assumptions has not been fully established by quantum mechanical studies. This study follows our earlier works(1,2) and uses the ab initio frozen density functional theory (FDFT) method(3) to evaluate both the diabatic and the adiabatic free energy surfaces and to determine the corresponding off-diagonal coupling matrix elements for a series of S(N)2 reactions. It is found that the off-diagonal coupling matrix elements are almost the same regardless of the nucleophile and the leaving group but change upon changing the central group. Furthermore, it is also found that the off-diagonal elements are basically the same in gas phase and in solution, even when the solvent is explicitly included in the ab initio calculations. Furthermore, our study establishes that the FDFT diabatic profiles are parabolic to a good approximation, thus providing a first-principles support to the origin of LFER. These findings further support the basic approximation of the empirical valence bond treatment.
C1 [Rosta, Edina] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Rosta, Edina] Kings Coll London, Dept Chem, London SE1 1UL, England.
[Warshel, Arieh] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA.
RP Rosta, E (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
EM Edina.Rosta@kcl.ac.uk; warshel@usc.edu
OI Rosta, Edina/0000-0002-9823-4766
FU NIH [GM 24492]; NSF [MCB-0342276]; National Institute of Diabetes and
Digestive and Kidney Diseases
FX This work was supported by the NIH grant GM 24492, NSF grant MCB-0342276
and by the Intramural Research Program of the National Institute of
Diabetes and Digestive and Kidney Diseases. The computational work was
supported by the University of Southern California High Performance
Computing and Communication Center (HPCC) and by the Biowulf Linux
cluster at the NIH. We thank Dr. Attila Szabo for many helpful
suggestions and Dr. Gongyi Hong for useful help in the calculations.
NR 93
TC 10
Z9 10
U1 2
U2 33
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9618
J9 J CHEM THEORY COMPUT
JI J. Chem. Theory Comput.
PD OCT
PY 2012
VL 8
IS 10
BP 3574
EP 3585
DI 10.1021/ct2009329
PG 12
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 016GN
UT WOS:000309505600015
PM 23329895
ER
PT J
AU Konig, G
Miller, BT
Boresch, S
Wu, XW
Brooks, BR
AF Koenig, Gerhard
Miller, Benjamin T.
Boresch, Stefan
Wu, Xiongwu
Brooks, Bernard R.
TI Enhanced Sampling in Free Energy Calculations: Combining SGLD with the
Bennett's Acceptance Ratio and Enveloping Distribution Sampling Methods
SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION
LA English
DT Article
ID GUIDED LANGEVIN DYNAMICS; HYDRATION FREE-ENERGIES; MOLECULAR-DYNAMICS;
BINDING AFFINITIES; SINGLE SIMULATION; LIGAND-BINDING; TERMS;
PREDICTION; CHALLENGE; EFFICIENT
AB One of the key requirements for the accurate calculation of free energy differences is proper sampling of conformational space. Especially in biological applications, molecular dynamics simulations are often confronted with rugged energy surfaces and high energy barriers, leading to insufficient sampling and, in turn, poor convergence of the free energy results. In this work, we address this problem by employing enhanced sampling methods. We explore the possibility of using self-guided Langevin dynamics (SGLD) to speed up the exploration process in free energy simulations. To obtain improved free energy differences from such simulations, it is necessary to account for the effects of the bias due to the guiding forces. We demonstrate how this can be accomplished for the Bennett's acceptance ratio (BAR) and the enveloping distribution sampling (EDS) methods. While BAR is considered among the most efficient methods available for free energy calculations, the EDS method developed by Christ and van Gunsteren is a promising development that reduces the computational costs of free energy calculations by simulating a single reference state. To evaluate the accuracy of both approaches in connection with enhanced sampling, EDS was implemented in CHARMM. For testing, we employ benchmark systems with analytical reference results and the mutation of alanine to serine. We find that SGLD with reweighting can provide accurate results for BAR and EDS where conventional molecular dynamics simulations fail. In addition, we compare the performance of EDS with other free energy methods. We briefly discuss the implications of our results and provide practical guidelines for conducting free energy simulations with SGLD.
C1 [Koenig, Gerhard; Miller, Benjamin T.; Wu, Xiongwu; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
[Boresch, Stefan] Univ Vienna, Fac Chem, Dept Computat Biol Chem, A-1090 Vienna, Austria.
RP Konig, G (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM gerhard.koenig@nih.gov
RI Boresch, Stefan/F-3467-2014;
OI Boresch, Stefan/0000-0002-2793-6656; Miller,
Benjamin/0000-0003-1647-0122
FU NHLBI, NIH
FX The authors would like to thank R. Pastor for critically reading the
manuscript. This work was primarily supported by the intramural research
program of NHLBI, NIH. The authors would like to dedicate this article
to Wilfred van Gunsteren in honor of his 65th birthday.
NR 56
TC 9
Z9 9
U1 1
U2 30
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9618
J9 J CHEM THEORY COMPUT
JI J. Chem. Theory Comput.
PD OCT
PY 2012
VL 8
IS 10
BP 3650
EP 3662
DI 10.1021/ct300116r
PG 13
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 016GN
UT WOS:000309505600022
PM 26593010
ER
PT J
AU Zhu, FQ
Hummer, G
AF Zhu, Fangqiang
Hummer, Gerhard
TI Theory and Simulation of Ion Conduction in the Pentameric GLIC Channel
SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION
LA English
DT Article
ID NICOTINIC ACETYLCHOLINE-RECEPTOR; MOLECULAR-DYNAMICS SIMULATIONS;
HISTOGRAM ANALYSIS METHOD; FREE-ENERGY CALCULATIONS; CYS-LOOP RECEPTOR;
X-RAY-STRUCTURE; BROWNIAN DYNAMICS; WATER PERMEATION; K+ CHANNEL; MEAN
FORCE
AB GLIC is a bacterial member of the large family of pentameric ligand-gated ion channels. To study ion conduction through GLIC and other membrane channels, we combine the one-dimensional potential of mean force for ion passage with a Smoluchowski diffusion model, making it possible to calculate single-channel conductance in the regime of low ion concentrations from all-atom molecular dynamics (MD) simulations. We then perform MD simulations to examine sodium ion conduction through the GLIC transmembrane pore in two systems with different bulk ion concentrations. The ion potentials of mean force, calculated from umbrella sampling simulations with Hamiltonian replica exchange, reveal a major barrier at the hydrophobic constriction of the pore. The relevance of this barrier for ion transport is confirmed by a committor function that rises sharply in the barrier region. From the free evolution of Na+ ions starting at the barrier top, we estimate the effective diffusion coefficient in the barrier region and subsequently calculate the conductance of the pore. The resulting diffusivity compares well with the position-dependent ion diffusion coefficient obtained from restrained simulations. The ion conductance obtained from the diffusion model agrees with the value determined via a reactive-flux rate calculation. Our results show that the conformation in the GLIC crystal structure, with an estimated conductance of similar to 1 picosiemens at 140 mM ion concentration, is consistent with a physiologically open state of the channel.
C1 [Zhu, Fangqiang; Hummer, Gerhard] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Hummer, G (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
EM gerhard.hummer@nih.gov
RI Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
FU NIDDK, NIH
FX This research was supported by the Intramural Research Programs of the
NIDDK, NIH, and utilized the high-performance computational capabilities
of the Biowulf Linux cluster at the National Institutes of Health,
Bethesda, MD (http://biowulf.nih.gov).
NR 51
TC 25
Z9 25
U1 2
U2 39
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9618
EI 1549-9626
J9 J CHEM THEORY COMPUT
JI J. Chem. Theory Comput.
PD OCT
PY 2012
VL 8
IS 10
BP 3759
EP 3768
DI 10.1021/ct2009279
PG 10
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 016GN
UT WOS:000309505600031
PM 23413364
ER
PT J
AU Johnson, NA
Slack, GW
Savage, KJ
Connors, JM
Ben-Neriah, S
Rogic, S
Scott, DW
Tan, KL
Steidl, C
Sehn, LH
Chan, WC
Iqbal, J
Meyer, PN
Lenz, G
Wright, G
Rimsza, LM
Valentino, C
Brunhoeber, P
Grogan, TM
Braziel, RM
Cook, JR
Tubbs, RR
Weisenburger, DD
Campo, E
Rosenwald, A
Ott, G
Delabie, J
Holcroft, C
Jaffe, ES
Staudt, LM
Gascoyne, RD
AF Johnson, Nathalie A.
Slack, Graham W.
Savage, Kerry J.
Connors, Joseph M.
Ben-Neriah, Susana
Rogic, Sanja
Scott, David W.
Tan, King L.
Steidl, Christian
Sehn, Laurie H.
Chan, Wing C.
Iqbal, Javeed
Meyer, Paul N.
Lenz, Georg
Wright, George
Rimsza, Lisa M.
Valentino, Carlo
Brunhoeber, Patrick
Grogan, Thomas M.
Braziel, Rita M.
Cook, James R.
Tubbs, Raymond R.
Weisenburger, Dennis D.
Campo, Elias
Rosenwald, Andreas
Ott, German
Delabie, Jan
Holcroft, Christina
Jaffe, Elaine S.
Staudt, Louis M.
Gascoyne, Randy D.
TI Concurrent Expression of MYC and BCL2 in Diffuse Large B-Cell Lymphoma
Treated With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine,
and Prednisone
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID C-MYC; R-CHOP; PROGNOSTIC-SIGNIFICANCE; BURKITT-LYMPHOMA;
ELDERLY-PATIENTS; IN-VIVO; SURVIVAL; BIOMARKER; PREDICTS; DISTINCT
AB Purpose
Diffuse large B-cell lymphoma (DLBCL) is curable in 60% of patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MYC translocations, with or without BCL2 translocations, have been associated with inferior survival in DLBCL. We investigated whether expression of MYC protein, with or without BCL2 protein expression, could risk-stratify patients at diagnosis.
Patients and Methods
We determined the correlation between presence of MYC and BCL2 proteins by immunohistochemistry (IHC) with survival in two independent cohorts of patients with DLBCL treated with R-CHOP. We further determined if MYC protein expression correlated with high MYC mRNA and/or presence of MYC translocation.
Results
In the training cohort (n = 167), MYC and BCL2 proteins were detected in 29% and 44% of patients, respectively. Concurrent expression (MYC positive/BCL2 positive) was present in 21% of patients. MYC protein correlated with presence of high MYC mRNA and MYC translocation (both P < .001), but the latter was less frequent (both 11%). MYC protein expression was only associated with inferior overall and progression-free survival when BCL2 protein was coexpressed (P < .001). Importantly, the poor prognostic effect of MYC positive/BCL2 positive was validated in an independent cohort of 140 patients with DLBCL and remained significant (P < .05) after adjusting for presence of high-risk features in a multivariable model that included elevated international prognostic index score, activated B-cell molecular subtype, and presence of concurrent MYC and BCL2 translocations.
Conclusion
Assessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis. J Clin Oncol 30:3452-3459. (C) 2012 by American Society of Clinical Oncology
C1 [Slack, Graham W.; Savage, Kerry J.; Connors, Joseph M.; Ben-Neriah, Susana; Rogic, Sanja; Scott, David W.; Tan, King L.; Steidl, Christian; Sehn, Laurie H.; Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 1L3, Canada.
[Johnson, Nathalie A.; Holcroft, Christina] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada.
[Chan, Wing C.; Iqbal, Javeed; Meyer, Paul N.; Weisenburger, Dennis D.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Lenz, Georg] Charite, D-13353 Berlin, Germany.
[Rosenwald, Andreas; Ott, German] Univ Wurzburg, Wurzburg, Germany.
[Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany.
[Ott, German] Robert Bosch Krankenhaus, Stuttgart, Germany.
[Wright, George; Jaffe, Elaine S.; Staudt, Louis M.] NCI, NIH, Bethesda, MD 20892 USA.
[Rimsza, Lisa M.; Valentino, Carlo; Brunhoeber, Patrick; Grogan, Thomas M.] Univ Arizona, Tucson, AZ USA.
[Braziel, Rita M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Campo, Elias] Hosp Clin Barcelona, Barcelona, Spain.
[Cook, James R.; Tubbs, Raymond R.] Cleveland Clin, Cleveland, OH 44106 USA.
[Delabie, Jan] Radiumhospitalet, Oslo, Norway.
RP Gascoyne, RD (reprint author), British Columbia Canc Agcy, 675 W 10th Ave,Room 5-113, Vancouver, BC V5Z 1L3, Canada.
EM rgascoyn@bccancer.bc.ca
RI Lenz, Georg/I-6844-2012;
OI Delabie, Jan/0000-0001-5023-0689; Jaffe, Elaine/0000-0003-4632-0301;
Campo, elias/0000-0001-9850-9793
FU NCIC [019005]; Michael Smith Foundation for Health Research
[ST-PDF-01793]; Fonds de Recherche en Sante du Quebec; Terry Fox
Foundation [019001]; Terry Fox Foundation Strategic Health Research
Training Program in Cancer Research at Canadian Institutes of Health
Research [TGT-53912]; National Cancer Institute [U01 CA 114778];
Hoffmann-La Roche (Roche Canada)
FX Supported by Awards No. 019005 from the NCIC and ST-PDF-01793 from the
Michael Smith Foundation for Health Research for research fellow of the
Terry Fox Foundation and by an award from the "Fonds de Recherche en
Sante du Quebec (N.A.J.); by the NCIC and Grant No. 019001 from the
Terry Fox Foundation (J.M.C., R. D. G.); and by Grant No. TGT-53912 from
the Terry Fox Foundation Strategic Health Research Training Program in
Cancer Research at Canadian Institutes of Health Research (D. W. S., K.
L. T.). Members of the Lymphoma/Leukemia Molecular Profiling Project are
supported by Strategic Partnering to Evaluate Cancer Signatures Grant
No. U01 CA 114778 from the National Cancer Institute.; Kerry J. Savage,
Hoffmann-La Roche (Roche Canada); Joseph M. Connors, Hoffmann-La Roche
(Roche Canada); Lisa M. Rimsza, Ventana Medical Systems; Randy D.
Gascoyne, Hoffmann-La Roche (Roche Canada)
NR 47
TC 256
Z9 272
U1 7
U2 22
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 1
PY 2012
VL 30
IS 28
BP 3452
EP 3459
DI 10.1200/JCO.2011.41.0985
PG 8
WC Oncology
SC Oncology
GA 016KS
UT WOS:000309517700009
PM 22851565
ER
PT J
AU Alter, HJ
AF Alter, Harvey J.
TI To have B or not to have B: Vaccine and the potential eradication of
hepatitis B
SO JOURNAL OF HEPATOLOGY
LA English
DT Editorial Material
ID AUSTRALIA-ANTIGEN; HEPATOCELLULAR-CARCINOMA; DOWNS SYNDROME; SERUM;
PARTICLES
C1 NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Alter, HJ (reprint author), NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
EM halter@dtm.cc.nih.gov
NR 13
TC 6
Z9 6
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD OCT
PY 2012
VL 57
IS 4
BP 715
EP 717
DI 10.1016/j.jhep.2012.05.021
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 015JS
UT WOS:000309442800002
PM 22771560
ER
PT J
AU Abdelmegeed, MA
Banerjee, A
Yoo, SH
Jang, S
Gonzalez, FJ
Song, BJ
AF Abdelmegeed, Mohamed A.
Banerjee, Atrayee
Yoo, Seong-Ho
Jang, Sehwan
Gonzalez, Frank J.
Song, Byoung-Joon
TI Critical role of cytochrome P450 2E1 (CYP2E1) in the development of high
fat-induced non-alcoholic steatohepatitis
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Liver; CYP2E1; Null mice; High-fat diet; NAFLD; NASH; Oxidative stress;
Protein modifications; Inflammation; Insulin resistance
ID LIVER-DISEASE; OB/OB MICE; MITOCHONDRIAL DYSFUNCTION; METABOLIC
SYNDROME; OXIDATIVE STRESS; NITRIC-OXIDE; DIET; PROTEIN; EXPRESSION;
INJURY
AB Background & Aims: Ethanol-inducible cytochrome P450 2E1 (CYP2E1) activity contributes to oxidative stress. However, CYP2E1 may have an important role in the pathogenesis of high-fat mediated non-alcoholic steatohepatitis (NASH). Thus, the role of CYP2E1 in high-fat mediated NASH development was evaluated.
Methods: Male wild type (WT) and Cyp2el-null mice were fed a low-fat diet (LFD, 10% energy-derived) or a high-fat diet (HFD, 60% energy-derived) for 10 weeks. Liver histology and tissue homogenates were examined for various parameters of oxidative stress and inflammation.
Results: Liver histology showed that only WT mice fed a HFD developed NASH despite the presence of increased steatosis in both WT and Cyp2el-null mice fed HFD. Markers of oxidative stress such as elevated CYP2E1 activity and protein amounts, lipid peroxidation, protein carbonylation, nitration, and glycation with increased phospho-JNK were all markedly elevated only in the livers of HFD-fed WT mice. Furthermore, while the levels of inflammation markers osteopontin and F4/80 were higher in HFD-fed WT mice, TNF alpha and MCP-1 levels were lower compared to the corresponding LFD-fed WT. Finally, only HFD-fed WT mice exhibited increased insulin resistance and impaired glucose tolerance.
Conclusions: These data suggest that CYP2E1 is critically important in NASH development by promoting oxidative/nitrosative stress, protein modifications, inflammation, and insulin resistance. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
C1 [Abdelmegeed, Mohamed A.; Banerjee, Atrayee; Yoo, Seong-Ho; Jang, Sehwan; Song, Byoung-Joon] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA.
[Yoo, Seong-Ho] Seoul Natl Univ, Coll Med, Dept Forens Med, Seoul, South Korea.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM bj.song@nih.gov
RI Yoo, Sung Ho/J-5549-2012
FU NIH Institutes of Health; Intramural Research Program of National
Institute on Alcohol Abuse and Alcoholism
FX The authors who have taken part in this study declared that they do not
have anything to disclose regarding funding or conflict of interest with
respect to this manuscript. The underlying research reported in the
study was funded by the NIH Institutes of Health.; This research was
supported by the Intramural Research Program of National Institute on
Alcohol Abuse and Alcoholism.
NR 41
TC 69
Z9 72
U1 1
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD OCT
PY 2012
VL 57
IS 4
BP 860
EP 866
DI 10.1016/j.jhep.2012.05.019
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 015JS
UT WOS:000309442800022
PM 22668639
ER
PT J
AU Thalhammer, C
Renz, W
Winter, L
Hezel, F
Rieger, J
Pfeiffer, H
Graessl, A
Seifert, F
Hoffmann, W
von Knobelsdorff-Brenkenhoff, F
Tkachenko, V
Schulz-Menger, J
Kellman, P
Niendorf, T
AF Thalhammer, Christof
Renz, Wolfgang
Winter, Lukas
Hezel, Fabian
Rieger, Jan
Pfeiffer, Harald
Graessl, Andreas
Seifert, Frank
Hoffmann, Werner
von Knobelsdorff-Brenkenhoff, Florian
Tkachenko, Valeriy
Schulz-Menger, Jeanette
Kellman, Peter
Niendorf, Thoralf
TI Two-Dimensional Sixteen Channel Transmi eceive Coil Array for Cardiac
MRI at 7.0 T: Design, Evaluation, d Application
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
ID 7 TESLA; HIGH-FIELD; FEASIBILITY; ANGIOGRAPHY; SEPARATION
C1 [Thalhammer, Christof; Renz, Wolfgang; Winter, Lukas; Hezel, Fabian; Rieger, Jan; Pfeiffer, Harald; Graessl, Andreas; Seifert, Frank; Hoffmann, Werner; von Knobelsdorff-Brenkenhoff, Florian; Schulz-Menger, Jeanette; Niendorf, Thoralf] Max Delbruck Ctr Mol Med, Berlin Ultrahigh Field Facil, D-13125 Berlin, Germany.
[Renz, Wolfgang] Siemens Healthcare, Erlangen, Germany.
[Rieger, Jan] MRI TOOLS GmbH, Berlin, Germany.
[von Knobelsdorff-Brenkenhoff, Florian; Tkachenko, Valeriy; Schulz-Menger, Jeanette] HELIOS Klinikum Berlin Buch, Dept Cardiol & Nephrol, Berlin, Germany.
[von Knobelsdorff-Brenkenhoff, Florian; Tkachenko, Valeriy; Schulz-Menger, Jeanette; Niendorf, Thoralf] Expt & Clin Res Ctr, Berlin, Germany.
[Kellman, Peter] NHLBI, Lab Cardiac Energet, NIH, Bethesda, MD 20892 USA.
RP Niendorf, T (reprint author), Max Delbruck Ctr Mol Med, Berlin Ultrahigh Field Facil, Robert Roessle Str 10, D-13125 Berlin, Germany.
EM Thoralf.Niendorf@mdc-berlin.de
RI Niendorf, Thoralf/H-7738-2013
OI Niendorf, Thoralf/0000-0001-7584-6527
FU Intramural NIH HHS [Z99 HL999999]
NR 40
TC 32
Z9 32
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
EI 1522-2586
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD OCT
PY 2012
VL 36
IS 4
BP 847
EP 857
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 007JJ
UT WOS:000308884300008
PM 22706727
ER
PT J
AU Bell, JA
Saikus, CE
Ratnayaka, K
Barbash, IM
Faranesh, AZ
Franson, DN
Sonmez, M
Slack, MC
Lederman, RJ
Kocaturk, O
AF Bell, Jamie A.
Saikus, Christina E.
Ratnayaka, Kanishka
Barbash, Israel M.
Faranesh, Anthony Z.
Franson, Dominique N.
Sonmez, Merdim
Slack, Michael C.
Lederman, Robert J.
Kocaturk, Ozgur
TI Active delivery cable tuned to device deployment state: Enhanced
visibility of nitinol occluders during preclinical interventional MRI
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE interventional MRI; structural heart disease; cardiac implants; active
MRI devices
ID CLOSURE
AB Purpose: To develop an active delivery system that enhances visualization of nitinol cardiac occluder devices during deployment under real-time magnetic resonance imaging (MRI). Materials and Methods: We constructed an active delivery cable incorporating a loopless antenna and a custom titanium microscrew to secure the occluder devices. The delivery cable was tuned and matched to 50O at 64 MHz with the occluder device attached. We used real-time balanced steady state free precession in a wide-bore 1.5T scanner. Device-related images were reconstructed separately and combined with surface-coil images. The delivery cable was tested in vitro in a phantom and in vivo in swine using a variety of nitinol cardiac occluder devices. Results: In vitro, the active delivery cable provided little signal when the occluder device was detached and maximal signal with the device attached. In vivo, signal from the active delivery cable enabled clear visualization of occluder device during positioning and deployment. Device release resulted in decreased signal from the active cable. Postmortem examination confirmed proper device placement. Conclusion: The active delivery cable enhanced the MRI depiction of nitinol cardiac occluder devices during positioning and deployment, both in conventional and novel applications. We expect enhanced visibility to contribute to the effectiveness and safety of new and emerging MRI-guided treatments. J. Magn. Reson. Imaging 2012;36:972978. (c) 2012 Wiley Periodicals, Inc.
C1 [Bell, Jamie A.; Saikus, Christina E.; Ratnayaka, Kanishka; Barbash, Israel M.; Faranesh, Anthony Z.; Franson, Dominique N.; Sonmez, Merdim; Lederman, Robert J.; Kocaturk, Ozgur] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Ratnayaka, Kanishka; Slack, Michael C.] Childrens Natl Med Ctr, Div Cardiol, Washington, DC 20010 USA.
RP Lederman, RJ (reprint author), NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bldg 10,Room 2C713, Bethesda, MD 20892 USA.
EM lederman@nih.gov
RI Kocaturk, Ozgur/A-1419-2016;
OI lederman, robert/0000-0003-1202-6673
FU Division of Intramural Research, National Heart Lung and Blood
Institute, National Institutes of Health [Z01-HL005062, Z01-HL006041]
FX Contract grant sponsor: Division of Intramural Research, National Heart
Lung and Blood Institute, National Institutes of Health; Contract grant
numbers: Z01-HL005062, Z01-HL006041.
NR 8
TC 2
Z9 2
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD OCT
PY 2012
VL 36
IS 4
BP 972
EP 978
DI 10.1002/jmri.23722
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 007JJ
UT WOS:000308884300023
PM 22707441
ER
PT J
AU Das, M
Moxley, RT
Hilbert, JE
Martens, WB
Letren, L
Greene, MH
Gadalla, SM
AF Das, Maya
Moxley, Richard T., III
Hilbert, James E.
Martens, William B.
Letren, Lisa
Greene, Mark H.
Gadalla, Shahinaz M.
TI Correlates of tumor development in patients with myotonic dystrophy
SO JOURNAL OF NEUROLOGY
LA English
DT Article
DE Myotonic dystrophy; Comorbidity; Neoplasms; Risk factors; Repeat
expansion size
ID TRIPLET REPEAT EXPANSION; BASAL-CELL CARCINOMA; PROTEIN-KINASE GENE;
MUSCULAR-DYSTROPHY; TRUE ASSOCIATION; CTG REPEAT; MOSAICISM; MUTATIONS;
VALIDITY; REGISTRY
AB Patients with myotonic dystrophy (DM) have recently been reported to be at increased risk of tumor development, but clinical associations related to this observation are unknown. We calculated the odds ratios (ORs) and 95 % confidence intervals (CI) of self-reported tumor development by patients' demographic and clinical characteristics to evaluate factors associated with tumor development in DM patients, using data from the National Registry of Myotonic Dystrophy and Facioscapulohumeral Dystrophy Patients and Family Members. Of the 911 participants, 47.5 % were male and 85.7 % had DM type 1 (DM1). Compared to DM1, patients with DM type 2 (DM2) were older at registry enrollment (median age 55 vs. 44 years, p < 0.0001) and at DM diagnosis (median age 48 vs. 30 years, p < 0.0001); and more likely to be females (p = 0.001). At enrollment, 95 (10.4 %) DM patients reported a history of benign or malignant tumor. Tumors were associated with female gender (OR 1.9, 95 % CI 1.2-3.1, p = 0.007) and DM1 (OR 2.1, 95 % CI 1.1-4.1, p = 0.03). In a subgroup analysis of patients with blood-based DNA testing results (397 DM1, 54 DM2), repeat expansion size was not associated with tumor risk in DM1 (p = 0.26) or DM2 (p = 0.34). In conclusion, female gender and DM1 subtype, but not DNA repeat expansion size, were associated with increased risk of tumors in DM. Follow-up studies are warranted to determine if oncogenes associated with dystrophia myotonica-protein kinase are altered in DM, and to determine if repeat expansion size, as in our study, is not associated with tumor development.
C1 [Gadalla, Shahinaz M.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Das, Maya; Letren, Lisa] Univ Maryland, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Moxley, Richard T., III; Hilbert, James E.; Martens, William B.] Univ Rochester, Med Ctr, Dept Neurol, Neuromuscular Dis Ctr, Rochester, NY 14642 USA.
[Greene, Mark H.; Gadalla, Shahinaz M.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Gadalla, SM (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7030, Rockville, MD 20852 USA.
EM gadallas@mail.nih.gov
FU National Cancer Institute, USA; University of Rochester's Senator Paul
D. Wellstone Muscular Dystrophy Cooperative Research Center
[NIH/U54/NS048843]; National Registry of Myotonic Dystrophy and
Facioscapulohumeral Muscular Dystrophy Patients and Family Members
[NIH/N01-AR-50-227450]; National Center for Research Resources; National
Center for Advancing Translational Sciences [NIH: UL1 RR024160];
University of Maryland School of Medicine
FX This study was supported in-part by the Intramural Research Program of
the National Cancer Institute, USA, and the University of Rochester's
Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center
(NIH/U54/NS048843), the National Registry of Myotonic Dystrophy and
Facioscapulohumeral Muscular Dystrophy Patients and Family Members
(NIH/N01-AR-50-227450), and the National Center for Research Resources
and the National Center for Advancing Translational Sciences (NIH: UL1
RR024160). Dr. Das is supported by the Preventive Medicine Residency
Program, University of Maryland School of Medicine.
NR 29
TC 16
Z9 16
U1 0
U2 2
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5354
J9 J NEUROL
JI J. Neurol.
PD OCT
PY 2012
VL 259
IS 10
BP 2161
EP 2166
DI 10.1007/s00415-012-6476-8
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 017BD
UT WOS:000309562800019
PM 22619053
ER
PT J
AU Jagoda, EM
Lang, LX
Bhadrasetty, V
Histed, S
Williams, M
Kramer-Marek, G
Mena, E
Rosenblum, L
Marik, J
Tinianow, JN
Merchant, M
Szajek, L
Paik, C
Cecchi, F
Raffensperger, K
Jose-Dizon, JM
Bottaro, DP
Choyke, P
AF Jagoda, Elaine M.
Lang, Lixin
Bhadrasetty, Veerendra
Histed, Stephanie
Williams, Mark
Kramer-Marek, Gabriela
Mena, Esther
Rosenblum, Lauren
Marik, Jan
Tinianow, Jeff N.
Merchant, Mark
Szajek, Lawrence
Paik, Chang
Cecchi, Fabiola
Raffensperger, Kristen
Jose-Dizon, Joe-Marie
Bottaro, Donald P.
Choyke, Peter
TI Immuno-PET of the Hepatocyte Growth Factor Receptor Met Using the
1-Armed Antibody Onartuzumab
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE immuno-PET imaging; Met receptor; Br-76-onartuzumab;
Zr-89-df-onartuzumab; MetMAb
ID MONOCLONAL-ANTIBODIES; NUDE-MICE; IN-VIVO; CANCER; XENOGRAFTS;
RESISTANCE; THERAPY
AB The overexpression and overactivation of hepatocyte growth factor receptor (Met) in various cancers has been linked to increased proliferation, progression to metastatic disease, and drug resistance. Developing a PET agent to assess Met expression would aid in the diagnosis and monitoring of responses to Met-targeted therapies. In these studies, onartuzumab, the experimental therapeutic 1-armed monoclonal antibody, was radiolabeled with Br-76 or Zr-89 and evaluated as an imaging agent in Met-expressing cell lines and mouse xenografts. Methods: Zr-89-desferrioxamine (df)-onartuzumab was synthesized using a df-conjugate; Br-76-onartuzumab was labeled directly. Met-binding studies were performed using the human tumor derived cell lines MKN-45, SNU-16, and U87-MG, which have relatively high, moderate, and low levels of Met, respectively. Biodistribution and small-animal PET studies were performed in MKN-45 and U87-MG xenografts. Results: Br-76-onartuzumab and Zr-89-df-onartuzumab exhibited specific, high-affinity Met binding (in the nanomolar range) that was concordant with established Met expression levels. In MKN-45 (gastric carcinoma) xenografts, both tracers cleared slowly from nontarget tissues, with the highest uptake in tumor, blood, kidneys, and lungs. Br-76-onartuzumab MKN-45 tumor uptake remained relatively constant from 18 h (5 percentage injected dose per gram of tissue [%ID/g]) to 48 h (3 %ID/g) and exhibited tumor-to-muscle ratios ranging from 4:1 to 6:1. In contrast, Zr-89-df-onartuzumab MKN-45 tumor uptake continued to accumulate from 18 h (10 %ID/g) to 120 h (23 %ID/g), attaining tumor-to-muscle ratios ranging from 20:1 to 27:1. MKN-45 tumors were easily visualized in imaging studies with both tracers at 18 h, but after 48 h Zr-89-df-onartuzumab image quality improved, with at least 2-fold-greater tumor uptake than nontarget tissues. MKN-45 tumor uptake for both tracers correlated significantly with tumor mass and Met expression and was not affected by the presence of plasma shed Met. Conclusion: Zr-89-df-onartuzumab and Br-76-onartuzumab specifically targeted Met in vitro and in vivo; Zr-89-df-onartuzumab achieved higher tumor uptake and tumor-to-muscle ratios than Br-76-onartuzumab at later times, suggesting that Zr-89-df-onartuzumab would be better suited to image Met for diagnostic and prognostic purposes.
C1 [Jagoda, Elaine M.; Bhadrasetty, Veerendra; Histed, Stephanie; Williams, Mark; Mena, Esther; Rosenblum, Lauren; Choyke, Peter] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Lang, Lixin] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA.
[Kramer-Marek, Gabriela] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Marik, Jan; Tinianow, Jeff N.; Merchant, Mark] Genentech Inc, San Francisco, CA 94080 USA.
[Szajek, Lawrence] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA.
[Paik, Chang] NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD USA.
[Cecchi, Fabiola; Raffensperger, Kristen; Jose-Dizon, Joe-Marie; Bottaro, Donald P.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Jagoda, EM (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,Bldg 10,Room B3B69, Bethesda, MD 20892 USA.
EM ejagoda@mail.nih.gov
RI Bottaro, Donald/F-8550-2010;
OI Bottaro, Donald/0000-0002-5057-5334; Cecchi, Franco/0000-0002-2035-5621;
Merchant, Mark/0000-0003-0690-8581
FU Intramural NIH HHS [ZIA BC010656-09, ZIA BC011124-06]
NR 24
TC 19
Z9 19
U1 1
U2 7
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD OCT
PY 2012
VL 53
IS 10
BP 1592
EP 1600
DI 10.2967/jnumed.111.102293
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 015FS
UT WOS:000309432400019
PM 22917884
ER
PT J
AU Capala, J
Kong, A
Kramer-Marek, G
Gijsen, M
AF Capala, Jacek
Kong, Anthony
Kramer-Marek, Gabriela
Gijsen, Merel
TI PET Prediction of Response to Trastuzumab in ErbB2-Positive Human
Xenograft Model REPLY
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Letter
ID BREAST-CANCER; PREOPERATIVE TRASTUZUMAB; DOWN-REGULATION; HER2;
IMMUNOHISTOCHEMISTRY; APOPTOSIS
C1 [Capala, Jacek; Kong, Anthony; Kramer-Marek, Gabriela; Gijsen, Merel] NIH, Bethesda, MD 20892 USA.
RP Capala, J (reprint author), NIH, 10 Ctr Dr,Bldg 10,Room B3B69D, Bethesda, MD 20892 USA.
EM capalaj@mail.nih.gov
NR 15
TC 0
Z9 0
U1 0
U2 2
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD OCT
PY 2012
VL 53
IS 10
BP 1655
EP 1656
DI 10.2967/jnumed.112.109496
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 015FS
UT WOS:000309432400026
ER
PT J
AU Lujan-Zilbermann, J
Warshaw, MG
Williams, PL
Spector, SA
Decker, MD
Abzug, MJ
Heckman, B
Manzella, A
Kabat, B
Jean-Philippe, P
Nachman, S
Siberry, GK
AF Lujan-Zilbermann, Jorge
Warshaw, Meredith G.
Williams, Paige L.
Spector, Stephen A.
Decker, Michael D.
Abzug, Mark J.
Heckman, Barb
Manzella, Adam
Kabat, Bill
Jean-Philippe, Patrick
Nachman, Sharon
Siberry, George K.
CA Int Maternal Pediat Adolescent AID
TI Immunogenicity and Safety of 1 vs 2 Doses of Quadrivalent Meningococcal
Conjugate Vaccine in Youth Infected with Human Immunodeficiency Virus
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; POLYSACCHARIDE VACCINE; PNEUMOCOCCAL
CONJUGATE; ANTIBODY-RESPONSES; HIV-INFECTION; TYPE-1 INFECTION;
CHILDREN; MEMORY; ADOLESCENTS; PREDICTORS
AB Objective To compare the immunogenicity of 1 vs 2 doses of meningococcal polysaccharide conjugate vaccine (MCV4) in youth infected with human immunodeficiency virus (HIV).
Study design P1065 was a phase I/II immunogenicity and safety trial of MCV4 in 324 youth infected with HIV performed at 27 sites of the International Maternal Pediatric Adolescent AIDS Clinical Trials Group network in the US. At entry subjects received 1 dose of MCV4. At 24 weeks, those with screening cluster of differentiation 4 (CD4)% >= 15 were randomized to receive a second dose or not, and all with screening CD4% <15 received a second dose. Immunogenicity was evaluated as the proportion of subjects with >= 4-fold rise from entry in serum bactericidal antibody against each meningococcal serogroup (SG) at weeks 28 and 72. Logistic regression models adjusting for HIV disease severity were used to evaluate the effect of 1 vs 2 MCV4 doses among those with screening CD4% >= 15.
Results Subjects randomized to receive 2 vs 1 MCV4 dose had significantly higher response rates to all SGs at week 28 and to all except Neisseria meningitidis SGY at week 72, with adjusted ORs of 2.5-5.6. In 31 subjects with screening CD4% <15 who received 2 MCV4 doses, response rates ranged from 22%-55% at week 28 and 6%-28% at week 72.
Conclusion In youth infected with HIV with a CD4% >= 15, a second dose of MCV4 given 6 months after the initial dose significantly improves response rates at 28 and 72 weeks. Subjects with CD4% <15 at entry had lower response rates despite 2 doses of MCV4. (J Pediatr 2012;161:676-81).
C1 [Lujan-Zilbermann, Jorge] Univ S Florida, Coll Med, Tampa, FL 33620 USA.
[Warshaw, Meredith G.; Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Spector, Stephen A.] Rady Childrens Hosp, San Diego, CA USA.
[Spector, Stephen A.] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Decker, Michael D.] Sanofi Pasteur Inc, Swiftwater, PA USA.
[Abzug, Mark J.] Univ Colorado, Sch Med, Aurora, CO USA.
[Abzug, Mark J.] Childrens Hosp Colorado, Aurora, CO USA.
[Heckman, Barb; Manzella, Adam] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA.
[Kabat, Bill] Childrens Mem Hosp, Div Infect Dis & Pathol, Special Infect Dis Lab, Chicago, IL 60614 USA.
[Jean-Philippe, Patrick] NIAID, Henry Jackson Fdn Adv Mil Med, Div Aids, Bethesda, MD 20892 USA.
[Nachman, Sharon] SUNY Stony Brook, Dept Pediat, Stony Brook, NY 11794 USA.
[Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD USA.
RP Lujan-Zilbermann, J (reprint author), Univ S Florida, Coll Med, Tampa, FL 33620 USA.
OI Decker, Michael/0000-0003-1008-7472
FU National Institute of Allergy and Infectious Diseases (NIAID) [U01
AI068632]; Eunice Kennedy Shriver National Institute of Child Health and
Human Development (NICHD); National Institute of Mental Health (NIMH)
[AI068632]; Statistical and Data Analysis Center at Harvard School of
Public Health (under the National Institute of Allergy and Infectious
Diseases) [5 [U01 AI41110]]; Pediatric AIDS Clinical Trials Group [1
[U01 AI068616]]; IMPAACT Group; NICHD [N01-DK-9-001/HHSN267200800001C];
National Institute of Allergy and Infectious Diseases/National
Institutes of Health (NIAID/NIH) Department of Health and Human Services
[HHSN272200800014C]
FX Supported by the National Institute of Allergy and Infectious Diseases
(NIAID) (U01 AI068632), the Eunice Kennedy Shriver National Institute of
Child Health and Human Development (NICHD), the National Institute of
Mental Health (NIMH) (AI068632), and the Statistical and Data Analysis
Center at Harvard School of Public Health (under the National Institute
of Allergy and Infectious Diseases cooperative agreement #5 [U01
AI41110] with the Pediatric AIDS Clinical Trials Group and #1 [U01
AI068616] with the IMPAACT Group). Support of the sites was provided by
NIAID, NICHD International and Domestic Pediatric and Maternal HIV
Clinical Trials Network (funded by NICHD [contract
N01-DK-9-001/HHSN267200800001C]). Additional support was provided with
federal funds from the National Institute of Allergy and Infectious
Diseases/National Institutes of Health (NIAID/NIH) Department of Health
and Human Services (under contract HHSN272200800014C). Sanofi-Pasteur
Inc. provided study vaccine and performed meningococcal serum
bactericidal antibody activity assays. M. D. is an employee and stock
holder of Sanofi-Pasteur, the manufacturer of the vaccine evaluated in
this study. S. S. holds stock in Sanofi-Pasteur, manufacturer of the
vaccine evaluated in this study. The other authors declare no conflicts
of interest.
NR 24
TC 16
Z9 16
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD OCT
PY 2012
VL 161
IS 4
BP 676
EP +
DI 10.1016/j.jpeds.2012.04.005
PG 8
WC Pediatrics
SC Pediatrics
GA 016KH
UT WOS:000309516400024
PM 22622049
ER
PT J
AU Lansberg, MG
Straka, M
Kemp, S
Mlynash, M
Wechsler, LR
Jovin, TG
Wilder, MJ
Lutsep, HL
Czartoski, TJ
Bernstein, RA
Chang, CWJ
Warach, S
Fazekas, F
Inoue, M
Tipirneni, A
Hamilton, SA
Zaharchuk, G
Marks, MP
Bammer, R
Albers, GW
AF Lansberg, Maarten G.
Straka, Matus
Kemp, Stephanie
Mlynash, Michael
Wechsler, Lawrence R.
Jovin, Tudor G.
Wilder, Michael J.
Lutsep, Helmi L.
Czartoski, Todd J.
Bernstein, Richard A.
Chang, Cherylee W. J.
Warach, Steven
Fazekas, Franz
Inoue, Manabu
Tipirneni, Aaryani
Hamilton, Scott A.
Zaharchuk, Greg
Marks, Michael P.
Bammer, Roland
Albers, Gregory W.
CA DEFUSE 2 Study Investigators
TI MRI profile and response to endovascular reperfusion after stroke
(DEFUSE 2): a prospective cohort study
SO LANCET NEUROLOGY
LA English
DT Article
ID ACUTE ISCHEMIC-STROKE; PERFUSION IMAGING EVALUATION; EVOLUTION DEFUSE;
MERCI TRIAL; DIFFUSION; THERAPY; INTRAARTERIAL; DEFINITION; SELECTION;
MISMATCH
AB Background Whether endovascular stroke treatment improves clinical outcomes is unclear because of the paucity of data from randomised placebo-controlled trials. We aimed to establish whether MRI can be used to identify patients who are most likely to benefit from endovascular reperfusion.
Methods In this prospective cohort study we consecutively enrolled patients scheduled to have endovascular treatment within 12 h of onset of stroke at eight centres in the USA and one in Austria. Aided by an automated image analysis computer program, investigators interpreted a baseline MRI scan taken before treatment to establish whether the patient had an MRI profile (target mismatch) that suggested salvageable tissue was present. Reperfusion was assessed on an early follow-up MRI scan (within 12 h of the revascularisation procedure) and defined as a more than 50% reduction in the volume of the lesion from baseline on perfusion-weighted MRI. The primary outcome was favourable clinical response, defined as an improvement of 8 or more on the National Institutes of Health Stroke Scale between baseline and day 30 or a score of 0-1 at day 30. The secondary clinical endpoint was good functional outcome, defined as a modified Rankin scale score of 2 or less at day 90. Analyses were adjusted for imbalances in baseline predictors of outcome. Investigators assessing outcomes were masked to baseline data.
Findings 138 patients were enrolled. 110 patients had catheter angiography and of these 104 had an MRI profile and 99 could be assessed for reperfusion. 46 of 78 (59%) patients with target mismatch and 12 of 21 (57%) patients without target mismatch had reperfusion after endovascular treatment. The adjusted odds ratio (OR) for favourable clinical response associated with reperfusion was 8.8 (95% CI 2.7-29.0) in the target mismatch group and 0.2 (0.0-1.6) in the no target mismatch group (p=0.003 for difference between ORs). Reperfusion was associated with increased good functional outcome at 90 days (OR 4.0,95% CI 1.3-12.2) in the target mismatch group, but not in the no target mismatch group (1.9,0.2-18.7).
Interpretation Target mismatch patients who had early reperfiision after endovascular stroke treatment had more favourable clinical outcomes. No association between reperfusion and favourable outcomes was present in patients without target mismatch. Our data suggest that a randomised controlled trial of endovascular treatment for patients with the target mismatch profile is warranted.
C1 [Lansberg, Maarten G.; Straka, Matus; Kemp, Stephanie; Mlynash, Michael; Inoue, Manabu; Tipirneni, Aaryani; Hamilton, Scott A.; Zaharchuk, Greg; Marks, Michael P.; Bammer, Roland; Albers, Gregory W.] Stanford Univ, Sch Med, Stanford Stroke Ctr, Stanford, CA 94305 USA.
[Wechsler, Lawrence R.; Jovin, Tudor G.] Univ Pittsburgh, Med Ctr, Stroke Inst, Sch Med, Pittsburgh, PA USA.
[Wilder, Michael J.] Univ Utah, Hlth Sci Ctr, Div Vasc Neurol, Salt Lake City, UT USA.
[Lutsep, Helmi L.] Oregon Hlth & Sci Univ, Oregon Stroke Ctr, Portland, OR 97201 USA.
[Czartoski, Todd J.] Swedish Med Ctr, Swedish Neurosci Inst, Seattle, WA USA.
[Bernstein, Richard A.] Northwestern Univ, Dept Neurol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Chang, Cherylee W. J.] Univ Hawaii, John A Burns Sch Med, Queens Med Ctr, Honolulu, HI 96822 USA.
[Warach, Steven] NINDS, Sect Stroke Diagnost & Therapeut, Div Intramural Res, Bethesda, MD 20892 USA.
[Fazekas, Franz] Graz Univ, Sch Med, Dept Neurol, Graz, Austria.
RP Albers, GW (reprint author), 780 Welch Rd,Suite 205, Palo Alto, CA 94304 USA.
EM albers@stanford.edu
FU National Institute for Neurological Disorders and Stroke; Lundbeck;
Covidien; Concentric for serving on a data safety and monitoring board;
GE Healthcare; AGA Medical for serving on the neurology executive
committee of the RESPECT trial; National Institute for Neurological
Disorders and Stroke [R01 NS03932505, K23 NS051372, 1ZIANS003043]
FX Funding National Institute for Neurological Disorders and Stroke.; GWA
has received consulting fees and expenses from Lundbeck and Covidien for
steering committee work and consulting fees from Concentric for serving
on a data safety and monitoring board. GWA and RB are equity
shareholders in iSchemaView. GZ is a member of the neuroradiology
advisory board for GE Healthcare, and receives research funding support
from GE Healthcare. HLL has received consulting fees and expenses from
Concentric Medical for serving on the executive committee of the TREVO2
trial, from Co-Axia for serving on the data safety and monitoring board
for the SENTIS trial, and from AGA Medical for serving on the neurology
executive committee of the RESPECT trial. All other authors declare that
they have no conflicts of interest.; The study was funded by grants from
the National Institute for Neurological Disorders and Stroke (R01
NS03932505 to GWA, K23 NS051372 to MGL, and 1ZIANS003043 to SW).
NR 25
TC 269
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U1 0
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
J9 LANCET NEUROL
JI Lancet Neurol.
PD OCT
PY 2012
VL 11
IS 10
BP 860
EP 867
DI 10.1016/S1474-4422(12)70203-X
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 018BG
UT WOS:000309634300011
PM 22954705
ER
PT J
AU Rotunno, M
Lam, TK
Vogt, A
Bertazzi, PA
Lubin, JH
Caporaso, NE
Landi, MT
AF Rotunno, Melissa
Lam, Tram K.
Vogt, Aurelie
Bertazzi, Pier Alberto
Lubin, Jay H.
Caporaso, Neil E.
Landi, Maria Teresa
TI GSTM1 and GSTT1 copy numbers and mRNA expression in lung cancer
SO MOLECULAR CARCINOGENESIS
LA English
DT Article
DE GST; copy numbers; gene expression; lung cancer; smoking and gender
differences
ID GLUTATHIONE-S-TRANSFERASE; GENE-EXPRESSION; POLYMORPHISMS; RISK;
SMOKING; METABOLISM; GENOTYPES; ISOTHIOCYANATES; ADENOCARCINOMA;
SUSCEPTIBILITY
AB Large fractions of the human population do not express GSTM1 and GSTT1 (GSTM1/T1) enzymes because of deletions in these genes. These variations affect xenobiotic metabolism and have been evaluated in relation to lung cancer risk, mostly based on null/present gene models. We measured GSTM1/T1 heterozygous deletions, not tested in genome-wide association studies, in 2,120 controls and 2,100 cases from the Environment And Genetics in Lung cancer Etiology (EAGLE) study. We evaluated their effect on mRNA expression on lung tissue and peripheral blood samples and their association with lung cancer risk overall and by histology types. We tested the null/present, dominant, and additive models using logistic regression. Cigarette smoking and gender were studied as possible modifiers. Gene expression from blood and lung tissue cells was strongly down regulated in subjects carrying GSTM1/T1 deletions by both trend and dominant models (P?0.001). In contrast to the null/present model, analyses distinguishing subjects with 0, 1, or 2 GSTM1/T1 deletions revealed several associations. There was a decreased lung cancer risk in never-smokers (OR?=?0.44; 95%CI?=?0.230.82; P?=?0.01) and women (OR?=?0.50; 95%CI?=?0.280.90; P?=?0.02) carrying 1 or 2 GSTM1 deletions. Analogously, male smokers had an increased risk (OR?=?1.13; 95%CI?=?1.01.28; P?=?0.05) and women a decreased risk (OR?=?0.78; 95%CI?=?0.630.97; P?=?0.02) for increasing GSTT1 deletions. The corresponding gene smoking and genegender interactions were significant (P?0.05). Our results suggest that decreased activity of GSTM1/T1 enzymes elevates lung cancer risk in male smokers, likely due to impaired carcinogens' detoxification. A protective effect of the same mutations may be operative in never-smokers and women, possibly because of reduced activity of other genotoxic chemicals. (c) 2012 Wiley Periodicals, Inc.
C1 [Rotunno, Melissa; Lam, Tram K.; Vogt, Aurelie; Lubin, Jay H.; Caporaso, Neil E.; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Bertazzi, Pier Alberto] Univ Milan, Epidemiol Unit, Fdn IRCCS Osped Maggiore Policlin, Milan, Italy.
[Bertazzi, Pier Alberto] Univ Milan, Dept Occupat & Environm Hlth, Milan, Italy.
RP Landi, MT (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, 6120 Execut Blvd,MSC 7114, Bethesda, MD 20892 USA.
RI bertazzi, pietro alberto/D-5039-2017
OI bertazzi, pietro alberto/0000-0003-3475-2449
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health,
DHHS, Bethesda, MD
FX We are deeply indebted to the EAGLE participants and the study
collaborators (listed in http://dceg.cancer.gov/eagle). This work was
supported by the Intramural Research Program of the Division of Cancer
Epidemiology and Genetics, National Cancer Institute, National
Institutes of Health, DHHS, Bethesda, MD.
NR 41
TC 1
Z9 1
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0899-1987
J9 MOL CARCINOGEN
JI Mol. Carcinog.
PD OCT
PY 2012
VL 51
SU 1
SI SI
BP E142
EP E150
DI 10.1002/mc.21890
PG 9
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 015NJ
UT WOS:000309452900015
PM 22392686
ER
PT J
AU DeFranco, DB
Margolis, R
McKenna, N
AF DeFranco, Donald B.
Margolis, Ronald
McKenna, Neil
TI Molecular Endocrinology Articles in the Spotlight for October 2012
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Editorial Material
C1 [DeFranco, Donald B.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15260 USA.
[Margolis, Ronald] NIDDKD, NIH, Bethesda, MD 20892 USA.
[McKenna, Neil] Baylor Coll Med, Dept Mol & Cellular Biol & Nucl Receptor Signalin, Houston, TX 77030 USA.
RP DeFranco, DB (reprint author), Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15260 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD OCT
PY 2012
VL 26
IS 10
BP 1645
EP 1645
DI 10.1210/me.2012-1301
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 016HW
UT WOS:000309509500001
PM 23023930
ER
PT J
AU Uchida, N
Hargrove, PW
Lap, CJ
Evans, ME
Phang, O
Bonifacino, AC
Krouse, AE
Metzger, ME
Nguyen, AD
Hsieh, MM
Wolfsberg, TG
Donahue, RE
Persons, DA
Tisdale, JF
AF Uchida, Naoya
Hargrove, Phillip W.
Lap, Coen J.
Evans, Molly E.
Phang, Oswald
Bonifacino, Aylin C.
Krouse, Allen E.
Metzger, Mark E.
Anh-Dao Nguyen
Hsieh, Matthew M.
Wolfsberg, Tyra G.
Donahue, Robert E.
Persons, Derek A.
Tisdale, John F.
TI High-efficiency Transduction of Rhesus Hematopoietic Repopulating Cells
by a Modified HIV1-based Lentiviral Vector
SO MOLECULAR THERAPY
LA English
DT Article
ID MURINE BETA-THALASSEMIA; GENE-THERAPY; STEM-CELLS; CD34(+) CELLS;
PHENOTYPIC CORRECTION; TRANSGENE EXPRESSION; RESTRICTION FACTOR;
ENVELOPE PROTEINS; GLOBIN GENE; INTEGRATION
AB Human immunodeficiency virus type 1 (HIV1) vectors poorly transduce rhesus hematopoietic cells due to species-specific restriction factors, including the tripartite motif-containing 5 isoform alpha (TRIM5 alpha) which targets the HIV1 capsid. We previously developed a chimeric HIV1 (chi HIV) vector system wherein the vector genome is packaged with the simian immunodeficiency virus (SIV) capsid for efficient transduction of both rhesus and human CD34(+) cells. To evaluate whether chi HIV vectors could efficiently transduce rhesus hematopoietic repopulating cells, we performed a competitive repopulation assay in rhesus macaques, in which half of the CD34(+) cells were transduced with standard SIV vectors and the other half with chi HIV vectors. As compared with SIV vectors, chi HIV vectors achieved higher vector integration, and the transgene expression rates were two- to threefold higher in granulocytes and red blood cells and equivalent in lymphocytes and platelets for 2 years. A recipient of chi HIV vector-only transduced cells reached up to 40% of transgene expression rates in granulocytes and lymphocytes and 20% in red blood cells. Similar to HIV1 and SIV vectors, chi HIV vector frequently integrated into gene regions, especially into introns. In summary, our chi HIV vector demonstrated efficient transduction for rhesus long-term repopulating cells, comparable with SIV vectors. This chi HIV vector should allow preclinical testing of HIV1-based therapeutic vectors in large animal models.
C1 [Uchida, Naoya; Lap, Coen J.; Evans, Molly E.; Phang, Oswald; Hsieh, Matthew M.; Tisdale, John F.] NIDDK, Mol & Clin Hematol Branch, NHLBI, NIH, Bethesda, MD 20892 USA.
[Hargrove, Phillip W.; Persons, Derek A.] St Jude Childrens Res Hosp, Dept Hematol, Memphis, TN 38105 USA.
[Bonifacino, Aylin C.; Krouse, Allen E.; Metzger, Mark E.; Donahue, Robert E.] NHLBI, Hematol Branch, NIH, Rockville, MD USA.
[Anh-Dao Nguyen; Wolfsberg, Tyra G.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Tisdale, JF (reprint author), NIDDK, Mol & Clin Hematol Branch, NHLBI, NIH, 9000 Rockville Pike,Bldg 10,9N112, Bethesda, MD 20892 USA.
EM johntis@mail.nih.gov
OI Lap, Coen/0000-0001-6815-0695
FU National Institute of Diabetes, Digestive, and Kidney Diseases; National
Heart, Lung, and Blood Institute; National Human Genome Research
Institute at the National Institutes of Health
FX This work is supported by the intramural research programs of the
National Institute of Diabetes, Digestive, and Kidney Diseases, the
National Heart, Lung, and Blood Institute, and the National Human Genome
Research Institute at the National Institutes of Health. We thank the
animal care staff and technicians at 5 Research Court for their
excellent care and handling of the animals. We would also like to thank
William DeGraff and Dr Jim Mitchell of the Radiation Biology Branch,
National Cancer Institute, for the use of the Eldorado Cobalt-60
irradiator. We would like to thank Heidi Dorward, Medical Genetics
Branch, National Human Genome Research Institute, for the use of the
confocal microscope. The authors have declared that no conflict of
interest exists.
NR 42
TC 11
Z9 11
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD OCT
PY 2012
VL 20
IS 10
BP 1882
EP 1892
DI 10.1038/mt.2012.159
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 016LE
UT WOS:000309519000011
PM 22871664
ER
PT J
AU Barese, CN
Krouse, AE
Metzger, ME
King, CA
Traversari, C
Marini, FC
Donahue, RE
Dunbar, CE
AF Barese, Cecilia N.
Krouse, Allen E.
Metzger, Mark E.
King, Connor A.
Traversari, Catia
Marini, Frank C.
Donahue, Robert E.
Dunbar, Cynthia E.
TI Thymidine Kinase Suicide Gene-mediated Ganciclovir Ablation of
Autologous Gene-modified Rhesus Hematopoiesis
SO MOLECULAR THERAPY
LA English
DT Article
ID SEVERE COMBINED IMMUNODEFICIENCY; GRAFT-VERSUS-LEUKEMIA; STEM-CELLS;
NONHUMAN-PRIMATES; T-CELLS; INSERTIONAL MUTAGENESIS; GAMMARETROVIRAL
VECTORS; LENTIVIRAL VECTOR; DONOR LYMPHOCYTES; VIRUS VECTORS
AB Despite the genotoxic complications encountered in clinical gene therapy trials for primary immunodeficiency diseases targeting hematopoietic cells with integrating vectors; this strategy holds promise for the cure of several monogenic blood, metabolic and neurodegenerative diseases. In this study, we asked whether the inclusion of a suicide gene in a standard retrovirus vector would allow elimination of vector-containing stem and progenitor cells and their progeny in vivo following transplantation, using our rhesus macaque transplantation model. Following stable engraftment with autologous CD34(+) cells transduced with a retrovirus vector encoding a highly sensitive modified Herpes simplex virus thymidine kinase SR39, the administration of the antiviral prodrug ganciclovir (GCV) was effective in completely eliminating vector-containing cells in all hematopoietic lineages in vivo. The sustained absence of vector-containing cells over time, without additional GCV administration, suggests that the ablation of TkSR39 GCV-sensitive cells occurred in the most primitive hematopoietic long-term repopulating stem or progenitor cell compartment. These results are a proof-of-concept that the inclusion of a suicide gene in integrating vectors, in addition to a therapeutic gene, can provide a mechanism for later elimination of vector-containing cells, thereby increasing the safety of gene transfer.
C1 [Barese, Cecilia N.; Krouse, Allen E.; Metzger, Mark E.; King, Connor A.; Donahue, Robert E.; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Traversari, Catia] MolMed SpA, Milan, Italy.
[Marini, Frank C.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA.
RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Room 4E-5132,10 Ctr Dri,Bldg 10 CRC, Bethesda, MD 20892 USA.
EM dunbarc@nhlbi.nih.gov
RI Marini, Frank/L-8018-2016
FU [RC1CA146381]; [P50CA083639]; [R01CA109451]
FX We thank Dr Claudio Bordignon (Universita Vita-Salute S. Raffaele, and
Molmed S. p. A., Milan, Italy) for providing vector constructs used in
these studies and for helpful discussion. We are grateful to Barrington
Thompson and Sandra Price for assistance with blood sampling and animal
monitoring. We are also grateful to Keyvan Keyvanfar for his expertise
and his assistance with flow cytometry analyses and sorting, Stephanie
Sellers and Aylin Bonifacino for expert assistance in gene transfer
procedures and selection of rhesus CD34+ cells, respectively,
and Susan Wong for assistance with qPCR analyses. Frank C Marini is
supported in part by RC1CA146381, P50CA083639, R01CA109451.
NR 51
TC 10
Z9 11
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD OCT
PY 2012
VL 20
IS 10
BP 1932
EP 1943
DI 10.1038/mt.2012.166
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 016LE
UT WOS:000309519000016
PM 22910293
ER
PT J
AU Afonin, KA
Kireeva, M
Grabow, WW
Kashlev, M
Jaeger, L
Shapiro, BA
AF Afonin, Kirill A.
Kireeva, Maria
Grabow, Wade W.
Kashlev, Mikhail
Jaeger, Luc
Shapiro, Bruce A.
TI Co-transcriptional Assembly of Chemically Modified RNA Nanoparticles
Functionalized with siRNAs
SO NANO LETTERS
LA English
DT Article
DE RNA nanotechnology; self-assembly; siRNA; chemical modifications;
transcription; T7 RNA polymerase
ID EMERGING FIELD; DESIGN; NANOTECHNOLOGY; POLYMERASE
AB We report a generalized methodology for the one-pot production of chemically modified functional RNA nanoparticles during in vitro transcription with T7 RNA polymerase. The efficiency of incorporation of 2'-fluoro-dNTP in the transcripts by the wild type T7 RNA polymerase dramatically increases in the presence of manganese ions, resulting in a high-yield production of chemically modified RNA nanoparticles functionalized with siRNAs that are resistant to nucleases from human blood serum. Moreover, the unpurified transcription mixture can be used for functional ex vivo pilot experiments.
C1 [Grabow, Wade W.; Jaeger, Luc] Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA.
[Jaeger, Luc] Univ Calif Santa Barbara, Biomol Sci & Engn Program, Santa Barbara, CA 93106 USA.
[Afonin, Kirill A.; Shapiro, Bruce A.] NCI, Computat RNA Struct Grp, Ctr Canc Res, Nanobiol Program,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Kireeva, Maria; Kashlev, Mikhail] NCI, Gene Regulat & Chromosome Biol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Jaeger, L (reprint author), Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA.
EM jaeger@chem.ucsb.edu; shapirbr@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Frederick National Laboratory for Cancer Research, Center for Cancer
Research; NIH [R01GM-079604]
FX K.A.A would like to dedicate this work to Anna Kravtsova and all the
Kravtsova family. The authors thank Faye Walker for technical assistance
at early stages of this project. This research was supported (in part)
by the Intramural Research Program of the NIH, National Cancer
Institute, Frederick National Laboratory for Cancer Research, Center for
Cancer Research. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government. This research
was also supported by NIH Grant R01GM-079604 (to L.J.).
NR 17
TC 39
Z9 39
U1 3
U2 23
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1530-6984
EI 1530-6992
J9 NANO LETT
JI Nano Lett.
PD OCT
PY 2012
VL 12
IS 10
BP 5192
EP 5195
DI 10.1021/nl302302e
PG 4
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA 017TX
UT WOS:000309615000021
PM 23016824
ER
PT J
AU Cheng, KCC
Inglese, J
AF Cheng, Ken C-C
Inglese, James
TI A coincidence reporter-gene system for high-throughput screening
SO NATURE METHODS
LA English
DT Letter
ID CELLS
C1 [Cheng, Ken C-C; Inglese, James] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Inglese, James] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Cheng, KCC (reprint author), NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
EM jinglese@mail.nih.gov
FU Intramural NIH HHS [Z01 HG200319-05]
NR 5
TC 16
Z9 16
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
J9 NAT METHODS
JI Nat. Methods
PD OCT
PY 2012
VL 9
IS 10
BP 937
EP 937
DI 10.1038/nmeth.2170
PG 1
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 016LG
UT WOS:000309519300004
PM 23018994
ER
PT J
AU Khare, T
Pai, S
Koncevicius, K
Pal, M
Kriukiene, E
Liutkeviciute, Z
Irimia, M
Jia, PX
Ptak, C
Xia, MH
Tice, R
Tochigi, M
Morera, S
Nazarians, A
Belsham, D
Wong, AHC
Blencowe, BJ
Wang, SC
Kapranov, P
Kustra, R
Labrie, V
Klimasauskas, S
Petronis, A
AF Khare, Tarang
Pai, Shraddha
Koncevicius, Karolis
Pal, Mrinal
Kriukiene, Edita
Liutkeviciute, Zita
Irimia, Manuel
Jia, Peixin
Ptak, Carolyn
Xia, Menghang
Tice, Raymond
Tochigi, Mamoru
Morera, Solange
Nazarians, Anaies
Belsham, Denise
Wong, Albert H. C.
Blencowe, Benjamin J.
Wang, Sun Chong
Kapranov, Philipp
Kustra, Rafal
Labrie, Viviane
Klimasauskas, Saulius
Petronis, Arturas
TI 5-hmC in the brain is abundant in synaptic genes and shows differences
at the exon-intron boundary
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID HISTONE DEACETYLASE INHIBITOR; DNA METHYLATION; RESTRICTION
ENDONUCLEASES; DEOXYRIBONUCLEIC-ACID; MAMMALIAN DNA; THYMINE DNA;
5-HYDROXYMETHYLCYTOSINE; 5-METHYLCYTOSINE; 5-CARBOXYLCYTOSINE;
BIOINFORMATICS
AB The 5-methylcytosine (5-mC) derivative 5-hydroxymethylcytosine (5-hmC) is abundant in the brain for unknown reasons. Here we characterize the genomic distribution of 5-hmC and 5-mC in human and mouse tissues. We assayed 5-hmC by using glucosylation coupled with restriction-enzyme digestion and microarray analysis. We detected 5-hmC enrichment in genes with synapse-related functions in both human and mouse brain. We also identified substantial tissue-specific differential distributions of these DNA modifications at the exon-intron boundary in human and mouse. This boundary change was mainly due to 5-hmC in the brain but due to 5-mC in non-neural contexts. This pattern was replicated in multiple independent data sets and with single-molecule sequencing. Moreover, in human frontal cortex, constitutive exons contained higher levels of 5-hmC relative to alternatively spliced exons. Our study suggests a new role for 5-hmC in RNA splicing and synaptic function in the brain.
C1 [Khare, Tarang; Pai, Shraddha; Koncevicius, Karolis; Pal, Mrinal; Jia, Peixin; Ptak, Carolyn; Wang, Sun Chong; Labrie, Viviane; Petronis, Arturas] Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Krembil Family Epigenet Lab, Toronto, ON, Canada.
[Koncevicius, Karolis] Vilnius State Univ, Inst Math & Informat, Vilnius, Lithuania.
[Kriukiene, Edita; Liutkeviciute, Zita; Klimasauskas, Saulius] Vilnius State Univ, Inst Biotechnol, Dept Biol DNA Modificat, Vilnius, Lithuania.
[Irimia, Manuel; Blencowe, Benjamin J.] Univ Toronto, Donnelly Ctr, Toronto, ON, Canada.
[Xia, Menghang] US Natl Inst Hlth, Natl Ctr Adv Translat Sci, Bethesda, MD USA.
[Tice, Raymond] NIEHS, Div Natl Toxicol Program, Biomol Screening Branch, Durham, NC USA.
[Tochigi, Mamoru] Univ Tokyo, Grad Sch Med, Dept Neuropsychiat, Tokyo, Japan.
[Morera, Solange] CNRS, Lab Enzymol & Biochim Struct, Gif Sur Yvette, France.
[Nazarians, Anaies; Belsham, Denise] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A1, Canada.
[Nazarians, Anaies; Belsham, Denise] Univ Toronto, Dept Med, Toronto, ON, Canada.
[Wong, Albert H. C.] Ctr Addict & Mental Hlth, Dept Neurosci, Toronto, ON, Canada.
[Wang, Sun Chong] Natl Cent Univ, Inst Syst Biol & Bioinformat, Jhongli, Taiwan.
[Kapranov, Philipp] St Laurent Inst, Cambridge, MA USA.
[Kustra, Rafal] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
RP Petronis, A (reprint author), Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Krembil Family Epigenet Lab, Toronto, ON, Canada.
EM klimasau@ibt.lt; arturas_petronis@camh.net
RI Irimia, Manuel/E-3040-2010; Klimasauskas, Saulius/M-3053-2016;
OI Klimasauskas, Saulius/0000-0002-1395-2030; Wong,
Albert/0000-0002-9753-3182; Irimia, Manuel/0000-0002-2179-2567
FU Canadian Institutes of Health Research [199170, 186007]; US National
Institutes of Health [MH074127, MH088413, DP3DK085698, HG005758,
HG004535]; Canadian Institutes of Health Research; Research Council of
Lithuania; French Ministry of Foreign and European affairs under the
Lithuania-France bilateral collaboration program Gilibert
[TAP-13/2011-2012]; European Social Fund under the Global Grant measure
[VP1-3.1-SMM-07-K-01-105]; Tapscott Chair in Schizophrenia Studies at
the University of Toronto; Ontario Mental Health Foundation; Human
Frontier Science Program Organization Long Term Fellowship
FX We thank N. Miller and C. Austin (National Center for Advancing
Translational Sciences, US National Institutes of Health, Bethesda,
Maryland, USA) for providing cell lines for the SAHA experiment. We also
thank J.-S. Doucet (Centre for Addiction and Mental Health Toronto,
Canada) for assistance with mouse brain sample preparation. This
research has been supported by the Canadian Institutes of Health
Research (grants 199170 and 186007) and the US National Institutes of
Health (grants MH074127, MH088413, DP3DK085698, HG005758 and HG004535)
to A.P. and Canadian Institutes of Health Research grants to B.J.B., by
the Research Council of Lithuania and the French Ministry of Foreign and
European affairs under the Lithuania-France bilateral collaboration
program Gilibert (grant TAP-13/2011-2012) to S.M. and S.K., and by the
European Social Fund under the Global Grant measure (grant
VP1-3.1-SMM-07-K-01-105) to S.K. A.P. is supported as a Tapscott Chair
in Schizophrenia Studies at the University of Toronto and by the Ontario
Mental Health Foundation. M.I. is supported by a Human Frontier Science
Program Organization Long Term Fellowship.
NR 49
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U1 1
U2 16
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD OCT
PY 2012
VL 19
IS 10
BP 1037
EP U94
DI 10.1038/nsmb.2372
PG 9
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 017LI
UT WOS:000309591000013
PM 22961382
ER
PT J
AU Hall, D
Huerta, MF
McAuliffe, MJ
Farber, GK
AF Hall, Dan
Huerta, Michael F.
McAuliffe, Matthew J.
Farber, Gregory K.
TI Sharing Heterogeneous Data: The National Database for Autism Research
SO NEUROINFORMATICS
LA English
DT Review
DE Autism; Database; Common data elements; Unique subject identifier; Data
federation; Data repository
ID SPECTRUM DISORDERS; RISK-FACTORS; NEUROSCIENCE; LANDSCAPE; RESOURCE;
DICOM; NIH
AB The National Database for Autism Research (NDAR) is a secure research data repository designed to promote scientific data sharing and collaboration among autism spectrum disorder investigators. The goal of the project is to accelerate scientific discovery through data sharing, data harmonization, and the reporting of research results. Data from over 25,000 research participants are available to qualified investigators through the NDAR portal. Summary information about the available data is available to everyone through that portal.
C1 [Farber, Gregory K.] NIMH, Off Technol Dev & Coordinat, NIH, Rockville, MD 20892 USA.
[Hall, Dan] OMNITEC Solut Inc, Rockville, MD 20892 USA.
[Huerta, Michael F.] Natl Lib Med, Off Hlth Informat Programs Dev, Bethesda, MD 20894 USA.
[McAuliffe, Matthew J.] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Farber, GK (reprint author), NIMH, Off Technol Dev & Coordinat, NIH, 6001 Execut Blvd,Suite 7162, Rockville, MD 20892 USA.
EM halldan@mail.nih.gov; mike.huerta@nih.gov; matthew.mcauliffe@nih.gov;
farberg@mail.nih.gov
FU Intramural NIH HHS [Z99 MH999999]
NR 28
TC 39
Z9 40
U1 2
U2 20
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1539-2791
EI 1559-0089
J9 NEUROINFORMATICS
JI Neuroinformatics
PD OCT
PY 2012
VL 10
IS 4
BP 331
EP 339
DI 10.1007/s12021-012-9151-4
PG 9
WC Computer Science, Interdisciplinary Applications; Neurosciences
SC Computer Science; Neurosciences & Neurology
GA 017AS
UT WOS:000309561700002
PM 22622767
ER
PT J
AU Panchal, RG
Geller, BL
Mellbye, B
Lane, D
Iversen, PL
Bavari, S
AF Panchal, Rekha G.
Geller, Bruce L.
Mellbye, Brett
Lane, Douglas
Iversen, Patrick L.
Bavari, Sina
TI Peptide Conjugated Phosphorodiamidate Morpholino Oligomers Increase
Survival of Mice Challenged with Ames Bacillus anthracis
SO NUCLEIC ACID THERAPEUTICS
LA English
DT Article
ID COLI-IN-VITRO; ESCHERICHIA-COLI; PURE CULTURE; RESISTANCE; ANTIBIOTICS;
DOXYCYCLINE; INHIBITION; BACTERIA; STERNE; GROWTH
AB Targeting bacterial essential genes using antisense phosphorodiamidate morpholino oligomers (PMOs) represents an important strategy in the development of novel antibacterial therapeutics. PMOs are neutral DNA analogues that inhibit gene expression in a sequence-specific manner. In this study, several cationic, membrane-penetrating peptides were conjugated to PMOs (PPMOs) that target 2 bacterial essential genes: acyl carrier protein (acpP) and gyrase A (gyrA). These were tested for their ability to inhibit growth of Bacillus anthracis, a gram-positive spore-forming bacterium and causative agent of anthrax. PPMOs targeted upstream of both target gene start codons and conjugated with the bacterium-permeating peptide (RFF)(3)R were found to be most effective in inhibiting bacterial growth in vitro. Both of the gene-targeted PPMOs protected macrophages from B. anthracis induced cell death. Subsequent, in vivo testing of the PPMOs resulted in increased survival of mice challenged with the virulent Ames strain of B. anthracis. Together, these studies suggest that PPMOs targeting essential genes have the potential of being used as antisense antibiotics to treat B. anthracis infections.
C1 [Panchal, Rekha G.; Bavari, Sina] USA, Med Res Inst Infect Dis, Frederick, MD USA.
[Geller, Bruce L.; Mellbye, Brett; Iversen, Patrick L.] AVI BioPharma Inc, Corvallis, OR USA.
[Geller, Bruce L.; Mellbye, Brett; Iversen, Patrick L.] Oregon State Univ, Corvallis, OR 97331 USA.
[Lane, Douglas] NCI, Target Struct Based Drug Discovery Grp, SAIC Frederick, Frederick, MD 21701 USA.
RP Panchal, RG (reprint author), Dept Target Discovery & Expt Microbiol, 1425 Porter St, Ft Detrick, MD 21702 USA.
EM rekha.panchal@amedd.army.mil
OI Mellbye, Brett/0000-0002-3586-1885
FU Department of Defense Chemical Biological Defense Program through the
Defense Threat Reduction Agency; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]; Developmental Therapeutics
Program in the Division of Cancer Treatment and Diagnosis of the
National Cancer Institute
FX We thank Brett Eaton for technical support. This project was partially
funded by the Department of Defense Chemical Biological Defense Program
through the Defense Threat Reduction Agency. This project has been
funded in whole or in part with federal funds from the National Cancer
Institute, National Institutes of Health, under contract
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government. This research
was supported, in part, by the Developmental Therapeutics Program in the
Division of Cancer Treatment and Diagnosis of the National Cancer
Institute. Opinions, interpretations, conclusions, and recommendations
are those of the authors and are not necessarily endorsed by the U.S.
Army.
NR 29
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U1 0
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2159-3337
EI 2159-3345
J9 NUCLEIC ACID THER
JI Nucl. Acid Ther.
PD OCT
PY 2012
VL 22
IS 5
BP 316
EP 322
DI 10.1089/nat.2012.0362
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Medicine,
Research & Experimental
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Research &
Experimental Medicine
GA 017MJ
UT WOS:000309593700004
PM 22978365
ER
PT J
AU Alvheim, AR
Malde, MK
Osei-Hyiaman, D
Lin, YH
Pawlosky, RJ
Madsen, L
Kristiansen, K
Froyland, L
Hibbeln, JR
AF Alvheim, Anita R.
Malde, Marian K.
Osei-Hyiaman, Douglas
Lin, Yu Hong
Pawlosky, Robert J.
Madsen, Lise
Kristiansen, Karsten
Froyland, Livar
Hibbeln, Joseph R.
TI Dietary Linoleic Acid Elevates Endogenous 2-AG and Anandamide and
Induces Obesity
SO OBESITY
LA English
DT Article
ID POLYUNSATURATED FATTY-ACIDS; ADIPOCYTE DIFFERENTIATION; DOCOSAHEXAENOIC
ACID; RAT-BRAIN; ENDOCANNABINOIDS; LIVER; TISSUES; SYSTEM;
PREADIPOCYTES; ACTIVATION
AB Suppressing hyperactive endocannabinoid tone is a critical target for reducing obesity. The backbone of both endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) is the omega-6 fatty acid arachidonic acid (AA). Here we posited that excessive dietary intake of linoleic acid (LA), the precursor of AA, would induce endocannabinoid hyperactivity and promote obesity. LA was isolated as an independent variable to reflect the dietary increase in LA from 1 percent of energy (en%) to 8 en% occurring in the United States during the 20th century. Mice were fed diets containing 1 en% LA, 8 en% LA, and 8 en% LA + 1 en% eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) in medium-fat diets (35 en% fat) and high-fat diets (60 en%) for 14 weeks from weaning. Increasing LA from 1 en% to 8 en% elevated AA-phospholipids (PL) in liver and erythrocytes, tripled 2-AG + 1-AG and AEA associated with increased food intake, feed efficiency, and adiposity in mice. Reducing AA-PL by adding 1 en% long-chain omega-3 fats to 8 en% LA diets resulted in metabolic patterns resembling 1 en% LA diets. Selectively reducing LA to 1 en% reversed the obesogenic properties of a 60 en% fat diet. These animal diets modeled 20th century increases of human LA consumption, changes that closely correlate with increasing prevalence rates of obesity. In summary, dietary LA increased tissue AA, and subsequently elevated 2-AG + 1-AG and AEA resulting in the development of diet-induced obesity. The adipogenic effect of LA can be prevented by consuming sufficient EPA and DHA to reduce the AA-PL pool and normalize endocannabinoid tone.
C1 [Alvheim, Anita R.; Osei-Hyiaman, Douglas; Lin, Yu Hong; Pawlosky, Robert J.; Hibbeln, Joseph R.] NIAAA, NIH, Bethesda, MD USA.
[Alvheim, Anita R.; Malde, Marian K.; Madsen, Lise; Froyland, Livar] Natl Inst Nutr & Seafood Res NIFES, Bergen, Norway.
[Alvheim, Anita R.] Univ Bergen, Dept Biomed, Bergen, Norway.
[Osei-Hyiaman, Douglas] Nippon Boehringer Ingelheim, CardioMetabol Dis Res, Dept Mol & Cellular Biol, Kobe, Hyogo, Japan.
[Osei-Hyiaman, Douglas] RIKEN, Ctr Mol Imaging Sci, Kobe, Hyogo, Japan.
[Kristiansen, Karsten] Univ Copenhagen, Dept Biol, Copenhagen, Denmark.
RP Hibbeln, JR (reprint author), NIAAA, NIH, Bethesda, MD USA.
EM jhibbeln@mail.nih.gov
RI Madsen, Lise/C-6246-2012; Kristiansen, Karsten/J-5148-2014; Kjellevold,
Marian/C-2973-2012
OI Madsen, Lise/0000-0003-4468-1947; Kristiansen,
Karsten/0000-0002-6024-0917; Kjellevold, Marian/0000-0001-7070-5784
FU Intramural Research program of the National Institute on Alcohol Abuse
and Alcoholism, NIH, the National Institute of Nutrition and Seafood
Research (NIFES), Bergen, Norway; Research Council of Norway
[186908/l10]
FX The study was supported by the Intramural Research program of the
National Institute on Alcohol Abuse and Alcoholism, NIH, the National
Institute of Nutrition and Seafood Research (NIFES), Bergen, Norway, and
the Research Council of Norway 186908/l10. The fish oil concentrate was
provided by Axellus, Norway. The funders had no role in study design,
data collection and analysis, decision to publish or preparation of the
manuscript.
NR 40
TC 79
Z9 79
U1 0
U2 29
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD OCT
PY 2012
VL 20
IS 10
BP 1984
EP 1994
DI 10.1038/oby.2012.38
PG 11
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 016IH
UT WOS:000309510700004
PM 22334255
ER
PT J
AU Aicher, BO
Haser, EK
Freeman, LA
Carnie, AV
Stonik, JA
Wang, XD
Remaley, AT
Kato, GJ
Cannon, RO
AF Aicher, Brittany O.
Haser, Erin K.
Freeman, Lita A.
Carnie, Andrea V.
Stonik, John A.
Wang, Xunde
Remaley, Alan T.
Kato, Gregory J.
Cannon, Richard O., III
TI Diet-Induced Weight Loss in Overweight or Obese Women and Changes in
High-Density Lipoprotein Levels and Function
SO OBESITY
LA English
DT Article
ID RADICAL ABSORBENCY CAPACITY; NITRIC-OXIDE SYNTHASE; CHOLESTEROL EFFLUX;
PLASMA-LIPOPROTEINS; PHYSICAL-ACTIVITY; HDL CHOLESTEROL; EXERCISE; FAT;
MEN; MORTALITY
AB Diet-induced weight loss in women may be associated with decreases not only in plasma levels of low-density lipoprotein cholesterol (LDL-C), but also in high-density lipoprotein cholesterol (HDL-C). Whether a decrease in HDL-C is associated with altered HDL function is unknown. One hundred overweight or obese women (age 46 +/- 11 years, 60 black; 12 diabetic) were enrolled in the 6-month program of reduced fat and total energy diet and low-intensity exercise. Serum cholesterol efflux capacity was measured in H-3-cholesterol-labeled BHK cells expressing ABCA1, ABCG1, or SR-B1 transporters and incubated with 1% apolipoprotein B (apoB)-depleted serum. Antioxidant properties of HDL were estimated by paraoxonase-1 (PON1) activity and oxygen radical absorbance capacity (ORAC). Endothelial nitric oxide synthase (eNOS) activation was measured by conversion of L-arginine to L-citrulline in endothelial cells incubated with HDL from 49 subjects. Participants achieved an average weight loss of 2.2 +/- 3.9 kg (P < 0.001), associated with reductions in both LDL-C (-6 +/- 21 mg/dl, P = 0.004) and HDL-C (-3 +/- 9 mg/dl, P = 0.016). Cholesterol efflux capacity by the ABCA1 transporter decreased by 10% (P = 0.006); efflux capacities by the ABCG1 and SR-B1 transporters were not significantly altered. ORAC decreased by 15% (P = 0.018); neither PON1 activity nor eNOS activation was significantly altered by reduction in HDL-C. Findings were similar for diabetic and nondiabetic subjects. Diet-induced weight loss in overweight or obese women is associated with a decrease in HDL-C levels, but overall HDL function is relatively spared, suggesting that decrease in HDL-C in this setting is not deleterious to cardiovascular risk.
C1 [Aicher, Brittany O.; Haser, Erin K.; Freeman, Lita A.; Carnie, Andrea V.; Stonik, John A.; Wang, Xunde; Remaley, Alan T.; Kato, Gregory J.; Cannon, Richard O., III] NHLBI, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA.
RP Cannon, RO (reprint author), NHLBI, Cardiovasc & Pulm Branch, Bldg 10, Bethesda, MD 20892 USA.
EM cannonr@nih.gov
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU National Heart, Lung, and Blood Institute, National Institutes of Health
FX We gratefully acknowledge the contributions of Maureen Sampson, Shannon
Jenkins, Gloria Zalos, Kevin Smith, Amber Courville, Diane Dellavalle,
Kong Y. Chen, Greg McMahon, Catherine Marinac, and Megan Sabo to this
study. This research was supported by the intramural research program of
the National Heart, Lung, and Blood Institute, National Institutes of
Health.
NR 26
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U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD OCT
PY 2012
VL 20
IS 10
BP 2057
EP 2062
DI 10.1038/oby.2012.56
PG 6
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 016IH
UT WOS:000309510700013
PM 22402736
ER
PT J
AU Li, ZZ
Xu, YW
Warner, D
Volkow, ND
AF Li, Zizhong
Xu, Youwen
Warner, Don
Volkow, Nora D.
TI Alcohol ADME in Primates Studied with Positron Emission Tomography
SO PLOS ONE
LA English
DT Article
ID BRAIN ETHANOL-METABOLISM; RAT-BRAIN; SYSTEM PET; ACETALDEHYDE;
DEUTERIUM; OXIDATION; LIVER; KINETICS; CONSUMPTION; POLYMORPHISMS
AB Background and Purpose: The sensitivity to the intoxicating effects of alcohol as well as its adverse medical consequences differ markedly among individuals, which reflects in part differences in alcohol's absorption, distribution, metabolism, and elimination (ADME) properties. The ADME of alcohol in the body and its relationship with alcohol's brain bioavailability, however, is not well understood.
Experimental Approach: The ADME of C-11 labeled alcohol, (CH3CH2OH)-C-11, 1 and C-11 and deuterium dual labeled alcohol, (CH3CD2OH)-C-11, 2 in baboons was compared based on the principle that C-D bond is stronger than C-H bond, thus the reaction is slower if C-D bond breaking occurs in a rate-determining metabolic step. The following ADME parameters in peripheral organs and brain were derived from time activity curve (TAC) of positron emission tomography (PET) scans: peak uptake (C-max); peak uptake time (T-max), half-life of peak uptake (T-1/2), the area under the curve (AUC(60min)), and the residue uptake (C-60min).
Key Results: For 1 the highest uptake occurred in the kidney whereas for 2 it occurred in the liver. A deuterium isotope effect was observed in the kidneys in both animals studied and in the liver of one animal but not the other. The highest uptake for 1 and 2 in the brain was in striatum and cerebellum but 2 had higher uptake than 1 in all brain regions most evidently in thalamus and cingulate. Alcohol's brain uptake was significantly higher when given intravenously than when given orally and also when the animal was pretreated with a pharmacological dose of alcohol.
Conclusion and Implications: The study shows that alcohol metabolism in peripheral organs had a large effect on alcohol's brain bioavailability. This study sets the stage for clinical investigation on how genetics, gender and alcohol abuse affect alcohol's ADME and its relationship to intoxication and medical consequences.
C1 [Li, Zizhong; Xu, Youwen; Warner, Don] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Volkow, Nora D.] NIAAA, Bethesda, MD USA.
[Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA.
RP Li, ZZ (reprint author), Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
EM Zizhong_li@eisai.com
FU Brookhaven National Laboratory (LDRD) [03-103]; National Institute on
Alcoholism and Alcohol Abuse [5R21AA014018-03]; United States Department
of Energy [DE-AC02-98CH1-886]; National Institutes of Health (Intramural
Research Program of the National Institute on Alcoholism and Alcohol
Abuse)
FX ZL was supported by a grant from Brookhaven National Laboratory
(LDRD#03-103) and he is the author of a grant from National Institute on
Alcoholism and Alcohol Abuse (5R21AA014018-03). This research was also
funded by United States Department of Energy (DE-AC02-98CH1-886) and
National Institutes of Health (Intramural Research Program of the
National Institute on Alcoholism and Alcohol Abuse). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 56
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U1 1
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 1
PY 2012
VL 7
IS 10
AR e46676
DI 10.1371/journal.pone.0046676
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 014PQ
UT WOS:000309388500039
PM 23049712
ER
PT J
AU Husky, MM
Olfson, M
He, JP
Nock, MK
Swanson, SA
Merikangas, KR
AF Husky, Mathilde M.
Olfson, Mark
He, Jian-ping
Nock, Matthew K.
Swanson, Sonja Alsemgeest
Merikangas, Kathleen Ries
TI Twelve-Month Suicidal Symptoms and Use of Services Among Adolescents:
Results From the National Comorbidity Survey
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID MENTAL-HEALTH TREATMENT; COGNITIVE-BEHAVIORAL THERAPY; SUPPLEMENT NCS-A;
UNITED-STATES; RISK-FACTORS; SURVEY REPLICATION; HELP-SEEKING;
PRIMARY-CARE; IDEATION; YOUTH
AB Objective: The study assessed the prevalence of suicidal ideation, suicide plans, and suicide attempts as well as patterns of mental health service use among adolescents. Methods: Data came from the National Comorbidity Survey Adolescent Supplement, a nationally representative sample of 10,123 adolescents aged 13 to 18 years who participated in computer-assisted, face-to-face interviews between February 2001 and January 2004. Prevalences of suicidal thoughts and behaviors in the past year were determined. Past-year use of any mental health treatment and receipt of four or more visits from one provider among youths with suicidal ideation, plans, or attempts were also assessed. Associations were evaluated by using logistic regression. Results: During the course of 12 months, 3.6% of adolescents reported suicidal ideation without a plan or attempt,.6% reported a suicide plan without an attempt, and 1.9% made a suicide attempt. Overall, two-thirds of adolescents with suicidal ideation (67.3%) and half of those with a plan (54.4%) or attempt (56.9%) did not have any contact with a mental health specialist in the past year. Different predictors of use of care were identified for each group. Conclusions: Adolescent suicidality often is untreated in the United States. Increased outreach efforts to improve treatment access for youths with suicidal ideation and attempts are needed. (Psychiatric Services 63: 989-996, 2012; doi: 10.1176/appi.ps.201200058)
C1 [Husky, Mathilde M.] Univ Bordeaux, Aquitaine Inst Cognit & Integrat Neurosci, Dept Psychol, F-33000 Bordeaux, France.
[Olfson, Mark] Columbia Univ, Dept Psychiat, Med Ctr, New York State Psychiat Inst, New York, NY USA.
[He, Jian-ping] NIMH, Div Intramural Res Programs, Bethesda, MD 20892 USA.
[Merikangas, Kathleen Ries] NIMH, Sect Dev Genet Epidemiol, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
[Swanson, Sonja Alsemgeest] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Nock, Matthew K.] Harvard Univ, Dept Psychol, Boston, MA 02115 USA.
RP Husky, MM (reprint author), Univ Bordeaux, Aquitaine Inst Cognit & Integrat Neurosci, Dept Psychol, Pl Victoire, F-33000 Bordeaux, France.
EM mathilde.husky@u-bordeaux1.fr
FU Carmel Hill Fund to Columbia University; TeenScreen and the Agency for
Healthcare Research and Quality [U18 HS02112]; New York State
Psychiatric Institute; Intramural Research Program of the National
Institute of Mental Health [Z01 MH002808-08]; National Institute of
Mental Health [U01-MH60220]; Bristol-Myers Squibb; Eli Lilly Company
FX This research was funded by grants from the Carmel Hill Fund to Columbia
University, TeenScreen and the Agency for Healthcare Research and
Quality (U18 HS02112) (Dr. Olfson) as well as the New York State
Psychiatric Institute. This work was also ported by the Intramural
Research Program of the National Institute of Mental Health (Z01
MH002808-08). The National Comorbidity Survey Adolescent Supplement
(NCS-A) was supported by the National Institute of Mental Health
(U01-MH60220). The views and opinions expressed in this article are
those of the authors and should not be construed to represent the views
of any of the sponsoring organizations or agencies or the U.S.
government.; Dr. Olfson has received research grants from Bristol-Myers
Squibb and Eli Lilly & Company. The other authors report no competing
interests.
NR 54
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U1 0
U2 13
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
EI 1557-9700
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD OCT
PY 2012
VL 63
IS 10
BP 989
EP 996
DI 10.1176/appi.ps.201200058
PG 8
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 015ZX
UT WOS:000309488100007
PM 22910768
ER
PT J
AU Arai, AE
Leung, S
Kellman, P
AF Arai, Andrew E.
Leung, Steve
Kellman, Peter
TI Controversies in Cardiovascular MR Imaging: Reasons Why Imaging
Myocardial T2 Has Clinical and Pathophysiologic Value in Acute
Myocardial Infarction
SO RADIOLOGY
LA English
DT Article
ID EMISSION-COMPUTED-TOMOGRAPHY; NUCLEAR-MAGNETIC-RESONANCE; AUTOMATED
FEATURE ANALYSIS; DELAYED ENHANCEMENT MRI; ISCHEMIC CELL-DEATH; GD-DTPA
INJECTION; COLLATERAL FLOW; CONTRAST ENHANCEMENT; CONTRACTILE FUNCTION;
WAVEFRONT PHENOMENON
C1 [Arai, Andrew E.; Leung, Steve; Kellman, Peter] NHLBI, Cardiovasc & Pulm Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Arai, AE (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, US Dept HHS, Bldg 10,Room B1D416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA.
EM araia@nih.gov
RI Leung, Steve/E-5624-2011
OI Leung, Steve/0000-0003-2832-2258
FU National Institutes of Health [Z01-HL004607-12]
FX This research was supported by the National Institutes of Health (grant
Z01-HL004607-12).
NR 65
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U1 0
U2 6
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD OCT
PY 2012
VL 265
IS 1
BP 23
EP 32
DI 10.1148/radiol.12112491
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 016KR
UT WOS:000309517600005
PM 22993218
ER
PT J
AU Kontzias, A
Efthimiou, P
AF Kontzias, Apostolos
Efthimiou, Petros
TI The Use of Canakinumab, a Novel IL-1 beta Long-Acting Inhibitor, in
Refractory Adult-Onset Still's Disease
SO SEMINARS IN ARTHRITIS AND RHEUMATISM
LA English
DT Review
DE adult-onset Still's disease; anakinra; canakinumab
ID JUVENILE IDIOPATHIC ARTHRITIS; INFLAMMATORY DISORDERS; PERIODIC
SYNDROMES; FERRITIN LEVELS; ANAKINRA; RILONACEPT; EFFICACY; PATHOGENESIS
AB Objectives: We describe the successful treatment of adult-onset Still's disease (AOSD) with canakinumab, a novel anti-interleukin (IL)-1 beta, long-acting, monoclonal antibody, on patients refractory to anakinra and rilonacept. In many cases the expected positive therapeutic effect of short-acting IL-1 inhibitors is transient or completely absent, leading to our hypothesis that their short half-life may be associated with incomplete IL-1 blockade, given the cyclic nature of the disease.
Methods: We report 2 cases of AOSD resistant to short-acting IL-1 blockade, which were subsequently treated with canakinumab. A retrospective chart review was conducted of patients diagnosed with AOSD in our regional referral center.
Results: Response to treatment was assessed by its effect on the systemic symptoms (resolution of fever and rash), polyarthritis (using the disease activity score 28--C-reactive protein score), and the levels of serum ferritin. Canakinumab demonstrated sustained efficacy in both patients as evidenced by clinical and laboratory parameters with minimal adverse reactions.
Conclusions: This is the first documented report of successful use of canakinumab, a novel IL-1 beta inhibitor, in AOSD patients refractory to traditional disease-modifying antirheumatic drugs and short- to moderate-acting IL-1 blockade. Prospective comparative studies are needed to validate canakinumab's efficacy and safety. (C) 2012 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 42:201-205
C1 [Efthimiou, Petros] Lincoln Med & Mental Hlth Ctr, Div Rheumatol, New York, NY 10451 USA.
[Efthimiou, Petros] Cornell Univ, Weill Med Coll, New York, NY USA.
[Kontzias, Apostolos] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Efthimiou, P (reprint author), Lincoln Med & Mental Hlth Ctr, Div Rheumatol, 234 E 149th St, New York, NY 10451 USA.
EM pe53@cornell.edu
NR 26
TC 27
Z9 28
U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0049-0172
EI 1532-866X
J9 SEMIN ARTHRITIS RHEU
JI Semin. Arthritis Rheum.
PD OCT
PY 2012
VL 42
IS 2
BP 201
EP 205
DI 10.1016/j.semarthrit.2012.03.004
PG 5
WC Rheumatology
SC Rheumatology
GA 017VE
UT WOS:000309618300011
PM 22512815
ER
PT J
AU Bao, R
Esser, L
Sadhukhan, A
Nair, MKM
Schifferli, DM
Xia, D
AF Bao, Rui
Esser, Lothar
Sadhukhan, Annapurna
Nair, Manoj K. M.
Schifferli, Dieter M.
Xia, Di
TI Crystallization and preliminary X-ray diffraction analysis of PsaA, the
adhesive pilin subunit that forms the pH 6 antigen on the surface of
Yersinia pestis
SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION
COMMUNICATIONS
LA English
DT Article
ID EPITHELIAL-CELLS; FIMBRIAE
AB Yersinia pestis has been responsible for a number of high-mortality epidemics throughout human history. Like all other bacterial infections, the pathogenesis of Y. pestis begins with the attachment of bacteria to the surface of host cells. At least five surface proteins from Y. pestis have been shown to interact with host cells. Psa, the pH 6 antigen, is one of them and is deployed on the surface of bacteria as thin flexible fibrils that are the result of the polymerization of a single PsaA pilin subunit. Here, the crystallization of recombinant donor-strand complemented PsaA by the hanging-drop vapor-diffusion method is reported. X-ray diffraction data sets were collected to 1.9 angstrom resolution from a native crystal and to 1.5 angstrom resolution from a bromide-derivatized crystal. These crystals displayed the symmetry of the orthorhombic space group P222(1), with unit-cell parameters a = 26.3, b = 54.6, c = 102.1 angstrom. Initial phases were derived from single isomorphous replacement with anomalous scattering experiments, resulting in an electron-density map that showed a single molecule in the crystallographic asymmetric unit. Sequence assignment was aided by residues binding to bromide ions of the heavy-atom derivative.
C1 [Bao, Rui; Esser, Lothar; Xia, Di] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Sadhukhan, Annapurna; Nair, Manoj K. M.; Schifferli, Dieter M.] Univ Penn, Dept Pathobiol, Sch Vet Med, Philadelphia, PA 19104 USA.
RP Xia, D (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM xiad@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; Trans NIH/FDA Intramural Biodefense Program;
NIH [AI076695]; University of Pennsylvania Research Foundation; Research
Initiative Funds from the University of Pennsylvania Veterinary Center
for Infectious Disease
FX The authors wish to thank the beamline staff of SER-CAT at APS, ANL for
their assistance in data collection. We thank George Leiman for
editorial assistance during the preparation of the manuscript. This
research was supported in part by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research, by a grant
from the Trans NIH/FDA Intramural Biodefense Program (to DX), by NIH
grant AI076695, by a University of Pennsylvania Research Foundation
grant and by Research Initiative Funds from the University of
Pennsylvania Veterinary Center for Infectious Disease (to DMS).
NR 14
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1744-3091
J9 ACTA CRYSTALLOGR F
JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun.
PD OCT
PY 2012
VL 68
BP 1243
EP 1246
DI 10.1107/S1744309112033076
PN 10
PG 4
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 014EF
UT WOS:000309357200023
PM 23027758
ER
PT J
AU Hara, Y
Rapp, PR
Morrison, JH
AF Hara, Yuko
Rapp, Peter R.
Morrison, John H.
TI Neuronal and morphological bases of cognitive decline in aged rhesus
monkeys
SO AGE
LA English
DT Article
DE Aging; Area 46; Dentate gyrus; Executive function; Recognition memory;
Perforated synapse
ID PREFRONTAL SEROTONIN DEPLETION; LONG-TERM POTENTIATION; MEDIAL
TEMPORAL-LOBE; CARD SORTING TEST; CORTICOCORTICALLY PROJECTING NEURONS;
RECOGNITION MEMORY IMPAIRMENT; EXECUTIVE SYSTEM DYSFUNCTION; LAYER-2/3
PYRAMIDAL CELLS; MULTIPLE-SYNAPSE BOUTONS; PRIMATE CEREBRAL-CORTEX
AB Rhesus monkeys provide a valuable model for studying the basis of cognitive aging because they are vulnerable to age-related decline in executive function and memory in a manner similar to humans. Some of the behavioral tasks sensitive to the effects of aging are the delayed response working memory test, recognition memory tests including the delayed nonmatching-to-sample and the delayed recognition span task, and tests of executive function including reversal learning and conceptual set-shifting task. Much effort has been directed toward discovering the neurobiological parameters that are coupled to individual differences in age-related cognitive decline. Area 46 of the dorsolateral prefrontal cortex (dlPFC) has been extensively studied for its critical role in executive function while the hippocampus and related cortical regions have been a major target of research for memory function. Some of the key age-related changes in area 46 include decreases in volume, microcolumn strength, synapse density, and alpha 1- and alpha 2-adrenergic receptor binding densities. All of these measures significantly correlate with cognitive scores. Interestingly, the critical synaptic subtypes associated with cognitive function appear to be different between the dlPFC and the hippocampus. For example, the dendritic spine subtype most critical to task acquisition and vulnerable to aging in area 46 is the thin spine, whereas in the dentate gyrus, the density of large mushroom spines with perforated synapses correlates with memory performance. This review summarizes age-related changes in anatomical, neuronal, and synaptic parameters within brain areas implicated in cognition and whether these changes are associated with cognitive decline.
C1 [Morrison, John H.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA.
[Morrison, John H.] Mt Sinai Sch Med, Computat Neurobiol & Imaging Ctr, New York, NY 10029 USA.
[Rapp, Peter R.] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
[Hara, Yuko; Morrison, John H.] Mt Sinai Sch Med, Fishberg Dept Neurosci, New York, NY 10029 USA.
[Hara, Yuko; Morrison, John H.] Mt Sinai Sch Med, Kastor Neurobiol Aging Labs, New York, NY 10029 USA.
[Hara, Yuko; Morrison, John H.] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY 10029 USA.
[Morrison, John H.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA.
RP Morrison, JH (reprint author), Mt Sinai Sch Med, Dept Neurosci, 1 Gustave L Levy Pl,Box 1065, New York, NY 10029 USA.
EM john.morrison@mssm.edu
RI Hara, Yuko/B-9172-2012
OI Hara, Yuko/0000-0001-5828-442X
FU National Institute on Aging [R37 AG06647, R01 AG010606, P01 AG16765]
FX Original research and manuscript preparation was supported by National
Institute on Aging grants R37 AG06647, R01 AG010606, P01 AG16765 to
J.H.M. and in part by the Intramural Research Program of the National
Institute on Aging. This manuscript was prepared while Y.H. was an
Ellison Medical Foundation/AFAR Postdoctoral Fellow. We thank Erik Bloss
for critical discussion and helpful comments on the manuscript.
NR 164
TC 27
Z9 29
U1 1
U2 12
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0161-9152
J9 AGE
JI Age
PD OCT
PY 2012
VL 34
IS 5
BP 1051
EP 1073
DI 10.1007/s11357-011-9278-5
PG 23
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 011NB
UT WOS:000309170600002
PM 21710198
ER
PT J
AU Brenner, DR
Boffetta, P
Duell, EJ
Bickeboeller, H
Rosenberger, A
McCormack, V
Muscat, JE
Yang, P
Wichmann, HE
Brueske-Hohlfeld, I
Schwartz, AG
Cote, ML
Tjonneland, A
Friis, S
Le Marchand, L
Zhang, ZF
Morgenstern, H
Szeszenia-Dabrowska, N
Lissowska, J
Zaridze, D
Rudnai, P
Fabianova, E
Foretova, L
Janout, V
Bencko, V
Schejbalova, M
Brennan, P
Mates, IN
Lazarus, P
Field, JK
Raji, O
McLaughlin, JR
Liu, G
Wiencke, J
Neri, M
Ugolini, D
Andrew, AS
Lan, Q
Hu, W
Orlow, I
Park, BJ
Hung, RJ
AF Brenner, Darren R.
Boffetta, Paolo
Duell, Eric J.
Bickeboeller, Heike
Rosenberger, Albert
McCormack, Valerie
Muscat, Joshua E.
Yang, Ping
Wichmann, H. -Erich
Brueske-Hohlfeld, Irene
Schwartz, Ann G.
Cote, Michele L.
Tjonneland, Anne
Friis, Soren
Le Marchand, Loic
Zhang, Zuo-Feng
Morgenstern, Hal
Szeszenia-Dabrowska, Neonila
Lissowska, Jolanta
Zaridze, David
Rudnai, Peter
Fabianova, Eleonora
Foretova, Lenka
Janout, Vladimir
Bencko, Vladimir
Schejbalova, Miriam
Brennan, Paul
Mates, Ioan N.
Lazarus, Philip
Field, John K.
Raji, Olaide
McLaughlin, John R.
Liu, Geoffrey
Wiencke, John
Neri, Monica
Ugolini, Donatella
Andrew, Angeline S.
Lan, Qing
Hu, Wei
Orlow, Irene
Park, Bernard J.
Hung, Rayjean J.
TI Previous Lung Diseases and Lung Cancer Risk: A Pooled Analysis From the
International Lung Cancer Consortium
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Review
DE bronchitis; chronic; emphysema; lung diseases; lung neoplasms;
meta-analysis; pneumonia; pulmonary disease; chronic obstructive;
tuberculosis
ID OBSTRUCTIVE PULMONARY-DISEASE; ENVIRONMENTAL TOBACCO-SMOKE; RESIDENTIAL
RADON; PREDICTION MODEL; SCREENING TRIAL; NEVER-SMOKERS; INFLAMMATION;
ASSOCIATION; VALIDATION; VARIANTS
AB To clarify the role of previous lung diseases (chronic bronchitis, emphysema, pneumonia, and tuberculosis) in the development of lung cancer, the authors conducted a pooled analysis of studies in the International Lung Cancer Consortium. Seventeen studies including 24,607 cases and 81,829 controls (noncases), mainly conducted in Europe and North America, were included (19842011). Using self-reported data on previous diagnoses of lung diseases, the authors derived study-specific effect estimates by means of logistic regression models or Cox proportional hazards models adjusted for age, sex, and cumulative tobacco smoking. Estimates were pooled using random-effects models. Analyses stratified by smoking status and histology were also conducted. A history of emphysema conferred a 2.44-fold increased risk of lung cancer (95 confidence interval (CI): 1.64, 3.62 (16 studies)). A history of chronic bronchitis conferred a relative risk of 1.47 (95 CI: 1.29, 1.68 (13 studies)). Tuberculosis (relative risk 1.48, 95 CI: 1.17, 1.87 (16 studies)) and pneumonia (relative risk 1.57, 95 CI: 1.22, 2.01 (12 studies)) were also associated with lung cancer risk. Among never smokers, elevated risks were observed for emphysema, pneumonia, and tuberculosis. These results suggest that previous lung diseases influence lung cancer risk independently of tobacco use and that these diseases are important for assessing individual risk.
C1 [Brenner, Darren R.; McLaughlin, John R.; Hung, Rayjean J.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5T 3L9, Canada.
[Brenner, Darren R.; McLaughlin, John R.; Hung, Rayjean J.] Univ Toronto, Div Epidemiol, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Boffetta, Paolo] Mt Sinai Sch Med, Inst Translat Epidemiol, New York, NY USA.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
[Duell, Eric J.] Catalan Inst Oncol, Unit Nutr Environm & Canc, Canc Epidemiol Res Program, Barcelona, Spain.
[Bickeboeller, Heike; Rosenberger, Albert] Univ Gottingen, Sch Med, Dept Genet Epidemiol, Gottingen, Germany.
[McCormack, Valerie; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
[Muscat, Joshua E.] Penn State Univ, Penn State Canc Inst, Div Epidemiol, State Coll, PA USA.
[Lazarus, Philip] Penn State Univ, Penn State Canc Inst, Dept Pharmacol, State Coll, PA USA.
[Lazarus, Philip] Penn State Univ, Penn State Canc Inst, Dept Hlth Evaluat Sci, State Coll, PA USA.
[Yang, Ping] Mayo Clin, Epidemiol & Genet Lung Canc Res Program, Rochester, MN USA.
[Wichmann, H. -Erich; Brueske-Hohlfeld, Irene] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Epidemiol, Neuherberg, Germany.
[Schwartz, Ann G.; Cote, Michele L.] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI USA.
[Schwartz, Ann G.; Cote, Michele L.] Karmanos Canc Inst, Detroit, MI USA.
[Tjonneland, Anne; Friis, Soren] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Szeszenia-Dabrowska, Neonila] Inst Occupat Med, Dept Epidemiol, Lodz, Poland.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Zaridze, David] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia.
[Rudnai, Peter] Natl Inst Environm Hlth, Fodor Jozsef Natl Ctr Publ Hlth, Budapest, Hungary.
[Fabianova, Eleonora] Specialized State Hlth Inst, Dept Occupat Hlth, Banska Bystrica, Slovakia.
[Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[Janout, Vladimir] Palacky Univ, Dept Prevent Med, Fac Med, CR-77147 Olomouc, Czech Republic.
[Bencko, Vladimir; Schejbalova, Miriam] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic.
[Mates, Ioan N.] Univ Med & Pharm Carol Davila, Bucharest, Romania.
[Field, John K.; Raji, Olaide] Univ Liverpool, Canc Res Ctr, Roy Castle Lung Canc Res Programme, Dept Mol & Clin Canc Med, Liverpool L69 3BX, Merseyside, England.
[Liu, Geoffrey] Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M4X 1K9, Canada.
[Wiencke, John] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA.
[Neri, Monica] IRCCS Ist Ricovero & Cura Carattere Sci San Raffa, Unit Clin & Mol Epidemiol, Rome, Italy.
[Ugolini, Donatella] Univ Genoa, Epidemiol Unit, Genoa, Italy.
[Ugolini, Donatella] Univ Genoa, Biostat Unit, Genoa, Italy.
[Ugolini, Donatella] Natl Inst Canc Res, Epidemiol Unit, Genoa, Italy.
[Ugolini, Donatella] Natl Inst Canc Res, Biostat Unit, Genoa, Italy.
[Ugolini, Donatella] Natl Inst Canc Res, Unit Clin Trials, Genoa, Italy.
[Andrew, Angeline S.] Dartmouth Med Sch, Norris Cotton Canc Ctr, Unit Biostat & Epidemiol, Dept Community & Family Med, Lebanon, NH USA.
[Lan, Qing; Hu, Wei] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Orlow, Irene] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Park, Bernard J.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA.
RP Hung, RJ (reprint author), Mt Sinai Hosp, Samuel Lunenfeld Res Inst, 60 Murray St, Toronto, ON M5T 3L9, Canada.
EM rayjean.hung@lunenfeld.ca
RI Hung, Rayjean/A-7439-2013; McLaughlin, John/E-4577-2013; Zaridze,
David/K-5605-2013; Hu, Wei/M-3524-2013; Janout, Vladimir/M-5133-2014;
Szeszenia-Dabrowska, Neonila/F-7190-2010; Neri, Monica/J-6308-2012;
Mates, Ioan Nicolae/E-9255-2017;
OI Ioan Nicoale, Mates/0000-0001-7210-0615; Neri,
Monica/0000-0003-4796-3675; Duell, Eric J/0000-0001-5256-0163;
Lissowska, Jolanta/0000-0003-2695-5799; Field, John/0000-0003-3951-6365;
Orlow, Irene/0000-0001-6234-6961
FU Canadian Cancer Society Research Institute [020214]; National Center for
Research Resources, US National Institutes of Health [P20RR018787]; Roy
Castle Lung Cancer Foundation; Steps for Breath; Labrecque Foundation;
Society of Memorial Sloan-Kettering Cancer Center; World Cancer Research
Fund; European Commission's INCO-COPERNICUS [IC15-CT96-0313]; Polish
State Committee for Scientific Research
[SPUB-M-COPERNICUS/P-05/DZ-30/99/2000]; US National Institutes of Health
[R01CA060691, R01CA87895, N01-PC35145, P30CA22453]; US National
Institute of Environmental Health Sciences [ES06717]; US National Cancer
Institute [CA-113710]; Danish Cancer Society; German Federal Ministry of
Education, Science, Research and Technology; State of Bavaria; National
Genome Research Network; German Research Foundation [BI 576/2-1, BI
576/2-2]; Helmholtz Association; German Federal Office for Radiation
Protection [STSch4454]; Canadian Institutes of Health Research Canada
FX The Toronto study (18) was funded by the Canadian Cancer Society
Research Institute (grant 020214). The New England Lung Cancer Study
(25) was funded by the National Center for Research Resources, US
National Institutes of Health (grant P20RR018787). The Liverpool Lung
Project (35) was funded by the Roy Castle Lung Cancer Foundation. The
study from Memorial Sloan-Kettering Cancer Center (33) was funded by
Steps for Breath, the Labrecque Foundation, and the Society of Memorial
Sloan-Kettering Cancer Center. The Central Europe study (23) was funded
by the World Cancer Research Fund and the European Commission's
INCO-COPERNICUS Program (contract IC15-CT96-0313). The Warsaw portion of
the Central Europe study was funded by the Polish State Committee for
Scientific Research (grant SPUB-M-COPERNICUS/P-05/DZ-30/99/2000). The
Family Health Study (22) and the study of women's lung cancer
epidemiology (30), conducted by Wayne State University and the Karmanos
Cancer Institute, were funded by the US National Institutes of Health
(grants R01CA060691, R01CA87895, N01-PC35145, and P30CA22453). The study
at the University of California, San Francisco (29) was funded by the US
National Institute of Environmental Health Sciences (grant ES06717) and
the US National Cancer Institute (grant CA-113710 to S. S. O.). The
Danish Diet, Cancer, and Health Study (20) is funded by the Danish
Cancer Society. The Helmholtz Center Munich lung cancer study (39, 40,
69, 70) was funded by the German Federal Ministry of Education, Science,
Research and Technology, the State of Bavaria, the National Genome
Research Network, the German Research Foundation (grants BI 576/2-1 and
BI 576/2-2), the Helmholtz Association, and the German Federal Office
for Radiation Protection (grant STSch4454).; R. J. H. holds a Cancer
Care Ontario Chair in Population Studies. D. B. holds a Canadian
Institutes of Health Research Canada Graduate Scholarship.
NR 70
TC 42
Z9 46
U1 2
U2 21
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD OCT 1
PY 2012
VL 176
IS 7
BP 573
EP 585
DI 10.1093/aje/kws151
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 014YH
UT WOS:000309411400002
PM 22986146
ER
PT J
AU Weinberger, DM
Krause, TG
Molbak, K
Cliff, A
Briem, H
Viboud, C
Gottfredsson, M
AF Weinberger, Daniel M.
Krause, Tyra Grove
Molbak, Kare
Cliff, Andrew
Briem, Haraldur
Viboud, Cecile
Gottfredsson, Magnus
TI Influenza Epidemics in Iceland Over 9 Decades: Changes in Timing and
Synchrony With the United States and Europe
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE airline; Iceland; influenza; synchrony; transportation; wavelets
ID PANDEMIC INFLUENZA; GEOGRAPHIC SPREAD; SPATIAL HIERARCHIES;
MATHEMATICAL-MODEL; SPANISH FLU; PATTERNS; LESSONS; MEASLES; TRAVEL;
WAVES
AB Influenza epidemics exhibit a strongly seasonal pattern, with winter peaks that occur with similar timing across temperate areas of the Northern Hemisphere. This synchrony could be influenced by population movements, environmental factors, host immunity, and viral characteristics. The historical isolation of Iceland and subsequent increase in international contacts make it an ideal setting to study epidemic timing. The authors evaluated changes in the timing and regional synchrony of influenza epidemics using mortality and morbidity data from Iceland, North America, and Europe during the period from 1915 to 2007. Cross-correlations and wavelet analyses highlighted 2 major changes in influenza epidemic patterns in Iceland: first was a shift from nonseasonal epidemics prior to the 1930s to a regular winter-seasonal pattern, and second was a change in the early 1990s when a 1-month lag between Iceland and the United States and Europe was no longer detectable with monthly data. There was a moderate association between increased synchrony and the number of foreign visitors to Iceland, providing a plausible explanation for the second shift in epidemic timing. This suggests that transportation might have a minor effect on epidemic timing, but efforts to restrict air travel during influenza epidemics would likely have a limited impact, even for island populations.
C1 [Weinberger, Daniel M.; Viboud, Cecile; Gottfredsson, Magnus] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Krause, Tyra Grove; Molbak, Kare] Statens Serum Inst, Dept Epidemiol, DK-2300 Copenhagen, Denmark.
[Cliff, Andrew] Univ Cambridge, Dept Geog, Cambridge CB2 3EN, England.
[Briem, Haraldur] Directorate Hlth, Ctr Hlth Secur & Communicable Dis Protect, Reykjavik, Iceland.
[Gottfredsson, Magnus] Landspitali Univ Hosp, Reykjavik, Iceland.
[Briem, Haraldur; Gottfredsson, Magnus] Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland.
RP Weinberger, DM (reprint author), 16 Ctr Dr,Bldg 16,Room 307, Bethesda, MD 20892 USA.
EM dweinber@gmail.com
OI Molbak, Kare/0000-0002-3100-4990; Gottfredsson,
Magnus/0000-0003-2465-0422; Weinberger, Daniel/0000-0003-1178-8086
FU International Influenza Unit, Office of Global Affairs, Department of
Health and Human Services; Fulbright
FX This research was conducted in the context of the Multinational
Influenza Seasonal Mortality Study (MISMS), an ongoing international
collaborative effort to understand influenza epidemiologic and
evolutionary patterns, led by the Fogarty International Center, National
Institutes of Health (http://www.origem.info/misms/index.php). MISMS is
funded by the International Influenza Unit, Office of Global Affairs,
Department of Health and Human Services. M. G. was supported by a
Fulbright fellowship.
NR 32
TC 6
Z9 6
U1 0
U2 15
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD OCT 1
PY 2012
VL 176
IS 7
BP 649
EP 655
DI 10.1093/aje/kws140
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 014YH
UT WOS:000309411400011
PM 22962250
ER
PT J
AU Dampier, CD
Wager, CG
Harrison, R
Hsu, LL
Minniti, CP
Smith, WR
AF Dampier, Carlton D.
Wager, Carrie G.
Harrison, Ryan
Hsu, Lewis L.
Minniti, Caterina P.
Smith, Wally R.
CA Investigators Sickle Cell Dis Clin
TI Impact of PCA strategies on pain intensity and functional assessment
measures in adults with sickle cell disease during hospitalized
vaso-occlusive episodes
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID LONGITUDINAL DATA; CLINICAL-TRIALS; RECOMMENDATIONS; CHILDREN
C1 [Dampier, Carlton D.] Emory Univ, Sch Med, Aflac Canc & Blood Disorders Ctr, Dept Pediat, Atlanta, GA 30322 USA.
[Dampier, Carlton D.] Childrens Healthcare Atlanta, Atlanta, GA USA.
[Wager, Carrie G.; Harrison, Ryan] New England Res Inst, Watertown, MA 02172 USA.
[Hsu, Lewis L.] Univ Illinois, Chicago, IL USA.
[Minniti, Caterina P.] NIH, Hematol Branch, Bethesda, MD 20892 USA.
[Smith, Wally R.] Virginia Commonwealth Univ, Dept Med, Richmond, VA 23298 USA.
RP Dampier, CD (reprint author), Emory Univ, Sch Med, Aflac Canc & Blood Disorders Ctr, Dept Pediat, 2015 Uppergate Dr,Rm 464, Atlanta, GA 30322 USA.
EM cdampie@emory.edu
FU NHLBI NIH HHS [U54 HL090516, U10 HL083705, U10 HL083721, U10HL083721]
NR 19
TC 1
Z9 1
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD OCT
PY 2012
VL 87
IS 10
BP E71
EP E74
DI 10.1002/ajh.23302
PG 4
WC Hematology
SC Hematology
GA 010AB
UT WOS:000309065700003
PM 22886853
ER
PT J
AU Noguchi, CT
Teng, RF
AlNaeeli, M
AF Noguchi, Constance Tom
Teng, Ruifeng
AlNaeeli, Mawadda
TI Metabolic activity associated with erythropoietin
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Meeting Abstract
C1 [Noguchi, Constance Tom; Teng, Ruifeng; AlNaeeli, Mawadda] NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD OCT
PY 2012
VL 87
IS 10
BP E92
EP E92
PG 1
WC Hematology
SC Hematology
GA 010AB
UT WOS:000309065700026
ER
PT J
AU Galis, ZS
Hoots, WK
Kiley, JP
Lauer, MS
AF Galis, Zorina S.
Hoots, W. Keith
Kiley, James P.
Lauer, Michael S.
TI On the Value of Portfolio Diversity in Heart, Lung, and Blood Research
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Editorial Material
ID BIOMEDICAL-RESEARCH; SCIENCE; NIH
C1 [Galis, Zorina S.] NHLBI, Vasc Biol & Hypertens Branch, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Hoots, W. Keith] NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA.
[Kiley, James P.] NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA.
RP Galis, ZS (reprint author), NHLBI, Vasc Biol & Hypertens Branch, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
RI Lauer, Michael/L-9656-2013
OI Lauer, Michael/0000-0002-9217-8177
NR 26
TC 4
Z9 4
U1 0
U2 1
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD OCT 1
PY 2012
VL 186
IS 7
BP 575
EP 578
DI 10.1164/rccm.201208-1437ED
PG 4
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 014NV
UT WOS:000309383600001
PM 23027846
ER
PT J
AU Wilk, JB
Shrine, NRG
Loehr, LR
Zhao, JH
Manichaikul, A
Lopez, LM
Smith, AV
Heckbert, SR
Smolonska, J
Tang, WB
Loth, DW
Curjuric, I
Hui, J
Cho, MH
Latourelle, JC
Henry, AP
Aldrich, M
Bakke, P
Beaty, TH
Bentley, AR
Borecki, IB
Brusselle, GG
Burkart, KM
Chen, TH
Couper, D
Crapo, JD
Davies, G
Dupuis, J
Franceschini, N
Gulsvik, A
Hancock, DB
Harris, TB
Hofman, A
Imboden, M
James, AL
Khaw, KT
Lahousse, L
Launer, LJ
Litonjua, A
Liu, YM
Lohman, KK
Lomas, DA
Lumley, T
Marciante, KD
McArdle, WL
Meibohm, B
Morrison, AC
Musk, AW
Myers, RH
North, KE
Postma, DS
Psaty, BM
Rich, SS
Rivadeneira, F
Rochat, T
Rotter, JI
Artigas, MS
Starr, JM
Uitterlinden, AG
Wareham, NJ
Wijmenga, C
Zanen, P
Province, MA
Silverman, EK
Deary, IJ
Palmer, LJ
Cassano, PA
Gudnason, V
Barr, RG
Loos, RJF
Strachan, DP
London, SJ
Boezen, HM
Probst-Hensch, N
Gharib, SA
Hall, IP
O'Connor, GT
Tobin, MD
Stricker, BH
AF Wilk, Jemma B.
Shrine, Nick R. G.
Loehr, Laura R.
Zhao, Jing Hua
Manichaikul, Ani
Lopez, Lorna M.
Smith, Albert Vernon
Heckbert, Susan R.
Smolonska, Joanna
Tang, Wenbo
Loth, Daan W.
Curjuric, Ivan
Hui, Jennie
Cho, Michael H.
Latourelle, Jeanne C.
Henry, Amanda P.
Aldrich, Melinda
Bakke, Per
Beaty, Terri H.
Bentley, Amy R.
Borecki, Ingrid B.
Brusselle, Guy G.
Burkart, Kristin M.
Chen, Ting-hsu
Couper, David
Crapo, James D.
Davies, Gail
Dupuis, Josee
Franceschini, Nora
Gulsvik, Amund
Hancock, Dana B.
Harris, Tamara B.
Hofman, Albert
Imboden, Medea
James, Alan L.
Khaw, Kay-Tee
Lahousse, Lies
Launer, Lenore J.
Litonjua, Augusto
Liu, Yongmei
Lohman, Kurt K.
Lomas, David A.
Lumley, Thomas
Marciante, Kristin D.
McArdle, Wendy L.
Meibohm, Bernd
Morrison, Alanna C.
Musk, Arthur W.
Myers, Richard H.
North, Kari E.
Postma, Dirkje S.
Psaty, Bruce M.
Rich, Stephen S.
Rivadeneira, Fernando
Rochat, Thierry
Rotter, Jerome I.
Artigas, Maria Soler
Starr, John M.
Uitterlinden, Andre G.
Wareham, Nicholas J.
Wijmenga, Cisca
Zanen, Pieter
Province, Michael A.
Silverman, Edwin K.
Deary, Ian J.
Palmer, Lyle J.
Cassano, Patricia A.
Gudnason, Vilmundur
Barr, R. Graham
Loos, Ruth J. F.
Strachan, David P.
London, Stephanie J.
Boezen, H. Marike
Probst-Hensch, Nicole
Gharib, Sina A.
Hall, Ian P.
O'Connor, George T.
Tobin, Martin D.
Stricker, Bruno H.
TI Genome-Wide Association Studies Identify CHRNA5/3 and HTR4 in the
Development of Airflow Obstruction
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE chronic obstructive pulmonary disease; single-nucleotide polymorphism;
genes
ID NICOTINIC ACETYLCHOLINE-RECEPTOR; PULMONARY-DISEASE; LUNG-CANCER;
SUSCEPTIBILITY LOCUS; SMOKING-BEHAVIOR; 15Q25 LOCUS; RISK; EXPRESSION;
VARIANTS; COPD
AB Rationale: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known.
Objectives: Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic of COPD assessed by spirometry, in population-based cohorts examining all participants, ever smokers, never smokers, asthma-free participants, and more severe cases.
Methods: Fifteen cohorts were studied for discovery (3,368 affected; 29,507 unaffected), and a population-based family study and a meta-analysis of case-control studies were used for replication and regional follow-up (3,837 cases; 4,479 control subjects). Airflow obstruction was defined as FEV1 and its ratio to FVC (FEV1/FVC) both less than their respective lower limits of normal as determined by published reference equations.
Measurements and Main Results: The discovery meta-analyses identified one region on chromosome 15q25.1 meeting genome-wide significance in ever smokers that includes AGPHD1, IREB2, and CHRNA5/CHRNA3 genes. The region was also modestly associated among never smokers. Gene expression studies confirmed the presence of CHRNA5/3 in lung, airway smooth muscle, and bronchial epithelial cells. A single-nucleotide polymorphism in HTR4, a gene previously related to FEV1/FVC, achieved genome-wide statistical significance in combined meta-analysis. Top single-nucleotide polymorphisms in ADAM19, RARB, PPAP2B, and ADAMTS19 were nominally replicated in the COPD meta-analysis.
Conclusions: These results suggest an important role for the CHRNA5/3 region as a genetic risk factor for airflow obstruction that may be independent of smoking and implicate the HTR4 gene in the etiology of airflow obstruction.
C1 [Wilk, Jemma B.] Brigham & Womens Hosp, Div Aging, Dept Med, Boston, MA 02120 USA.
[Wilk, Jemma B.; Cho, Michael H.; Litonjua, Augusto; Silverman, Edwin K.] Harvard Univ, Sch Med, Boston, MA USA.
[Wilk, Jemma B.; Dupuis, Josee; O'Connor, George T.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Shrine, Nick R. G.; Artigas, Maria Soler; Tobin, Martin D.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
[Shrine, Nick R. G.; Artigas, Maria Soler; Tobin, Martin D.] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England.
[Loehr, Laura R.; Franceschini, Nora; North, Kari E.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Zhao, Jing Hua; Wareham, Nicholas J.; Loos, Ruth J. F.] Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
[Manichaikul, Ani; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Manichaikul, Ani] Univ Virginia, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA.
[Lopez, Lorna M.; Davies, Gail; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
[Lopez, Lorna M.; Davies, Gail; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland.
[Smith, Albert Vernon; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert Vernon; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Heckbert, Susan R.; Marciante, Kristin D.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Smolonska, Joanna; Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
[Tang, Wenbo; Cassano, Patricia A.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
[Loth, Daan W.; Hofman, Albert; Lahousse, Lies; Rivadeneira, Fernando; Uitterlinden, Andre G.; Stricker, Bruno H.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Loth, Daan W.; Stricker, Bruno H.] Inspectorate Healthcare, The Hague, Netherlands.
[Curjuric, Ivan; Imboden, Medea; Probst-Hensch, Nicole] Swiss Trop & Publ Hlth Inst SwissTPH, Basel, Switzerland.
[Curjuric, Ivan; Imboden, Medea; Probst-Hensch, Nicole] Univ Basel, Basel, Switzerland.
[Hui, Jennie; James, Alan L.; Musk, Arthur W.] Sir Charles Gairdner Hosp, Busselton Populat Med Res Inst, Nedlands, WA 6009, Australia.
[Hui, Jennie] QEII Med Ctr, PathW Lab Med Western Australia, Nedlands, WA, Australia.
[Hui, Jennie] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia.
[Hui, Jennie; Musk, Arthur W.] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia.
[Cho, Michael H.; Litonjua, Augusto; Silverman, Edwin K.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02120 USA.
[Cho, Michael H.; Litonjua, Augusto; Silverman, Edwin K.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02120 USA.
[Latourelle, Jeanne C.; Myers, Richard H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Henry, Amanda P.; Hall, Ian P.] Univ Nottingham, Div Therapeut & Mol Med, Nottingham NG7 2RD, England.
[Aldrich, Melinda] Vanderbilt Univ, Med Ctr, Dept Thorac Surg, Nashville, TN USA.
[Aldrich, Melinda] Vanderbilt Univ, Med Ctr, Div Epidemiol, Nashville, TN USA.
[Bakke, Per; Gulsvik, Amund] Univ Bergen, Haukeland Univ Hosp, Dept Thorac Med, Bergen, Norway.
[Bakke, Per; Gulsvik, Amund] Univ Bergen, Inst Med, Bergen, Norway.
[Beaty, Terri H.] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA.
[Bentley, Amy R.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Borecki, Ingrid B.; Province, Michael A.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
[Brusselle, Guy G.; Lahousse, Lies] Ghent Univ Hosp, Dept Resp Med, Ghent, Belgium.
[Burkart, Kristin M.; Barr, R. Graham] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA.
[Chen, Ting-hsu] Vet Adm Boston Healthcare Syst, Dept Med, Pulm & Crit Care Med Sect, Boston, MA USA.
[Chen, Ting-hsu; O'Connor, George T.] Boston Univ, Sch Med, Dept Med, Sect Pulm Allergy & Crit Care Med, Boston, MA 02118 USA.
[Couper, David] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Crapo, James D.] Natl Jewish Hlth, Denver, CO USA.
[Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Hancock, Dana B.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Hancock, Dana B.] Res Triangle Inst Int, Behav Hlth Epidemiol Program, Res Triangle Pk, NC USA.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.; Stricker, Bruno H.] NCHA, NGI, Leiden, Netherlands.
[James, Alan L.] Sir Charles Gairdner Hosp, Dept Pulm Physiol & Sleep Med, Nedlands, WA 6009, Australia.
[James, Alan L.; Musk, Arthur W.] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia.
[Khaw, Kay-Tee] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC USA.
[Lohman, Kurt K.] Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC USA.
[Lomas, David A.] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England.
[Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand.
[McArdle, Wendy L.] Univ Bristol, ALSPAC Lab, Sch Social & Community Med, Bristol, Avon, England.
[Meibohm, Bernd] Univ Tennessee, Ctr Hlth Sci, Coll Pharm, Memphis, TN 38163 USA.
[Morrison, Alanna C.] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA.
[Musk, Arthur W.] Sir Charles Gairdner Hosp, Dept Resp Med, Nedlands, WA 6009, Australia.
[Postma, Dirkje S.] Univ Groningen, Univ Med Ctr Groningen, Dept Pulmonol, Groningen, Netherlands.
[Postma, Dirkje S.; Boezen, H. Marike] Univ Groningen, Univ Med Ctr Groningen, Groningen Res Inst Asthma, Groningen, Netherlands.
[Postma, Dirkje S.; Boezen, H. Marike] Univ Groningen, Univ Med Ctr Groningen, COPD, Groningen, Netherlands.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Unit, Seattle, WA USA.
[Rivadeneira, Fernando; Uitterlinden, Andre G.; Stricker, Bruno H.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Rochat, Thierry] Univ Hosp Geneva, Div Pulm Med, Geneva, Switzerland.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland.
[Zanen, Pieter] Univ Med Ctr Utrecht, Div Heart & Lungs, Utrecht, Netherlands.
[Palmer, Lyle J.] Ontario Inst Canc Res, Toronto, ON, Canada.
[Palmer, Lyle J.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada.
[Cassano, Patricia A.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA.
[Barr, R. Graham] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Strachan, David P.] Univ London, Div Populat Hlth Sci & Educ, London, England.
[Boezen, H. Marike] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
[Gharib, Sina A.] Univ Washington, Dept Med, Div Pulm & Crit Care Med, Ctr Lung Biol, Seattle, WA USA.
[Stricker, Bruno H.] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands.
RP Wilk, JB (reprint author), Brigham & Womens Hosp, Div Aging, Dept Med, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA.
EM jwilk@rics.bwh.harvard.edu
RI Deary, Ian/C-6297-2009; Wijmenga, Cisca/D-2173-2009; Palmer,
Lyle/K-3196-2014; Gudnason, Vilmundur/K-6885-2015; Rivadeneira,
Fernando/O-5385-2015; Soler Artigas, Maria/L-6529-2013; Smith,
Albert/K-5150-2015;
OI Shrine, Nick/0000-0003-3641-4371; Manichaikul, Ani/0000-0002-5998-795X;
Hancock, Dana/0000-0003-2240-3604; Dupuis, Josee/0000-0003-2871-3603;
Wijmenga, Cisca/0000-0002-5635-1614; Hall, Ian/0000-0001-9933-3216;
Lahousse, Lies/0000-0002-3494-4363; London,
Stephanie/0000-0003-4911-5290; Litonjua, Augusto/0000-0003-0422-5875;
Palmer, Lyle/0000-0002-1628-3055; Gudnason,
Vilmundur/0000-0001-5696-0084; Rivadeneira,
Fernando/0000-0001-9435-9441; Soler Artigas, Maria/0000-0002-3213-1107;
Smith, Albert/0000-0003-1942-5845; O'Connor, George/0000-0002-6476-3926;
Latourelle, Jeanne/0000-0002-4218-9572; Myers,
Richard/0000-0002-8365-2674
FU Flight Attendant Medical Research Institute; NHLBI's Framingham Heart
Study [N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278]; Robert Dawson
Evans Endowment of the Department of Medicine at Boston University
School of Medicine and Boston Medical Center; National Heart, Lung, and
Blood Institute [HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641,
R01HL59367, R01HL086694]; National Human Genome Research Institute
[U01HG004402]; National Institutes of Health [HHSN268200625226C,
UL1RR025005]; NIH Roadmap for Medical Research; Division of Intramural
Research, National Institute of Environmental Health [ZO1 ES43012];
NHLBI [N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01
HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HL080295, HL075366,
HL087652, HL105756, N01HR76101, N01HR76102]; National Institute of
Neurological Disorders and Stroke; National Institute on Aging (NIA)
[AG-023629, AG-15928, AG-20098, AG-027058]; Cedars-Sinai Board of
Govemors' Chair in Medical Genetics; National Center for Research
Resources CTSI grant [UL 1RR033176]; National Institute of Diabetes and
Digestive and Kidney Diseases [DK063491]; European Union [201379];
Medical Research Council [G0000934]; Wellcome Trust [068545/Z/02,
076113/B104/Z]; National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK), National Institute of Allergy and Infectious Diseases,
National Human Genome Research Institute, National Institute of Child
Health and Human Development; Juvenile Diabetes Research Foundation
International (IDRFI); JDRFI; National Institute for Health Research
Cambridge Biomedical Research Centre; European Commission Framework
Program 6 [018996]; French Ministry of Research; Cancer Research UK;
Medical Research Council; NIH [N01-AG-12100]; NIA Intramural Research
Program; Hjartavernd (the Icelandic Heart Association),; Althingi (the
Icelandic Parliament); Swiss National Science Foundation
[33CS30-134276/1, 33CSCO-108796, 3247BO-104283, 3247BO-104288,
3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532,
4026-028099, 3233-054996, PDFMP3-12317I]; Federal Office for Forest,
Environment, and Landscape; Federal Office of Public Health; Federal
Office of Roads and Transport; canton's government of Aargau,
Basel-Stadt, Basel-Land, Geneva, Luzern; Ticino, Valais, Zurich, the
Swiss Lung League, the canton's Lung League of Basel Stadt/Basel
Landschaft, Geneva, Ticin; Valais and Zurich, Schweizerische
Unfallversicherungsanstalt (SUVA), Freiwillige Akademische Gesellschaft,
UBS Wealth Foundation; Talecris Biotherapeutics GmbH; Abbott
Diagnostics; Healthways, Western Australia; Great Wine Estates of the
Margaret River region of Western Australia; AXA Research Fund;
Biotechnology and Biological Sciences Research Council (BBSRC)
[BB/F019394/1]; Research Into Ageing [LBC1936]; Age UK (Disconnected
Mind; cross council Lifelong Health and Wellbeing Initiative
[G0700704/84698]; BBSRC; Engineering and Physical Sciences Research
Council; Economic and Social Research Council; Medical Research Council
(MRC); U.S. NIH [R01 HL075478, R01 HL084323, P01 HL083069, 1101
HL089856, K12HL089990, K08 HL097029, U01 HL089897]; Centers for Medicare
and Medicaid Services; Agency for Healthcare Research and Quality;
Cooperative Studies Program/ERIC of the U.S. Department of Veterans
Affairs; GlaxoSmithKline; COPD Foundation; Intramural Research Programs
of the NIH, the National Institute of Environmental Health Sciences
[Z01ES043012]; CHARGE Consortium; U.K. MRC Senior Clinical Fellowship
[G0902313]; MRC [G1000861]; [U01 DK062418]; [N01HR76103];
[N01HR76104]; [N01HR76105]; [N01HR76106]; [N01HR76107];
[N01HR76108]; [N01HR76109]; [N01 HR76110]; [N01HR76111];
[N01HR76112]; [N01HR76113]; [N01HR76114]; [N01HR76115];
[N01HR76116]; [N01HR76118]; [N01HR76119]
FX J.B.W. is supported by a Young Clinical Scientist Award from the Flight
Attendant Medical Research Institute. Research was conducted in part
using data and resources from the Framingham Heart Study of the National
Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of
Health (NIH) and Boston University School of Medicine. The analyses
reflect intellectual input and resource development from the Framingham
investigators participating in the SNP Health Association Resource
(SHARe) project. This work was partially supported by the NHLBI's
Framingham Heart Study (contract N01-HC-25195) and its contract with
Affymetrix, Inc. for genotyping services (contract N02-HL-6-4278). A
portion of this research used the Linux Cluster for Genetic Analysis
(LinGA-II) funded by the Robert Dawson Evans Endowment of the Department
of Medicine at Boston University School of Medicine and Boston Medical
Center.; The Atherosclerosis Risk in Communities Study is performed as a
collaborative study supported by National Heart, Lung, and Blood
Institute contracts (HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C),
R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research
Institute contract U01HG004402; and National Institutes of Health
contract HHSN268200625226C. Infrastructure was partly supported by grant
number UL1RR025005, a component of the National Institutes of Health and
NIH Roadmap for Medical Research. Work was supported in part by the
Division of Intramural Research, National Institute of Environmental
Health Sciences ZO1 ES43012.; This CHS research was supported by NHLBI
contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129,
N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133 and NHLBI grants
HL080295, HL075366, HL087652, HL105756 with additional contribution from
National Institute of Neurological Disorders and Stroke. Additional
support was provided through AG-023629, AG-15928, AG-20098, and
AG-027058 from the National Institute on Aging (NIA) and the
Cedars-Sinai Board of Govemors' Chair in Medical Genetics (P.R.). DNA
handling and genotyping was supported in part by National Center for
Research Resources CTSI grant UL 1RR033176 and National Institute of
Diabetes and Digestive and Kidney Diseases grant DK063491 to the
Southern California Diabetes Endocrinology Research Center.; COPACETIC
(i.e., COPD Pathology: Addressing Critical gaps, Early Treatment and
diagnosis and Innovative Concepts) is funded by the European Union FP7
program, grant agreement number 201379.; We acknowledge use of phenotype
and genotype data from the British 1958 Birth Cohort DNA collection,
funded by the Medical Research Council grant G0000934 and the Wellcome
Trust grant 068545/Z/02. (http://www.b58cgene.sgul.ac.uk/). Genotyping
for the B58C-VVTCCC subset was funded by the Wellcome Trust grant
076113/B104/Z. The B58C-T1DGC genotyping used resources provided by the
Type 1 Diabetes Genetics Consortium, a collaborative clinical study
sponsored by the National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK), National Institute of Allergy and Infectious Diseases,
National Human Genome Research Institute, National Institute of Child
Health and Human Development, and Juvenile Diabetes Research Foundation
International (IDRFI) and supported by U01 DK062418. B58C-T1DGC GWAS
data were deposited by the Diabetes and Inflammation Laboratory,
Cambridge Institute for Medical Research (CIMR), University of
Cambridge, which is funded by JDRFI, the Wellcome Trust, and the
National Institute for Health Research Cambridge Biomedical Research
Centre; the CIMR is in receipt of a Wellcome Trust Strategic Award
(079895). The B58C-GABRIEL genotyping was supported by a contract from
the European Commission Framework Program 6 (018996) and grants from the
French Ministry of Research.; The EPIC-Norfolk is supported by research
program grant funding from Cancer Research UK and the Medical Research
Council.; The AGES-Reykjavik Study is funded by NIH contract
N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the
Icelandic Heart Association), and the Althingi (the Icelandic
Parliament).; The Health, Aging, and Body Composition Study was
supported by NIA contracts N01AG62101, N01AG2103, and N01AG62106 and in
part by the Intramural Research Program of the NIA, NIH. The genome-wide
association study was funded by NIA grant 1R01AG032098-01A1 to Wake
Forest Health Sciences, and genotyping services were provided by the
Center for Inherited Disease Research, which is fully funded through a
federal contract from the National Institutes of Health to The Johns
Hopkins University, contract number HHSN268200782096C. This research was
further supported by RC1AG035835.; The Rotterdam Studies were funded by
the Netherlands Organization of Scientific Research NWO Investments, nr.
175.010.2005.011, 911-03-012, Research Institute for Diseases in the
Elderly, 014-93-015; RIDE2, the Netherlands Genomics Initiative
(NGI)/Netherlands Organization for Scientific Research (NWO) project nr.
050-060-810, the Ministry of Education, Culture and Science, the
Ministry for Health, Welfare and Sports, the European Commission (DG
XII) Municipality of Rotterdam.; SAPALDIA was supported by the Swiss
National Science Foundation (grants no 33CS30-134276/1, 33CSCO-108796,
3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302,
3200-052720, 3200-042532, 4026-028099, 3233-054996, PDFMP3-12317I), the
Federal Office for Forest, Environment, and Landscape, the Federal
Office of Public Health, the Federal Office of Roads and Transport, the
canton's government of Aargau, Basel-Stadt, Basel-Land, Geneva, Luzern,
Ticino, Valais, Zurich, the Swiss Lung League, the canton's Lung League
of Basel Stadt/Basel Landschaft, Geneva, Ticino, Valais and Zurich,
Schweizerische Unfallversicherungsanstalt (SUVA), Freiwillige
Akademische Gesellschaft, UBS Wealth Foundation, Talecris
Biotherapeutics GmbH, Abbott Diagnostics. Genotyping in the GABRIEL
framework was supported by grants European Commission 018996 and
Wellcome Trust WT 084703MA.; The 1994 Busse Iton follow-up Health Study
was supported by Healthways, Western Australia. The Busse Iton Health
Study is supported by The Great Wine Estates of the Margaret River
region of Western Australia. The study gratefully acknowledges the
assistance of the Western Australian DNA Bank (NHMRC Enabling Facility)
with DNA samples and the support provided by The Ark at University of
Western Australia for this study.; L.M.L. is the beneficiary of a
postdoctoral grant from the AXA Research Fund. The Lothian Birth Cohort
1936 (LBC1936) whole genome association study was funded by the
Biotechnology and Biological Sciences Research Council (BBSRC) (ref.
BB/F019394/1). The LBC1936 research was initially supported by a program
grant from Research Into Ageing (ref. 251) and continues with program
grants from Age UK (Disconnected Mind). The work was undertaken by The
University of Edinburgh Centre for Cognitive Ageing and Cognitive
Epidemiology, part of the cross council Lifelong Health and Wellbeing
Initiative (ref. G0700704/84698). Funding from the BBSRC, Engineering
and Physical Sciences Research Council, Economic and Social Research
Council, and Medical Research Council (MRC) is gratefully acknowledged.;
The COPD cohorts meta-analysis was supported by U.S. NIH grants R01
HL075478, R01 HL084323, P01 HL083069, 1101 HL089856 (E.K.S.);
K12HL089990 and K08 HL097029 (M.H.C); and U01 HL089897 (J.D.C.). The
National Emphysema Treatment Trial was supported by the National Heart,
Lung, and Blood Institute, the Centers for Medicare and Medicaid
Services, and the Agency for Healthcare Research and Quality. The
National Emphysema Treatment Trial was supported by NHLBI contracts
N01HR76101, N01HR76102, N01HR76103, N01HR76104, N01HR76105, N01HR76106,
N01HR76107, N01HR76108, N01HR76109, N01 HR76110, N01HR76111, N01HR76112,
N01HR76113, N01HR76114, N01HR76115, N01HR76116, N01HR76118, and
N01HR76119. The Normative Aging Study is supported by the Cooperative
Studies Program/ERIC of the U.S. Department of Veterans Affairs and is a
component of the Massachusetts Veterans Epidemiology Research and
Information Center. The Norway GenKOLS study (Genetics of Chronic
Obstructive Lung Disease, GSK code RES11080) and the ECLIPSE study
(clinicaltrials.gov identifier NCT00292552; GSK code SC0104960) are
funded by GlaxoSmithKline. The COPDGene project is also supported by the
COPD Foundation through contributions made to an Industry Advisory
comprised of AstraZeneca, Boehringer Ingelheim, Novartis, and Sepracor.;
This work was supported, in part, by Intramural Research Programs of the
NIH, the National Institute of Environmental Health Sciences
(Z01ES043012). The CHARGE Pulmonary Working Group acknowledges funding
from the NHLBI (HL105756) and the CHARGE Consortium's organizational
support.; Martin D. Tobin is supported by U.K. MRC Senior Clinical
Fellowship G0902313. I.P.H. is supported by MRC (G1000861).; The Family
Heart Study (FamHS) was supported by NIH grants R01-HL-087700 and
R01-HL-088215 (MAP., PI) from NHLBI; and R01-DK-8925601 and R01DK-075681
(I.B.B, PI) from NIDDK.; MESA was supported by contracts N01-HC-95159
through N01-HC-95169 from the NHLBI and RR-024156. The MESA Lung study
was supported by grants R01HL077612 and RC1-HL100543 from the NHLBI.
Funding for SHARe genotyping was provided by NHLBI contract
N02-HL-6-4278.
NR 41
TC 68
Z9 70
U1 1
U2 20
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD OCT 1
PY 2012
VL 186
IS 7
BP 622
EP 632
DI 10.1164/rccm.201202-0366OC
PG 11
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 014NV
UT WOS:000309383600013
PM 22837378
ER
PT J
AU Abecassis, M
Bridges, ND
Clancy, CJ
Dew, MA
Eldadah, B
Englesbe, MJ
Flessner, MF
Frank, JC
Friedewald, J
Gill, J
Gries, C
Halter, JB
Hartmann, EL
Hazzard, WR
Horne, FM
Hosenpud, J
Jacobson, P
Kasiske, BL
Lake, J
Loomba, R
Malani, PN
Moore, TM
Murray, A
Nguyen, MH
Powe, NR
Reese, PP
Reynolds, H
Samaniego, MD
Schmader, KE
Segev, DL
Shah, AS
Singer, LG
Sosa, JA
Stewart, ZA
Tan, JC
Williams, WW
Zaas, DW
High, KP
AF Abecassis, M.
Bridges, N. D.
Clancy, C. J.
Dew, M. A.
Eldadah, B.
Englesbe, M. J.
Flessner, M. F.
Frank, J. C.
Friedewald, J.
Gill, J.
Gries, C.
Halter, J. B.
Hartmann, E. L.
Hazzard, W. R.
Horne, F. M.
Hosenpud, J.
Jacobson, P.
Kasiske, B. L.
Lake, J.
Loomba, R.
Malani, P. N.
Moore, T. M.
Murray, A.
Nguyen, M. -H.
Powe, N. R.
Reese, P. P.
Reynolds, H.
Samaniego, M. D.
Schmader, K. E.
Segev, D. L.
Shah, A. S.
Singer, L. G.
Sosa, J. A.
Stewart, Z. A.
Tan, J. C.
Williams, W. W.
Zaas, D. W.
High, K. P.
TI Solid-Organ Transplantation in Older Adults: Current Status and Future
Research
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Review
DE Aging; elderly; heart; kidney; liver; lung; transplantation
ID QUALITY-OF-LIFE; LIVING KIDNEY DONORS; RENAL-TRANSPLANTATION; LONG-TERM;
LIVER-TRANSPLANTATION; HEART-TRANSPLANTATION; LUNG TRANSPLANTATION;
COGNITIVE IMPAIRMENT; ELDERLY-PATIENTS; ALLOGRAFT SURVIVAL
AB An increasing number of patients older than 65 years are referred for and have access to organ transplantation, and an increasing number of older adults are donating organs. Although short-term outcomes are similar in older versus younger transplant recipients, older donor or recipient age is associated with inferior long-term outcomes. However, age is often a proxy for other factors that might predict poor outcomes more strongly and better identify patients at risk for adverse events. Approaches to transplantation in older adults vary across programs, but despite recent gains in access and the increased use of marginal organs, older patients remain less likely than other groups to receive a transplant, and those who do are highly selected. Moreover, few studies have addressed geriatric issues in transplant patient selection or management, or the implications on health span and disability when patients age to late life with a transplanted organ. This paper summarizes a recent trans-disciplinary workshop held by ASP, in collaboration with NHLBI, NIA, NIAID, NIDDK and AGS, to address issues related to kidney, liver, lung, or heart transplantation in older adults and to propose a research agenda in these areas.
C1 [High, K. P.] Wake Forest Sch Med, Winston Salem, NC USA.
[Abecassis, M.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA.
[Abecassis, M.] Northwestern Univ, Feinberg Sch Med, Dept Microbiol Immunol, Chicago, IL 60611 USA.
[Bridges, N. D.] NIAID, Transplantat Immunobiol Branch, Bethesda, MD 20892 USA.
[Bridges, N. D.] NIAID, Clin Transplantat Sect, Bethesda, MD 20892 USA.
[Dew, M. A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Eldadah, B.] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA.
[Englesbe, M. J.] Univ Michigan, Sch Med, Dept Surg, Div Transplantat, Ann Arbor, MI USA.
[Flessner, M. F.] NIDDK, Div Kidney Urol & Hematol Dis, Bethesda, MD USA.
[Frank, J. C.] Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA USA.
[Friedewald, J.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA.
[Gill, J.] Univ British Columbia, Div Nephrol, Vancouver, BC V5Z 1M9, Canada.
[Gries, C.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Halter, J. B.] Univ Michigan, Sch Med, Div Geriatr & Palliat Med, Ann Arbor, MI USA.
[Hartmann, E. L.] Piedmont Transplant Inst, Atlanta, GA USA.
[Hazzard, W. R.] Univ Washington, Div Gerontol & Geriatr Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
[Horne, F. M.] Assoc Specialty Prof, Alexandria, VA USA.
[Hosenpud, J.] Mayo Clin, Dept Heart Transplant, Jacksonville, FL 32224 USA.
[Jacobson, P.] Univ Minnesota, Dept Expt & Clin Pharmacol, Minneapolis, MN USA.
[Kasiske, B. L.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
[Lake, J.] Univ Minnesota, Liver Transplant Program, Minneapolis, MN USA.
[Loomba, R.] Univ Calif San Diego, San Diego Sch Med, San Diego, CA 92103 USA.
[Malani, P. N.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA.
[Moore, T. M.; Reynolds, H.] NHLBI, Bethesda, MD 20892 USA.
[Murray, A.] Univ Minnesota, Div Geriatr, Minneapolis, MN USA.
[Powe, N. R.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Reese, P. P.] Univ Penn, Philadelphia, PA 19104 USA.
[Schmader, K. E.] Duke Univ, Sch Med, GRECC, Durham VA Med Ctr, Durham, NC USA.
[Schmader, K. E.] Duke Univ, Sch Med, Div Geriatr Med, Durham, NC USA.
[Segev, D. L.] Johns Hopkins Univ, Sch Med, Div Transplant Surg, Baltimore, MD USA.
[Shah, A. S.] Johns Hopkins Univ, Sch Med, Div Cardiac Surg, Baltimore, MD USA.
[Singer, L. G.] Univ Toronto, Toronto Lung Transplant Program, Toronto, ON, Canada.
[Sosa, J. A.] Yale Univ, Sch Med, Dept Surg, Div Endocrine Surg, New Haven, CT 06510 USA.
[Sosa, J. A.] Yale Univ, Sch Med, Dept Surg, Div Surg Oncol, New Haven, CT 06510 USA.
[Stewart, Z. A.] Univ Iowa, Carver Coll Med, Iowa City, IA USA.
[Tan, J. C.] Stanford Univ, Adult Kidney & Pancreas Transplant Program, Palo Alto, CA 94304 USA.
[Williams, W. W.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Zaas, D. W.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA.
RP High, KP (reprint author), Wake Forest Sch Med, Winston Salem, NC USA.
EM khigh@wakehealth.edu
OI Englesbe, Michael/0000-0001-8691-9111; Shah, Ashish/0000-0002-1821-9110;
Friedewald, John/0000-0002-9344-9928
FU National Institute on Aging [1 U13 AG040938-01]; John A. Hartford
Foundation
FX This workshop was supported by generous grants to ASP from the National
Institute on Aging (1 U13 AG040938-01) and the John A. Hartford
Foundation. The content is solely the responsibility of the authors and
does not necessarily represent the official views of NIA or the National
Institutes of Health. In addition, the views expressed in written
conference materials or publications and by speakers and moderators do
not necessarily reflect the official policies of the Department of
Health and Human Services; nor does mention by trade names, commercial
practices, or organizations imply endorsement by the U.S. Government.
NR 138
TC 38
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U1 1
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD OCT
PY 2012
VL 12
IS 10
BP 2608
EP 2622
DI 10.1111/j.1600-6143.2012.04245.x
PG 15
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 011QN
UT WOS:000309180000009
PM 22958872
ER
PT J
AU Lipsky, LM
Nansel, TR
Haynie, DL
Mehta, SN
Laffel, LMB
AF Lipsky, L. M.
Nansel, T. R.
Haynie, D. L.
Mehta, S. N.
Laffel, L. M. B.
TI Associations of food preferences and household food availability with
dietary intake and quality in youth with type 1 diabetes
SO APPETITE
LA English
DT Article
DE Preference; Availability; Dietary intake; Dietary quality; Youth; Type 1
Diabetes
ID VEGETABLE CONSUMPTION; HOME AVAILABILITY; PROJECT EAT; FRUIT;
ADOLESCENTS; CHILDREN; JUICE; VALIDITY; BEHAVIOR; SCHOOLCHILDREN
AB The objective of this study was to examine associations of food preferences and availability with dietary intake in youth with type 1 diabetes, for whom dietary intake and quality are essential to disease management. Youth (n = 252, age 13.2 +/- 2.8 y, diabetes duration 6.3 +/- 3.4 y) reported preferences and parents reported household availability for 61 food items categorized as fruit, vegetables, whole grains, refined grains and fats/sweets. Youth energy-adjusted daily servings of food groups, Healthy Eating Index-2005 and Nutrient Rich Foods 9.3 scores were calculated from 3-day diet records. Associations of dietary intake and quality variables with preference and availability of all food groups were evaluated by linear regressions adjusted for sociodemographic characteristics. Fruit and whole grain intake were positively related to corresponding preference and availability; whole grain intake and refined grain availability were inversely related. Vegetable, refined grain and fats/sweets intake were unrelated to preference and availability. Diet quality measures were related positively to fruit preference and whole grain availability and inversely to refined grains availability. Findings indicate associations of dietary intake with food preference and availability vary by food group in youth with type 1 diabetes. Measures of overall dietary quality were more consistently associated with food group availability than preferences. Published by Elsevier Ltd.
C1 [Lipsky, L. M.; Nansel, T. R.; Haynie, D. L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Mehta, S. N.; Laffel, L. M. B.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol,Pediat Adolescent & Young, Boston, MA 02215 USA.
RP Lipsky, LM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, NIH, Dept Hlth & Human Serv, 6100 Execut Blvd,Suite 7B13, Rockville, MD 20852 USA.
EM lipskylm@mail.nih.gov
OI Nansel, Tonja/0000-0002-8298-7595; Haynie, Denise/0000-0002-8270-6079;
Lipsky, Leah/0000-0003-2645-4388
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development [HHSN267200703434C]
FX This research was supported by the intramural research program of the
National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development, Contract Number
HHSN267200703434C.
NR 46
TC 5
Z9 5
U1 0
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0195-6663
EI 1095-8304
J9 APPETITE
JI Appetite
PD OCT
PY 2012
VL 59
IS 2
BP 218
EP 223
DI 10.1016/j.appet.2012.05.005
PG 6
WC Behavioral Sciences; Nutrition & Dietetics
SC Behavioral Sciences; Nutrition & Dietetics
GA 013MR
UT WOS:000309310000004
PM 22595289
ER
PT J
AU Amir, E
Cecchini, RS
Ganz, PA
Costantino, JP
Beddows, S
Hood, N
Goodwin, PJ
AF Amir, Eitan
Cecchini, Reena S.
Ganz, Patricia A.
Costantino, Joseph P.
Beddows, Samantha
Hood, Nicola
Goodwin, Pamela J.
TI 25-Hydroxy vitamin-D, obesity, and associated variables as predictors of
breast cancer risk and tamoxifen benefit in NSABP-P1 (vol 133, pg 1077,
2012)
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Correction
C1 [Beddows, Samantha; Hood, Nicola; Goodwin, Pamela J.] Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada.
[Amir, Eitan; Goodwin, Pamela J.] Princess Margaret Hosp, Div Med Oncol & Hematol, Toronto, ON M4X 1K9, Canada.
[Amir, Eitan; Beddows, Samantha; Hood, Nicola; Goodwin, Pamela J.] Univ Toronto, Toronto, ON M5G 1X5, Canada.
[Cecchini, Reena S.; Costantino, Joseph P.] Natl Surg Adjuvant Breast & Bowel Project, Ctr Biostat, Pittsburgh, PA USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles Sch Med, Los Angeles, CA 90024 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Costantino, Joseph P.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
RP Goodwin, PJ (reprint author), Mt Sinai Hosp, Dept Med, 1284-600 Univ Ave, Toronto, ON M5G 1X5, Canada.
EM pgoodwin@mtsinai.on.ca
NR 1
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD OCT
PY 2012
VL 135
IS 3
BP 923
EP 923
DI 10.1007/s10549-012-2178-2
PG 1
WC Oncology
SC Oncology
GA 003ZB
UT WOS:000308648800030
ER
PT J
AU DiMichele, DM
AF DiMichele, Donna M.
TI Immune tolerance in haemophilia: the long journey to the fork in the
road
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Review
DE gene transfer; haemophilia A; haemophilia B; immune modulation; immune
tolerance; inhibitors
ID RECOMBINANT FACTOR-VIII; HIGH-RESPONDING INHIBITORS;
VON-WILLEBRAND-FACTOR; HIGH-TITER INHIBITORS; FACTOR-IX INHIBITORS;
REGULATORY T-CELLS; PREVIOUSLY UNTREATED PATIENTS; MEMORY B-CELLS; A
PATIENTS; GENE-TRANSFER
AB Antibody eradication is the ultimate goal of inhibitor management. The only clinically proven strategy for achieving antigen-specific tolerance to factor VIII is immune tolerance induction (ITI). Our knowledge about ITI in haemophilia A and B was, historically, derived from small cohort studies and retrospective national and international ITI registries. Practice is now further influenced by prospective cohort data, and the results of a single prospective randomized international ITI trial. However, due to the low incidence of inhibitors in haemophilia B, there are few comparable data from which to develop a useful evidence-based approach to the prevention and eradication of factor IX inhibitors. The lack of an effective strategy is particularly problematic given the morbidity associated with the unique occurrence of allergic and anaphylactic reactions that often herald factor IX antibody development and preclude effective eradication. This paper will discuss our current understanding of immune tolerance outcome and outcome predictors for haemophilia A and B; review the current consensus practice recommendations for ITI; and summarize the emerging body of immunological science relating to antibody formation and tolerance. It will conclude by suggesting how our knowledge might inform the future investigative priorities impacting the therapeutic and preventative tolerance strategies of tomorrow.
C1 NHLBI, Div Blood Dis & Resources, Bethesda, MD 20892 USA.
RP DiMichele, DM (reprint author), NHLBI, Div Blood Dis & Resources, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM donna.dimichele@nih.gov
NR 112
TC 30
Z9 30
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD OCT
PY 2012
VL 159
IS 2
BP 123
EP 134
DI 10.1111/bjh.12028
PG 12
WC Hematology
SC Hematology
GA 012NC
UT WOS:000309242000003
PM 22924753
ER
PT J
AU Ibarretxe, G
Aurrekoetxea, M
Crende, O
Badiola, I
Jimenez-Rojo, L
Nakamura, T
Yamada, Y
Unda, F
AF Ibarretxe, Gaskon
Aurrekoetxea, Maitane
Crende, Olatz
Badiola, Iker
Jimenez-Rojo, Lucia
Nakamura, Takashi
Yamada, Yoshihiko
Unda, Fernando
TI Epiprofin/Sp6 regulates Wnt-BMP signaling and the establishment of
cellular junctions during the bell stage of tooth development
SO CELL AND TISSUE RESEARCH
LA English
DT Article
DE Tooth development; Epiprofin/Sp6; Cell junction; Wnt/beta-catenin;
MDPC-23; Mouse Epfn(+/-); Epfn(-/-)
ID BETA-CATENIN; TRANSCRIPTION FACTOR; MOUSE INCISORS; MORPHOGENESIS;
EXPRESSION; PROLIFERATION; EPITHELIUM; GROWTH; DENTIN; TEETH
AB Epiprofin/Specificity Protein 6 (Epfn) is a Kruppel-like family (KLF) transcription factor that is critically involved in tooth morphogenesis and dental cell differentiation. However, its mechanism of action is still not fully understood. We have employed both loss-of-function and gain-of-function approaches to address the role of Epfn in the formation of cell junctions in dental cells and in the regulation of junction-associated signal transduction pathways. We have evaluated the expression of junction proteins in bell-stage incisor and molar tooth sections from Epfn(-/-) mice and in dental pulp MDPC-23 cells overexpressing Epfn. In Epfn(-/-) mice, a dramatic reduction occurs in the expression of tight junction and adherens junction proteins and of the adherens-junction-associated beta-catenin protein, a major effector of canonical Wnt signaling. Loss of cell junctions and beta-catenin in Epfn(-/-) mice is correlated with a clear decrease in bone morphogenetic protein 4 (BMP-4) expression, a decrease in nestin in the tooth mesenchyme, altered cell proliferation, and failure of ameloblast cell differentiation. Overexpression of Epfn in MDPC-23 cells results in an increased cellular accumulation of beta-catenin protein, indicative of upregulation of canonical Wnt signaling. Together, these results suggest that Epfn enhances canonical Wnt/beta-catenin signaling in the developing dental pulp mesenchyme, a condition that promotes the activity of other downstream signaling pathways, such as BMP, which are fundamental for cellular induction and ameloblast differentiation. These altered signaling events might underlie some of the most prominent dental defects observed in Epfn(-/-) mice, such as the absence of ameloblasts and enamel, and might throw light on developmental malformations of the tooth, including hyperdontia.
C1 [Ibarretxe, Gaskon; Aurrekoetxea, Maitane; Crende, Olatz; Badiola, Iker; Unda, Fernando] Univ Basque Country UPV EHU, Fac Med & Dent, Cell Biol & Histol Dept, Bizkaia 48940, Spain.
[Jimenez-Rojo, Lucia] Univ Zurich, Inst Oral Biol, ZZM, Fac Med, CH-8032 Zurich, Switzerland.
[Nakamura, Takashi] Tohoku Univ, Grad Sch Dent, Dept Oral Hlth & Dev Sci, Sendai, Miyagi 9808575, Japan.
[Yamada, Yoshihiko] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Unda, F (reprint author), Univ Basque Country UPV EHU, Fac Med & Dent, Cell Biol & Histol Dept, Bizkaia 48940, Spain.
EM fernando.unda@ehu.es
RI Jimenez, Lucia/K-3377-2012; Nakamura, Takashi/P-7796-2016;
OI Nakamura, Takashi/0000-0001-9904-1037; CRENDE ARRUABARRENA,
OLATZ/0000-0002-3245-9575
FU University of the Basque Country (UPV/EHU) [GIU09/70]; Unidades de
Formacion e Investigacion [UFI11/44]; Basque Government [SAIOTEK
SPE11UN051]; University of Zurich; UPV/EHU; Jesus Gangoiti Barrera
Foundation
FX This work was supported by research projects from the University of the
Basque Country (UPV/EHU; GIU09/70) and Unidades de Formacion e
Investigacion (UFI11/44), by Basque Government project grant SAIOTEK
SPE11UN051, and by projects from the University of Zurich to L.J. M. A.
received PhD fellowships from UPV/EHU and the Jesus Gangoiti Barrera
Foundation.
NR 28
TC 11
Z9 11
U1 1
U2 18
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0302-766X
J9 CELL TISSUE RES
JI Cell Tissue Res.
PD OCT
PY 2012
VL 350
IS 1
BP 95
EP 107
DI 10.1007/s00441-012-1459-8
PG 13
WC Cell Biology
SC Cell Biology
GA 015UH
UT WOS:000309471300009
PM 22868911
ER
PT J
AU Desrosiers, NA
Lee, D
Schwope, DM
Milman, G
Barnes, AJ
Gorelick, DA
Huestis, MA
AF Desrosiers, Nathalie A.
Lee, Dayong
Schwope, David M.
Milman, Garry
Barnes, Allan J.
Gorelick, David A.
Huestis, Marilyn A.
TI On-Site Test for Cannabinoids in Oral Fluid
SO CLINICAL CHEMISTRY
LA English
DT Article
ID DRIVERS; DEVICES; DRUGS
AB BACKGROUND: Oral fluid (OF) testing offers noninvasive sample collection for on-site drug testing; however, to date, test performance for Delta(9)-tetrahydrocannabinol (THC) detection has had unacceptable diagnostic sensitivity. On-site tests must accurately identify cannabis exposure because this drug accounts for the highest prevalence in workplace drug testing and driving under the influence of drugs (DUID) programs.
METHODS: Ten cannabis smokers (9 males, 1 female) provided written informed consent to participate in this institutional review board-approved study and smoked 16.8%-THC cigarette ad libitum. OF was collected with the Draeger DrugTest (R) 5000 test cassette and Quantisal (TM) device 0.5 h before and up to 22 h after smoking. Test cassettes were analyzed within 15 min (n = 66), and Quantisal GC-MS THC results obtained within 24 h. Final THC detection times and test performances were assessed at different cannabinoid cutoffs.
RESULTS: Diagnostic sensitivity, diagnostic specificity, and efficiency at DrugTest 5000's 5 mu g/L screening cutoff and various THC confirmation cutoffs were 86.2-90.7, 75.0-77.8, and 84.8-87.9%, respectively. Last detection times were > 22 h, longer than previously suggested. Confirmation of 11-nor-9-carboxy-THC, absent in THC smoke, minimized the potential for passive OF contamination and still provided 22-h windows of detection, appropriate for workplace drug testing, whereas confirmation of cannabidiol, and/or cannabinol yielded shorter 6-h windows of detection, appropriate for DUID OF testing.
CONCLUSIONS: The DrugTest 5000 on-site device provided high diagnostic sensitivity for detection of cannabinoid exposure, and the selection of OF confirmation analytes and cutoffs provided appropriate windows of detection to meet the goals of different drug testing programs. (c) 2012 American Association for Clinical Chemistry
C1 [Desrosiers, Nathalie A.; Lee, Dayong; Schwope, David M.; Milman, Garry; Barnes, Allan J.; Gorelick, David A.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Desrosiers, Nathalie A.; Lee, Dayong] Univ Maryland, Toxicol Program, Baltimore, MD 21201 USA.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200,Rm 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU NIDA Intramural Research Program; Intramural Research Program, National
Institute on Drug Abuse, NIH
FX NIDA Intramural Research Program.; We acknowledge the contributions of
the clinical staffs of the National Institute on Drug Abuse, Intramural
Research Program, and Behavioral Pharmacology Research Unit, Johns
Hopkins Bayview Medical Center, as well as the Graduate Partnership
Program, NIH. This research was funded by the Intramural Research
Program, National Institute on Drug Abuse, NIH. The Draeger DrugTest
devices and Quantisal collection devices were provided to NIH through a
Materials Transfer Agreement.
NR 18
TC 19
Z9 19
U1 3
U2 28
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
J9 CLIN CHEM
JI Clin. Chem.
PD OCT
PY 2012
VL 58
IS 10
BP 1418
EP 1425
DI 10.1373/clinchem.2012.189001
PG 8
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 014NU
UT WOS:000309383500010
PM 22912396
ER
PT J
AU Mabry, E
AF Mabry, Ella
TI Interventions to Manage Compassion Fatigue in Oncology Nursing
SO CLINICAL JOURNAL OF ONCOLOGY NURSING
LA English
DT Letter
C1 NIH, Bethesda, MD 20892 USA.
RP Mabry, E (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM mabryea@cc.nih.gov
NR 0
TC 0
Z9 0
U1 2
U2 16
PU ONCOLOGY NURSING SOC
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 1092-1095
J9 CLIN J ONCOL NURS
JI Clin. J. Oncol. Nurs.
PD OCT
PY 2012
VL 16
IS 5
BP 447
EP 447
PG 1
WC Oncology; Nursing
SC Oncology; Nursing
GA 014NJ
UT WOS:000309382300002
PM 23022926
ER
PT J
AU Ranganathan, R
AF Ranganathan, Rajesh
TI The response of NINDS to recommendations from the working group's 2012
review of the Program
SO EPILEPSIA
LA English
DT Article
C1 NINDS, Off Translat Res, NIH, Bethesda, MD 20892 USA.
RP Ranganathan, R (reprint author), NINDS, Off Translat Res, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM rajesh.ranganathan@nih.gov
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD OCT
PY 2012
VL 53
IS 10
BP 1839
EP 1840
DI 10.1111/j.1528-1167.2012.03668.x
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 015LF
UT WOS:000309446700023
PM 23030262
ER
PT J
AU Porter, RJ
AF Porter, Roger J.
TI Addressing the need for new therapies for epilepsy
SO EPILEPSIA
LA English
DT Article
C1 NINDS, NIH 1987 1992, Bethesda, MD 20892 USA.
RP Porter, RJ (reprint author), NINDS, NIH 1987 1992, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM rjportermd@gmail.com
NR 0
TC 3
Z9 3
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD OCT
PY 2012
VL 53
IS 10
BP 1840
EP 1841
DI 10.1111/j.1528-1167.2012.03670.x
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 015LF
UT WOS:000309446700024
PM 23030263
ER
PT J
AU Falk, GW
Buttar, NS
Foster, NR
Ziegler, KLA
Demars, CJ
Romero, Y
Marcon, NE
Schnell, T
Corley, DA
Sharma, P
Cruz-Correa, MR
Hur, C
Fleischer, DE
Chak, A
Devault, KR
Weinberg, DS
Della'Zanna, G
Richmond, E
Smyrk, TC
Mandrekar, SJ
Limburg, PJ
AF Falk, Gary W.
Buttar, Navtej S.
Foster, Nathan R.
Ziegler, Katie L. Allen
Demars, Catherine J.
Romero, Yvonne
Marcon, Norman E.
Schnell, Thomas
Corley, Douglas A.
Sharma, Prateek
Cruz-Correa, Marcia R.
Hur, Chin
Fleischer, David E.
Chak, Amitabh
Devault, Kenneth R.
Weinberg, David S.
Della'Zanna, Gary
Richmond, Ellen
Smyrk, Thomas C.
Mandrekar, Sumithra J.
Limburg, Paul J.
CA Canc Prevention Network
TI A Combination of Esomeprazole and Aspirin Reduces Tissue Concentrations
of Prostaglandin E-2 in Patients With Barrett's Esophagus
SO GASTROENTEROLOGY
LA English
DT Article
DE Esophageal Cancer; NSAIDs; Inflammation; Esophagus
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED-TRIAL; URSODEOXYCHOLIC
ACID; CELL-PROLIFERATION; ADENOCARCINOMA; CYCLOOXYGENASE-2; PROGRESSION;
CANCER; RISK; CHEMOPREVENTION
AB BACKGROUND& AIMS: Proton pump inhibitors and nonsteroidal anti-inflammatory drugs might prevent esophageal adenocarcinoma in patients with Barrett's esophagus (BE), but there are limited data from clinical trials to support this concept. We conducted a randomized, double-blind, placebo-controlled, phase 2 trial to assess the effects of the combination of aspirin (3 different doses) and esomeprazole on tissue concentrations of prostaglandin (PG) E-2 in patients with BE with no dysplasia or low-grade dysplasia. METHODS: Participants were recruited through the multicenter Cancer Prevention Network and randomly assigned to groups that were given 40 mg esomeprazole twice daily in combination with an aspirin placebo once daily (arm A; n = 30), with 81 mg aspirin once daily (arm B; n = 47), or with 325 mg aspirin once daily (arm C; n = 45) for 28 days. We collected esophageal biopsy specimens before and after the intervention period to determine the absolute change in mean concentration of PGE(2) (the primary end point). RESULTS: Based on data from 114 patients, baseline characteristics were similar among groups. The absolute mean tissue concentration of PGE(2) was reduced by 67.6 +/- 229.68 pg/mL in arm A, 123.9 +/- 284.0 pg/mL in arm B (P = .10 vs arm A), and 174.9 +/- 263.62 pg/mL in arm C (P = .02 vs arm A). CONCLUSIONS: In combination with esomeprazole, short-term administration of higher doses of aspirin, but not lower doses or no aspirin, significantly reduced tissue concentrations of PGE(2) in patients with BE with either no dysplasia or low-grade dysplasia. These data support further evaluation of higher doses of aspirin and esomeprazole to prevent esophageal adenocarcinoma in these patients. Clinical trial registration number NCT00474903.
C1 [Falk, Gary W.] Hosp Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA.
[Buttar, Navtej S.; Foster, Nathan R.; Ziegler, Katie L. Allen; Demars, Catherine J.; Romero, Yvonne; Smyrk, Thomas C.; Mandrekar, Sumithra J.; Limburg, Paul J.] Mayo Clin, Rochester, MN USA.
[Marcon, Norman E.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada.
[Schnell, Thomas] Hines Vet Adm, Hines, IL USA.
[Corley, Douglas A.] Kaiser Permanente Med Grp, San Francisco, CA USA.
[Sharma, Prateek] Kansas City VA Med Ctr, Kansas City, MO USA.
[Cruz-Correa, Marcia R.] Univ Puerto Rico, Ctr Canc, San Juan, PR 00936 USA.
[Hur, Chin] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Fleischer, David E.] Mayo Clin Arizona, Scottsdale, AZ USA.
[Chak, Amitabh] Univ Hosp Case Med Ctr, Cleveland, OH USA.
[Devault, Kenneth R.] Mayo Clin Florida, Jacksonville, FL USA.
[Weinberg, David S.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Della'Zanna, Gary; Richmond, Ellen] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Falk, GW (reprint author), Hosp Univ Penn, Div Gastroenterol, Penn Tower,9th Floor,1 Convent Ave, Philadelphia, PA 19104 USA.
EM gary.falk@uphs.upenn.edu
OI Falk, Gary/0000-0002-7143-1436; Hur, Chin/0000-0002-2819-7576
FU National Cancer Institute [N01CN35000]; AstraZeneca; [M01-RR00585]
FX The authors thank the staff of the Mayo Clinic Clinical Research Unit
(supported by grant M01-RR00585); Drs Wilma Lingle, Schuyler Sanderson,
Tsung-Teh Wu, and Kenneth Wang as well as Mary Fredericksen, Deb Geno,
Colleen Garvey, Sharon Kaufman, and Maria Resner for their assistance
with study design, administration, and manuscript preparation; and the
dedicated study coordinators at the member organizations: Denise
Buonocore-Sassano, Trish O'Brien, Sally Melloy, Jolanda DeBoer, April
Higbee, Zehra Omer, Michael Lee, Barbara Berg, Maria Cirocco, Nancy
Bassett, Beth Bednarchik, and Jessica Hernandez.; Supported by a
contract from the National Cancer Institute (N01CN35000). Research
support (equipment and drug supplies) was also provided by AstraZeneca,
Bayer, and Boston Scientific.; The authors disclose the following: Dr
Limburg served as a consultant for Genomic Health, Inc, from August 12,
2008, to April 19, 2010. Mayo Clinic has licensed Dr Limburg's
intellectual property to Exact Sciences, and he and Mayo Clinic have
contractual rights to receive royalties through this agreement. Dr
Romero receives funding from AstraZeneca for Mayo Clinic Barrett's
esophagus registry and tissue bank. The remaining authors disclose no
conflicts.
NR 42
TC 18
Z9 18
U1 0
U2 7
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD OCT
PY 2012
VL 143
IS 4
BP 917
EP +
DI 10.1053/j.gastro.2012.06.044
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 014FY
UT WOS:000309361800023
PM 22796132
ER
PT J
AU Persson, EC
Shiels, MS
Dawsey, SM
Bhatia, K
Anderson, LA
Engels, EA
AF Persson, E. Christina
Shiels, Meredith S.
Dawsey, Sanford M.
Bhatia, Kishor
Anderson, Lesley A.
Engels, Eric A.
TI Increased Risk of Stomach and Esophageal Malignancies in People With
AIDS (Retracted article. See vol. 150, pg. 1048, 2016)
SO GASTROENTEROLOGY
LA English
DT Article; Retracted Publication
DE MALT Lymphoma; Epidemiology; Virus-Associated Cancers; Immunosuppression
ID HELICOBACTER-PYLORI INFECTION; ACTIVE ANTIRETROVIRAL THERAPY;
EPSTEIN-BARR-VIRUS; HIV-POSITIVE PATIENTS; UNITED-STATES;
GASTRIC-CANCER; TRANSPLANT RECIPIENTS; ENDOSCOPIC FINDINGS;
CIGARETTE-SMOKING; LOW-PREVALENCE
AB BACKGROUND & AIMS: People infected with human immunodeficiency virus (HIV) have an increased risk of some malignancies, but little is known about the effects of infection on risk of cancers of the upper gastrointestinal tract. We evaluated the risks of different histologic and anatomic subtypes of carcinomas and non-Hodgkin lymphomas (NHLs) of the stomach and esophagus in people with acquired immunodeficiency syndrome (AIDS). METHODS: We analyzed data from the HIV/AIDS Cancer Match Study, which links data collected from 1980 to 2007 for 16 US population-based HIV and AIDS and cancer registries. We compared risks of stomach and esophageal malignancies in people with AIDS (N = 596,955) with those of the general population using standardized incidence ratios (SIRs). We assessed calendar trends using Poisson regression. RESULTS: People with AIDS had increased risks of carcinomas of the esophagus (SIR, 1.69; 95% confidence interval [CI], 1.37-2.07; n = 95) and stomach (SIR, 1.44; 95% CI, 1.17-1.76; n = 96). Risk was increased for esophageal adenocarcinoma (SIR, 1.91; 95% CI, 1.31-2.70) and squamous cell carcinoma (SIR, 1.47; 95% CI, 1.10-1.92). People with AIDS had greater risks of carcinomas of the gastric cardia (SIR, 1.36; 95% CI, 0.83-2.11) and noncardia (SIR, 1.53; 95% CI, 1.12-2.05) than the general population. Although most stomach and esophageal NHLs that developed in people with AIDS were diffuse large B-cell lymphomas, these individuals also had an increased risk of stomach mucosa-associated lymphoid tissue lymphoma (SIR, 5.99; 95% CI, 3.19-10.2; n = 13). The incidence of carcinomas remained fairly constant over time, but rates of NHL decreased from 1980 to 2007 (P-trend < .0001). CONCLUSIONS: People with AIDS are at increased risk for developing esophageal and stomach carcinomas and NHLs. Although the incidence of NHL decreased from 1980 to 2007 as treatments for HIV infection improved, HIV-infected individuals face continued risks of esophageal and stomach carcinomas.
C1 [Persson, E. Christina] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Anderson, Lesley A.] Queens Univ Belfast, Ctr Publ Hlth, Inst Clin & Populat Sci, Canc Epidemiol & Hlth Serv Res Grp, Belfast, Antrim, North Ireland.
RP Persson, EC (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM christina.persson@nih.gov
FU Intramural Research Program of the National Cancer Institute; National
Institutes of Health; Department of Health and Human Services [Z01
CP010150-12]
FX Supported by the Intramural Research Program of the National Cancer
Institute, National Institutes of Health, and Department of Health and
Human Services grant Z01 CP010150-12.
NR 56
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Z9 17
U1 0
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD OCT
PY 2012
VL 143
IS 4
BP 943
EP +
DI 10.1053/j.gastro.2012.07.013
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 014FY
UT WOS:000309361800026
PM 22796240
ER
PT J
AU Park, SH
Shin, EC
Capone, S
Caggiari, L
De Re, V
Nicosia, A
Folgori, A
Rehermann, B
AF Park, Su-Hyung
Shin, Eui-Cheol
Capone, Stefania
Caggiari, Laura
De Re, Valli
Nicosia, Alfredo
Folgori, Antonella
Rehermann, Barbara
TI Successful Vaccination Induces Multifunctional Memory T-Cell Precursors
Associated With Early Control of Hepatitis C Virus
SO GASTROENTEROLOGY
LA English
DT Article
DE CD8 (+) T Cells; IFN; TNF; Vaccine Development; CD127
ID IMMUNE-RESPONSES; NEUTRALIZING ANTIBODY; PROGRAMMED DEATH-1; CHRONIC
INFECTION; CHIMPANZEES; EXPRESSION; PERSISTENCE; IMMUNIZATION;
DETERMINANTS; PROTECTION
AB BACKGROUND & AIMS: T cells are an important component for development of a vaccine against hepatitis C virus (HCV), but little is known about the features of successful vaccine-induced T cells. METHODS: We compared the phenotype, function, and kinetics of vaccine-induced and infection-induced T cells in chimpanzees with HCV infection using multicolor flow cytometry and real-time polymerase chain reaction. RESULTS: In chimpanzees successfully vaccinated with recombinant adenovirus and DNA against HCV NS3-5, HCV-specific T cells appeared earlier, maintained better functionality, and persisted at higher frequencies for a longer time after HCV challenge, than those of mock-vaccinated chimpanzees. Vaccine-induced T cells displayed higher levels of CD127, a marker of memory precursors, and lower levels of programmed death-1 (PD-1) than infection-induced T cells. Vaccine-induced, but not infection- induced, T cells were multifunctional; their ability to secrete interferon gamma and tumor necrosis factor alpha correlated with early expression of CD127 but not PD-1. Based on a comparison of vaccine-induced and infection-induced T cells from the same chimpanzee, the CD127(+) memory precursor phenotype was induced by the vaccine itself rather than by low viremia. In contrast, induction of PD-1 correlated with viremia, and levels of intrahepatic PD-1, PD-L1, and 2,5-OAS-1 messenger RNAs correlated with peak titers of HCV. CONCLUSIONS: Compared with infection, vaccination-induced HCV-specific CD127(+) T cells with high functionality that persisted at higher levels for a longer time. Control of viremia prevented up-regulation of PD-1 on T cells and induction of PD-1, PD-L1, and 2,5-OAS-1 in the liver. Early development of a memory T-cell phenotype and, via control of viremia, attenuation of the inhibitory PD1-PD-L1 pathway might be necessary components of successful vaccine-induced protection against HCV.
C1 [Park, Su-Hyung; Shin, Eui-Cheol; Rehermann, Barbara] NIDDKD, Immunol Sect, Liver Dis Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Shin, Eui-Cheol] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Lab Immunol & Infect Dis, Taejon 305701, South Korea.
[Capone, Stefania; Nicosia, Alfredo; Folgori, Antonella] Okairos, Rome, Italy.
[Caggiari, Laura; De Re, Valli] IRCCS Natl Canc Inst, Expt & Clin Pharmacol Unit, CRO Ctr Riferimento Oncol, Aviano, Italy.
[Nicosia, Alfredo] CEINGE, Naples, Italy.
RP Rehermann, B (reprint author), NIDDKD, Immunol Sect, Liver Dis Branch, NIH,Dept Hlth & Human Serv, 10 Ctr Dr,Bldg 10,Room 9B16, Bethesda, MD 20892 USA.
EM rehermann@nih.gov
RI Shin, Eui-Cheol/C-1690-2011; Park, Su-Hyung/N-3514-2014;
OI Capone, Stefania/0000-0002-2272-120X
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health intramural research program [AIRC-10266];
Associazione Italiana per la Ricerca sul Cancro
FX Supported by the National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health intramural research program
(B.R.) and grant AIRC-10266 (to V.D.R.).
NR 35
TC 25
Z9 26
U1 0
U2 19
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD OCT
PY 2012
VL 143
IS 4
BP 1048
EP +
DI 10.1053/j.gastro.2012.06.005
PG 17
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 014FY
UT WOS:000309361800036
PM 22705008
ER
PT J
AU Andersen, JB
Thorgeirsson, SS
AF Andersen, Jesper B.
Thorgeirsson, Snorri S.
TI Genomic and Genetic Characterization of Cholangiocarcinoma Identifies
Therapeutics Targets for Tyrosine Kinase Inhibitors Reply
SO GASTROENTEROLOGY
LA English
DT Letter
ID INTRAHEPATIC CHOLANGIOCARCINOMA; RESECTION
C1 [Andersen, Jesper B.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Andersen, JB (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
OI Andersen , Jesper B/0000-0003-1760-5244
NR 7
TC 0
Z9 0
U1 0
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD OCT
PY 2012
VL 143
IS 4
BP E21
EP E21
DI 10.1053/j.gastro.2012.08.033
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 014FY
UT WOS:000309361800008
ER
PT J
AU Ramkumar, HL
Shen, DF
Tuo, JS
Braziel, RM
Coupland, SE
Smith, JR
Chan, CC
AF Ramkumar, Hema L.
Shen, De Fen
Tuo, Jingsheng
Braziel, Rita M.
Coupland, Sarah E.
Smith, Justine R.
Chan, Chi-Chao
TI IL-10-1082 SNP and IL-10 in primary CNS and vitreoretinal lymphomas
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
DE Primary vitreoretinal lymphoma; Primary CNS lymphoma; Interleukin-10;
Single-nucleotide polymorphism; PDCD4 (program cell death 4)
ID PRIMARY INTRAOCULAR LYMPHOMA; NON-HODGKIN-LYMPHOMA; NERVOUS-SYSTEM
LYMPHOMA; B-CELL LYMPHOMA; INTERLEUKIN-10 GENE PROMOTER; INTRAVITREAL
METHOTREXATE; CEREBROSPINAL-FLUID; AQUEOUS-HUMOR; PLASMA-LEVELS;
POLYMORPHISMS
AB Most primary central nervous system lymphomas (PCNSLs) and primary vitreoretinal lymphomas (PVRLs) are B-cell lymphomas that produce high levels of interleukin (IL)-10, which is linked to rapid disease progression. The IL-10 (-1082) G -> aEuro parts per thousand A polymorphism (IL-10 SNP) is associated with improved survival in certain non-CNS lymphoma patients. PDCD4 is a tumor suppressor gene and upstream regulator of IL-10. This study examined the correlation between the IL-10 SNP, PDCD4 mRNA expression, and IL-10 expression (at transcript and protein levels) in these lymphoma cells.
Single-nucleotide polymorphism (SNP)-typing at IL-10 (-1082) was performed after microdissecting cytospun PVRL cells from 26 specimens. Vitreal IL-10 and IL-6 levels were measured by ELISA. PCNSL cells from 52 paraffin-embedded sections were microdissected and SNP typed on genomic DNA. RT-PCR was performed to analyze expression of IL-10 and PDCD4 mRNA. IL-10 (-1082) SNP typing was performed on blood samples of 96 healthy controls. We measured IL-10 (-1082) SNP expression in 26 PVRLs and 52 PCNSLs and examined its relationship with IL-10 protein and gene expression, respectively.
More PVRL patients expressed one copy of the IL-10 (-1082) G -> aEuro parts per thousand A SNP with the GA genotype compared to controls. The frequencies of the three genotypes (AA, AG, GG) significantly differed in PVRL versus controls and in PCNSL versus controls. In PVRLs, the vitreal IL-10/IL-6 ratio was higher in IL-10 (-1082) AG and IL-10 (-1082) AA patients, compared to IL-10 (-1082) GG patients. IL-10 mRNA expression was higher in IL-10 (-1082) AG and IL-10 (-1082) AA PCNSLs, compared to IL-10 (-1082) GG PCNSLs. No correlation was found between IL-10 and PDCD4 expression levels in 37 PCNSL samples.
PVRL and PCNSL patients had similar IL-10 (-1082) A allele frequencies, but genotype distributions differed from healthy controls. The findings suggest that the IL-10 (-1082) A allele is a risk factor for higher IL-10 levels in PVRLs and PCNSLs. Higher IL-10 levels have been correlated with more aggressive disease in both PVRLs and PCNSLs, making this finding an important and potentially clinically significant observation.
C1 [Ramkumar, Hema L.; Shen, De Fen; Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Ramkumar, Hema L.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Braziel, Rita M.] Oregon Hlth & Sci Univ, Dept Surg Pathol, Portland, OR 97201 USA.
[Smith, Justine R.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA.
[Smith, Justine R.] Oregon Hlth & Sci Univ, Dept Cell & Dev Biol, Portland, OR 97201 USA.
[Coupland, Sarah E.] Univ Liverpool, Dept Cellular & Mol Pathol, Liverpool L69 3BX, Merseyside, England.
RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, 10 Ctr Dr,10-10 N103, Bethesda, MD 20892 USA.
EM chanc@nei.nih.gov
OI Tuo, Jingsheng/0000-0002-1372-7810; Ramkumar, Hema/0000-0002-1452-0694
FU National Eye Institute Intramural Research Program; Howard Hughes
Medical Institute; Research to Prevent Blindness; Schnitzer-Novack
Foundation; Eye Tumour Research Fund
FX We would like to thank the National Eye Institute Intramural Research
Program, Howard Hughes Medical Institute, Research to Prevent
Blindness's unrestricted grant to Casey Eye Institute, the
Schnitzer-Novack Foundation, and the Eye Tumour Research Fund for
financial support. We thank Dr. Nussenblatt and the NEI clinical fellows
for the contribution of their patients' vitreous specimen to this study.
We also appreciate the physicians from other institutions who provided
vitreous specimens.
NR 54
TC 10
Z9 10
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0721-832X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD OCT
PY 2012
VL 250
IS 10
BP 1541
EP 1548
DI 10.1007/s00417-012-2037-1
PG 8
WC Ophthalmology
SC Ophthalmology
GA 013ZR
UT WOS:000309345300019
PM 22628023
ER
PT J
AU Read, JS
Cohen, RA
Hance, LF
Machado, ES
Mussi-Pinhata, MM
Ceriotto, M
Santos, B
Succi, R
Pilotto, JH
Alarcon, JO
Kreitchmann, R
AF Read, Jennifer S.
Cohen, Rachel A.
Hance, Laura Freimanis
Machado, Elizabeth S.
Mussi-Pinhata, Marisa M.
Ceriotto, Mariana
Santos, Breno
Succi, Regina
Pilotto, Jose H.
Alarcon, Jorge O.
Kreitchmann, Regis
CA NISDI Perinatal LILAC Study Grp
TI Missed opportunities for prevention of mother-to-child transmission of
HIV-1 in the NISDI Perinatal and LILAC cohorts
SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS
LA English
DT Article
DE HIV-1; Mother-to-child transmission; Prevention
ID IMMUNODEFICIENCY-VIRUS TYPE-1; RISK-FACTORS; PREGNANCY
AB Objective: To evaluate cases of mother-to-child transmission of HIV-1 at multiple sites in Latin America and the Caribbean in terms of missed opportunities for prevention. Methods: Pregnant women infected with HIV-1 were eligible for inclusion if they were enrolled in either the NISDI Perinatal or LILAC protocols by October 20, 2009, and had delivered a live infant with known HIV-1 infection status after March 1, 2006. Results: Of 711 eligible mothers, 10 delivered infants infected with HIV-1. The transmission rate was 1.4% (95% CI, 0.7-2.6). Timing of transmission was in utero or intrapartum (n = 5), intrapartum (n = 2), intrapartum or early postnatal (n = 1), and unknown (n = 2). Possible missed opportunities for prevention included poor control of maternal viral load during pregnancy; late initiation of antiretrovirals during pregnancy; lack of cesarean delivery before labor and before rupture of membranes; late diagnosis of HIV-1 infection; lack of intrapartum antiretrovirals; and incomplete avoidance of breastfeeding. Conclusion: Early knowledge of HIV-1 infection status (ideally before or in early pregnancy) would aid timely initiation of antiretroviral treatment and strategies designed to prevent mother-to-child transmission. Use of antiretrovirals must be appropriately monitored in terms of adherence and drug resistance. If feasible, breastfeeding should be completely avoided. Presented in part at the XIX International AIDS Conference (Washington, DC; July 22-27, 2012); abstract WEPE163. (c) 2012 Published by Elsevier Ireland Ltd. on behalf of International Federation of Gynecology and Obstetrics.
C1 [Read, Jennifer S.] NICHD, Pediat Adolescent & Maternal AIDS Branch, CRMC, NIH,DHHS, Bethesda, MD USA.
[Cohen, Rachel A.; Hance, Laura Freimanis] WESTAT Corp, Rockville, MD 20850 USA.
[Machado, Elizabeth S.] Univ Fed Rio de Janeiro, Infect Dis Serv, Clementino Fraga Filho Univ Hosp, Rio De Janeiro, Brazil.
[Mussi-Pinhata, Marisa M.] Univ Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto, Brazil.
[Ceriotto, Mariana] Dr Cecilia Grierson Hosp, Infect Dis Unit, Buenos Aires, DF, Argentina.
[Santos, Breno] Nossa Senhora da Conceicao Hosp, Infect Dis Serv, Porto Alegre, RS, Brazil.
[Succi, Regina] Univ Fed Sao Paulo, Paulista Sch Med, Dept Pediat, Sao Paulo, Brazil.
[Pilotto, Jose H.] Hosp Geral Nova Iguacu, HIV Family Care Clin, Rio De Janeiro, Brazil.
[Pilotto, Jose H.] Lab AIDS & Mol Immunol IOC Fiocruz, Rio De Janeiro, Brazil.
[Alarcon, Jorge O.] UNMSM, Epidemiol Sect, DA Carrion Inst Trop Med, Lima, Peru.
[Kreitchmann, Regis] Irmandade Santa Casa de Misericordia Porto Alegre, Porto Alegre, RS, Brazil.
RP Read, JS (reprint author), NVPO OASH OS DHHS, 200 Independence Ave SW,Room 739G6, Washington, DC 20201 USA.
EM jennifer.read@hhs.gov
RI Mussi-Pinhata, Marisa/G-6568-2012; Inca, Inct/K-2204-2013;
OI Alarcon, Jorge/0000-0002-0800-2380
FU National Institute of Child Health and Human Development (NICHD)
[N01-HD-3-3345]; NICHD [HHSN267200800001C, N01-HD-8-0001]
FX The present study was supported by National Institute of Child Health
and Human Development (NICHD) Contract # N01-HD-3-3345 (2002-2007) and
by NICHD Contract # HHSN267200800001C (NICHD Control #: N01-HD-8-0001;
2007-2012).
NR 16
TC 4
Z9 5
U1 0
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0020-7292
J9 INT J GYNECOL OBSTET
JI Int. J. Gynecol. Obstet.
PD OCT
PY 2012
VL 119
IS 1
BP 70
EP 75
DI 10.1016/j.ijgo.2012.05.026
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 012OU
UT WOS:000309247200018
PM 22819316
ER
PT J
AU Shive, CL
Biancotto, A
Funderburg, NT
Pilch-Cooper, HA
Valdez, H
Margolis, L
Sieg, SF
McComsey, GA
Rodriguez, B
Lederman, MM
AF Shive, Carey L.
Biancotto, Angelique
Funderburg, Nicholas T.
Pilch-Cooper, Heather A.
Valdez, Hernan
Margolis, Leonid
Sieg, Scott F.
McComsey, Grace A.
Rodriguez, Benigno
Lederman, Michael M.
TI HIV-1 Is Not a Major Driver of Increased Plasma IL-6 Levels in Chronic
HIV-1 Disease
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE IL-6; HIV-1 RNA; histocultures; macrophages; LPS; flagellin
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY;
TUMOR-NECROSIS-FACTOR; T-CELL-ACTIVATION; MICROBIAL TRANSLOCATION;
IMMUNE ACTIVATION; MONONUCLEAR-CELLS; INFECTED PATIENTS; TYPE-1
INFECTION; INTERLEUKIN-6
AB Objective: Increased plasma IL-6 levels have been associated with HIV-1 disease progression risk, yet the drivers of IL-6 production in HIV-1 infection are not known. This study was designed to explore the relationship between HIV-1 replication and IL-6 induction.
Design: Correlations between plasma levels of IL-6 and HIV-1 RNA were examined in 2 clinical studies. To more directly assess the induction of IL-6 by HIV-1, several cell and tissue types that support HIV-1 replication in vivo were infected with HIV-1, and expression of IL-6 was measured.
Methods: Spearman rank correlations were used to examine the relationship between plasma levels of IL-6 and HIV-1 RNA. Macrophages and colonic and lymph node histocultures were infected with HIV-1 or stimulated with bacterial products, lipopolysaccharide (LPS) or flagellin, and IL-6 levels in supernatant were measured by enzyme-linked immunosorbent assay or multiplex bead assay.
Results: In the clinical studies, there was weak or no correlation between plasma levels of IL-6 and HIV-1 RNA, but IL-6 levels were correlated with plasma levels of the LPS coreceptor CD14. Macrophages stimulated with LPS or flagellin showed robust production of IL-6, but there was no increase in IL-6 production after HIV-1 infection. IL-6 expression was not increased in lymph node histocultures obtained from HIV-1-infected subjects nor after productive HIV-1 infection of colonic or lymph node histocultures ex vivo.
Conclusions: We find no evidence that HIV-1 replication is an important driver of IL-6 expression in vivo or in in vitro systems.
C1 [Shive, Carey L.; Funderburg, Nicholas T.; Pilch-Cooper, Heather A.; Sieg, Scott F.; Rodriguez, Benigno; Lederman, Michael M.] Case Western Reserve Univ, Sch Med, Div Infect Dis, Cleveland, OH 44106 USA.
[Shive, Carey L.; Funderburg, Nicholas T.; Pilch-Cooper, Heather A.; Sieg, Scott F.; McComsey, Grace A.; Rodriguez, Benigno; Lederman, Michael M.] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA.
[Biancotto, Angelique; Margolis, Leonid] NICHHD, Lab Mol & Cellular Biophys, Bethesda, MD 20892 USA.
[Valdez, Hernan] Pfizer Inc, New York, NY USA.
[McComsey, Grace A.] Case Western Reserve Univ, Sch Med, Dept Pediat, Ctr AIDS Res, Cleveland, OH 44106 USA.
RP Lederman, MM (reprint author), Case Western Reserve Univ, Sch Med, Div Infect Dis, 2061 Cornell Rd, Cleveland, OH 44106 USA.
EM mxl6@case.edu
RI Funderburg, Nicholas/L-8022-2013; Rodriguez, Benigno/C-3365-2009
OI Rodriguez, Benigno/0000-0001-9736-7957
FU Center for AIDS Research at Case Western Reserve University [AI-36219];
Tissue Procurement, Histology, and Immunohistochemistry Core Facility of
the Case Comprehensive Cancer Center [CA43703]; Fasenmyer Foundation;
National institute of Health [AI-76174]; Bristol Myers Squibb;
GlaxoSmithKline; Abbott; Merck; Gilead Sciences; Pfizer
FX Supported by the Center for AIDS Research at Case Western Reserve
University, AI-36219, and by the Tissue Procurement, Histology, and
Immunohistochemistry Core Facility of the Case Comprehensive Cancer
Center CA43703 and by grant awards from the Fasenmyer Foundation and
AI-76174 from the National institute of Health.; Dr M.M.L has received
grant support and has consulted for Pfizer. Dr H. V. is employed by
Pfizer. G. A. M has served as a scientific advisor for Bristol Myers
Squibb, GlaxoSmithKline, Abbott, Tibotec, and Gilead Sciences; has
received research grants from Bristol Myers Squibb, GlaxoSmithKline,
Abbott, Merck, and Gilead Sciences; and is currently serving as the DSMB
Chair for a Pfizer-sponsored study.
NR 37
TC 18
Z9 18
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD OCT 1
PY 2012
VL 61
IS 2
BP 145
EP 152
DI 10.1097/QAI.0b013e31825ddbbf
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 012EQ
UT WOS:000309218700010
PM 22659649
ER
PT J
AU Korthuis, PT
Fiellin, DA
McGinnis, KA
Skanderson, M
Justice, AC
Gordon, AJ
Doebler, DA
Asch, SM
Fiellin, LE
Bryant, K
Gibert, CL
Crystal, S
Goetz, MB
Rimland, D
Rodriguez-Barradas, MC
Kraemer, KL
AF Korthuis, P. Todd
Fiellin, David A.
McGinnis, Kathleen A.
Skanderson, Melissa
Justice, Amy C.
Gordon, Adam J.
Doebler, Donna Almario
Asch, Steven M.
Fiellin, Lynn E.
Bryant, Kendall
Gibert, Cynthia L.
Crystal, Stephen
Goetz, Matthew Bidwell
Rimland, David
Rodriguez-Barradas, Maria C.
Kraemer, Kevin L.
TI Unhealthy Alcohol and Illicit Drug Use Are Associated With Decreased
Quality of HIV Care
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE alcohol; quality of health care; HIV; quality indicators; health care;
opioid-related disorders
ID HUMAN-IMMUNODEFICIENCY-VIRUS; SUBSTANCE-ABUSE TREATMENT; ACTIVE
ANTIRETROVIRAL THERAPY; HEALTH-CARE; UNITED-STATES; OF-CARE; TREATMENT
OUTCOMES; PERFORMANCE-MEASURES; INFECTED PERSONS; MEDICAL-CARE
AB Background: HIV-infected patients with substance use experience suboptimal health outcomes, possibly because of variations in care.
Objectives: To assess the association between substance use and the quality of HIV care (QOC) received.
Research Design: Retrospective cohort study.
Subjects: HIV-infected patients enrolled in the Veterans Aging Cohort Study.
Measures: We collected self-report substance use data and abstracted 9 HIV quality indicators (QIs) from medical records. Independent variables were unhealthy alcohol use (AUDIT-C score >= 4) and illicit drug use (self-report of stimulants, opioids, or injection drug use in past year). Main outcome was the percentage of QIs received, if eligible. We estimated associations between substance use and QOC using multivariable linear regression.
Results: The majority of the 3410 patients were male (97.4%) and black (67.0%) with a mean age of 49.1 years (SD = 8.8). Overall, 25.8% reported unhealthy alcohol use, 22% illicit drug use, and participants received 81.5% (SD - 18.9) of QIs. The mean percentage of QIs received was lower for those with unhealthy alcohol use versus not (59.3% vs. 70.0%, P < 0.001) and those using illicit drugs vs. not (57.8% vs. 70.7%, P < 0.001). In multivariable models, unhealthy alcohol use (adjusted beta -2.74; 95% confidence interval: -4.23 to -1.25) and illicit drug use (adjusted beta -3.51; 95% CI: -4.99 to -2.02) remained inversely associated with the percentage of QIs received.
Conclusions: Although the overall QOC for these HIV-infected Veteran patients was high, gaps persist for those with unhealthy alcohol and illicit drug use. Interventions that address substance use in HIV-infected patients may improve the QOC received.
C1 [Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA.
[Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA.
[Fiellin, David A.; Justice, Amy C.; Fiellin, Lynn E.] Yale Univ, Sch Med, Dept Gen Med, New Haven, CT USA.
[Fiellin, David A.; Justice, Amy C.; Fiellin, Lynn E.] Yale Univ, Sch Med, Dept Publ Hlth, Div Gen Internal Med, New Haven, CT 06510 USA.
[Fiellin, David A.; Justice, Amy C.; Fiellin, Lynn E.] Yale Univ, Sch Med, Ctr Interdisciplinary Res AIDS, New Haven, CT USA.
[McGinnis, Kathleen A.; Skanderson, Melissa; Gordon, Adam J.; Doebler, Donna Almario] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA.
[Justice, Amy C.] VA Connecticut Healthcare Syst, Vet Aging Cohort Study Coordinating Ctr, Dept Gen Med, West Haven, CT USA.
[Justice, Amy C.] VA Connecticut Healthcare Syst, Vet Aging Cohort Study Coordinating Ctr, Dept Publ Hlth, West Haven, CT USA.
[Gordon, Adam J.; Doebler, Donna Almario; Kraemer, Kevin L.] Univ Pittsburgh, Dept Med, Ctr Res Hlth Care, Pittsburgh, PA USA.
[Asch, Steven M.] Stanford Univ, VA Greater Palo Alto Healthcare Syst, Palo Alto, CA 94304 USA.
[Bryant, Kendall] NIAAA, HIV AIDS Res, Rockville, MD 20852 USA.
[Gibert, Cynthia L.] VA Med Ctr, Washington, DC USA.
[Gibert, Cynthia L.] George Washington Univ, Med Ctr, Washington, DC 20037 USA.
[Crystal, Stephen] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, New Brunswick, NJ 08903 USA.
[Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90095 USA.
[Rimland, David] VA Med Ctr, Dept Med, Atlanta, GA USA.
[Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA.
[Rodriguez-Barradas, Maria C.] Michael E DeBakey VA Med Ctr, Dept Med, Infect Dis Sect, Houston, TX USA.
[Rodriguez-Barradas, Maria C.] Baylor Coll Med, Houston, TX 77030 USA.
RP Korthuis, PT (reprint author), Oregon Hlth & Sci Univ, Dept Med, 3181 SW Sam Jackson Pk Rd,Mail Code L-475, Portland, OR 97239 USA.
EM korthuis@ohsu.edu
OI Goetz, Matthew/0000-0003-4542-992X; Fiellin, David/0000-0002-4006-010X
FU National Institutes of Health, National Institute on Alcohol Abuse and
Alcoholism [U10AA013566]; National Institutes of Health, National
Institute on Drug Abuse [K23 DA019809]
FX Supported by the National Institutes of Health, National Institute on
Alcohol Abuse and Alcoholism Grant U10AA013566; National Institutes of
Health, National Institute on Drug Abuse Grant K23 DA019809 (to Dr
Korthuis).
NR 53
TC 12
Z9 12
U1 3
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD OCT 1
PY 2012
VL 61
IS 2
BP 171
EP 178
DI 10.1097/QAI.0b013e31826741aa
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 012EQ
UT WOS:000309218700014
PM 22820808
ER
PT J
AU Yu, MS
Henning, R
Walker, A
Kim, G
Perroy, A
Alessandro, R
Virador, V
Kohn, EC
AF Yu, Minshu
Henning, Ryan
Walker, Amanda
Kim, Geoffrey
Perroy, Alyssa
Alessandro, Riccardo
Virador, Victoria
Kohn, Elise C.
TI L-asparaginase inhibits invasive and angiogenic activity and induces
autophagy in ovarian cancer
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE asparaginase; ovarian cancer; sialyl Lewis X; angiogenesis; autophagy
ID FOCAL ADHESION KINASE; COLON-CARCINOMA CELLS; INTEGRIN GLYCOSYLATION;
GLYCOPROTEIN SYNTHESIS; PREDICTIVE BIOMARKER; EXTRACELLULAR-MATRIX;
SIGNAL-TRANSDUCTION; LEUKEMIA CELLS; PHASE-II; EXPRESSION
AB Recent work identified L-asparaginase (L-ASP) as a putative therapeutic target for ovarian cancer. We suggest that L-ASP, a dysregulator of glycosylation, would interrupt the local microenvironment, affecting the ovarian cancer cellendothelial cell interaction and thus angiogenesis without cytotoxic effects. Ovarian cancer cell lines and human microvascular endothelial cells (HMVEC) were exposed to L-ASP at physiologically attainable concentrations and subjected to analyses of endothelial tube formation, invasion, adhesion and the assessment of sialylated proteins involved in matrix-associated and heterotypic cell adhesion. Marked reduction in HMVEC tube formation in vitro, HMVEC and ovarian cancer cell invasion, and heterotypic cell-cell and cell-matrix adhesion was observed (P < 0.05-0.0001). These effects were associated with reduced binding to beta 1integrin, activation of FAK, and cell surface sialyl LewisX (sLex) expression. No reduction in HMVEC E-selectin expression was seen consistent with the unidirectional inhibitory actions observed. L-ASP concentrations were non-toxic to either ovarian cancer or HMVEC lines in the time frame of the assays. However, early changes of autophagy were observed in both cell types with induction of ATG12, beclin-1, and cleavage of LC-3, indicating cell injury did occur. These data and the known mechanism of action of L-ASP on glycosylation of nascent proteins suggest that L-ASP reduces of ovarian cancer dissemination and progression through modification of its microenvironment. The reduction of ovarian cancer cell surface sLex inhibits interaction with HMVEC and thus HMVEC differentiation into tubes, inhibits interaction with the local matrix reducing invasive behaviour, and causes cell injury initiating autophagy in tumour and vascular cells.
C1 [Yu, Minshu; Henning, Ryan; Walker, Amanda; Kim, Geoffrey; Perroy, Alyssa; Virador, Victoria; Kohn, Elise C.] NCI, Mol Signaling Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Alessandro, Riccardo] Univ Palermo, Sez Biol & Genet, Dipartimento Biopatol & Biotecnol Med & Forensi, Palermo, Italy.
RP Kohn, EC (reprint author), 10 Ctr Dr,MSC 1906, Bethesda, MD 20892 USA.
EM ek1b@nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 54
TC 8
Z9 9
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1582-1838
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD OCT
PY 2012
VL 16
IS 10
BP 2369
EP 2378
DI 10.1111/j.1582-4934.2012.01547.x
PG 10
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 012LK
UT WOS:000309237500013
PM 22333033
ER
PT J
AU Mukhopadhyay, P
Das, S
Ahsan, MK
Otani, H
Das, DK
AF Mukhopadhyay, Partha
Das, Somak
Ahsan, Md Kaimul
Otani, Hajime
Das, Dipak K.
TI Modulation of microRNA 20b with resveratrol and longevinex is linked
with their potent anti-angiogenic action in the ischaemic myocardium and
synergestic effects of resveratrol and ?-tocotrienol
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE ischaemia; reperfusion; redox; cardiovascular; microRNA; resveratrol;
longevinex; -tocotrienol
ID RED WINE; SURVIVAL SIGNAL; DEATH SIGNAL; NITRIC-OXIDE; CELL-DEATH;
VITAMIN-E; IN-VIVO; CARDIOPROTECTION; HEART; EXPRESSION
AB Resveratrol, a constituent of red wine, and ?-tocotrienol, a constituent of palm oil are important for cardioprotection. Although microRNAs are known regulators for genes involved in cardiac remodelling, the regulatory pathway involving microRNA has not been studied so far. We explored the cardioprotection by resveratrol, longevinex and ?-tocotrienol in ischaemia/reperfusion(I/R) model of rat and determined miRNA profile from isolated RNA. Systemic analyses of miRNA array and theirs targets were determined using a number of computational approaches. Resveratrol and ?-tocotrienol, either alone or in combination, modulated the expression pattern of miRNAs close to the control level based on PCA analyses. Differential expression was observed in over 75 miRNAs, some of them, such as miR-21 and miR-20b (anti-angiogenic) were previously implicated in cardiac remodelling. The target genes for the highest differentially expressed miRNA include genes of various molecular functions such as TGF beta 1Smad3 signalling pathway, inflammation and their transcription factors, which may play key role in reducing I/R injury. Administration of antagomiR-20 attenuated I/R induced vascular endothelial growth factor and HIF1a level. All the interventions treated for 3 weeks lead to significant cardioprotection against ischaemia/reperfusion injury. A unique signature of miRNA profile is observed in control heart pretreated with resveratrol or ?-tocotrienol. We have determined specific group of miRNA in heart that have altered during IR injuries. Most of those altered microRNA expressions modulated close to their basal level in resveratrol or longevinex treated I/R rat. Interestingly, resveratrol and ?-tocotrienol resulted in synergestic action.
C1 [Das, Somak; Das, Dipak K.] Univ Connecticut, Sch Med, Cardiovasc Res Ctr, Farmington, CT 06030 USA.
[Mukhopadhyay, Partha] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA.
[Ahsan, Md Kaimul] Yale Univ, Sect Digest Dis, New Haven, CT USA.
[Otani, Hajime] Kansai Med Univ, Dept Internal Med, Moriguchi, Osaka 570, Japan.
RP Das, DK (reprint author), Univ Connecticut, Sch Med, Cardiovasc Res Ctr, Farmington, CT 06030 USA.
EM ddas@neuron.uchc.edu
FU Intramural Research Program of NIH / NIAAA; NIAAA
FX This work supported by Intramural Research Program of NIH / NIAAA (P.
P.). The authors thank Dr. Pal Pacher for providing new tools and
resources related to miRNA measurements. The authors also thank Dr.
Nikolai Gorbunov for his assistance with the confocal immunofluorescence
image analysis in this article. In this article, Dr. Partha Mukhopadhyay
contributed microRNA array analyses of the RNA samples provided and
associated text. This part of work has been approved by Dr. Pal Pacher
and funded through intramural program of NIAAA Dr. Pacher.
NR 41
TC 14
Z9 14
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1582-1838
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD OCT
PY 2012
VL 16
IS 10
BP 2504
EP 2517
DI 10.1111/j.1582-4934.2011.01480.x
PG 14
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 012LK
UT WOS:000309237500026
PM 22050707
ER
PT J
AU Kuehl, WM
Bergsagel, PL
AF Kuehl, W. Michael
Bergsagel, P. Leif
TI Molecular pathogenesis of multiple myeloma and its premalignant
precursor
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Review
ID PLASMA-CELL LEUKEMIA; UNDETERMINED SIGNIFICANCE MGUS; INDEPENDENT
RISK-FACTOR; LIGHT-CHAIN RATIO; KAPPA-B PATHWAY; MONOCLONAL GAMMOPATHY;
RAS MUTATIONS; BONE-MARROW; GENE-EXPRESSION; FLOW-CYTOMETRY
AB Multiple myeloma is a monoclonal tumor of plasma cells, and its development is preceded by a premalignant tumor with which it shares genetic abnormalities, including universal dysregulation of the cyclin D/retinoblastoma (cyclin D/RB) pathway. A complex interaction with the BM microenvironment, characterized by activation of osteoclasts and suppression of osteoblasts, leads to lytic bone disease. Intratumor genetic heterogeneity, which occurs in addition to intertumor heterogeneity, contributes to the rapid emergence of drug resistance in high-risk disease. Despite recent therapeutic advances, which have doubled the median survival time, myeloma continues to be a mostly incurable disease. Here we review the current understanding of myeloma pathogenesis and insight into new therapeutic strategies provided by animal models and genetic screens.
C1 [Bergsagel, P. Leif] Mayo Clin, Coll Med, Ctr Comprehens Canc, Scottsdale, AZ 10021 USA.
[Kuehl, W. Michael] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Bergsagel, PL (reprint author), Mayo Clin, Coll Med, Ctr Comprehens Canc, 13208 E Shea Blvd,C-007, Scottsdale, AZ 10021 USA.
EM bergsagel.leif@mayo.edu
FU NIH [CA100707, CA136671, CA133966, AG020686]
FX We thank Marta Chesi for many fruitful discussions. This work was
supported by the NIH grants CA100707, CA136671, CA133966, and AG020686
(to P.L. Bergsagel).
NR 82
TC 111
Z9 113
U1 4
U2 25
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD OCT
PY 2012
VL 122
IS 10
BP 3456
EP 3463
DI 10.1172/JCI61188
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 013VK
UT WOS:000309333800014
PM 23023717
ER
PT J
AU Johnson, KD
Hsu, AP
Ryu, MJ
Wang, JY
Gao, X
Boyer, ME
Liu, YG
Lee, Y
Calvo, KR
Keles, S
Zhang, J
Holland, SM
Bresnick, EH
AF Johnson, Kirby D.
Hsu, Amy P.
Ryu, Myung-Jeom
Wang, Jinyong
Gao, Xin
Boyer, Meghan E.
Liu, Yangang
Lee, Youngsook
Calvo, Katherine R.
Keles, Sunduz
Zhang, Jing
Holland, Steven M.
Bresnick, Emery H.
TI Cis-element mutated in GATA2-dependent immunodeficiency governs
hematopoiesis and vascular integrity
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID TRANSCRIPTION FACTOR GATA-2; ACUTE MYELOID-LEUKEMIA; SPORADIC
MONOCYTOPENIA; AUTOSOMAL-DOMINANT; ENDOTHELIAL-CELLS; TARGETED DELETION;
BINDING PROTEIN; STEM-CELLS; IN-VIVO; EXPRESSION
AB Haploinsufficiency for GATA2 causes human immunodeficiency syndromes characterized by mycobacterial infection, myelodysplasia, lymphedema, or aplastic anemia that progress to myeloid leukemia. GATA2 encodes a master regulator of hematopoiesis that is also linked to endothelial biology. Though the disease-causing mutations commonly occur in the GATA-2 DNA binding domain, we identified a patient with mycobacterial infection and myelodysplasia who had an uncharacterized heterozygous deletion in a GATA2 cis-element consisting of an E-box and a GATA motif. Targeted deletion of the equivalent murine element to yield homozygous mutant mice revealed embryonic lethality later than occurred with global Gata2 knockout, hematopoietic stem/progenitor cell depletion, and impaired vascular integrity. Heterozygous mutant mice were viable, but embryos exhibited deficits in definitive, but not primitive, hematopoietic stem/progenitor activity and reduced expression of Gata2 and its target genes. Mechanistic analysis revealed disruption of the endothelial cell transcriptome and loss of vascular integrity. Thus, the composite element disrupted in a human immunodeficiency is essential for establishment of the murine hematopoietic stem/progenitor cell compartment in the fetal liver and for essential vascular processes.
C1 [Johnson, Kirby D.; Gao, Xin; Boyer, Meghan E.; Lee, Youngsook; Bresnick, Emery H.] Univ Wisconsin, Sch Med & Publ Hlth, UW Carbone Canc Ctr, Wisconsin Inst Med Res,Dept Cell & Regenerat Biol, Madison, WI 53705 USA.
[Hsu, Amy P.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Ryu, Myung-Jeom; Wang, Jinyong; Liu, Yangang; Zhang, Jing] Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53706 USA.
[Calvo, Katherine R.] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Keles, Sunduz] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat, Madison, WI 53705 USA.
[Keles, Sunduz] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med Informat & Stat, Madison, WI 53705 USA.
RP Bresnick, EH (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, UW Carbone Canc Ctr, Wisconsin Inst Med Res 4009, 1111 Highland Ave, Madison, WI 53705 USA.
EM zhang@oncology.wisc.edu; SHOL-LAND@niaid.nih.gov; ehbresni@wisc.edu
RI Calvo, Katherine/A-8109-2009;
OI Calvo, Katherine/0000-0002-0771-4191
FU NIH [DK68634, DK50107, HG006716]; Howard Temin Award [CA152108]; Shaw
Scientist Award; ASH Scholar Award; V Foundation Scholar Award; American
Heart Association postdoctoral fellowship; NIH/NCI - UW Comprehensive
Cancer Center [P30 CA014520]; Division of Intramural Research, NIAID
NIH; National Human Genome Research Institute (NHGRI) funds as part of
the ENCODE Project
FX This research was supported by NIH grants DK68634 and DK50107 to E.H.
Bresnick; HG006716 to S. Keles; CA152108, Howard Temin Award, Shaw
Scientist Award, ASH Scholar Award, and V Foundation Scholar Award to J.
Zhang; and American Heart Association postdoctoral fellowship to M.J.
Ryu; and by the NIH/NCI P30 CA014520 - UW Comprehensive Cancer Center.
This work was supported in part by the Division of Intramural Research,
NIAID NIH. The content does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, and organizations imply
endorsement by the United States government. We appreciate advice and
discussion with the NIDDK Center of Excellence in Hematology at
Children's Hospital, Harvard Medical School. GATA-2 ChIP-seq data were
produced by Peggy Farnham (University of Southern California). Data
generation/analysis was supported by National Human Genome Research
Institute (NHGRI) funds as part of the ENCODE Project. We thank Peggy
Farnham and the Data Coordination Center at UCSC for providing access to
this data. We acknowledge the technical assistance of Amelia Linnemann
in facilitating initial ChIP-seq data analysis and Margaret Baron for
sharing the protocol to quantitate primitive hematopoietic precursor
colony-forming activity.
NR 59
TC 50
Z9 51
U1 1
U2 4
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD OCT
PY 2012
VL 122
IS 10
BP 3692
EP 3704
DI 10.1172/JCI61623
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 013VK
UT WOS:000309333800038
PM 22996659
ER
PT J
AU Cohen, LK
Nylen, MU
AF Cohen, L. K.
Nylen, M. U.
TI In Memoriam - David B. Scott, the 52nd President of the IADR
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Biographical-Item
C1 [Cohen, L. K.; Nylen, M. U.] NIH, Bethesda, MD 20892 USA.
RP Cohen, LK (reprint author), NIH, 45 Ctr Dr,MSC 6401, Bethesda, MD 20892 USA.
EM lois.cohen@nih.gov; munylen@gmail.com
NR 1
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
J9 J DENT RES
JI J. Dent. Res.
PD OCT
PY 2012
VL 91
IS 10
BP 905
EP 906
DI 10.1177/0022034512455803
PG 2
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 007HH
UT WOS:000308878900001
ER
PT J
AU Chang, TH
Xu, SX
Tailor, P
Kanno, T
Ozato, K
AF Chang, Tsung-Hsien
Xu, Songxiao
Tailor, Prafullakumar
Kanno, Tomohiko
Ozato, Keiko
TI The Small Ubiquitin-like Modifier-Deconjugating Enzyme Sentrin-Specific
Peptidase 1 Switches IFN Regulatory Factor 8 from a Repressor to an
Activator during Macrophage Activation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SEQUENCE-BINDING PROTEIN; SUMO-SPECIFIC PROTEASE; GENE-EXPRESSION;
TRANSCRIPTIONAL REPRESSION; DE-SUMOYLATION; CUTTING EDGE;
DIFFERENTIATION; STRESS; CONJUGATION; DEACETYLASE
AB Macrophages, when activated by IFN-gamma and TLR signaling, elicit innate immune responses. IFN regulatory factor 8 (IRF8) is a transcription factor that facilitates macrophage activation and innate immunity. We show that, in resting macrophages, some IRF8 is conjugated to small ubiquitin-like modifiers (SUMO) 2/3 through the lysine residue 310. SUMO3-conjugated IRF8 failed to induce IL12p40 and other IRF8 target genes, consistent with SUMO-mediated transcriptional repression reported for other transcription factors. SUMO3-conjugated IRF8 showed reduced mobility in live nuclei and bound poorly to the IL12p40 gene. However, macrophage activation caused a sharp reduction in the amount of SUMOylated IRF8. This reduction coincided with the induction of a deSUMOylating enzyme, sentrin-specific peptidase 1 (SENP1), in activated macrophages. In transfection analysis, SENP1 removed SUMO3 from IRF8 and enhanced expression of IL12p40 and other target genes. Conversely, SENP1 knockdown repressed IRF8 target gene expression. In parallel with IRF8 deSUMOylation, macrophage activation led to the induction of proteins active in the SUMO pathway and caused a global shift in nuclear protein SUMOylation patterns. Together, the IRF8 SUMO conjugation/deconjugation switch is part of a larger transition in SUMO modifications that takes place upon macrophage activation, serving as a mechanism to trigger innate immune responses. The Journal of Immunology, 2012, 189: 3548-3556.
C1 [Chang, Tsung-Hsien; Xu, Songxiao; Tailor, Prafullakumar; Kanno, Tomohiko; Ozato, Keiko] NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
RP Ozato, K (reprint author), NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
EM ozatok@nih.gov
FU National Institute of Child Health and Human Development; National
Institutes of Health
FX This work was supported by the intramural programs of the National
Institute of Child Health and Human Development and the National
Institutes of Health intramural AIDS Targeted Antiviral program.
NR 54
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U1 0
U2 7
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD OCT 1
PY 2012
VL 189
IS 7
BP 3548
EP 3556
DI 10.4049/jimmunol.1201104
PG 9
WC Immunology
SC Immunology
GA 011KT
UT WOS:000309164300031
PM 22942423
ER
PT J
AU Driessen, NN
Boshoff, HIM
Maaskant, JJ
Gilissen, SAC
Vink, S
van der Sar, AM
Vandenbroucke-Grauls, CMJE
Bewley, CA
Appelmelk, BJ
Geurtsen, J
AF Driessen, Nicole N.
Boshoff, Helena I. M.
Maaskant, Janneke J.
Gilissen, Sebastiaan A. C.
Vink, Simone
van der Sar, Astrid M.
Vandenbroucke-Grauls, Christina M. J. E.
Bewley, Carole A.
Appelmelk, Ben J.
Geurtsen, Jeroen
TI Cyanovirin-N Inhibits Mannose-Dependent Mycobacterium-C-Type Lectin
Interactions but Does Not Protect against Murine Tuberculosis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HUMAN DENDRITIC CELLS; DC-SIGN; BINDING-SITES; RECEPTOR; MACROPHAGES;
LIPOARABINOMANNAN; RECOGNITION; IMMUNITY; HOST; BCG
AB Cyanovirin-N (CV-N) is a mannose-binding lectin that inhibits HIV-1 infection by blocking mannose-dependent target cell entry via C-type lectins. Like HIV-1, Mycobacterium tuberculosis expresses mannosylated surface structures and exploits C-type lectins to gain cell access. In this study, we investigated whether CV-N, like HIV-1, can inhibit M. tuberculosis infection. We found that CV-N specifically interacted with mycobacteria by binding to the mannose-capped lipoglycan lipoarabinomannan. Furthermore, CV-N competed with the C-type lectins DC-SIGN and mannose receptor for ligand binding and inhibited the binding of M. tuberculosis to dendritic cells but, unexpectedly, not to macrophages. Subsequent in vivo infection experiments in a mouse model demonstrated that, despite its activity, CV-N did not inhibit or delay M. tuberculosis infection. This outcome argues against a critical role for mannose-dependent C-type lectin interactions during the initial stages of murine M. tuberculosis infection and suggests that, depending on the circumstances, M. tuberculosis can productively infect cells using different modes of entry. The Journal of Immunology, 2012, 189: 3585-3592.
C1 [Geurtsen, Jeroen] Free Univ Amsterdam, Med Ctr, Fac Med, Dept Med Microbiol & Infect Control, NL-1081 BT Amsterdam, Netherlands.
[Boshoff, Helena I. M.] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Bewley, Carole A.] NIDDKD, Lab Bioorgan Chem, NIH, Bethesda, MD 20892 USA.
RP Geurtsen, J (reprint author), Free Univ Amsterdam, Med Ctr, Fac Med, Dept Med Microbiol & Infect Control, Van der Boechorststr 7, NL-1081 BT Amsterdam, Netherlands.
EM jeroen.geurtsen@vumc.nl
RI van der Sar, Astrid/A-3698-2008;
OI van der Sar, Astrid/0000-0001-5790-5036
FU National Institutes of Health Intramural AIDS Targeted Antiviral
Program, Office of the Directory; National Institutes of Health
Intramural Research Program (National Institute of Diabetes and
Digestive and Kidney Diseases); National Institutes of Health Intramural
Research Program (National Institute for Allergy and Infectious
Diseases); Netherlands Organization for Scientific Research through a
VENI research grant [016.101.001]; National Institutes of Health [NO1
AI-75320]
FX This work was supported by the National Institutes of Health Intramural
AIDS Targeted Antiviral Program, Office of the Directory (to C. A. B.),
and the National Institutes of Health Intramural Research Program
(National Institute of Diabetes and Digestive and Kidney Diseases and
National Institute for Allergy and Infectious Diseases). J.G. is
supported financially by The Netherlands Organization for Scientific
Research through a VENI research grant (016.101.001).; We thank
Jacqueline Gonzales for help with the mouse infections. We thank Drs. T.
B. H. Geijtenbeek and S. I. Gringhuis (Academic Medical Center,
University of Amsterdam, Amsterdam, The Netherlands) for providing
DC-SIGN-Fc, Dr. L. Martinez-Pomares (University of Nottingham,
Nottingham, U. K.) and Dr. R.J. Stillion (University of Oxford, Oxford,
U. K.) for providing MMR-Fc, and Dr. O. Neyrolles (Centre National de la
Recherche Scientifique, Universite de Toulouse, Toulouse, France) for
providing (SIGNR1/SIGNR3-transfected) RAW264.7 cells. Glycolipids were a
gift from Dr. J.T. Belisle (Colorado State University, Fort Collins, CO)
and the National Institutes of Health (contract NO1 AI-75320).
NR 43
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U1 0
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD OCT 1
PY 2012
VL 189
IS 7
BP 3585
EP 3592
DI 10.4049/jimmunol.1102408
PG 8
WC Immunology
SC Immunology
GA 011KT
UT WOS:000309164300035
PM 22942435
ER
PT J
AU Steinhagen, F
Meyer, C
Tross, D
Gursel, M
Maeda, T
Klaschik, S
Klinman, DM
AF Steinhagen, Folkert
Meyer, Corinna
Tross, Debra
Gursel, Mayda
Maeda, Takahiro
Klaschik, Sven
Klinman, Dennis M.
TI Activation of type I interferon-dependent genes characterizes the "core
response" induced by CpG DNA
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE human; pDC; CAL-1; TLR9; gene regulation; oligonucleotide
ID PLASMACYTOID DENDRITIC CELLS; VIRUS-INFECTION; TOLL-LIKE-RECEPTOR-9
ACTIVATION; IMMUNE ACTIVATION; INNATE IMMUNITY; IFN-ALPHA/BETA;
BACTERIAL-DNA; RNASE-L; EXPRESSION; MICE
AB Synthetic ODNs expressing CpG motifs trigger an innate immune response via TLR9. pDCs are major effectors of this response. Two structurally distinct classes of CpG ODNs have been identified that differentially activate pDCs. "K" ODNs trigger the production of TNF-alpha and IL-6, whereas "D" ODNs preferentially induce the secretion of IFN-alpha. As K and D ODNs have distinct therapeutic effects, knowledge of their shared and sequence-specific activity is of considerable importance. This work uses the CAL-1 human pDC line to analyze the effect of CpG stimulation on gene expression. Genes up-regulated by both K and D ODNs (n = 92) were largely dependent on type I IFN signaling and characterized functionally by antiviral activity. K ODNs induced a short-term increase in IFN-alpha/beta production and uniquely up-regulated genes that supported antibacterial responses. In contrast, D ODNs triggered a persistent increase in IFN-alpha/beta production and uniquely up-regulated genes associated with metabolic functions. Thus, the core functionality of human pDCs mediated by TLR9 ligation rests on a type I IFN response that differs from the response induced by the structural elements unique to specific classes of ODNs. J. Leukoc. Biol. 92: 775-785; 2012.
C1 [Steinhagen, Folkert; Meyer, Corinna; Tross, Debra; Gursel, Mayda; Klaschik, Sven; Klinman, Dennis M.] NCI, Expt Immunol Lab, Canc & Inflammat Program, NIH, Frederick, MD 21702 USA.
[Steinhagen, Folkert; Meyer, Corinna; Klaschik, Sven] Univ Hosp Bonn, Dept Anesthesiol & Intens Care Med, Bonn, Germany.
[Gursel, Mayda] Middle E Tech Univ, Dept Biol, TR-06531 Ankara, Turkey.
[Maeda, Takahiro] Nagasaki Univ, Dept Isl & Community Med, Nagasaki 852, Japan.
RP Klinman, DM (reprint author), NCI, Expt Immunol Lab, Canc & Inflammat Program, NIH, Bldg 567,Room 205, Frederick, MD 21702 USA.
EM klinmand@mail.nih.gov
OI Gursel, Mayda/0000-0003-0044-9054
FU U.S. National Institutes of Health, NCI
FX This research was supported by the Intramural Research Program of the
U.S. National Institutes of Health, NCI. Analyses were performed using
BRB ArrayTools, developed by Richard Simon and Amy Peng Lam.
NR 48
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U1 0
U2 4
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD OCT
PY 2012
VL 92
IS 4
BP 775
EP 785
DI 10.1189/jlb.1011522
PG 11
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 016GZ
UT WOS:000309507100010
PM 22750547
ER
PT J
AU Chen, CC
Carrasquillo, JA
AF Chen, Clara C.
Carrasquillo, Jorge A.
TI Molecular imaging of adrenal neoplasms
SO JOURNAL OF SURGICAL ONCOLOGY
LA English
DT Review
DE MIBG; somatostatin; FDG; fluorodopa; pheochromocytoma; neuroblastoma
ID POSITRON-EMISSION-TOMOGRAPHY; HIGH-RISK NEUROBLASTOMA; I-123
METAIODOBENZYLGUANIDINE SCINTIGRAPHY; 11-BETA-HYDROXYLASE TRACER
C-11-METOMIDATE; PROSPECTIVE MULTICENTER TRIAL; INRG TASK-FORCE;
FOLLOW-UP; F-18-FDG PET/CT; ADRENOCORTICAL CARCINOMA; SOMATOSTATIN
RECEPTORS
AB The adrenal glands are complex structures from which a variety of benign and malignant tumors may arise and are a common site of metastatic disease. Several radiopharmaceuticals are used for imaging the adrenals, including I-123/I-131 metaiodobenzylguanidine (MIBG), norcholesterol derivatives, In-111 pentetreotide and Ga-68 somatostatin analogs, [F-18]fluorodeoxyglucose, [F-18]fluorodopa, [F-18]fluorodopamine, C-11 meta hydroxyephedrine, and C-11/F-18/I-123 Metomidate (MTO) or its analogs. In this review we focus on the role of these reagents in metastatic lesions, cortical neoplasms, pheochromocytoma/paraganglioma, and neuroblastoma (NB). J. Surg. Oncol. 2012; 106:532542. (C) 2012 Wiley Periodicals, Inc.
C1 [Carrasquillo, Jorge A.] Mem Sloan Kettering Canc Ctr, Dept Radiol, Mol Imaging & Therapy Serv, New York, NY 10021 USA.
[Carrasquillo, Jorge A.] Weill Cornell Med Ctr, Dept Radiol, New York, NY USA.
[Chen, Clara C.] NIH, Div Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
RP Carrasquillo, JA (reprint author), 1275 York Ave New York, New York, NY 10065 USA.
EM carrasj1@mskcc.org
OI Carrasquillo, Jorge/0000-0002-8513-5734
NR 109
TC 5
Z9 6
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-4790
J9 J SURG ONCOL
JI J. Surg. Oncol.
PD OCT
PY 2012
VL 106
IS 5
SI SI
BP 532
EP 542
DI 10.1002/jso.23162
PG 11
WC Oncology; Surgery
SC Oncology; Surgery
GA 007FC
UT WOS:000308873200002
PM 22628250
ER
PT J
AU Jain, M
Rechache, N
Kebebew, E
AF Jain, Meenu
Rechache, Nesrin
Kebebew, Electron
TI Molecular markers of adrenocortical tumors
SO JOURNAL OF SURGICAL ONCOLOGY
LA English
DT Review
DE adrenal neoplasm; adrenocortical carcinoma; genomics; diagnosis; miRNA;
mRNA; epigenetics; methylation; CGH
ID GENE-EXPRESSION; DIFFERENTIAL EXPRESSION; TRANSCRIPTOME ANALYSIS;
ADRENAL-TUMORS; BETA-CATENIN; CARCINOMA; CANCER; PATHOGENESIS; SURVIVAL;
CLASSIFICATION
AB Adrenocortical tumors are common and incidentally discovered in up to 14% of axial imaging studies performed for other indications. Most of these tumors are nonfunctioning but may require removal because of the risk of adrenocortical carcinoma. Unfortunately, most clinical and imaging features are still not accurate enough to allow definitive diagnosis and an increasing number of patients undergo adrenalectomy to exclude a cancer diagnosis. Adrenocortical carcinoma is an aggressive malignancy with no effective therapy for patients with locally advanced and metastatic disease. Studies using new genomic approaches including mRNA, miRNA, methylation, and CGH profiling have identified dysregulated genes and pathways that may have clinical implications in improved molecular diagnosis and prognostication of adrenocortical cancer (ACC). In this review, we highlight recent advances in the molecular diagnosis of adrenocortical tumors. Published 2012. J. Surg. Oncol. 2012; 106:549556. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Kebebew, Electron] NCI, Endocrine Oncol Sect, Surg Branch, CRC Hatfield Clin Res Ctr 10, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Sect, Surg Branch, CRC Hatfield Clin Res Ctr 10, Bethesda, MD 20892 USA.
EM electron.kebebew@nih.gov
NR 66
TC 10
Z9 10
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-4790
J9 J SURG ONCOL
JI J. Surg. Oncol.
PD OCT
PY 2012
VL 106
IS 5
SI SI
BP 549
EP 556
DI 10.1002/jso.23119
PG 8
WC Oncology; Surgery
SC Oncology; Surgery
GA 007FC
UT WOS:000308873200004
PM 22504887
ER
PT J
AU Carrasquillo, JA
Pandit-Taskar, N
Chen, CC
AF Carrasquillo, Jorge A.
Pandit-Taskar, Neeta
Chen, Clara C.
TI Radionuclide therapy of adrenal tumors
SO JOURNAL OF SURGICAL ONCOLOGY
LA English
DT Review
DE MIBG; somatostatin; pheochromocytoma; neuroblastoma; I-131
ID METASTATIC CARCINOID-TUMORS; I-131-METAIODOBENZYLGUANIDINE I-131-MIBG
THERAPY; HIGH-DOSE I-131-METAIODOBENZYLGUANIDINE; NEURAL CREST TUMORS;
LONG-TERM EFFICACY; MALIGNANT PHEOCHROMOCYTOMA; NEUROENDOCRINE TUMORS;
REFRACTORY NEUROBLASTOMA; PHASE-I; TARGETED RADIOTHERAPY
AB Adrenal tumors arising from chromaffin cells will often accumulate radiolabeled metaiodobenzylguanidine (MIBG) and thus are amenable to therapy with I-131 MIBG. More recently, therapy studies have targeted the somatostatin receptors using Lu-177 or Y-90 radiolabeled somatostatin analogs. Because pheochromocytoma (PHEO)/paraganglioma (PGL) and neuroblastoma (NB), which often arise from the adrenals, express these receptors, clinical trials have been performed with these reagents. We will review the experience using radionuclide therapy for targeting PHEO/PGL and NBs. J. Surg. Oncol. 2012; 106:632642. (C) 2012 Wiley Periodicals, Inc.
C1 [Carrasquillo, Jorge A.; Pandit-Taskar, Neeta] Weill Cornell Med Ctr, Mol Imaging & Therapy Serv, Dept Radiol, Mem Sloan Kettering & Radiol Dept, New York, NY USA.
[Chen, Clara C.] NIH, Div Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
RP Carrasquillo, JA (reprint author), 1275 York Ave, New York, NY 10065 USA.
EM carrasj1@mskcc.org
OI Carrasquillo, Jorge/0000-0002-8513-5734
NR 119
TC 11
Z9 11
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-4790
EI 1096-9098
J9 J SURG ONCOL
JI J. Surg. Oncol.
PD OCT
PY 2012
VL 106
IS 5
SI SI
BP 632
EP 642
DI 10.1002/jso.23196
PG 11
WC Oncology; Surgery
SC Oncology; Surgery
GA 007FC
UT WOS:000308873200018
PM 22718415
ER
PT J
AU Wadiwala, MF
Kamal, AK
AF Wadiwala, Muhammad Faisal
Kamal, Ayeesha Kamran
TI Are Robots any better in stroke rehabilitation?
SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Kamal, Ayeesha Kamran] Aga Khan Univ Hosp, Stroke Serv, Karachi, Pakistan.
Aga Khan Univ Hosp, Vasc Fellowship Program, Fogarty Int Ctr, Int Cerebrovasc Translat Clin Res Training Progra, Karachi, Pakistan.
Aga Khan Univ Hosp, Natl Inst Neurol Disorders & Stroke, Karachi, Pakistan.
RP Kamal, AK (reprint author), Aga Khan Univ Hosp, Stroke Serv, Karachi, Pakistan.
EM ayeesha.kamal@aku.edu
FU FIC NIH HHS [D43TW008660, D43 TW008660]
NR 1
TC 0
Z9 0
U1 0
U2 2
PU PAKISTAN MEDICAL ASSOC
PI KARACHI
PA PMA HOUSE, AGA KHAN III RD, KARACHI, 00000, PAKISTAN
SN 0030-9982
J9 J PAK MED ASSOC
JI J. Pak. Med. Assoc.
PD OCT
PY 2012
VL 62
IS 10
BP 1104
EP 1105
PG 2
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 010ND
UT WOS:000309100200030
PM 23866460
ER
PT J
AU Remeeva, EA
Panyutin, IV
Neumann, RD
Panyutin, IG
AF Remeeva, E. A.
Panyutin, I. V.
Neumann, R. D.
Panyutin, I. G.
TI The effect of ionizing radiation on differentiation of human embryonic
stem cells
SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
LA English
DT Meeting Abstract
C1 [Remeeva, E. A.; Panyutin, I. V.; Neumann, R. D.; Panyutin, I. G.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1932-6254
J9 J TISSUE ENG REGEN M
JI J. Tissue Eng. Regen. Med.
PD OCT
PY 2012
VL 6
SU 2
SI SI
MA TS058
BP 36
EP 36
PG 1
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Engineering, Biomedical
SC Cell Biology; Biotechnology & Applied Microbiology; Engineering
GA 015QN
UT WOS:000309461100059
ER
PT J
AU Wells, ML
Huang, WC
Li, LP
Gerrish, KE
Fargo, DC
Ozsolak, F
Blackshear, PJ
AF Wells, Melissa L.
Huang, Weichun
Li, Leping
Gerrish, Kevin E.
Fargo, David C.
Ozsolak, Fatih
Blackshear, Perry J.
TI Posttranscriptional Regulation of Cell-Cell Interaction Protein-Encoding
Transcripts by Zfs1p in Schizosaccharomyces pombe
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID ZINC-FINGER PROTEINS; MESSENGER-RNA DEADENYLATION; AU-RICH ELEMENT;
FISSION YEAST; SACCHAROMYCES-CEREVISIAE; BIOFILM FORMATION;
IRON-DEFICIENCY; TRISTETRAPROLIN; FLOCCULATION; BINDING
AB Members of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins can bind directly to AU-rich elements in mRNAs and promote transcript deadenylation and decay. The yeast Schizosaccharomyces pombe expresses a single TTP family member, Zfs1p. In this study, we identified probable Zfs1p target mRNAs by comparing transcript levels in wild-type yeast and zfs1 Delta mutants, using deep sequencing and microarray approaches. We also used direct RNA sequencing to determine polyadenylation site locations and to confirm the presence of potential Zfs1p target sequences within the target mRNA. These studies identified a set of transcripts containing potential Zfs1p binding sites that accumulated significantly in the zfs1 Delta mutants; a subset of these transcripts decayed more slowly in the zfs1 Delta mutants and bound directly to Zfs1p in coimmunoprecipitation assays. One apparent direct target encodes the transcription factor Cbf12p, which is known to increase cell-cell adhesion and flocculation when overexpressed. Studies of zfs1 Delta cbf12 Delta double mutants demonstrated that the increased flocculation seen in zfs1 Delta mutants is due, at least in part, to a direct effect on the turnover of cbf12 mRNA. These data suggest that Zfs1p can both directly and indirectly regulate the levels of transcripts involved in cell-cell adhesion in this species.
C1 [Wells, Melissa L.; Huang, Weichun; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
[Li, Leping] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
[Gerrish, Kevin E.] NIEHS, Microarray Grp, Res Triangle Pk, NC 27709 USA.
[Fargo, David C.] NIEHS, Integrat Bioinformat Grp, Res Triangle Pk, NC 27709 USA.
[Ozsolak, Fatih] Helicos BioSci Corp, Cambridge, MA USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
RP Blackshear, PJ (reprint author), NIEHS, Lab Signal Transduct, POB 12233, Res Triangle Pk, NC 27709 USA.
EM black009@niehs.nih.gov
FU National Institutes of Health, National Institute of Environmental
Health Sciences
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Environmental
Health Sciences.
NR 40
TC 7
Z9 7
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD OCT
PY 2012
VL 32
IS 20
BP 4206
EP 4214
DI 10.1128/MCB.00325-12
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 015JG
UT WOS:000309441600011
PM 22907753
ER
PT J
AU Lorenz, DR
Mikheyeva, IV
Johansen, P
Meyer, L
Berg, A
Grewal, SIS
Cam, HP
AF Lorenz, David R.
Mikheyeva, Irina V.
Johansen, Peter
Meyer, Lauren
Berg, Anastasia
Grewal, Shiv I. S.
Cam, Hugh P.
TI CENP-B Cooperates with Set1 in Bidirectional Transcriptional Silencing
and Genome Organization of Retrotransposons
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID FISSION YEAST HOMOLOGS; RNA INTERFERENCE; HISTONE H3; TRANSPOSABLE
ELEMENTS; SCHIZOSACCHAROMYCES-POMBE; EPIGENETIC CONTROL; CHROMOSOME
SEGREGATION; LYSINE-9 METHYLATION; GENE-EXPRESSION; HP1 PROTEINS
AB Regulation of transposable elements (TEs) is critical to the integrity of the host genome. The fission yeast Schizosaccharomyces pombe homologs of mammalian CENP-B perform a host genome surveillance role by controlling Tf2 long terminal repeat (LTR) retrotransposons. However, the mechanisms by which CENP-Bs effect their functions are ill defined. Here, we show that the multifaceted roles of Abp1, the prominent member of fission yeast CENP-Bs, are mediated in part via recognition of a 10-bp AT-rich motif present in most LTRs and require the DNA-binding, transposase, and dimerization domains of Abp1 to maintain transcriptional repression and genome organization. Expression profiling analyses indicated that Abp1 recruits class I/II histone deacetylases (HDACs) to repress Tf2 retrotransposons and genes activated in response to stresses. We demonstrate that class I/II HDACs and sirtuins mediate the clustering of dispersed Tf2 retrotransposons into Tf bodies. Intriguingly, we uncovered an unexpected cooperation between Abp1 and the histone H3K4 methyltransferase Set] in regulating sense and antisense transcriptional silencing of Tf2 retrotransposons and Tf body integrity. Moreover, Set1-mediated regulation of Tf2 expression and nuclear organization appears to be largely independent of H3K4 methylation. Our study illuminates a molecular pathway involving a transposase-containing transcription factor that cooperates with chromatin modifiers to regulate TE activities.
C1 [Lorenz, David R.; Mikheyeva, Irina V.; Johansen, Peter; Meyer, Lauren; Berg, Anastasia; Cam, Hugh P.] Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA.
[Grewal, Shiv I. S.] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Cam, HP (reprint author), Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA.
EM hugh.cam@bc.edu
FU Boston College Wielers Faculty Research Fund; March of Dimes Basil
O'Connor Starter Scholar Research Award; National Institutes of Health
FX Work in the Cam laboratory is supported by the Boston College Wielers
Faculty Research Fund and the March of Dimes Basil O'Connor Starter
Scholar Research Award. This study was initiated in the Laboratory of
Biochemistry and Molecular Biology at the National Cancer Institute and
supported in part by the Intramural Research Program of the National
Institutes of Health.
NR 75
TC 22
Z9 22
U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD OCT
PY 2012
VL 32
IS 20
BP 4215
EP 4225
DI 10.1128/MCB.00395-12
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 015JG
UT WOS:000309441600012
PM 22907751
ER
PT J
AU Park, YM
Hwang, SJ
Masuda, K
Choi, KM
Jeong, MR
Nam, DH
Gorospe, M
Kim, HH
AF Park, Young Mi
Hwang, Su Jin
Masuda, Kiyoshi
Choi, Kyung-Min
Jeong, Mi-Ran
Nam, Do-Hyun
Gorospe, Myriam
Kim, Hyeon Ho
TI Heterogeneous Nuclear Ribonucleoprotein C1/C2 Controls the Metastatic
Potential of Glioblastoma by Regulating PDCD4
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID TUMOR-SUPPRESSOR PDCD4; RNA-BINDING PROTEINS; MESSENGER-RNA; MICRORNA
EXPRESSION; GENE-EXPRESSION; CELL INVASION; UP-REGULATION; HNRNP-C;
CANCER; MIR-21
AB MicroRNAs (miRNAs) have been implicated in the pathogenesis and progression of brain tumors. miR-21 is one of the most highly overexpressed miRNAs in glioblastoma multiforme (GBM), and its level of expression correlates with the tumor grade. Programmed cell death 4 (PDCD4) is a well-known miR-21 target and is frequently downregulated in glioblastomas in accordance with increased miR-21 expression. Downregulation of miR-21 or overexpression of PDCD4 can inhibit metastasis. Here, we investigate the role of heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNPC) in the metastatic potential of the glioblastoma cell line T98G. hnRNPC bound directly to primary miR-21 (pri-miR-21) and promoted miR-21 expression in T98G cells. Silencing of hnRNPC lowered miR-21 levels, in turn increasing the expression of PDCD4, suppressing Akt and p70S6K activation, and inhibiting migratory and invasive activities. Silencing of hnRNPC reduced cell proliferation and enhanced etoposide-induced apoptosis. In support of a role for hnRNPC in the invasiveness of GBM, highly aggressive U87MG cells showed higher hnRNPC expression levels and hnRNPC abundance in tissue arrays and also showed elevated levels as a function of brain tumor grade. Taken together, our data indicate that hnRNPC controls the aggressiveness of GBM cells through the regulation of PDCD4, underscoring the potential usefulness of hnRNPC as a prognostic and therapeutic marker of GBM.
C1 [Park, Young Mi; Hwang, Su Jin; Kim, Hyeon Ho] Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Dept Hlth Sci & Technol, Seoul, South Korea.
[Kim, Hyeon Ho] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Samsung Biomed Res Inst, Seoul, South Korea.
[Masuda, Kiyoshi; Gorospe, Myriam] NIA, Lab Mol Biol & Immunol, IRP, NIH, Baltimore, MD 21224 USA.
[Choi, Kyung-Min; Jeong, Mi-Ran] Inst Jinan Red Ginseng, Jeonbuk, South Korea.
[Nam, Do-Hyun] Sungkyunkwan Univ, Sch Med, Canc Stem Cell Res Ctr, Seoul, South Korea.
[Nam, Do-Hyun] Sungkyunkwan Univ, Sch Med, Dept Neurosurg, Seoul, South Korea.
RP Kim, HH (reprint author), Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Dept Hlth Sci & Technol, Seoul, South Korea.
EM myriam-gorospe@nih.gov; hyeonhkim@skku.edu
FU National Research Foundation of Korea; Ministry of Education, Science,
and Technology [2011-009329]; Korea Health Care Technology R&D project,
Ministry of Health and Welfare Affairs, Republic of Korea [A092255];
National Institute on Aging, National Institutes of Health, United
States
FX This study was supported by a grant from the Basic Science Research
Program, National Research Foundation of Korea by the Ministry of
Education, Science, and Technology (2011-009329 to H. H. Kim) and the
Korea Health Care Technology R&D project, Ministry of Health and Welfare
Affairs, Republic of Korea (A092255). M.G. was supported by the
Intramural Research Program of the National Institute on Aging, National
Institutes of Health, United States.
NR 49
TC 13
Z9 15
U1 2
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD OCT
PY 2012
VL 32
IS 20
BP 4237
EP 4244
DI 10.1128/MCB.00443-12
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 015JG
UT WOS:000309441600014
PM 22907752
ER
PT J
AU Cui, L
Wang, ZL
Miao, J
Miao, M
Chandra, R
Jiang, HY
Su, XZ
Cui, LW
AF Cui, Long
Wang, Zenglei
Miao, Jun
Miao, Miao
Chandra, Ramesh
Jiang, Hongying
Su, Xin-zhuan
Cui, Liwang
TI Mechanisms of in vitro resistance to dihydroartemisinin in Plasmodium
falciparum
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID PFMDR1 COPY NUMBER; ANTIMALARIAL-DRUG-RESISTANCE; ARTEMISININ
RESISTANCE; MALARIA PARASITES; CHLOROQUINE RESISTANCE; MEFLOQUINE
RESISTANCE; COMBINATION THERAPIES; ARTESUNATE-MEFLOQUINE;
GENE-EXPRESSION; SOUTHEAST-ASIA
AB The recent reports of artemisinin (ART) resistance in the ThaiCambodian border area raise a serious concern on the long-term efficacy of ARTs. To elucidate the resistance mechanisms, we performed in vitro selection with dihydroartemisinin (DHA) and obtained two parasite clones from Dd2 with more than 25-fold decrease in susceptibility to DHA. The DHA-resistant clones were more tolerant of stressful growth conditions and more resistant to several commonly used antimalarial drugs than Dd2. The result is worrisome as many of the drugs are currently used as ART partners in malaria control. This study showed that the DHA resistance is not limited to ring stage, but also occurred in trophozoites and schizonts. Microarray and biochemical analyses revealed pfmdr1 amplification, elevation of the antioxidant defence network, and increased expression of many chaperones in the DHA-resistant parasites. Without drug pressure, the DHA-resistant parasites reverted to sensitivity in approximately 8 weeks, accompanied by de-amplification of pfmdr1 and reduced antioxidant activities. The parallel decrease and increase in pfmdr1 copy number and antioxidant activity and the up and down of DHA sensitivity strongly suggest that pfmdr1 and antioxidant defence play a role in in vitro resistance to DHA, providing potential molecular markers for ART resistance.
C1 [Cui, Long; Wang, Zenglei; Miao, Jun; Miao, Miao; Chandra, Ramesh; Cui, Liwang] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA.
[Jiang, Hongying; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Cui, LW (reprint author), Penn State Univ, Dept Entomol, 501 ASI Bldg, University Pk, PA 16802 USA.
EM luc2@psu.edu
RI Chandra, Ramesh/K-7672-2012;
OI Chandra, Ramesh/0000-0002-4473-5071; Su, Xinzhuan/0000-0003-3246-3248
FU NIAID, NIH [1R21AI085518, U19AI089672]
FX We want to thank Hao Meng for technical assistance, Daniel Parker and
Guodong Ning for helping with the statistical analysis, and Yongjun Liu
for assistance with microarray data analysis. This work was supported by
NIAID, NIH (1R21AI085518 and U19AI089672).
NR 90
TC 25
Z9 27
U1 0
U2 18
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0950-382X
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD OCT
PY 2012
VL 86
IS 1
BP 111
EP 128
DI 10.1111/j.1365-2958.2012.08180.x
PG 18
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 009ZH
UT WOS:000309063600011
PM 22812578
ER
PT J
AU Gannavaram, S
Connelly, PS
Daniels, MP
Duncan, R
Salotra, P
Nakhasi, HL
AF Gannavaram, Sreenivas
Connelly, Patricia S.
Daniels, Mathew P.
Duncan, Robert
Salotra, Poonam
Nakhasi, Hira L.
TI Deletion of mitochondrial associated ubiquitin fold modifier protein
Ufm1 in Leishmania donovani results in loss of ss-oxidation of fatty
acids and blocks cell division in the amastigote stage
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID TRYPANOSOMA-BRUCEI; PLASMODIUM-FALCIPARUM; METABOLISM; PATHWAY;
IDENTIFICATION; METACASPASES; EXPRESSION; ENZYMES; SYSTEM
AB Recently, we described the existence of the ubiquitin fold modifier 1 (Ufm1) and its conjugation pathway in Leishmania donovani. We demonstrated the conjugation of Ufm1 to proteins such as mitochondrial trifunctional protein (MTP) that catalyses beta-oxidation of fatty acids in L. donovani. To elucidate the biological roles of the Ufm1-mediated modifications, we made an L. donovani Ufm1 null mutant (Ufm1-/-). Loss of Ufm1 and consequently absence of Ufm1 conjugation with MTP resulted in diminished acetyl-CoA, the end-product of the beta-oxidation in the Ufm1-/- amastigote stage. The Ufm1-/- mutants showed reduced survival in the amastigote stage in vitro and ex vivo in human macrophages. This survival was restored by re-expression of wild-type Ufm1 with concomitant induction of acetyl-CoA but not by re-expressing the non-conjugatable Ufm1, indicating the essential nature of Ufm1 conjugation and beta-oxidation. Both cell cycle analysis and ultrastructural studies of Ufm1-/- parasites confirmed the role of Ufm1 in amastigote growth. The defect in vitro growth of amastigotes in human macrophages was further substantiated by reduced survival. Therefore, these studies suggest the importance of Ufm1 in Leishmania pathogenesis with larger impact on other organisms and further provide an opportunity to test Ufm1-/- parasites as drug and vaccine targets.
C1 [Gannavaram, Sreenivas; Duncan, Robert; Nakhasi, Hira L.] US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Connelly, Patricia S.; Daniels, Mathew P.] NHLBI, Electron Microscopy Core Facil, NIH, Bethesda, MD 20892 USA.
[Salotra, Poonam] Natl Inst Pathol, New Delhi, India.
RP Nakhasi, HL (reprint author), US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
EM hira.nakhasi@fda.hhs.gov
RI Duncan, Robert/I-8168-2015
OI Duncan, Robert/0000-0001-8409-2501
FU Intramural NIH HHS [ZIC HL005906-06]
NR 39
TC 12
Z9 13
U1 2
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0950-382X
EI 1365-2958
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD OCT
PY 2012
VL 86
IS 1
BP 187
EP 198
DI 10.1111/j.1365-2958.2012.08183.x
PG 12
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 009ZH
UT WOS:000309063600016
PM 22897198
ER
PT J
AU Forni, PE
Wray, S
AF Forni, Paolo E.
Wray, Susan
TI Neural Crest and Olfactory System: New Prospective
SO MOLECULAR NEUROBIOLOGY
LA English
DT Article
DE Olfactory placode; Neural crest; Olfactory ensheathing cells; Migratory
mass; GnRH-1 neurons
ID HORMONE-RELEASING HORMONE; ENSHEATHING GLIA TRANSPLANTS; MESENCHYMAL
STEM-CELLS; DUAL EMBRYONIC ORIGIN; QUAIL-CHICK CHIMERAS; FACTOR RECEPTOR
1; KALLMANN-SYNDROME; SCHWANN-CELLS; IN-VITRO; DEVELOPING MOUSE
AB Sensory neurons in vertebrates are derived from two embryonic transient cell sources: neural crest (NC) and ectodermal placodes. The placodes are thickenings of ectodermal tissue that are responsible for the formation of cranial ganglia as well as complex sensory organs that include the lens, inner ear, and olfactory epithelium. The NC cells have been indicated to arise at the edges of the neural plate/dorsal neural tube, from both the neural plate and the epidermis in response to reciprocal interactions Moury and Jacobson (Dev Biol 141:243-253, 1990). NC cells migrate throughout the organism and give rise to a multitude of cell types that include melanocytes, cartilage and connective tissue of the head, components of the cranial nerves, the dorsal root ganglia, and Schwann cells. The embryonic definition of these two transient populations and their relative contribution to the formation of sensory organs has been investigated and debated for several decades (Basch and Bronner-Fraser, Adv Exp Med Biol 589:24-31, 2006; Basch et al., Nature 441:218-222, 2006) review (Baker and Bronner-Fraser, Dev Biol 232:1-61, 2001). Historically, all placodes have been described as exclusively derived from non-neural ectodermal progenitors. Recent genetic fate-mapping studies suggested a NC contribution to the olfactory placodes (OP) as well as the otic (auditory) placodes in rodents (Murdoch and Roskams, J Neurosci Off J Soc Neurosci 28:4271-4282, 2008; Murdoch et al., J Neurosci 30:9523-9532, 2010; Forni et al., J Neurosci Off J Soc Neurosci 31:6915-6927, 2011b; Freyer et al., Development 138:5403-5414, 2011; Katoh et al., Mol Brain 4:34, 2011). This review analyzes and discusses some recent developmental studies on the OP, placodal derivatives, and olfactory system.
C1 [Forni, Paolo E.; Wray, Susan] NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Wray, S (reprint author), NINDS, Cellular & Dev Neurobiol Sect, NIH, Bldg 35,Rm 3A-1012, Bethesda, MD 20892 USA.
EM wrays@ninds.nih.gov
OI wray, susan/0000-0001-7670-3915
FU National Institutes of Health, National Institute of Neurological
Disorders and Stroke
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Neurological
Disorders and Stroke.
NR 159
TC 17
Z9 17
U1 1
U2 14
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0893-7648
EI 1559-1182
J9 MOL NEUROBIOL
JI Mol. Neurobiol.
PD OCT
PY 2012
VL 46
IS 2
BP 349
EP 360
DI 10.1007/s12035-012-8286-5
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 013YF
UT WOS:000309341500010
PM 22773137
ER
PT J
AU Tan, HY
Chen, AG
Chen, Q
Browne, LB
Verchinski, B
Kolachana, B
Zhang, F
Apud, J
Callicott, JH
Mattay, VS
Weinberger, DR
AF Tan, H. Y.
Chen, A. G.
Chen, Q.
Browne, L. B.
Verchinski, B.
Kolachana, B.
Zhang, F.
Apud, J.
Callicott, J. H.
Mattay, V. S.
Weinberger, D. R.
TI Epistatic interactions of AKT1 on human medial temporal lobe biology and
pharmacogenetic implications
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE BDNF; COMT; hippocampus; lithium; schizophrenia; valproate
ID LONG-TERM-MEMORY; NEUROTROPHIC FACTOR; VAL66MET POLYMORPHISM;
HIPPOCAMPAL FUNCTION; PREFRONTAL CORTEX; GENETIC-VARIATION; COMT
GENOTYPE; SCHIZOPHRENIA; BRAIN; BDNF
AB AKT1 controls important processes in medial temporal lobe (MTL) development and plasticity, but the impact of human genetic variation in AKT1 on these processes is not known in healthy or disease states. Here, we report that an AKT1 variant (rs1130233) previously associated with AKT1 protein expression, prefrontal function and schizophrenia, affects human MTL structure and memory function. Further, supporting AKT1's role in transducing hippocampal neuroplasticity and dopaminergic processes, we found epistasis with functional polymorphisms in BDNF and COMT-genes also implicated in MTL biology related to AKT1. Consistent with prior predictions that these biologic processes relate to schizophrenia, we found epistasis between the same AKT1, BDNF and COMT functional variants on schizophrenia risk, and pharmacogenetic interactions of AKT1 with the effects on cognition and brain volume measures by AKT1 activators in common clinical use-lithium and sodium valproate. Our findings suggest that AKT1 affects risk for schizophrenia and accompanying cognitive deficits, at least in part through specific genetic interactions related to brain neuroplasticity and development, and that these AKT1 effects may be pharmacologically modulated in patients. Molecular Psychiatry (2012) 17, 1007-1016; doi:10.1038/mp.2011.91; published online 26 July 2011
C1 [Weinberger, D. R.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,Div Intramural Res Program, Bethesda, MD 20892 USA.
RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,Div Intramural Res Program, Rm 3C-103A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM weinberd@mail.nih.gov
RI Callicott, Joseph/C-9102-2009
OI Callicott, Joseph/0000-0003-1298-3334
FU National Institute of Mental Health Intramural Research Program
FX This work was funded by the National Institute of Mental Health
Intramural Research Program.
NR 53
TC 18
Z9 18
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD OCT
PY 2012
VL 17
IS 10
BP 1007
EP 1016
DI 10.1038/mp.2011.91
PG 10
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 012DB
UT WOS:000309214500006
PM 21788944
ER
PT J
AU Ren, H
Du, C
Yuan, Z
Park, K
Volkow, ND
Pan, Y
AF Ren, H.
Du, C.
Yuan, Z.
Park, K.
Volkow, N. D.
Pan, Y.
TI Cocaine-induced cortical microischemia in the rodent brain: clinical
implications
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE 3D optical angiography; 3D optical Doppler tomography; cocaine toxicity;
microischemia
ID OPTICAL COHERENCE TOMOGRAPHY; BLOOD-FLOW; MECHANISM; ANGIOGRAPHY;
EXPRESSION; MICROSCOPY; STROKE; YOUNG
AB Cocaine-induced stroke is among the most serious medical complications associated with its abuse. However, the extent to which acute cocaine may induce silent microischemia predisposing the cerebral tissue to neurotoxicity has not been investigated; in part, because of limitations of current neuroimaging tools, that is, lack of high spatiotemporal resolution and sensitivity to simultaneously measure cerebral blood flow (CBF) in vessels of different calibers (including capillaries) quantitatively and over a large field of view. Here we combine ultrahigh-resolution optical coherence tomography to enable tracker-free three-dimensional (3D) microvascular angiography and a new phase-intensity-mapping algorithm to enhance the sensitivity of 3D optical Doppler tomography for simultaneous capillary CBF quantization. We apply the technique to study the responses of cerebral microvascular networks to single and repeated cocaine administration in the mouse somatosensory cortex. We show that within 2-3 min after cocaine administration CBF markedly decreased (for example, similar to 70%), but the magnitude and recovery differed for the various types of vessels; arterioles had the fastest recovery (similar to 5 min), capillaries varied drastically (from 4-20 min) and venules showed relatively slower recovery (similar to 12 min). More importantly, we showed that cocaine interrupted CBF in some arteriolar branches for over 45 min and this effect was exacerbated with repeated cocaine administration. These results provide evidence that cocaine doses within the range administered by drug abusers induces cerebral microischemia and that these effects are exacerbated with repeated use. Thus, cocaine-induced microischemia is likely to be a contributor to its neurotoxic effects. Molecular Psychiatry (2012) 17, 1017-1025; doi:10.1038/mp.2011.160; published online 29 November 2011
C1 [Ren, H.; Du, C.; Yuan, Z.; Park, K.; Pan, Y.] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA.
[Du, C.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Volkow, N. D.] NIDA, NIH, Bethesda, MD 20892 USA.
RP Pan, Y (reprint author), SUNY Stony Brook, Dept Biomed Engn, Bioengn Bldg,Room G17, Stony Brook, NY 11794 USA.
EM congwu@bnl.gov; yingtian.pan@sunysb.edu
RI Ren, Hugang/G-7342-2011
FU National Institutes of Health [K25-DA021200, 2R01-DK059265,
1RC1DA028534, 1R21-DA032228]; NIAAA Intramural Research Program
FX This work was supported in part by the National Institutes of Health
Grants K25-DA021200 (CD), 2R01-DK059265 (YP), 1RC1DA028534 (CD and YP),
1R21-DA032228 (CD and YP) and NIAAA Intramural Research Program (NDV).
NR 29
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U1 2
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD OCT
PY 2012
VL 17
IS 10
BP 1017
EP 1025
DI 10.1038/mp.2011.160
PG 9
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 012DB
UT WOS:000309214500007
PM 22124273
ER
PT J
AU Lakdawala, SS
Subbarao, K
AF Lakdawala, Seema S.
Subbarao, Kanta
TI The ongoing battle against influenza The challenge of flu transmission
SO NATURE MEDICINE
LA English
DT Editorial Material
ID VIRUS; FERRETS; MODEL
AB Influenza viruses can cause a broad spectrum of disease severity, including devastating cases in some people. Several factors influence the epidemiological success of the virus; the mechanisms of transmission and the strategies for prevention and treatment have an impact on the disease outcome and the incidence of flu infection in the population. Understanding how and why the viruses spread so efficiently among people and determining possible ways to harness this transmission have been arduous tasks, given the limitations of flu animal models. In 'Bedside to Bench', Kanta Subbarao and Seema S. Lakdawala peruse a study that used a human challenge model to assess influenza transmission; this experimental approach shows how transmission can be studied in humans and emphasizes factors that are different compared to animals, such as distinct disease severity and incidence. Lessons can be taken to optimize animal studies. Another issue that dictates the severity of flu episodes is the potential emergence of drug-resistant strains in treated individuals. In 'Bench to Bedside', Anne Kelso and Aeron C. Hurt discuss another concern-the presence of drug-resistant viruses with additional permissive mutations that make them fit to infect and compete with wild-type strains. The fact that these strains can be found in untreated people and can spread poses a public health concern and a challenge for scientists to find new drugs and assess antiviral combinations.
C1 [Lakdawala, Seema S.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Lakdawala, SS (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM ksubbarao@niaid.nih.gov
RI Wei, Jianjian/F-7788-2011
OI Wei, Jianjian/0000-0001-8859-8462
NR 19
TC 9
Z9 9
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD OCT
PY 2012
VL 18
IS 10
BP 1468
EP 1470
DI 10.1038/nm.2953
PG 3
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 017JZ
UT WOS:000309587500018
PM 23042349
ER
PT J
AU Holmes, A
Fitzgerald, PJ
MacPherson, KP
DeBrouse, L
Colacicco, G
Flynn, SM
Masneuf, S
Pleil, KE
Li, C
Marcinkiewcz, CA
Kash, TL
Gunduz-Cinar, O
Camp, M
AF Holmes, Andrew
Fitzgerald, Paul J.
MacPherson, Kathryn P.
DeBrouse, Lauren
Colacicco, Giovanni
Flynn, Shaun M.
Masneuf, Sophie
Pleil, Kristen E.
Li, Chia
Marcinkiewcz, Catherine A.
Kash, Thomas L.
Gunduz-Cinar, Ozge
Camp, Marguerite
TI Chronic alcohol remodels prefrontal neurons and disrupts NMDAR-mediated
fear extinction encoding
SO NATURE NEUROSCIENCE
LA English
DT Article
ID BASOLATERAL AMYGDALA; CONDITIONED FEAR; CORTEX; EXPRESSION; ETHANOL;
CONSOLIDATION; DYSFUNCTION; WITHDRAWAL; RESISTANCE; MEMORY
AB Alcoholism is frequently co-morbid with post-traumatic stress disorder, but it is unclear how alcohol affects the neural circuits mediating recovery from trauma. We found that chronic intermittent ethanol (CIE) impaired fear extinction and remodeled the dendritic arbor of medial prefrontal cortical (mPFC) neurons in mice. CIE impaired extinction encoding by infralimbic mPFC neurons in vivo and functionally downregulated burst-mediating NMDA GluN1 receptors. These findings suggest that alcohol may increase risk for trauma-related anxiety disorders by disrupting mPFC-mediated extinction of fear.
C1 [Holmes, Andrew; Fitzgerald, Paul J.; MacPherson, Kathryn P.; DeBrouse, Lauren; Colacicco, Giovanni; Flynn, Shaun M.; Masneuf, Sophie; Gunduz-Cinar, Ozge; Camp, Marguerite] NIAAA, Lab Behav & Genom Neurosci, US Natl Inst Hlth, Bethesda, MD 90034 USA.
[Flynn, Shaun M.; Gunduz-Cinar, Ozge] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Pleil, Kristen E.; Li, Chia; Marcinkiewcz, Catherine A.; Kash, Thomas L.] Univ N Carolina, Dept Pharmacol, Bowles Ctr Alcohol Studies, Chapel Hill, NC USA.
RP Holmes, A (reprint author), NIAAA, Lab Behav & Genom Neurosci, US Natl Inst Hlth, Bethesda, MD 90034 USA.
EM andrew.holmes@nih.gov
RI Gunduz Cinar, Ozge/B-2970-2009; Kash, Thomas/G-9625-2013; Gunduz Cinar,
Ozge/E-5756-2010
OI Gunduz Cinar, Ozge/0000-0002-3826-8905
FU US Department of Defense in the Center for Neuroscience and Regenerative
Medicine; US National Institutes of Health grants [AA019454, AA017668,
AA020911, AA021043]; US Department of Defense grant [PT090344]; US
National Alliance for Research on Schizophrenia and Depression; Bowles
Center for Alcohol Studies; US National Institute on Alcohol Abuse and
Alcoholism Intramural Research Program
FX We thank Y. Shaham and C. Wellman for valuable comments, and B. Hurd, A.
Plitt, D. Fisher and R. Daut for assistance with the CIE procedure. This
work was supported by the US Department of Defense in the Center for
Neuroscience and Regenerative Medicine (A.H., S.M.F. and O.G.-C.), US
National Institutes of Health grants AA019454, AA017668 and AA020911 to
T.L.K., C.L. and C,A,M., and AA021043 to K.E.P., US Department of
Defense grant PT090344 (T.L.K. and K.E.P.), US National Alliance for
Research on Schizophrenia and Depression (T.L.K.), Bowles Center for
Alcohol Studies (T.L.K.), and the US National Institute on Alcohol Abuse
and Alcoholism Intramural Research Program (A.H., P.J.F., K.P.M., L.D.,
S.M., G.C., O.G.-C. and M.C.).
NR 17
TC 79
Z9 80
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD OCT
PY 2012
VL 15
IS 10
BP 1359
EP 1361
DI 10.1038/nn.3204
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA 013VZ
UT WOS:000309335300012
PM 22941108
ER
PT J
AU Adelman, K
Lis, JT
AF Adelman, Karen
Lis, John T.
TI Promoter-proximal pausing of RNA polymerase II: emerging roles in
metazoans
SO NATURE REVIEWS GENETICS
LA English
DT Review
ID EMBRYONIC STEM-CELLS; HEAT-SHOCK GENES; TRANSCRIPTION ELONGATION-FACTOR;
BROMODOMAIN PROTEIN BRD4; NF-KAPPA-B; P-TEFB; IN-VIVO;
DROSOPHILA-MELANOGASTER; POL-II; NUCLEOSOME ORGANIZATION
AB Recent years have witnessed a sea change in our understanding of transcription regulation: whereas traditional models focused solely on the events that brought RNA polymerase II (Pol II) to a gene promoter to initiate RNA synthesis, emerging evidence points to the pausing of Pol II during early elongation as a widespread regulatory mechanism in higher eukaryotes. Current data indicate that pausing is particularly enriched at genes in signal-responsive pathways. Here the evidence for pausing of Pol II from recent high-throughput studies will be discussed, as well as the potential interconnected functions of promoter-proximally paused Pol II.
C1 [Adelman, Karen] Natl Inst Environm Hlth Sci, Lab Mol Carcinogenesis, Res Triangle Pk, NC 27709 USA.
[Lis, John T.] Cornell Univ, Ithaca, NY 14853 USA.
RP Adelman, K (reprint author), Natl Inst Environm Hlth Sci, Lab Mol Carcinogenesis, Res Triangle Pk, NC 27709 USA.
EM adelmank@niehs.nih.gov; johnlis@cornell.edu
FU US National Institutes of Health (NIH) [GM25232]; NIH National Institute
of Environmental Health Sciences [Z01 ES101987]
FX We thank the members of the Lis and Adelman laboratories for their
helpful discussions on this Review. Funding for this work was provided
by US National Institutes of Health (NIH) grant GM25232 to J.L. and the
Intramural Research Program of the NIH National Institute of
Environmental Health Sciences (Z01 ES101987) to K.A.
NR 98
TC 302
Z9 304
U1 1
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-0056
J9 NAT REV GENET
JI Nat. Rev. Genet.
PD OCT
PY 2012
VL 13
IS 10
BP 720
EP 731
DI 10.1038/nrg3293
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 009XR
UT WOS:000309059200011
PM 22986266
ER
PT J
AU Liu, BY
Sen, HN
Nussenblatt, R
AF Liu, Baoying
Sen, H. Nida
Nussenblatt, Robert
TI Susceptibility Genes and Pharmacogenetics in Ocular Inflammatory
Disorders
SO OCULAR IMMUNOLOGY AND INFLAMMATION
LA English
DT Review
DE Age-related macular degeneration; Pharmacogenetics; Uveitis
ID COMPLEMENT FACTOR-H; ACUTE ANTERIOR UVEITIS; JUVENILE IDIOPATHIC
ARTHRITIS; GENOME-WIDE ASSOCIATION; TNF-ALPHA-BLOCKERS; MACULAR
DEGENERATION; BEHCETS-DISEASE; RHEUMATOID-ARTHRITIS; TUBULOINTERSTITIAL
NEPHRITIS; SYMPATHETIC OPHTHALMIA
AB Ocular inflammatory disorders encompass uveitis, scleritis, keratitis, and other ocular diseases where inflammation may play a role. Although age-related macular degeneration (AMD) is clinically characterized by degenerative changes in the macula, accumulating evidence suggests that inflammation plays an important role in its pathogenesis. Pharmacogenetics is the study of the influence of genetic variation and its effects on drug efficacy or toxicity. There are no pharmacogenetic studies in uveitis and very few in AMD therapies. In this review, the authors describe the susceptibility genes related to uveitis and AMD and the important advances in pharmacogenetic research in relation to AMD and uveitis therapy. They propose polygenic and composite models of treatment responses to fulfill individualized drug therapy in intraocular inflammatory disorders.
C1 [Liu, Baoying; Sen, H. Nida; Nussenblatt, Robert] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Nussenblatt, R (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM drbob@nei.nih.gov
FU NEI Intramural Research Program
FX The authors report no conflicts of interest. The authors alone are
responsible for the content and writing of the paper. This research is
supported by the NEI Intramural Research Program.
NR 101
TC 3
Z9 4
U1 1
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0927-3948
J9 OCUL IMMUNOL INFLAMM
JI Ocul. Immunol. Inflamm.
PD OCT
PY 2012
VL 20
IS 5
BP 315
EP 323
DI 10.3109/09273948.2012.710706
PG 9
WC Ophthalmology
SC Ophthalmology
GA 015UM
UT WOS:000309471900001
PM 22974049
ER
PT J
AU Wendler, D
Abdoler, E
Wiener, L
Grady, C
AF Wendler, David
Abdoler, Emily
Wiener, Lori
Grady, Christine
TI Views of Adolescents and Parents on Pediatric Research Without the
Potential for Clinical Benefit
SO PEDIATRICS
LA English
DT Article
DE research; adolescents; ethics
ID RANDOMIZED CONTROLLED-TRIALS; INFORMED-CONSENT; CHILDRENS PARTICIPATION;
BIOMEDICAL-RESEARCH; ATTITUDES; CANCER; PERSPECTIVES; PERCEPTIONS;
ETHICS; MINORS
AB OBJECTIVE: Critics argue that pediatric research without the potential for clinical benefit is unethical because it treats children as mere means, exposing those who cannot consent to risks for the benefit of others. The present survey was designed to assess whether this claim is consistent with the views of adolescents who actually participate in research, or their parents.
METHODS: Interviews were conducted with adolescents participating in research at the NIH Clinical Center or Seattle Children's Hospital, and their parents, from June 2008 through April 2010.
RESULTS: Interviews were completed with 177 of 186 adolescent/parent pairs (response rate = 95.2%). Overall, 90% of the adolescents and parents were willing to have the adolescent undergo a few extra blood draws, and 65% were willing to have the adolescent undergo an extra skin biopsy, for research purposes. The vast majority felt that the adolescents were making an important contribution to help others, and 80.8% of the adolescents felt proud to be doing so. Respondents overall were equally willing to have the adolescent face risks to help others in a research study or in a charitable activity.
CONCLUSIONS: The views and experiences of these respondents do not support the claim that pediatric research without the potential for clinical benefit treats subjects as mere means. Instead, the findings provide proof of principle for the claim that non-beneficial pediatric research involves a type of charitable activity which offers children the opportunity to contribute to a valuable project to help others. Pediatrics 2012;130:692-699
C1 [Wendler, David; Abdoler, Emily; Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
[Wiener, Lori] NCI, Pediat Branch, Bethesda, MD 20892 USA.
RP Wendler, D (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM dwendler@nih.gov
FU National Institutes of Health Clinical Center; National Institutes of
Health Program Evaluation Funds; National Institutes of Health (NIH)
FX This work was supported by the Intramural Research Program at the
National Institutes of Health Clinical Center and National Institutes of
Health Program Evaluation Funds. The Clinical Center and the Evaluation
Program had no role in the analysis of the data, writing of the
manuscript, or the decision to submit the manuscript for publication.
Funded by the National Institutes of Health (NIH).
NR 33
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U1 0
U2 11
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD OCT
PY 2012
VL 130
IS 4
BP 692
EP 699
DI 10.1542/peds.2012-0068
PG 8
WC Pediatrics
SC Pediatrics
GA 014YO
UT WOS:000309412100054
PM 22966027
ER
PT J
AU Park, S
Hong, JH
Ohana, E
Muallem, S
AF Park, Seonghee
Hong, Jeong Hee
Ohana, Ehud
Muallem, Shmuel
TI The WNK/SPAK and IRBIT/PP1 Pathways in Epithelial Fluid and Electrolyte
Transport
SO PHYSIOLOGY
LA English
DT Review
ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; SODIUM-CHLORIDE COTRANSPORTER;
AMINO-TERMINAL DOMAIN; NA+-CL-COTRANSPORTER; SPAK-KNOCKOUT MICE; WNK
KINASES; PROTEIN-KINASES; IP3 RECEPTOR; BINDING PROTEIN; BLOOD-PRESSURE
AB Fluid and electrolyte homeostasis is a fundamental physiological function required for survival and is associated with a plethora of diseases when aberrant. Systemic fluid and electrolyte composition is regulated by the kidney, and all secretory epithelia generate biological fluids with defined electrolyte composition by vectorial transport of ions and the obligatory water. A major regulatory pathway that immerged in the last several years is regulation of ion transporters by the WNK/SPAK kinases and IRBIT/PP1 pathways. The IRBIT/PP1 pathway functions to reverse the effects of the WNK/SPAK kinases pathway, as was demonstrated for NBCe1-B and CFTR. Since many transporters involved in fluid and electrolyte homeostasis are affected by PP1 and/or calcineurin, it is possible that WNK/SPAK and IRBIT/PP1 form a common regulatory pathway to tune the activity of fluid and electrolyte transport in response to physiological demands.
C1 [Park, Seonghee; Hong, Jeong Hee; Ohana, Ehud; Muallem, Shmuel] Natl Inst Dent & Craniofacial Res, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
[Park, Seonghee] Ewha Womans Univ, Dept Physiol, Sch Med, Seoul, South Korea.
RP Park, S (reprint author), Natl Inst Dent & Craniofacial Res, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
EM Shmuel.muallem@nih.gov
FU National Institutes of Health, National Institute of Dental and
Craniofacial Research [Z1A-DE-000735]; National Research Foundation of
Korea [NRF-2009-352-E00046]; Korean Government
FX The work in the authors' laboratory was funded by Intramural Research
Program of the National Institutes of Health, National Institute of
Dental and Craniofacial Research Grant Z1A-DE-000735, and by the
National Research Foundation of Korea Grant NRF-2009-352-E00046 funded
by the Korean Government.
NR 62
TC 15
Z9 15
U1 0
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1548-9213
J9 PHYSIOLOGY
JI Physiology
PD OCT
PY 2012
VL 27
IS 5
BP 291
EP 299
DI 10.1152/physiol.00028.2012
PG 9
WC Physiology
SC Physiology
GA 016IT
UT WOS:000309512000003
PM 23026752
ER
PT J
AU Logan, J
Carruthers, NI
Letavic, MA
Sands, S
Jiang, XH
Shea, C
Muench, L
Xu, YW
Carter, P
King, P
Fowler, JS
AF Logan, Jean
Carruthers, Nicholas I.
Letavic, Michael A.
Sands, Steven
Jiang, Xiaohui
Shea, Colleen
Muench, Lisa
Xu, Youwen
Carter, Pauline
King, Payton
Fowler, Joanna S.
TI Blockade of the brain histamine H3 receptor by JNJ-39220675: preclinical
PET studies with [C-11]GSK189254 in anesthetized baboon
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Histamine H-3; PET; JNJ-39220675
ID H-3 RECEPTOR; DOPAMINE TRANSPORTERS; ANTAGONISTS; DISORDERS; TARGET;
IDENTIFICATION; RADIOLIGAND; AGONIST
AB The preclinical characterization of a series of aryloxypyridine amides has identified JNJ-39220675 ((4-cyclobutyl-1,4-diazepan-1-yl)(6-(4-fluorophenoxy)pyridin-3-yl)methanone) as a high-affinity histamine H-3 receptor antagonist and a candidate for further drug development particularly in the treatment of alcohol-related behaviors.
This study measured brain histamine H-3 receptor blockade by JNJ-39220675 (1 mg/kg) in the female baboon.
Positron emission tomography imaging and [C-11]GSK189254, a reversible high-affinity radiotracer with specificity for the histamine H-3 receptor, was used to measure histamine H-3 receptor availability at baseline and after i.v. and oral administration of JNJ-39220675 (1 mg/kg) in the anesthetized baboon. Histamine H-3 receptor availability was estimated as the total distribution volume (V (T)) in brain regions. The sensitivity of [C-11]GSK189254 binding to injected mass and carryover effects was determined.
JNJ-39220675 produces robust (ca. 90 %) blockade of [C-11]GSK189254 binding after i.v. and oral administration. After oral administration of JNJ-39220675 (1 mg/kg), the fractional receptor occupancy was > 0.9 at 90 min with a slight increase from 90 to 240 min. Similar to prior studies in humans, V (T) was highly sensitive to the mass of GSK189254 with ED50 estimated to be 0.16 mu g/kg.
The robust blockade of binding of [C-11]GSK189254 by JNJ-39220675 demonstrates that this compound readily penetrates the blood-brain barrier and occupies the histamine H-3 receptor after oral administration at low plasma concentrations (similar to 1 ng/cc) supporting further drug development for alcohol addiction and other disorders. This study corroborates prior reports of the high sensitivity of [C-11]GSK189254 to injected mass at doses > 0.1 mu g/kg.
C1 [Logan, Jean; Shea, Colleen; Xu, Youwen; Carter, Pauline; King, Payton; Fowler, Joanna S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Carruthers, Nicholas I.; Letavic, Michael A.; Sands, Steven; Jiang, Xiaohui] Johnson & Johnson Pharmaceut Res & Dev LLC, San Diego, CA 92121 USA.
[Muench, Lisa] NIAAA, Bethesda, MD 20852 USA.
RP Logan, J (reprint author), Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
EM logan@bnl.gov
FU Brookhaven National Laboratory [DE-AC02-98CH10886]; Johnson & Johnson
Pharmaceutical Research Development; NIH [K05DA020001]
FX This study was carried out using the infrastructure of Brookhaven
National Laboratory under contract DE-AC02-98CH10886 and supported by
Johnson & Johnson Pharmaceutical Research & Development. Johnson &
Johnson Pharmaceutical Research & Development was involved in the
conception and design of the study, monitoring of the results, and in
the writing and approval of the manuscript. JSF is supported in part by
a K award from the NIH (K05DA020001). The authors are grateful to Joan
Terry and Hai-Dee Lee for CRC operations, Don Warner for PET operations,
and Michael Schueller and David Schlyer for cyclotron operations. All
experiments complied with the current laws of USA.
NR 24
TC 7
Z9 7
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD OCT
PY 2012
VL 223
IS 4
BP 447
EP 455
DI 10.1007/s00213-012-2733-x
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 012RH
UT WOS:000309253700008
PM 22614669
ER
PT J
AU McDermott, MM
Liu, K
Ferrucci, L
Tian, L
Guralnik, J
Kopp, P
Tao, HM
Van Horn, L
Liao, YH
Green, D
Kibbe, M
Criqui, MH
AF McDermott, Mary M.
Liu, Kiang
Ferrucci, Luigi
Tian, Lu
Guralnik, Jack
Kopp, Peter
Tao, Huimin
Van Horn, Linda
Liao, Yihua
Green, David
Kibbe, Melina
Criqui, Michael H.
TI Vitamin D status and functional performance in peripheral artery disease
SO VASCULAR MEDICINE
LA English
DT Article
DE intermittent claudication; peripheral artery; physical functioning;
vitamin D
ID LOWER-EXTREMITY ISCHEMIA; 1,25-DIHYDROXYVITAMIN D-3; PHYSICAL-ACTIVITY;
DAILY-LIFE; MUSCLE; ASSOCIATION; CELLS; IMPAIRMENT; PREVALENCE;
RECEPTORS
AB The clinical implications of low vitamin D in peripheral artery disease (PAD) are unknown. We hypothesized that among individuals with PAD, lower levels of 25-hydroxyvitamin D would be associated with poorer functional performance, more adverse calf muscle characteristics, and poorer peripheral nerve function. Participants were 402 men and women with PAD who underwent measurement of 25-hydroxyvitamin D (DiaSorin radioimmunoassay) along with 6-minute walk testing, measurement of walking velocity at usual and fastest pace, computed tomography-measured calf muscle density, and peripheral nerve conduction velocity (NCV). Among PAD participants, 20.4% had 25-hydroxyvitamin D levels < 30 nmol/L, consistent with deficient vitamin D status. Adjusting for age, sex, and race, lower 25-hydroxyvitamin D levels were associated with poorer 6-minute walk performance (p trend = 0.002), slower usual-paced 4-meter walking velocity (p trend = 0.031), slower fast-paced 4-meter walking velocity (p trend = 0.043), and lower calf muscle density (p trend = 0.031). After additional adjustment for body mass index (BMI) and diabetes, none of these associations remained statistically significant. However, lower levels of 25-hydroxyvitamin D were associated with poorer peroneal NCV (p trend = 0.013) and poorer sural NCV (p trend = 0.039), even after adjusting for age, sex, race, BMI, comorbidities, smoking, physical activity, and other confounders. In conclusion, vitamin D deficiency is common among people with PAD encountered in clinical settings. After adjusting for BMI and diabetes mellitus, we found no significant associations of lower levels of 25-hydroxyvitamin D with poorer functional performance or calf muscle characteristics. Associations of low vitamin D levels with poorer peripheral nerve function require further study.
C1 [McDermott, Mary M.; Kopp, Peter; Green, David] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
[McDermott, Mary M.; Liu, Kiang; Tao, Huimin; Van Horn, Linda; Liao, Yihua] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Baltimore, MD 21224 USA.
[Tian, Lu] Stanford Univ, Dept Hlth & Res Policy, Palo Alto, CA 94304 USA.
[Guralnik, Jack] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Kibbe, Melina] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA.
[Criqui, Michael H.] Univ Calif San Diego, San Diego, CA 92103 USA.
RP McDermott, MM (reprint author), 750 Lake Shore Dr,10th Floor, Chicago, IL 60611 USA.
EM mdm608@northwestern.edu
FU National Heart, Lung, and Blood Institute; Office of Dietary
Supplements, National Institutes of Health [R01-HL096849]; National
Institute on Aging
FX Funded by the National Heart, Lung, and Blood Institute and by the
Office of Dietary Supplements, National Institutes of Health
(R01-HL096849). Supported by the National Institute on Aging.
NR 30
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U1 1
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1358-863X
J9 VASC MED
JI Vasc. Med.
PD OCT
PY 2012
VL 17
IS 5
BP 294
EP 302
DI 10.1177/1358863X12448457
PG 9
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 014EV
UT WOS:000309358900002
PM 22814997
ER
PT J
AU Liebschner, D
Dauter, M
Rosenbaum, G
Dauter, Z
AF Liebschner, Dorothee
Dauter, Miroslawa
Rosenbaum, Gerold
Dauter, Zbigniew
TI How good can our beamlines be?
SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
LA English
DT Article
DE diffraction data precision; signal-to-noise ratio; measurement
uncertainty; beamline performance
ID DIFFRACTION DATA; RADIATION; CRYSTALS; ERRORS
AB The accuracy of X-ray diffraction data depends on the properties of the crystalline sample and on the performance of the data-collection facility (synchrotron beamline elements, goniostat, detector etc.). However, it is difficult to evaluate the level of performance of the experimental setup from the quality of data sets collected in rotation mode, as various crystal properties such as mosaicity, non-uniformity and radiation damage affect the measured intensities. A multiple-image experiment, in which several analogous diffraction frames are recorded consecutively at the same crystal orientation, allows minimization of the influence of the sample properties. A series of 100 diffraction images of a thaumatin crystal were measured on the SBC beamline 19BM at the APS (Argonne National Laboratory). The obtained data were analyzed in the context of the performance of the data-collection facility. An objective way to estimate the uncertainties of individual reflections was achieved by analyzing the behavior of reflection intensities in the series of analogous diffraction images. The multiple-image experiment is found to be a simple and adequate method to decompose the random errors from the systematic errors in the data, which helps in judging the performance of a data-collection facility. In particular, displaying the intensity as a function of the frame number allows evaluation of the stability of the beam, the beamline elements and the detector with minimal influence of the crystal properties. Such an experiment permits evaluation of the highest possible data quality potentially achievable at the particular beamline.
C1 [Rosenbaum, Gerold] Univ Georgia, Dept Biochem, Argonne, IL 60439 USA.
[Rosenbaum, Gerold] Argonne Natl Lab, Struct Biol Ctr, Argonne, IL 60439 USA.
[Dauter, Miroslawa] SAIC Frederick Inc, Argonne Natl Lab, Basic Res Program, Argonne, IL 60439 USA.
[Liebschner, Dorothee; Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab, Argonne, IL 60439 USA.
RP Rosenbaum, G (reprint author), Univ Georgia, Dept Biochem, Argonne, IL 60439 USA.
EM rosenbaum@anl.gov; dauter@anl.gov
FU National Cancer Institute, National Institutes of Health [NO1-CO-12400];
NIH, National Cancer Institute, Center for Cancer Research; Department
of Energy, Office of Biological and Environmental Research
[DE-AC02-06CH11357]; US Department of Energy, Office of Science, Office
of Basic Energy Sciences [W-31-109-Eng-38]
FX This work was supported in part by Federal funds from the National
Cancer Institute, National Institutes of Health contract No.
NO1-CO-12400 and the Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does the mention of trade
names, commercial products or organizations imply endorsement by the US
Government. Diffraction data were collected on beamline 19-BM of the
Structural Biology Center at the Advanced Photon Source, Argonne
National Laboratory operated under contract DE-AC02-06CH11357 of the
Department of Energy, Office of Biological and Environmental Research.
Use of the Advanced Photon Source was supported by the US Department of
Energy, Office of Science, Office of Basic Energy Sciences under
Contract No. W-31-109-Eng-38.
NR 11
TC 6
Z9 6
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0907-4449
J9 ACTA CRYSTALLOGR D
JI Acta Crystallogr. Sect. D-Biol. Crystallogr.
PD OCT
PY 2012
VL 68
BP 1430
EP 1436
DI 10.1107/S0907444912034658
PN 10
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 008CZ
UT WOS:000308936200018
PM 22993097
ER
PT J
AU Sun, XP
Komatsu, T
Lim, J
Laslo, M
Yolitz, J
Wang, C
Poirier, L
Alberico, T
Zou, S
AF Sun, Xiaoping
Komatsu, Toshimitsu
Lim, Jinhwan
Laslo, Mara
Yolitz, Jason
Wang, Cecilia
Poirier, Luc
Alberico, Thomas
Zou, Sige
TI Nutrient-dependent requirement for SOD1 in lifespan extension by protein
restriction in Drosophila melanogaster
SO AGING CELL
LA English
DT Article
DE aging; antioxidant; dietary composition; rapamycin; reactive oxygen
species; superoxide dismutase 1
ID AMYOTROPHIC-LATERAL-SCLEROSIS; SUPEROXIDE-DISMUTASE;
DIETARY-RESTRICTION; OXIDATIVE STRESS; CAENORHABDITIS-ELEGANS;
GENE-EXPRESSION; FRUIT-FLY; RAPAMYCIN; DAMAGE; LONGEVITY
AB Reactive oxygen species (ROS) modulate aging and aging-related diseases. Dietary composition is critical in modulating lifespan. However, how ROS modulate dietary effects on lifespan remains poorly understood. Superoxide dismutase 1 (SOD1) is a major cytosolic enzyme responsible for scavenging superoxides. Here we investigated the role of SOD1 in lifespan modulation by diet in Drosophila. We found that a high sugar-low protein (HS-LP) diet or low-calorie diet with low-sugar content, representing protein restriction, increased lifespan but not resistance to acute oxidative stress in wild-type flies, relative to a standard base diet. A low sugar-high protein diet had an opposite effect. Our genetic analysis indicated that SOD1 overexpression or dfoxo deletion did not alter lifespan patterns of flies responding to diets. However, sod1 reduction blunted lifespan extension by the HS-LP diet but not the low-calorie diet. HS-LP and low-calorie diets both reduced target of rapamycin (TOR) signaling and only the HS-LP diet increased oxidative damage. sod1 knockdown did not affect phosphorylation of S6 kinase, suggesting that SOD1 acts in parallel with or downstream of TOR signaling. Surprisingly, rapamycin decreased lifespan in sod1 mutant but not wild-type males fed the standard, HS-LP, and low-calorie diets, whereas antioxidant N-acetylcysteine only increased lifespan in sod1 mutant males fed the HS-LP diet, when compared to diet-matched controls. Our findings suggest that SOD1 is required for lifespan extension by protein restriction only when dietary sugar is high and support the context-dependent role of ROS in aging and caution the use of rapamycin and antioxidants in aging interventions.
C1 [Sun, Xiaoping; Komatsu, Toshimitsu; Lim, Jinhwan; Laslo, Mara; Yolitz, Jason; Wang, Cecilia; Poirier, Luc; Alberico, Thomas; Zou, Sige] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
RP Zou, S (reprint author), NIA, Lab Expt Gerontol, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM zous@grc.nia.nih.gov
FU IRP of the National Institute on Aging, NIH
FX We thank J. Hu for technical help, E. Spangler, M. Driscoll, and P. Rapp
for critical reading of the manuscript. This study was supported by the
IRP of the National Institute on Aging, NIH to S.Z.
NR 39
TC 17
Z9 17
U1 1
U2 22
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
J9 AGING CELL
JI Aging Cell
PD OCT
PY 2012
VL 11
IS 5
BP 783
EP 793
DI 10.1111/j.1474-9726.2012.00842.x
PG 11
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 007EK
UT WOS:000308871400007
PM 22672579
ER
PT J
AU Johnson, CH
Slanar, O
Krausz, KW
Kang, DW
Patterson, AD
Kim, JH
Luecke, H
Gonzalez, FJ
Idle, JR
AF Johnson, Caroline H.
Slanar, Ondrej
Krausz, Kristopher W.
Kang, Dong Wook
Patterson, Andrew D.
Kim, Jung-Hwan
Luecke, Hans
Gonzalez, Frank J.
Idle, Jeffrey R.
TI Novel metabolites and roles for alpha-tocopherol in humans and mice
discovered by mass spectrometry-based metabolomics
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID VITAMIN-E; OMEGA-HYDROXYLASE; HEPG2 CELLS; ACID; CANCER; IDENTIFICATION;
TOCOTRIENOLS; CHOLESTEROL; CONJUGATION; PREVENTION
AB Background: Contradictory results from clinical trials that examined the role of vitamin E in chronic disease could be a consequence of interindividual variation, caused by factors such as xenobiotic use. Cometabolism of vitamin E with other pharmaceutical products could affect the bioavailability of the drug. Thus, it is necessary to understand fully the metabolic routes and biological endpoints of vitamin E.
Objective: The objective was to uncover novel metabolites and roles of vitamin E in humans and mouse models.
Design: Human volunteers (n = 10) were fed almonds for 7 d and then an alpha-tocopherol dietary supplement for 14 d. Urine and serum samples were collected before and after dosing. C57BL/6 mice (n = 10) were also fed alpha-tocopherol-deficient and - enriched diets for 14 d. Urine, serum, and feces were collected before and after dosing, and liver samples were collected after euthanization. Ultraperformance liquid chromatography electrospray ionization time-of-flight mass spectrometry and multivariate data analysis tools were used to analyze the samples.
Results: Three novel urinary metabolites of alpha-tocopherol were discovered in humans and mice: alpha-carboxyethylhydroxychroman (alpha-CEHC) glycine, alpha-CEHC glycine glucuronide, and alpha-CEHC taurine. Another urinary metabolite, alpha-CEHC glutamine, was discovered in mice after alpha-CEHC gavage. Increases in liver fatty acids and decreases in serum and liver cholesterol were observed in mice fed the alpha-tocopherol-enriched diet.
Conclusion: Novel metabolites and metabolic pathways of vitamin E were identified by mass spectrometry-based metabolomics and will aid in understanding the disposition and roles of vitamin E in vivo. Am J Clin Nutr 2012;96:818-30.
C1 [Idle, Jeffrey R.] Univ Bern, Hepatol Res Grp, Dept Clin Res, CH-3010 Bern, Switzerland.
[Johnson, Caroline H.; Krausz, Kristopher W.; Patterson, Andrew D.; Kim, Jung-Hwan; Gonzalez, Frank J.; Idle, Jeffrey R.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Slanar, Ondrej] Charles Univ Prague, Inst Pharmacol, Fac Med 1, Prague, Czech Republic.
[Kang, Dong Wook; Luecke, Hans] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Idle, JR (reprint author), Univ Bern, Hepatol Res Grp, Dept Clin Res, CH-3010 Bern, Switzerland.
EM jeff.idle@ikp.unibe.ch
RI Patterson, Andrew/G-3852-2012
OI Patterson, Andrew/0000-0003-2073-0070
FU Office of Dietary Supplements, NIH (Bethesda, MD); Charles University
[PRVOUK P25/LF1/2]
FX Supported by a grant from the Office of Dietary Supplements, NIH
(Bethesda, MD), and Charles University (project PRVOUK P25/LF1/2).
NR 28
TC 16
Z9 16
U1 2
U2 32
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD OCT
PY 2012
VL 96
IS 4
BP 818
EP 830
DI 10.3945/ajcn.112.042929
PG 13
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 008SN
UT WOS:000308977000016
PM 22952181
ER
PT J
AU Krebs, NF
Mazariegos, M
Chomba, E
Sami, N
Pasha, O
Tshefu, A
Carlo, WA
Goldenberg, RL
Bose, CL
Wright, LL
Koso-Thomas, M
Goco, N
Kindem, M
McClure, EM
Westcott, J
Garces, A
Lokangaka, A
Manasyan, A
Imenda, E
Hartwell, TD
Hambidge, KM
AF Krebs, Nancy F.
Mazariegos, Manolo
Chomba, Elwyn
Sami, Neelofar
Pasha, Omrana
Tshefu, Antoinette
Carlo, Waldemar A.
Goldenberg, Robert L.
Bose, Carl L.
Wright, Linda L.
Koso-Thomas, Marion
Goco, Norman
Kindem, Mark
McClure, Elizabeth M.
Westcott, Jamie
Garces, Ana
Lokangaka, Adrien
Manasyan, Albert
Imenda, Edna
Hartwell, Tyler D.
Hambidge, K. Michael
TI Randomized controlled trial of meat compared with
multimicronutrient-fortified cereal in infants and toddlers with high
stunting rates in diverse settings
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID ANIMAL-SOURCE FOODS; YOUNG-CHILDREN; EDUCATIONAL INTERVENTION;
NUTRITIONAL-STATUS; FEEDING PRACTICES; GROWTH STANDARDS;
IRON-DEFICIENCY; ANEMIA; UNDERNUTRITION; PREVALENCE
AB Background: Improved complementary feeding is cited as a critical factor for reducing stunting. Consumption of meats has been advocated, but its efficacy in low-resource settings has not been tested.
Objective: The objective was to test the hypothesis that daily intake of 30 to 45 g meat from 6 to 18 mo of age would result in greater linear growth velocity and improved micronutrient status in comparison with an equicaloric multimicronutrient-fortified cereal.
Design: This was a cluster randomized efficacy trial conducted in the Democratic Republic of Congo, Zambia, Guatemala, and Pakistan. Individual daily portions of study foods and education messages to enhance complementary feeding were delivered to participants. Blood tests were obtained at trial completion.
Results: A total of 532 (86.1%) and 530 (85.8%) participants from the meat and cereal arms, respectively, completed the study. Linear growth velocity did not differ between treatment groups: 1.00 (95% CI: 0.99, 1.02) and 1.02 (95% CI: 1.00, 1.04) cm/mo for the meat and cereal groups, respectively (P = 0.39). From baseline to 18 mo, stunting [length-for-age z score (LAZ) <-2.0] rates increased from similar to 33% to nearly 50%. Years of maternal education and maternal height were positively associated with linear growth velocity (P = 0.0006 and 0.003, respectively); LAZ at 6 mo was negatively associated (P < 0.0001). Anemia rates did not differ by group; iron deficiency was significantly lower in the cereal group.
Conclusion: The high rate of stunting at baseline and the lack of effect of either the meat or multiple micronutrient-fortified cereal intervention to reverse its progression argue for multifaceted interventions beginning in the pre- and early postnatal periods. This trial was registered at clinicaltrials.gov as NCT01084109. Am J Clin Nutr 2012;96:840-7.
C1 [Krebs, Nancy F.; Westcott, Jamie; Hambidge, K. Michael] Univ Colorado Denver, Sect Nutr, Dept Pediat, Aurora, CO 80045 USA.
[Mazariegos, Manolo; Garces, Ana] Inst Nutr Cent Amer & Panama Fdn Food & Nutr Cent, Guatemala City, Guatemala.
[Chomba, Elwyn; Manasyan, Albert; Imenda, Edna] Univ Teaching Hosp, Lusaka, Zambia.
[Sami, Neelofar; Pasha, Omrana] Aga Khan Univ, Karachi, Pakistan.
[Tshefu, Antoinette; Lokangaka, Adrien] Kinshasa Sch Publ Hlth, Kinshasa, Zaire.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Goldenberg, Robert L.] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
[Bose, Carl L.] Univ N Carolina, Chapel Hill, NC USA.
[Wright, Linda L.; Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA.
[Koso-Thomas, Marion; Goco, Norman; McClure, Elizabeth M.; Hartwell, Tyler D.] RTI Int, Res Triangle Pk, NC USA.
RP Krebs, NF (reprint author), Univ Colorado Denver, Sect Nutr, Dept Pediat, 12700 E 19th Ave,Box C225, Aurora, CO 80045 USA.
EM nancy.krebs@ucdenver.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HD040657, HD043464, HD040607, HD043475, HD040636]; Office
of Dietary Supplements; National Institute of Diabetes and Digestive and
Kidney Diseases [9K24 DK083772]
FX Supported by grants from Eunice Kennedy Shriver National Institute of
Child Health and Human Development [HD040657 (UCD), HD043464 (UAB),
HD040607 (Drexel), HD043475 (UNC), HD040636 (RTI)], Office of Dietary
Supplements, and National Institute of Diabetes and Digestive and Kidney
Diseases 9K24 DK083772. The National Cattlemen's Beef Association
partially supported the analyses of the biomarkers for this project and
had no input into the study design, implementation, analysis, or
interpretation of the data.
NR 32
TC 24
Z9 24
U1 4
U2 16
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD OCT
PY 2012
VL 96
IS 4
BP 840
EP 847
DI 10.3945/ajcn.112.041962
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 008SN
UT WOS:000308977000018
PM 22952176
ER
PT J
AU Roberson, R
Kuddo, T
Horowitz, K
Caballero, M
Spong, CY
AF Roberson, Robin
Kuddo, Thea
Horowitz, Kari
Caballero, Madeline
Spong, Catherine Y.
TI Cytokine and Chemokine Alterations in Down Syndrome
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE down syndrome; cytokine; chemokine learning
ID MOUSE MODEL; INTERLEUKIN-1-BETA
AB Objective Down syndrome (DS) is the leading genetic cause of intellectual disability, affecting similar to 1/800 newborns. Previously we have shown alterations in N-methyl-D-aspartic acid (NMDA) receptors and neuropeptides (activity-dependant neuroprotective protein, glia fibrillary acidic protein) in a murine model of DS. Cytokines and chemokines have neuromodulatory and neurotransmitter roles and interact with the NMDA receptors. The objective of this study was to evaluate if cytokines and chemokines in the hippocampus and cerebellum are altered in this model.
Study Design We used 8- to 10-month-old animals from the well-characterized mouse model of DS (Ts65Dn). Learning and memory were assessed in the Morris water maze with the Ts65Dn animals demonstrating a learning deficit. After completion of the behavioral testing, the brains were removed and the hippocampus and cerebellum were separated by microdissection. A panel of cytokines, chemokines, and fractalkine were measured in the protein lysates using a microsphere-based multiplex immunoassay (Luminex xMAP, Millipore) and normalized to total protein concentration. Statistical analysis included the nonparametric Mann-Whitney U for the cytokine, chemokine, and fractalkine levels; p < 0.05 was considered significant.
Results Levels (median [range]) of interleukin (IL)-1 beta (6.95 [0.11 to 43.5] versus 14.2 [0.2 to 36.8] pg/mL); granulocyte-macrophage colony-stimulating factor (GM-CSF; 3.97 [0.19 to 19.6] versus 19.2 [0.2 to 31.1] pg/mL), and macrophage inflammatory protein (MIP)-1 alpha (20.3 [0.11 to 73.3] versus 37.0 [0.22 to 102.7] pg/mL) in the hippocampus from Ts65Dn were significantly lower compared with the euploid (control) animals. Many cytokines and chemokines were not detected in the hippocampus or cerebellum, and others were detectable but not different between the groups.
Conclusion We found a decreased in GM-CSF, IL-1 beta, and MIP-1 alpha in the hippocampus of DS pups. All three have known interactions with NMDA receptors and their decline may explain, in part, the learning deficits associated with DS.
C1 [Roberson, Robin; Kuddo, Thea; Caballero, Madeline; Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Perinatal & Dev Neurobiol, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Horowitz, Kari] Univ Connecticut, Ctr Hlth, Dept Obstet & Gynecol, Farmington, CT USA.
RP Roberson, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Perinatal & Dev Neurobiol, Div Intramural Res, NIH, Bldg 9,1W125 & 1W116, Bethesda, MD 20892 USA.
EM robersor@mail.nih.gov
NR 15
TC 2
Z9 2
U1 0
U2 3
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD OCT
PY 2012
VL 29
IS 9
BP 705
EP 708
DI 10.1055/s-0032-1314892
PG 4
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 006UY
UT WOS:000308845900007
PM 22644827
ER
PT J
AU Segel, SY
Carreno, CA
Weiner, SJ
Bloom, SL
Spong, CY
Varner, MW
Rouse, DJ
Caritis, SN
Grobman, WA
Sorokin, Y
Sciscione, A
Mercer, BM
Thorp, JM
Malone, FD
Harper, M
Lams, JD
AF Segel, Sally Y.
Carreno, Carlos A.
Weiner, Steven J.
Bloom, Steven L.
Spong, Catherine Y.
Varner, Michael W.
Rouse, Dwight J.
Caritis, Steve N.
Grobman, William A.
Sorokin, Yoram
Sciscione, Anthony
Mercer, Brian M.
Thorp, John M.
Malone, Fergal D.
Harper, Margaret
Lams, Jay D.
CA Eunice Kennedy Shriver Natl Inst
TI Relationship between Fetal Station and Successful Vaginal Delivery in
Nulliparous Women
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE labor; fetal station; vaginal delivery
ID CESAREAN DELIVERY; PRESENTING PART; ACTIVE LABOR; RISK-FACTOR; OBESITY;
DESCENT
AB Objective To study the relationship between fetal station and successful vaginal delivery in nulliparous women.
Study Design This was a secondary analysis from a previously reported trial of pulse oximetry. Vaginal delivery rates were evaluated and compared with respect to the fetal station. Spontaneous labor and induction of labor groups were evaluated separately. Multivariable logistic regression analysis was performed to adjust for confounding factors.
Results Successful vaginal delivery was more frequent with an engaged vertex for spontaneous labor (86.2% versus 78.6%; p = 0.01) and induced labor (87.7% versus 66.1%; p < 0.01). After adjustment, engaged fetal vertex was not associated with vaginal delivery for spontaneous labor (odds ratio [OR] 1.5; 95% confidence interval [CI] 0.95 to 2.3; p = 0.08) or for women with induced labor (OR 2.2; 95% CI 0.96 to 5.1; p = 0.06).
Conclusion Among nulliparous women enrolled in the FOX randomized trial in spontaneous labor or for labor induction, an engaged fetal vertex does not affect their vaginal delivery rate.
C1 [Segel, Sally Y.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA.
[Carreno, Carlos A.] Univ Texas Houston, Hlth Sci Ctr Houston, Houston, TX USA.
[Bloom, Steven L.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Varner, Michael W.] Univ Utah, Salt Lake City, UT USA.
[Rouse, Dwight J.] Univ Alabama Birmingham, Birmingham, AL USA.
[Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA.
[Grobman, William A.] Northwestern Univ, Chicago, IL 60611 USA.
[Sorokin, Yoram] Wayne State Univ, Detroit, MI USA.
[Sciscione, Anthony] Drexel Univ, Philadelphia, PA 19104 USA.
[Mercer, Brian M.] Case Western Reserve Univ, Metro Hlth Med Ctr, Cleveland, OH 44106 USA.
[Thorp, John M.] Univ N Carolina, Chapel Hill, NC USA.
[Malone, Fergal D.] Columbia Univ, New York, NY USA.
[Harper, Margaret] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Lams, Jay D.] Ohio State Univ, Columbus, OH 43210 USA.
[Weiner, Steven J.] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Segel, SY (reprint author), 01827 SW Palatine Hill Rd, Portland, OR 97219 USA.
EM sysegel@gmail.com
RI Varner, Michael/K-9890-2013
OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [HD21410, HD27860, HD27869, HD27915, HD27917,
HD34116, HD34136, HD34208, HD40485, HD40500, HD40512, HD40544, HD40545,
HD40560, HD36801]
FX The project described was supported by grants from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development (NICHD;
HD21410, HD27860, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208,
HD40485, HD40500, HD40512, HD40544, HD40545, HD40560, and HD36801) and
does not necessarily represent the official views of the NICHD or the
National Institutes of Health.
NR 16
TC 3
Z9 3
U1 0
U2 1
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD OCT
PY 2012
VL 29
IS 9
BP 723
EP 729
DI 10.1055/s-0032-1314895
PG 7
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 006UY
UT WOS:000308845900010
PM 22644826
ER
PT J
AU Ambalavanan, N
Carlo, WA
McDonald, SA
Das, A
Schendel, DE
Thorsen, P
Hougaard, DM
Skogstrand, K
Higgins, RD
AF Ambalavanan, Namasivayam
Carlo, Waldemar A.
McDonald, Scott A.
Das, Abhik
Schendel, Diana E.
Thorsen, Poul
Hougaard, David M.
Skogstrand, Kristin
Higgins, Rosemary D.
CA Eunice Kennedy Shriver Natl Inst
TI Cytokines and Posthemorrhagic Ventricular Dilation in Premature Infants
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE infant; premature; cytokines; hydrocephalus; intraventricular
hemorrhage; intracranial hemorrhage
ID NECROSIS-FACTOR-ALPHA; BIRTH-WEIGHT INFANTS; GROWTH-FACTOR-BETA;
INTERFERON-GAMMA EXPRESSION; WHITE-MATTER INJURY; PERIVENTRICULAR
LEUKOMALACIA; CEREBROSPINAL-FLUID; PRETERM INFANTS; CEREBRAL-PALSY;
TRANSFORMING GROWTH-FACTOR-BETA-1
AB Objective To determine in extremely low-birth-weight infants if elevated blood interferon-gamma (IFN-gamma), interleukin (IL)-1 beta, IL-18, tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta are associated with need for shunt following severe intraventricular hemorrhage (IVH) or with ventricular dilation following milder grades/no IVH.
Study Design Whole blood cytokines were measured on postnatal days 1,3,7, 14, and 21. Maximum IVH grade in the first 28 days, and shunt surgery or ventricular dilation on subsequent ultrasound (28 days' to 36 weeks' postmenstrual age) were determined.
Results Of 902 infants in the National Institute of Child Health and Human Development Neonatal Research Network Cytokine study who survived to 36 weeks or discharge, 3.1% had shunts. Of the 12% of infants with severe (grade III to IV) IVH, 26% had a shunt associated with elevated TNF-alpha. None of the infants without IVH (69%) or with grade I(12%) or II (7%) IVH received shunts, but 8.4% developed ventricular dilation, associated with lower IFN-gamma and higher IL-18.
Conclusion Statistically significant but clinically nondiscriminatory alterations in blood cytokines were noted in infants with severe IVH who received shunts and in those without severe IVH who developed ventricular dilation. Blood cytokines are likely associated with brain injury but may not be clinically useful as biomarkers for white matter damage.
C1 [Ambalavanan, Namasivayam; Carlo, Waldemar A.] Univ Alabama Birmingham, Div Neonatol, Dept Pediat, Birmingham, AL 35249 USA.
[McDonald, Scott A.; Das, Abhik] RTI Int, Res Triangle Pk, NC USA.
[Schendel, Diana E.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Thorsen, Poul] Lillebaelt Hosp, Dept Obstet & Gynecol, Kolding, Denmark.
[Hougaard, David M.; Skogstrand, Kristin] Statens Serum Inst, DK-2300 Copenhagen, Denmark.
[Higgins, Rosemary D.] NICHD Neonatal Res Network, Bethesda, MD USA.
RP Ambalavanan, N (reprint author), Univ Alabama Birmingham, Div Neonatol, Dept Pediat, 176F Suite,9380 Women & Infants Ctr,619 S 19th St, Birmingham, AL 35249 USA.
EM ambal@uab.edu
OI Skogstrand, Kristin/0000-0002-0026-3711; Ambalavanan,
Namasivayam/0000-0003-0731-9092
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development; Centers for Disease Control and
Prevention
FX The National Institutes of Health, the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, and the Centers for
Disease Control and Prevention provided grant support for recruitment
for 1999 to 2001 and data analysis for the Neonatal Research Network's
Cytokines Study.
NR 36
TC 2
Z9 3
U1 2
U2 6
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD OCT
PY 2012
VL 29
IS 9
BP 731
EP 740
DI 10.1055/s-0032-1316443
PG 10
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 006UY
UT WOS:000308845900011
PM 22773292
ER
PT J
AU Wang, C
Sen, A
Ruffin, MT
Nease, DE
Gramling, R
Acheson, LS
O'Neill, SM
Rubinstein, WS
AF Wang, Catharine
Sen, Ananda
Ruffin, Mack T.
Nease, Donald E., Jr.
Gramling, Robert
Acheson, Louise S.
O'Neill, Suzanne M.
Rubinstein, Wendy S.
CA Family Healthware Impact Trial
TI Family History Assessment Impact on Disease Risk Perceptions
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID PRIMARY-CARE; UNREALISTIC OPTIMISM; IMPROVING HEALTH; CANCER HISTORY;
PUBLIC-HEALTH; TOOL; MEDICINE; TRIAL; BEHAVIOR; MODEL
AB Background: Family Healthware (TM), a tool developed by the CDC, is a self-administered web-based family history tool that assesses familial risk for six diseases (coronary heart disease; stroke; diabetes; and colon, breast, and ovarian cancers) and provides personalized prevention messages based on risk. The Family Healthware Impact Trial (FHITr) set out to examine the clinical utility of presenting personalized preventive messages tailored to family history risk for improving health behaviors.
Purpose: The purpose of this study was to examine the impact of Family Healthware on modifying disease risk perceptions, particularly among those who initially underestimated their risk for certain diseases.
Design: A total of 3786 patients were enrolled in a cluster-randomized trial to evaluate the clinical utility of Family Healthware.
Setting/participants: Participants were recruited from 41 primary care practices among 13 states between 2005 and 2007.
Main outcome measures: Perceived risk for each disease was assessed at baseline and 6-month follow-up using a single-item comparative risk question. Analyses were completed in March 2012.
Results: Compared to controls, Family Healthware increased risk perceptions among those who underestimated their risk for heart disease (15% vs 9%, p < 0.005); stroke (11% vs 8%, p < 0.05); diabetes (18% vs 11%, p < 0.05); and colon cancer (17% vs 10%, p < 0.05) but not breast or ovarian cancers. The majority of underestimators did not shift in their disease risk perceptions.
Conclusions: Family Healthware was effective at increasing disease risk perceptions, particularly for metabolic conditions, among those who underestimated their risk. Results from this study also demonstrate the relatively resistant nature of risk perceptions.
C1 [Wang, Catharine] Boston Univ, Dept Community Hlth Sci, Sch Publ Hlth, Crosstown Ctr, Boston, MA 02118 USA.
[Sen, Ananda] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Sen, Ananda; Ruffin, Mack T.] Univ Michigan, Dept Family Med, Ann Arbor, MI 48109 USA.
[Nease, Donald E., Jr.] Univ Colorado, Dept Family Med, Hlth Sci Ctr, Aurora, CO USA.
[Gramling, Robert] Univ Rochester, Sch Med, Rochester, NY USA.
[Gramling, Robert] Univ Rochester, Sch Nursing, Rochester, NY USA.
[Acheson, Louise S.] Case Western Reserve Univ, Dept Family Med & Community Hlth, Cleveland, OH 44106 USA.
[Acheson, Louise S.] Case Western Reserve Univ, Dept Reprod Biol, Cleveland, OH 44106 USA.
Univ Hosp Case Med Ctr, Case Comprehens Canc Ctr, Cleveland, OH USA.
[O'Neill, Suzanne M.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Rubinstein, Wendy S.] NIH, Natl Ctr Biotechnol Informat, NLM, Bethesda, MD 20892 USA.
RP Wang, C (reprint author), Boston Univ, Dept Community Hlth Sci, Sch Publ Hlth, Crosstown Ctr, 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA.
EM clwang@bu.edu
RI Nease, Donald/B-6206-2013;
OI Nease, Donald/0000-0001-8323-3720; Ruffin, Mack/0000-0001-8336-478X;
Wang, Catharine/0000-0001-8584-2781
FU CDC; Association for Prevention Teaching and Research [ENH-U50/CCU300860
TS-1216]; American Association of Medical Colleges [UM U36/CCU319276
MM-0789, CWR U36/CCU319276 MM0630]; National Cancer Institute [K07
CA086958, K07 CA131103]
FX The Family Healthware "Impact Trial (FHITr) was supported through
cooperative agreements between the CDC; the Association for Prevention
Teaching and Research (ENH-U50/CCU300860 TS-1216); and the American
Association of Medical Colleges (UM U36/CCU319276 MM-0789 and CWR
U36/CCU319276 MM0630). LSA received salary support from the National
Cancer Institute (K07 CA086958). CW is supported also by the National
Cancer Institute (K07 CA131103) and a Peter T. Paul career development
professorship from Boston University.
NR 27
TC 20
Z9 20
U1 0
U2 19
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD OCT
PY 2012
VL 43
IS 4
BP 392
EP 398
DI 10.1016/j.amepre.2012.06.013
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 011UT
UT WOS:000309191600010
PM 22992357
ER
PT J
AU Yao, JH
Taveira-DaSilva, AM
Colby, TV
Moss, J
AF Yao, Jianhua
Taveira-DaSilva, Angelo M.
Colby, Thomas V.
Moss, Joel
TI CT Grading of Lung Disease in Lymphangioleiomyomatosis
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE computer-aided diagnosis; CT; cystic lung diseases;
lymphangioleiomyomatosis
ID TEXTURE CLASSIFICATION; QUANTIFICATION; EMPHYSEMA; SEVERITY
AB OBJECTIVE. The aim of this study was to determine whether a CT-based method shows lung lesions, grades disease severity, and evaluates lung tissue in areas adjacent to or remote from cysts in patients with lymphangioleiomyomatosis (LAM), a cystic lung disease that may cause respiratory failure and death.
MATERIALS AND METHODS. Three hundred twenty-six CT examinations of 52 patients with LAM were studied. After the lungs had been divided into segments and images had been subdivided into texture blocks, a multidimensional feature vector was used to differentiate and group each texture block. Cysts were outlined, and texture around and away from cysts was analyzed. Sequential CT scans and pulmonary function test results were evaluated to assess the trend of change. Histopathologic examinations were performed of biopsy specimens from 45 patients.
RESULTS. Differences in texture features between areas adjacent to and areas remote from the cysts were observed. The cyst score and sum entropy in areas around the cysts correlated with lung function (p < 0.0001). Emphysematouslike changes in noncystic areas were identified in lung tissue of 31 of 45 patients.
CONCLUSION. A computational method that uses texture analysis and feature correlation can identify and quantify cystic areas where LAM exists and can detect abnormalities in areas near cysts. Pathologic data also show lung damage in areas adjacent to cysts. Several texture features correlate with lung function. Declines in lung function paralleled changes in texture features. In LAM, cystic changes alone may not define the extent of lung destruction.
C1 [Taveira-DaSilva, Angelo M.; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Yao, Jianhua] NIH, Radiol & Imaging Sci Dept, Bethesda, MD 20892 USA.
[Colby, Thomas V.] Mayo Clin, Dept Lab Med, Scottsdale, AZ USA.
RP Taveira-DaSilva, AM (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10,Rm 6D05,MSC 1590, Bethesda, MD 20892 USA.
EM dasilvaa@nhlbi.nih.gov
FU Intramural NIH HHS [ZIA HL002541-17]
NR 23
TC 10
Z9 10
U1 0
U2 4
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD OCT
PY 2012
VL 199
IS 4
BP 787
EP 793
DI 10.2214/AJR.11.7888
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 010TP
UT WOS:000309117300029
PM 22997369
ER
PT J
AU Carney, JA
Ho, J
Kitsuda, K
Young, WF
Stratakis, CA
AF Carney, J. Aidan
Ho, Josephine
Kitsuda, Kazuteru
Young, William F., Jr.
Stratakis, Constantine A.
TI Massive Neonatal Adrenal Enlargement Due to Cytomegaly, Persistence of
the Transient Cortex, and Hyperplasia of the Permanent Cortex Findings
in Cushing Syndrome Associated With Hemihypertrophy
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE fetal adrenal gland; neonatal Cushing syndrome; cytomegaly;
hemihypertrophy; Beckwith-Wiedemann syndrome
ID ADRENOCORTICAL DISEASE; MUTATIONS; INFANCY; COMPLEX
AB Described in this article is the massive enlargement of both adrenal glands in 3 newborns-2 girls and 1 boy. Two had hemihypertrophy and other congenital abnormalities but no identified genetic mutation; the third had genetically proven Beckwith-Wiedemann syndrome. Two had severe Cushing syndrome, the third had hypercortisolemia but no clinical Cushing syndrome. Bilateral adrenalectomy cured Cushing syndrome in the 2 with severe symptoms; total adrenal weight in these patients was 44 and 53 g, respectively. Unilateral adrenalectomy was performed in the third patient: the gland weighed 52 g; postoperatively, the patient's hypercortisolemia normalized, and, concomitantly, the enlarged contralateral adrenal gland had a 5-fold decrease in size with slight enlargement 6 years postoperatively. Microscopically, the 3 patients had similar pathology: massive adrenal enlargement due to a combination of cytomegaly, persistence of the transient cortex, and hyperplasia of the permanent cortex. The pathologic findings were most likely the result of the genetic mutation identified in 1 patient and of an unknown mutation in the remaining 2 patients.
C1 [Carney, J. Aidan] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
[Young, William F., Jr.] Mayo Clin, Div Endocrinol Diabet Metab & Nutr, Rochester, MN 55905 USA.
[Ho, Josephine] Alberta Childrens Prov Gen Hosp, Dept Pediat, Calgary, AB T2T 5C7, Canada.
[Kitsuda, Kazuteru] Kitasato Univ, Sch Med, Dept Pediat, Sagamihara, Kanagawa 228, Japan.
[Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
RP Carney, JA (reprint author), Mayo Clin, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55905 USA.
EM carney.aidan@mayo.edu
FU NICHD, NIH [Z01 HD000642-04i]
FX C.A.S. was supported by the Intramural Program, NICHD, NIH, project: Z01
HD000642-04i. The authors have disclosed that they have no significant
relationships with, or financial interest in, any commercial companies
pertaining to this article.
NR 23
TC 11
Z9 11
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD OCT
PY 2012
VL 36
IS 10
BP 1452
EP 1463
DI 10.1097/PAS.0b013e31825d538b
PG 12
WC Pathology; Surgery
SC Pathology; Surgery
GA 010ST
UT WOS:000309115100004
PM 22982888
ER
PT J
AU Ma, Y
Yang, M
Gao, HK
Niu, G
Yan, YJ
Lang, LX
Kiesewetter, DO
Chen, XY
AF Ma, Ying
Yang, Min
Gao, Haokao
Niu, Gang
Yan, Yongjun
Lang, Lixin
Kiesewetter, Dale O.
Chen, Xiaoyuan
TI Evaluation of fluorine-labeled gastrin-releasing peptide receptor (GRPR)
agonists and antagonists by LC/MS
SO AMINO ACIDS
LA English
DT Article
DE LC/MS; Gastrin releasing peptide receptor (GRPR); Bombesin (BBN);
Agonist; Antagonist; PET
ID HUMAN PROSTATE ADENOCARCINOMA; RGD-BOMBESIN HETERODIMER; IN-VITRO;
CANCER; TUMORS; EXPRESSION; ANALOGS; SUBTYPES; TARGET; PROBES
AB An LC/MS method was used to evaluate 2-fluoropropionyl (FP) and 4-fluorobenzoyl (FB) modified bombsin peptides: GRPR agonist [Aca-QWAVGHLM-NH2] and antagonist [fQWAVGHL-NHEt], and their hydrophilic linker modified counterparts with the attachment of GGGRDN sequence. This study developed strategies to evaluate the in vitro receptor mediated cell uptake and metabolic profile of the various GRPR agonists and antagonists. We identified the metabolites produced by rat hepatocytes and quantitatively analyzed the uptake and internalization of the ligands in PC-3 human prostate cancer cells. The major metabolites of both GRPR agonists and antagonists were the result of peptide bond hydrolysis between WA and AV. The agonists also formed a unique metabolite resulting from hydrolysis of the C-terminal amide. The antagonists showed significantly higher stability against metabolism compared to the agonists in rat hepatocytes. The directly modified agonists (FP-BBN and FB-BBN) had higher internalization with similar cell binding compared to the unmodified agonist (BBN), whereas the hydrophilic linker modified agonists (G-BBN and FG-BBN) had much lower total cell uptake. The labeled antagonists (FP-NBBN, FB-NBBN, G-NBBN and FP-G-NBBN) displayed lower internalization. The optimal imaging agent will depend on the interplay of ligand metabolism, cellular uptake, and internalization in vivo.
C1 [Ma, Ying; Yang, Min; Gao, Haokao; Niu, Gang; Yan, Yongjun; Lang, Lixin; Kiesewetter, Dale O.; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
[Yang, Min] Jiangsu Inst Nucl Med, Jiangsu Key Lab Mol Nucl Med, Minist Hlth, Key Lab Nucl Med, Wuxi 214063, Jiangsu, Peoples R China.
RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, 31 Ctr Dr,Suite 1C14, Bethesda, MD 20892 USA.
EM dk7k@nih.gov; shawn.chen@nih.gov
FU National Institute of Biomedical Imaging and Bioengineering (NIBIB);
National Institutes of Health (NIH); National Science Foundation of
China (NSFC) [81028009]
FX This project was supported by the Intramural Research Program of the
National Institute of Biomedical Imaging and Bioengineering (NIBIB),
National Institutes of Health (NIH) and the International Cooperative
Program of the National Science Foundation of China (NSFC) (81028009).
NR 33
TC 4
Z9 4
U1 0
U2 13
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0939-4451
J9 AMINO ACIDS
JI Amino Acids
PD OCT
PY 2012
VL 43
IS 4
BP 1625
EP 1632
DI 10.1007/s00726-012-1238-6
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 010BZ
UT WOS:000309070700020
PM 22354143
ER
PT J
AU Borghese, CM
Xiong, W
Oh, SI
Ho, A
Mihic, SJ
Zhang, L
Lovinger, DM
Homanics, GE
Eger, EI
Harris, RA
AF Borghese, Cecilia M.
Xiong, Wei
Oh, S. Irene
Ho, Angel
Mihic, S. John
Zhang, Li
Lovinger, David M.
Homanics, Gregg E.
Eger, Edmond I., II
Harris, R. Adron
TI Mutations M287L and Q266I in the Glycine Receptor alpha 1 Subunit Change
Sensitivity to Volatile Anesthetics in Oocytes and Neurons, but Not the
Minimal Alveolar Concentration in Knockin Mice
SO ANESTHESIOLOGY
LA English
DT Article
ID ACID TYPE-A; GATED ION-CHANNEL; INHALED ANESTHETICS;
GENERAL-ANESTHETICS; MOLECULAR TARGETS; ISOFLURANE; GABA(A); ALCOHOLS;
IMMOBILITY; SITES
AB Background: Volatile anesthetics (VAs) alter the function of key central nervous system proteins but it is not clear which, if any, of these targets mediates the immobility produced by VAs in the face of noxious stimulation. A leading candidate is the glycine receptor, a ligand-gated ion channel important for spinal physiology. VAs variously enhance such function, and blockade of spinal glycine receptors with strychnine affects the minimal alveolar concentration (an anesthetic EC50) in proportion to the degree of enhancement.
Methods: We produced single amino acid mutations into the glycine receptor alpha 1 subunit that increased (M287L, third transmembrane region) or decreased (Q266I, second transmembrane region) sensitivity to isoflurane in recombinant receptors, and introduced such receptors into mice. The resulting knockin mice presented impaired glycinergic transmission, but heterozygous animals survived to adulthood, and we determined the effect of isoflurane on glycine-evoked responses of brainstem neurons from the knockin mice, and the minimal alveolar concentration for isoflurane and other VAs in the immature and mature knockin mice.
Results: Studies of glycine-evoked currents in brainstem neurons from knockin mice confirmed the changes seen with recombinant receptors. No increases in the minimal alveolar concentration were found in knockin mice, but the minimal alveolar concentration for isoflurane and enflurane (but not halothane) decreased in 2-week-old Q266I mice. This change is opposite to the one expected for a mutation that decreases the sensitivity to volatile anesthetics.
Conclusion: Taken together, these results indicate that glycine receptors containing the alpha 1 subunit are not likely to be crucial for the action of isoflurane and other VAs.
C1 [Borghese, Cecilia M.; Mihic, S. John; Harris, R. Adron] Univ Texas Austin, Waggoner Ctr Alcohol & Addict Res, Austin, TX 78712 USA.
[Xiong, Wei; Zhang, Li; Lovinger, David M.] NIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA.
[Oh, S. Irene; Eger, Edmond I., II] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA.
[Ho, Angel] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
[Homanics, Gregg E.] Univ Pittsburgh, Dept Anesthesiol & Pharmacol, Pittsburgh, PA USA.
[Homanics, Gregg E.] Univ Pittsburgh, Dept Biol Chem, Pittsburgh, PA USA.
RP Harris, RA (reprint author), Univ Texas Austin, Waggoner Ctr Alcohol & Addict Res, 1 Univ Stn A4800, Austin, TX 78712 USA.
EM harris@mail.utexas.edu
FU National Institutes of Health, Bethesda, Maryland [1PO1GM47818,
AA06399]; Division of Intramural Clinical and Biomedical Research,
National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health, Rockville, Maryland
FX Supported by grant nos. 1PO1GM47818 and AA06399 from the National
Institutes of Health, Bethesda, Maryland. Drs. Xiong, Zhang, and
Lovinger acknowledge support from the Division of Intramural Clinical
and Biomedical Research, National Institute on Alcohol Abuse and
Alcoholism, National Institutes of Health, Rockville, Maryland.
NR 32
TC 2
Z9 2
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-3022
J9 ANESTHESIOLOGY
JI Anesthesiology
PD OCT
PY 2012
VL 117
IS 4
BP 765
EP 771
DI 10.1097/ALN.0b013e31826a0d93
PG 7
WC Anesthesiology
SC Anesthesiology
GA 010RZ
UT WOS:000309113100011
PM 22885675
ER
PT J
AU Leiding, JW
Hughes, T
Chasik, A
Salit, RB
AF Leiding, Jennifer W.
Hughes, Thomas
Chasik, Ashley
Salit, Rachel B.
TI Successful sirolimus graded dose challenge in an erythromycin-allergic
patient
SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY
LA English
DT Letter
ID CLARITHROMYCIN DESENSITIZATION; ANTIBIOTICS
C1 [Leiding, Jennifer W.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Hughes, Thomas] NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA.
[Chasik, Ashley] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
[Salit, Rachel B.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Leiding, JW (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM leidingjw@niaid.nih.gov
FU Intramural NIH HHS
NR 8
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1081-1206
J9 ANN ALLERG ASTHMA IM
JI Ann. Allergy Asthma Immunol.
PD OCT
PY 2012
VL 109
IS 4
BP 284
EP 285
PG 3
WC Allergy; Immunology
SC Allergy; Immunology
GA 012UY
UT WOS:000309263300014
PM 23010239
ER
PT J
AU Balana-Fouce, R
Prada, CF
Requena, JM
Cushman, M
Pommier, Y
Alvarez-Velilla, R
Escudero-Martinez, JM
Calvo-Alvarez, E
Perez-Pertejo, Y
Reguera, RM
AF Balana-Fouce, Rafael
Prada, Christopher F.
Maria Requena, Jose
Cushman, Mark
Pommier, Yves
Alvarez-Velilla, Raquel
Miguel Escudero-Martinez, Jose
Calvo-Alvarez, Estefania
Perez-Pertejo, Yolanda
Reguera, Rosa M.
TI Indotecan (LMP400) and AM13-55: Two Novel Indenoisoquinolines Show
Potential for Treating Visceral Leishmaniasis
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID DNA TOPOISOMERASE-I; AFRICAN TRYPANOSOMES; ANTICANCER AGENTS;
CAMPTOTHECIN; IDENTIFICATION; MILTEFOSINE; RESISTANCE; INHIBITORS;
EFFICIENCY; DONOVANI
AB Visceral leishmaniasis is an emerging neglected tropical disease (NTD) caused by the protozoan Leishmania infantum in the countries bordering the Mediterranean Basin. Currently there is no effective vaccine against this disease, and the therapeutic approach is based on toxic derivatives of Sb-V. Therefore, the discovery of new therapeutic targets and the development of drugs designed to inhibit them comprise an extremely important approach to fighting this disease. DNA topoisomerases (Top) have been identified as promising targets for therapy against leishmaniasis. These enzymes are involved in solving topological problems generated during replication, transcription, and recombination of DNA. Being unlike that of the mammalian host, type IB DNA topoisomerase (TopIB) from Leishmania spp. is a unique bisubunit protein, which makes it very interesting as a selective drug target. In the present investigation, we studied the effect of two TopIB poisons with indenoisoquinoline structure, indotecan and AM13-55, on a murine BALB/c model of infected splenocytes with L. infantum, comparing their effectiveness with that of the clinically tested leishmanicidal drug paromomycin. Both compounds have high selectivity indexes compared with uninfected splenocytes. SDS-KCl-precipitable DNA-protein complexes in Leishmania promastigotes and in vitro cleaving assays confirmed that these drugs are Top poisons. The inhibitory potency of both indenoisoquinolines on L. infantum recombinant TopIB was assessed in vitro, with results showing that indotecan was the most active compound, preventing the relaxation of supercoiled DNA. Experimental infections in susceptible BALB/c mice treated with 2.5 mg/kg body weight/day once every other day for a total of 15 days showed that indotecan cleared more than 80% of the parasite burden of the spleen and liver, indicating promising activity against visceral leishmaniasis.
C1 [Balana-Fouce, Rafael; Prada, Christopher F.; Alvarez-Velilla, Raquel; Miguel Escudero-Martinez, Jose; Calvo-Alvarez, Estefania; Perez-Pertejo, Yolanda; Reguera, Rosa M.] Univ Leon, Dept Ciencias Biomed, E-24071 Leon, Spain.
[Maria Requena, Jose] Ctr Biol Mol Severo Ochoa, Dept Bioquim & Biol Mol, Madrid, Spain.
[Cushman, Mark] Purdue Univ, Dept Med Chem & Mol Pharmacol, Coll Pharm, W Lafayette, IN 47907 USA.
[Cushman, Mark] Purdue Univ, Purdue Ctr Canc Res, W Lafayette, IN 47907 USA.
[Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Balana-Fouce, R (reprint author), Univ Leon, Dept Ciencias Biomed, Campus Vegazana, E-24071 Leon, Spain.
EM rbalf@unileon.es
OI Requena Rolania, Jose Maria/0000-0003-3410-9488; perez-pertejo,
yolanda/0000-0003-2361-3785; Alvarez-Velilla,
Raquel/0000-0003-4334-8392; Fernandez-Prada,
Christopher/0000-0003-4834-4956; Reguera, Rosa M/0000-0001-9148-2997;
Balana-Fouce, Rafael/0000-0003-0418-6116
FU Ministerio de Ciencia y Tecnologia [AGL2009-11935/GAN,
AGL2010-16078/GAN]; Instituto de Salud Carlos III [PI09/0448]; Instituto
de Salud Carlos III (Network of Tropical Diseases RICET)
[RD06/0021/1004]; Junta de Castilla y Leon [Gr238]; National Institutes
of Health (NIH) [U01 CA89566]
FX This research was supported by Ministerio de Ciencia y Tecnologia
(grants AGL2009-11935/GAN and AGL2010-16078/GAN), Instituto de Salud
Carlos III (grant PI09/0448 and the Network of Tropical Diseases RICET
RD06/0021/1004), and Junta de Castilla y Leon (grant Gr238). R.A.-V., C.
F. P., and E.C.-A. are predoctoral fellows through RICET (ISCIII), Junta
de Castilla y Leon (ESF; European Social Founding), and the University
of Leon, respectively. This work was also made possible by the National
Institutes of Health (NIH) through support with research grant U01
CA89566.
NR 36
TC 17
Z9 17
U1 1
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD OCT
PY 2012
VL 56
IS 10
BP 5264
EP 5270
DI 10.1128/AAC.00499-12
PG 7
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 006GQ
UT WOS:000308807900036
PM 22850521
ER
PT J
AU Griffin, CE
Hoke, JM
Samarakoon, U
Duan, JH
Mu, JB
Ferdig, MT
Warhurst, DC
Cooper, RA
AF Griffin, Carol E.
Hoke, Jonathan M.
Samarakoon, Upeka
Duan, Junhui
Mu, Jianbing
Ferdig, Michael T.
Warhurst, David C.
Cooper, Roland A.
TI Mutation in the Plasmodium falciparum CRT Protein Determines the
Stereospecific Activity of Antimalarial Cinchona Alkaloids
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID CHLOROQUINE-RESISTANCE TRANSPORTER; DRUG-RESISTANCE; QUININE RESISTANCE;
MALARIA PARASITES; FERRIPROTOPORPHYRIN-IX; DIGESTIVE VACUOLE;
CRYSTAL-STRUCTURE; PFMDR1 MUTATIONS; PFCRT MUTATIONS; GENETIC-LINKAGE
AB The Cinchona alkaloids are quinoline aminoalcohols that occur as diastereomer pairs, typified by (-)-quinine and (+)-quinidine. The potency of (+)-isomers is greater than the (-)-isomers in vitro and in vivo against Plasmodium falciparum malaria parasites. They may act by the inhibition of heme crystallization within the parasite digestive vacuole in a manner similar to chloroquine. Earlier studies showed that a K76I mutation in the digestive vacuole-associated protein, PfCRT (P. falciparum chloroquine resistance transporter), reversed the normal potency order of quinine and quinidine toward P. falciparum. To further explore PfCRT-alkaloid interactions in the malaria parasite, we measured the in vitro susceptibility of eight clonal lines of P. falciparum derived from the 106/1 strain, each containing a unique pfcrt allele, to four Cinchona stereoisomer pairs: quinine and quinidine; cinchonidine and cinchonine; hydroquinine and hydroquinidine; 9-epiquinine and 9-epiquinidine. Stereospecific potency of the Cinchona alkaloids was associated with changes in charge and hydrophobicity of mutable PfCRT amino acids. In isogenic chloroquine-resistant lines, the IC50 ratio of (-)/(+) CA pairs correlated with side chain hydrophobicity of the position 76 residue. Second-site PfCRT mutations negated the K76I stereospecific effects: charge-change mutations C72R or Q352K/R restored potency patterns similar to the parent K76 line, while V369F increased susceptibility to the alkaloids and nullified stereospecific differences between alkaloid pairs. Interactions between key residues of the PfCRT channel/transporter with (-) and (+) alkaloids are stereospecifically determined, suggesting that PfCRT binding plays an important role in the antimalarial activity of quinine and other Cinchona alkaloids.
C1 [Griffin, Carol E.; Hoke, Jonathan M.; Cooper, Roland A.] Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA.
[Samarakoon, Upeka; Ferdig, Michael T.] Univ Notre Dame, Dept Biol Sci, Eck Inst Global Hlth, South Bend, IN USA.
[Duan, Junhui; Mu, Jianbing] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Warhurst, David C.] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Pathogen Mol Biol, London WC1, England.
[Cooper, Roland A.] Dominican Univ Calif, Dept Nat Sci & Math, San Rafael, CA USA.
RP Cooper, RA (reprint author), Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA.
EM roland.cooper@dominican.edu
RI Ferdig, Michael/C-6627-2016
FU NIH [AI071121]; Old Dominion University Undergraduate Honors College
FX This work was supported in part by NIH grant AI071121 (M. T. F. and R.
A. C.). C. E. G. was supported by an award from the Old Dominion
University Undergraduate Honors College.
NR 71
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PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD OCT
PY 2012
VL 56
IS 10
BP 5356
EP 5364
DI 10.1128/AAC.05667-11
PG 9
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 006GQ
UT WOS:000308807900048
PM 22869567
ER
PT J
AU Liu, JK
Musani, SK
Bidulescu, A
Carr, JJ
Wilson, JG
Taylor, HA
Fox, CS
AF Liu, Jiankang
Musani, Solomon K.
Bidulescu, Aurelian
Carr, J. Jeffery
Wilson, James G.
Taylor, Herman A.
Fox, Caroline S.
TI Fatty liver, abdominal adipose tissue and atherosclerotic calcification
in African Americans: The Jackson Heart Study
SO ATHEROSCLEROSIS
LA English
DT Article
DE Fatty liver; Abdominal adiposity; Artery calcification
ID CORONARY-ARTERY CALCIFICATION; BEAM COMPUTED-TOMOGRAPHY;
INSULIN-RESISTANCE; VISCERAL FAT; RISK-FACTORS; HEPATIC STEATOSIS;
UNITED-STATES; ETHNIC-GROUPS; DISEASE; HUMANS
AB Objective: Both fatty liver and abdominal visceral fat (VAT) are associated with cardiometabolic risk factors. Whether fatty liver and VAT are jointly associated with coronary artery (CAC) or abdominal aortic (AAC) calcification is not clear.
Methods: Jackson Heart Study (JHS) participants (n = 2884, mean age 60 years, 65% women) underwent non-contrast CT Exam for assessment of fatty liver, VAT, and CAC and AAC. Fatty liver was measured by liver attenuation (LA; low LA = high fatty liver). The Agatston score was used to quantify the amount of calcified artery plaque and the presence of calcified artery plaque was defined as Agatston score>0. Cross-sectional associations of LA and VAT with CAC and AAC were examined in logistic regression models.
Results: LA (per 1-standard deviation [SD] decrement) was associated inversely with CAC in age-sex-adjusted (OR 0.84, 95%CI 0.7-0.9, p = 0.0001) and multivariable-adjusted models (OR 0.89, 95%CI 0.8-0.9, p = 0.01). The association persisted for LA with CAC when additionally adjusted for body mass index (BMI) (OR 0.89, 95%CI 0.8-0.9, p = 0.03) or VAT (OR 0.90, 95%CI 0.8-0.9, p = 0.04). Abdominal VAT (per 1-SD increment) was positively associated with CAC in age-sex-adjusted models (OR 1.27, 95%CI 1.2-1.4, p = 0.0001), but the association was diminished with multivariable adjustment (OR 1.10, 95%CI 0.9-1.2, p = 0.09) and with additional adjustment for LA (p = 0.24) or BMI (p = 0.33). For AAC, the associations with LA and VAT were only present in age-sex-adjusted models. Finally, we did not observe interactions between LA and VAT for CAC (p = 0.18) or AAC (p = 0.24).
Conclusion: Fatty liver is associated with coronary atherosclerotic calcification independent of abdominal VAT or BMI in African Americans. Further investigations to uncover the clinical implications of fatty liver on coronary atherosclerosis in obesity are warranted. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Liu, Jiankang; Musani, Solomon K.; Wilson, James G.; Taylor, Herman A.] Jackson State Univ, Jackson Heart Study, Univ Mississippi, Med Ctr, Jackson, MS 39213 USA.
[Bidulescu, Aurelian] Morehouse Sch Med, Cardiovasc Res Inst, Atlanta, GA 30310 USA.
[Carr, J. Jeffery] Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC USA.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] NHLBI, Ctr Populat Studies, Framingham, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
RP Liu, JK (reprint author), Jackson State Univ, Jackson Heart Study, Univ Mississippi, Med Ctr, 350 W Woodrow Wilson Dr, Jackson, MS 39213 USA.
EM jliu@umc.edu
RI Bidulescu, Aurelian/N-2617-2014; Carr, John/A-1938-2012
OI Bidulescu, Aurelian/0000-0001-8211-8309; Carr, John/0000-0002-4398-8237
FU National Heart, Lung, and Blood Institute [N01-HC-95170, N01-HC-95171,
N01-C-95172]; National Center on Minority Health and Health Disparities
FX The Jackson Heart Study is supported by the National Heart, Lung, and
Blood Institute and the National Center on Minority Health and Health
Disparities. Funding for Dr. Herman A. Taylor was provided under
contracts N01-HC-95170, N01-HC-95171 and N01-C-95172 from the National
Heart, Lung and Blood Institute and the National Center on Minority
Health and Health Disparities.
NR 32
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD OCT
PY 2012
VL 224
IS 2
BP 521
EP 525
DI 10.1016/j.atherosclerosis.2012.07.042
PG 5
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 012UF
UT WOS:000309261400040
PM 22902209
ER
PT J
AU Newman, AH
Blaylock, BL
Nader, MA
Bergman, J
Sibley, DR
Skolnick, P
AF Newman, Amy Hauck
Blaylock, Brandi L.
Nader, Michael A.
Bergman, Jack
Sibley, David R.
Skolnick, Phil
TI Medication discovery for addiction: Translating the dopamine D3 receptor
hypothesis
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Cocaine; Methamphetamine; Buspirone; Psychostimulant abuse; Medication
development
ID POSITRON-EMISSION-TOMOGRAPHY; COCAINE-SEEKING BEHAVIOR; ABUSE
THERAPEUTIC AGENTS; RHESUS-MONKEYS; DISCRIMINATIVE STIMULUS;
HIGH-AFFINITY; PHARMACOLOGICAL ACTIONS; INDUCED REINSTATEMENT; ACTIVE
METABOLITE; PROGRESSIVE-RATIO
AB The dopamine D3 receptor (D3R) has been investigated as a potential target for medication development to treat substance use disorders (SUDs) with a particular focus on cocaine and methamphetamine. Currently, there are no approved medications to treat cocaine and methamphetamine addiction and thus developing pharmacotherapeutics to complement existing behavioral strategies is a fundamental goal. Novel compounds with high affinity and D3R selectivity have been evaluated in numerous animal models of drug abuse and favorable outcomes in nonhuman primate models of self-administration and relapse have provided compelling evidence to advance these agents into the clinic. One approach is to repurpose drugs that share the D3R mechanism and already have clinical utility, and to this end buspirone has been identified as a viable candidate for clinical trials. A second, but substantially more resource intensive and risky approach involves the development of compounds that exclusively target D3R, such as GSK598809 and PG 619. Clinical investigation of these drugs or other novel D3R-selective agents will provide a better understanding of the role D3R plays in addiction and whether or not antagonists or partial agonists that are D3R selective are effective in achieving abstinence in this patient population. Published by Elsevier Inc.
C1 [Newman, Amy Hauck] Natl Inst Drug Abuse, Intramural Res Program, Mol Targets & Medicat Discovery Branch, Med Chem Sect, Baltimore, MD 21224 USA.
[Blaylock, Brandi L.; Nader, Michael A.] Wake Forest Univ, Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27109 USA.
[Bergman, Jack] Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA.
[Sibley, David R.] NINDS, NIH, Mol Neuropharmacol Sect, Bethesda, MD 20892 USA.
[Skolnick, Phil] NIDA, NIH, Div Pharmacotherapies & Med Consequences Drug Abu, Bethesda, MD 20892 USA.
RP Newman, AH (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Mol Targets & Medicat Discovery Branch, Med Chem Sect, 333 Cassell Dr, Baltimore, MD 21224 USA.
FU NIDA [R01 DA12460, F31 DA033106]; NIDA ATDP
FX AHN would like to acknowledge the members of her lab, past and present,
and her many collaborators that have moved our D3R program forward. In
addition, we would like to thank Dr. Emilio Merlo-Pich for participating
in the 2011 ACNP mini-symposium that inspired this commentary and for
his substantial contributions to the D3R field while at GSK. Funding for
this work has come from the NIDA-Intramural Research Program, with
support from the NIDA ATDP. BLB and MAN would like to acknowledge the
support of Dr. Jane Acri and funding by NIDA grant R01 DA12460 (MAN) and
F31 DA033106 (BLB).
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD OCT 1
PY 2012
VL 84
IS 7
BP 882
EP 890
DI 10.1016/j.bcp.2012.06.023
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 004MR
UT WOS:000308686300002
PM 22781742
ER
PT J
AU Uehara, H
Hocart, SJ
Gonzalez, N
Mantey, SA
Nakagawa, T
Katsuno, T
Coy, DH
Jensen, RT
AF Uehara, Hirotsugu
Hocart, Simon J.
Gonzalez, Nieves
Mantey, Samuel A.
Nakagawa, Tomoo
Katsuno, Tatsuro
Coy, David H.
Jensen, Robert T.
TI The molecular basis for high affinity of a universal ligand for human
bombesin receptor (BnR) family members
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Gastrin-releasing peptide; Neuromedin B; Bombesin; BRS-3;
Receptor-mutagenesis
ID GASTRIN-RELEASING-PEPTIDE; SITE-DIRECTED MUTAGENESIS; CATION-PI
INTERACTIONS; NEUROMEDIN-B RECEPTOR; ANTAGONIST BINDING-SITES; HUMAN
ORPHAN RECEPTOR; AGONIST-BINDING; NEUROKININ-1 RECEPTOR; TRANSMEMBRANE
DOMAIN; EXTRACELLULAR LOOP
AB There is increased interest in the Bn-receptor family because they are frequently over/ectopically expressed by tumors and thus useful as targets for imaging or receptor-targeted-cytotoxicity. The synthetic Bn-analog, [D-Tyr(6), beta-Ala(11), Phe(13), Nle(14)]Bn(6-14) [Univ.Lig] has the unique property of having high affinity for all three human BNRs (GRPR, NMBR, BRS-3), and thus could be especially useful for this approach. However, the molecular basis of this property is unclear and is the subject of this study. To accomplish this, site-directed mutagenesis was used after identifying potentially important amino acids using sequence homology analysis of all BnRs with high affinity for Univ.Lig compared to the Cholecystokinin-receptor (CCKAR), which has low affinity. Using various criteria 74 amino acids were identified and 101 mutations made in GRPR by changing each to those of CCKAR or to alanine. 22 GRPR mutations showed a significant decrease in affinity for Univ.Lig (>2-fold) with 2 in EC2[D97N, G112V], 1 in UTM6[Y284A], 2 in EC4[R287N, H300S] showing >10-fold decrease in Univ.Lig affinity. Additional mutations were made to explore the molecular basis for these changes. Our results show that high affinity for Univ.Lig by human Bn-receptors requires positively charged amino acids in extracellular (EC)-domain 4 and to a lesser extent EC2 and EC3 suggesting charge-charge interactions may be particularly important for determining the general high affinity of this ligand. Furthermore, transmembrane amino acids particularly in UTM6 are important contributing both charge-charge interactions as well as interaction with a tyrosine residue in close proximity suggesting possible receptor-peptide cation-pi or H-bonding interactions are also important for determining its high affinity. Published by Elsevier Inc.
C1 [Uehara, Hirotsugu; Gonzalez, Nieves; Mantey, Samuel A.; Jensen, Robert T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA.
[Hocart, Simon J.; Coy, David H.] Tulane Hlth Sci Ctr, Dept Med, Peptide Res Labs, New Orleans, LA 70112 USA.
[Nakagawa, Tomoo; Katsuno, Tatsuro] Chiba Univ, Grad Sch Med, Dept Med & Clin Oncol K1, Chuo Ku, Chiba 2608670, Japan.
RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM robertj@bdg10.niddk.nih.gov
RI Gonzalez, Nieves/N-2199-2014
OI Gonzalez, Nieves/0000-0002-1551-2872
FU NIDDK, NIH
FX This work was partially supported by intramural funds of NIDDK, NIH.
NR 78
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD OCT 1
PY 2012
VL 84
IS 7
BP 936
EP 948
DI 10.1016/j.bcp.2012.07.010
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 004MR
UT WOS:000308686300008
PM 22828605
ER
PT J
AU Balaban, RS
AF Balaban, Robert S.
TI Dynamic imaging of mitochondrial function, in vivo
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Meeting Abstract
C1 [Balaban, Robert S.] NHLBI, Cardiac Energet Lab, Bethesda, MD 20892 USA.
EM balabanr@nhlbi.nih.gov
NR 0
TC 0
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U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD OCT
PY 2012
VL 1817
SU S
BP S6
EP S7
DI 10.1016/j.bbabio.2012.06.027
PG 2
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 002IN
UT WOS:000308525400017
ER
PT J
AU Covian, R
Chess, DJ
Billings, E
Glancy, B
French, S
Taylor, J
Murphy, E
Balaban, RS
AF Covian, Raul
Chess, David J.
Billings, Eric
Glancy, Brian
French, Stephanie
Taylor, Joni
Murphy, Elizabeth
Balaban, Robert S.
TI Monitoring of the activity and redox state of mitochondrial complexes in
physiological and pathological conditions using in-gel kinetics
acquisition and integrating sphere spectroscopy
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Meeting Abstract
C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA.
NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
EM raul.coviangarcia@nih.gov
RI Glancy, Brian/P-3163-2016
OI Glancy, Brian/0000-0002-8571-244X
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD OCT
PY 2012
VL 1817
SU S
BP S118
EP S118
DI 10.1016/j.bbabio.2012.06.316
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 002IN
UT WOS:000308525400293
ER
PT J
AU Dibrova, DV
Makarova, KS
Galperin, MY
Koonin, EV
Mulkidjanian, AY
AF Dibrova, Daria V.
Makarova, Kira S.
Galperin, Michael Y.
Koonin, Eugene V.
Mulkidjanian, Armen Y.
TI Comparative analysis of lipid biosynthesis in archaea, bacteria and
eukaryotes: What was the structure of the first membrane lipids?
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Meeting Abstract
C1 Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany.
Moscow MV Lomonosov State Univ, Sch Bioengn & Bioinformat, Moscow 119992, Russia.
NIH, NCBI, NLM, Bethesda, MD 20894 USA.
Moscow State Univ Moscow, AN Belozersky Inst Physicochem Biol, Moscow 119899, Russia.
EM ddibrova@uos.de
RI Mulkidjanian, Armen/J-8086-2013
OI Mulkidjanian, Armen/0000-0001-5844-3064
NR 4
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U1 0
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD OCT
PY 2012
VL 1817
SU S
BP S154
EP S154
DI 10.1016/j.bbabio.2012.06.404
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 002IN
UT WOS:000308525400378
ER
PT J
AU Dibrova, DV
Galperin, MY
Mulkidjanian, AY
AF Dibrova, Daria V.
Galperin, Michael Y.
Mulkidjanian, Armen Y.
TI The cytochrome bc(1) complex and the evolution of membrane bioenergetics
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Meeting Abstract
C1 [Dibrova, Daria V.; Mulkidjanian, Armen Y.] Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany.
[Dibrova, Daria V.] Moscow MV Lomonosov State Univ, Sch Bioengn & Bioinformat, Moscow 119992, Russia.
[Galperin, Michael Y.] NIH, NCBI, NLM, Bethesda, MD 20894 USA.
[Mulkidjanian, Armen Y.] Moscow MV Lomonosov State Univ, AN Belozersky Inst Phys Chem Biol, Moscow 119991, Russia.
EM amulkid@uos.de
RI Mulkidjanian, Armen/J-8086-2013
OI Mulkidjanian, Armen/0000-0001-5844-3064
NR 5
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U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD OCT
PY 2012
VL 1817
SU S
BP S91
EP S91
DI 10.1016/j.bbabio.2012.06.246
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 002IN
UT WOS:000308525400225
ER
PT J
AU Furushima-Shimogawara, R
Yagita, K
AF Furushima-Shimogawara, Rieko
Yagita, Kenji
TI Role of mitochondrial dynamics on the relationship of amoeba and
bacteria, as host-parasite and/or symbiont
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Meeting Abstract
C1 [Furushima-Shimogawara, Rieko; Yagita, Kenji] NIH, Bethesda, MD 20892 USA.
EM rfuru.vip@tmd.ac.jp
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD OCT
PY 2012
VL 1817
SU S
BP S72
EP S73
DI 10.1016/j.bbabio.2012.06.202
PG 2
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 002IN
UT WOS:000308525400184
ER
PT J
AU Glancy, B
Chess, DJ
Balaban, RS
AF Glancy, B.
Chess, D. J.
Balaban, R. S.
TI Thermodynamic analysis of the role of calcium in skeletal muscle
mitochondrial energy
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Meeting Abstract
C1 [Glancy, B.; Chess, D. J.; Balaban, R. S.] NHLBI, NIH, Cardiac Energet Lab, Bethesda, MD 20892 USA.
EM glancybp@nhlbi.nih.gov
RI Glancy, Brian/P-3163-2016
OI Glancy, Brian/0000-0002-8571-244X
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD OCT
PY 2012
VL 1817
SU S
BP S120
EP S120
DI 10.1016/j.bbabio.2012.06.322
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 002IN
UT WOS:000308525400299
ER
PT J
AU Youle, RJ
AF Youle, Richard J.
TI Damage control - How the PINK1/Parkin pathway can regulate removal of
impaired mitochondria by autophagy
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Meeting Abstract
C1 [Youle, Richard J.] NINDS, NIH, Bethesda, MD 20892 USA.
EM youler@ninds.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD OCT
PY 2012
VL 1817
SU S
BP S3
EP S3
DI 10.1016/j.bbabio.2012.06.018
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 002IN
UT WOS:000308525400008
ER
PT J
AU Peace, RM
Majors, BL
Patel, NS
Wang, D
Del Valle-Pinero, AY
Martino, AC
Henderson, WA
AF Peace, Ralph Michael
Majors, Benjamin L.
Patel, Nayan S.
Wang, Dan
Del Valle-Pinero, Arseima Y.
Martino, Angela C.
Henderson, Wendy A.
TI Stress and Gene Expression of Individuals With Chronic Abdominal Pain
SO BIOLOGICAL RESEARCH FOR NURSING
LA English
DT Article
DE stress; abdominal pain; gene expression; IL1A; IL-1 alpha
ID IRRITABLE-BOWEL-SYNDROME; RHEUMATOID-ARTHRITIS; PSYCHOLOGICAL STRESS;
GENDER-DIFFERENCES; BARRIER FUNCTION; DISORDERS; INFLAMMATION; RAT;
PATHOPHYSIOLOGY; PREVALENCE
AB Background: Research examining the role of stress in gastrointestinal (GI) symptoms such as chronic abdominal pain (CAP) is controversial. The purpose of this study was to examine the expression of genes involved in metabolic stress and toxicity in men and women with high and low levels of perceived stress with and without CAP. Methods: Data and samples were collected and the expression of genes involved in metabolic stress and toxicity was analyzed in 26 individuals who had consented to participate in a natural history protocol. Subjects completed the 10-item Perceived Stress scale (PSS). Fasting participants' peripheral whole blood was collected for proteomic and genomic studies. Polymerase chain reaction (PCR) array was used to analyze the expression of 84 key genes involved in human stress and toxicity plus 5 housekeeping genes. Plasma interleukin-1 alpha (IL-1 alpha) protein was quantified via enzyme-linked immunosorbent assay (ELISA). Results: Interleukin-1 alpha gene (IL1A) was upregulated in females with high stress versus females with low stress by 2.58-fold (95% CI [ 0.88, 4.28]). IL1A was upregulated in participants with high stress and CAP versus those with low stress and CAP by 3.47-fold (95% CI [ 1.14, 5.80]). Conclusions: An upregulation of the gene coding the pro-inflammatory cytokine IL-1 alpha suggests that the mechanism behind stress-related changes in GI symptoms is pro-inflammatory in nature. The results of this study contribute to the knowledge of the mechanism behind stress-related CAP symptoms and gender differences associated with these disorders.
C1 [Peace, Ralph Michael; Majors, Benjamin L.; Patel, Nayan S.; Wang, Dan; Del Valle-Pinero, Arseima Y.; Martino, Angela C.; Henderson, Wendy A.] NINR, Biobehav Unit, Intramural Res Program, NIH,DHHS, Bethesda, MD 20892 USA.
[Peace, Ralph Michael] Natl Inst Hlth Res Scholar, Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Henderson, WA (reprint author), NINR, Biobehav Unit, Intramural Res Program, NIH,DHHS, DHHS Bldg 10,2-1339, Bethesda, MD 20892 USA.
EM hendersw@mail.nih.gov
OI Henderson, Wendy/0000-0003-3924-7118
FU Howard Hughes Medical Institute-National Institutes of Health Research
Scholar Program; Burroughs Wellcome Fund; Intramural Research Program,
National Institute of Nursing Research [1ZIANR000018-01/02/03]
FX The authors disclosed receipt of the following financial support for the
research, authorship and/or publication of this article: Support was
provided to R. M. P. by the Howard Hughes Medical Institute-National
Institutes of Health Research Scholar Program and Burroughs Wellcome
Fund. Additional support was provided by the Intramural Research
Program, National Institute of Nursing Research (to W. A. H.,
1ZIANR000018-01/02/03 and Intramural Research Training Award to R. M.
P., B. L. M., N. S. P., and A. Y. D.).
NR 46
TC 2
Z9 2
U1 1
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1099-8004
J9 BIOL RES NURS
JI Biol. Res. Nurs.
PD OCT
PY 2012
VL 14
IS 4
SI SI
BP 405
EP 411
DI 10.1177/1099800412458350
PG 7
WC Nursing
SC Nursing
GA 010XD
UT WOS:000309126900009
PM 23007871
ER
PT J
AU Pasquini, MC
Voltarelli, J
Atkins, HL
Hamerschlak, N
Zhong, XB
Ahn, KW
Sullivan, KM
Carrum, G
Andrey, J
Bredeson, CN
Cairo, M
Gale, RP
Hahn, T
Storek, J
Horowitz, MM
McSweeney, PA
Griffith, LM
Muraro, PA
Pavletic, SZ
Nash, RA
AF Pasquini, Marcelo C.
Voltarelli, Julio
Atkins, Harold L.
Hamerschlak, Nelson
Zhong, Xiaobo
Ahn, Kwang Woo
Sullivan, Keith M.
Carrum, George
Andrey, Jeffrey
Bredeson, Christopher N.
Cairo, Mitchell
Gale, Robert Peter
Hahn, Theresa
Storek, Jan
Horowitz, Mary M.
McSweeney, Peter A.
Griffith, Linda M.
Muraro, Paolo A.
Pavletic, Steven Z.
Nash, Richard A.
TI Transplantation for Autoimmune Diseases in North and South America: A
Report of the Center for International Blood and Marrow Transplant
Research
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Autologous transplants; Multiple sclerosis; Autoimmunity
ID STEM-CELL TRANSPLANTATION; DOSE IMMUNOSUPPRESSIVE THERAPY; SEVERE
SYSTEMIC-SCLEROSIS; PROGRESSIVE MULTIPLE-SCLEROSIS;
RHEUMATOID-ARTHRITIS; LUPUS-ERYTHEMATOSUS; HEMATOPOIETIC SCT; EUROPEAN
GROUP; PRIME-TIME; CYCLOPHOSPHAMIDE
AB Hematopoietic cell transplantation (HCT) is an emerging therapy for patients with severe autoimmune diseases (AID). We report data on 368 patients with AID who underwent HCT in 64 North and South American transplantation centers reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2009. Most of the HCTs involved autologous grafts (n = 339); allogeneic HCT (n = 29) was done mostly in children. The most common indications for HCT were multiple sclerosis, systemic sclerosis, and systemic lupus erythematosus. The median age at transplantation was 38 years for autologous HCT and 25 years for allogeneic HCT. The corresponding times from diagnosis to HCT were 35 months and 24 months. Three-year overall survival after autologous HCT was 86% (95% confidence interval [CI], 81%-91%). Median follow-up of survivors was 31 months (range, 1-144 months). The most common causes of death were AID progression, infections, and organ failure. On multivariate analysis, the risk of death was higher in patients at centers that performed fewer than 5 autologous HCTs (relative risk, 3.5; 95% CI, 1.1-11.1; P = .03) and those that performed 5 to 15 autologous HCTs for AID during the study period (relative risk, 4.2; 95% CI, 1.5-11.7; P = .006) compared with patients at centers that performed more than 15 autologous HCTs for AID during the study period. AID is an emerging indication for HCT in the region. Collaboration of hematologists and other disease specialists with an outcomes database is important to promote optimal patient selection, analysis of the impact of prognostic variables and long-term outcomes, and development of clinical trials. Biol Blood Marrow Transplant 18: 1471-1478 (2012) (C) 2012 Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation
C1 [Pasquini, Marcelo C.; Zhong, Xiaobo; Ahn, Kwang Woo; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Voltarelli, Julio] Univ Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto, Brazil.
[Atkins, Harold L.; Bredeson, Christopher N.] Ottawa Gen Hosp, Blood & Marrow Transplant Program, Ottawa, ON K1H 8L6, Canada.
[Hamerschlak, Nelson] Hosp Israelita Albert Einstein, Sao Paulo, Brazil.
[Sullivan, Keith M.] Duke Univ, Med Ctr, Dept Internal Med, Div Cellular Therapy, Durham, NC 27710 USA.
[Carrum, George] Baylor Coll Med, Houston, TX 77030 USA.
[Andrey, Jeffrey] Scripps Hlth, San Diego, CA USA.
[Cairo, Mitchell] Columbia Univ, Med Ctr, New York, NY USA.
[Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, Dept Med, London, England.
[Hahn, Theresa] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Storek, Jan] Univ Calgary, Dept Med, Calgary, AB, Canada.
[McSweeney, Peter A.] Presbyterian St Lukes Med Ctr, Colorado Blood Canc Inst, Blood & Marrow Transplant Program, Denver, CO USA.
[Griffith, Linda M.] NIAID, Div Aggergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA.
[Muraro, Paolo A.] Univ London Imperial Coll Sci Technol & Med, Dept Neurol, London, England.
[Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Nash, Richard A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Pasquini, MC (reprint author), 9200 Wisconsin Ave,CCC5500, Milwaukee, WI 53226 USA.
EM mpasquini@mcw.edu
RI Hamerschlak, Nelson/M-8060-2015;
OI Hamerschlak, Nelson/0000-0002-5140-5310; Muraro,
Paolo/0000-0002-3822-1218
FU Public Health Service from the National Cancer Institute, National
Heart, Lung and Blood Institute [U24-CA76518]; National Institute of
Allergy and Infectious Diseases; National Heart, Lung and Blood
Institute and National Cancer Institute [5U01HL069294]; Health Resources
and Services Administration [HHSH234200637015C]; Office of Naval
Research [N00014-06-1-0704, N00014-08-1-0058]; Allos; Amgen; Angioblast
FX The Center for International Blood and Marrow Transplant Research is
supported by Public Health Service grant/cooperative agreement
U24-CA76518 from the National Cancer Institute, National Heart, Lung and
Blood Institute, and National Institute of Allergy and Infectious
Diseases; grant/cooperative agreement 5U01HL069294 from the National
Heart, Lung and Blood Institute and National Cancer Institute; contract
HHSH234200637015C with the Health Resources and Services Administration;
grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval
Research; and grants from Allos, Amgen, Angioblast, anonymous donation
to the Medical College of Wisconsin, Ariad, Be the Match Foundation,
Blue Cross and Blue Shield Association, Buchanan Family Foundation,
CaridianBCT, Celgene, CellGenix, Children's Leukemia Research
Association, Fresenius-Biotech North America, Gamida Cell Teva Joint
Venture, Genentech, Genzyme, GlaxoSmithKline, Kiadis Pharma, Leukemia
and Lymphoma Society, Medical College of Wisconsin, Millennium
Pharmaceuticals, Milliman USA, Miltenyi Biotec, National Marrow Donor
Program, Optum Healthcare Solutions, Otsuka America Pharmaceutical,
Seattle Genetics, Sigma-Tau Pharmaceuticals, Soligenix, Swedish Orphan
Biovitrum, Therakos, and Wellpoint. The views expressed in this article
do not reflect the official policy or position of the National
Institutes of Health, the Department of the Navy, the Department of
Defense, or any other agency of the US Government.
NR 47
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Z9 25
U1 0
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD OCT
PY 2012
VL 18
IS 10
BP 1471
EP 1478
DI 10.1016/j.bbmt.2012.06.003
PG 8
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 013OG
UT WOS:000309314100003
PM 22705497
ER
PT J
AU Inamoto, Y
Martin, PJ
Chai, XY
Jagasia, M
Palmer, J
Pidala, J
Cutler, C
Pavletic, SZ
Arora, M
Jacobsohn, D
Carpenter, PA
Flowers, MED
Khera, N
Vogelsang, GB
Weisdorf, D
Storer, BE
Lee, SJ
AF Inamoto, Yoshihiro
Martin, Paul J.
Chai, Xiaoyu
Jagasia, Madan
Palmer, Jeanne
Pidala, Joseph
Cutler, Corey
Pavletic, Steven Z.
Arora, Mukta
Jacobsohn, David
Carpenter, Paul A.
Flowers, Mary E. D.
Khera, Nandita
Vogelsang, Georgia B.
Weisdorf, Daniel
Storer, Barry E.
Lee, Stephanie J.
CA Chronic GVHD Consortium
TI Clinical Benefit of Response in Chronic Graft-versus-Host Disease
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Allogeneic; Hematopoietic cell transplantation; National Institutes of
Health; Response criteria
ID QUALITY-OF-LIFE; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT;
BONE-MARROW-TRANSPLANTATION; CELL TRANSPLANTATION; CHRONIC GVHD;
EXTRACORPOREAL PHOTOPHERESIS; END-POINTS; CRITERIA; TRIALS
AB To determine whether changes in objective response measures proposed by the National Institutes of Health correlate with clinical benefit, such as symptom burden, quality of life, and survival outcomes, we analyzed data from a multicenter prospective cohort of 283 patients with chronic graft-versus-host disease requiring systemic treatment. The median follow-up time of survivors was 25.1 months (range, 5.4-47.7 months) after enrollment. Symptom measures included the Lee symptom scale and 10-point patient-reported symptoms. Quality-of-life measures included the Short Form-36, Functional Assessment of Cancer Therapy Bone Marrow Transplantation, and Human Activities Profile. Overall and organ-specific responses were calculated by comparing manifestations at the 6-month visit and those at the enrollment visit using a provisional algorithm. Complete or partial responses were considered "response," and stable or progressive disease was considered "no response." Overall response rate at 6 months was 32%. Organ-specific response rates were 45% for skin, 23% for eyes, 32% for mouth, and 51% for gastrointestinal tract. Response at 6 months, as calculated according to the provisional response algorithm, was correlated with changes in symptom burden in patients with newly diagnosed chronic graft-versus-host disease, but not with changes in quality of life or survival outcomes. Modification of the algorithm or validation of other more meaningful clinical endpoints is warranted for future clinical trials of treatment for chronic graft-versus-host disease. Biol Blood Marrow Transplant 18: 1517-1524 (2012) (C) 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
C1 [Inamoto, Yoshihiro; Martin, Paul J.; Chai, Xiaoyu; Carpenter, Paul A.; Flowers, Mary E. D.; Khera, Nandita; Storer, Barry E.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
[Jagasia, Madan] Vanderbilt Univ, Med Ctr, Hematol & Stem Cell Transplant Program, Nashville, TN USA.
[Palmer, Jeanne] Med Coll Wisconsin, Div Hematol Oncol, Milwaukee, WI 53226 USA.
[Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Pavletic, Steven Z.] NCI, Bethesda, MD 20892 USA.
[Arora, Mukta; Weisdorf, Daniel] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN USA.
[Jacobsohn, David] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Div Blood & Marrow Transplantat, Washington, DC 20010 USA.
[Vogelsang, Georgia B.] Johns Hopkins Univ Hosp, Dept Oncol, Baltimore, MD 21287 USA.
RP Inamoto, Y (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, D5-290,1100 Fairview Ave N, Seattle, WA 98109 USA.
EM yinamoto@fhcrc.org
FU National Institutes of Health [CA118953, CA163438]; Japan Society for
the Promotion of Science
FX This work was supported by National Institutes of Health grants CA118953
and CA163438. Y.I. is a recipient of a Japan Society for the Promotion
of Science Postdoctoral Fellowship for Research Abroad. The authors have
no conflicts of interest to disclose.
NR 37
TC 15
Z9 16
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD OCT
PY 2012
VL 18
IS 10
BP 1517
EP 1524
DI 10.1016/j.bbmt.2012.05.016
PG 8
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 013OG
UT WOS:000309314100008
PM 22683612
ER
PT J
AU Shuch, B
Hofmann, JN
Merino, MJ
Nix, J
Vourganti, S
Linehan, WM
Schwartz, K
Ruterbusch, JJ
Colt, JS
Purdue, MP
Chow, WH
AF Shuch, B.
Hofmann, J. N.
Merino, M. J.
Nix, J.
Vourganti, S.
Linehan, W. M.
Schwartz, K.
Ruterbusch, J. J.
Colt, J. S.
Purdue, M. P.
Chow, W-H
TI Pathologic validation of renal cell carcinoma histology in the
surveillance, epidemiology, and end results program
SO BJU INTERNATIONAL
LA English
DT Meeting Abstract
CT 11th International Kidney Cancer Symposium
CY OCT 05-06, 2012
CL Chicago, IL
C1 [Shuch, B.; Nix, J.; Vourganti, S.; Linehan, W. M.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Hofmann, J. N.; Colt, J. S.; Purdue, M. P.; Chow, W-H] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Schwartz, K.; Ruterbusch, J. J.] Wayne State Sch Med, Div Populat Hlth Sci, Detroit, MI USA.
RI Purdue, Mark/C-9228-2016
OI Purdue, Mark/0000-0003-1177-3108
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
J9 BJU INT
JI BJU Int.
PD OCT
PY 2012
VL 110
SU 2
SI SI
MA 07
BP 3
EP 4
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 008BO
UT WOS:000308932400008
ER
PT J
AU Shuch, B
Ricketts, CJ
Vocke, CD
Metwalli, AR
Bratslavsky, G
Middelton, L
Yang, Y
Wei, MH
Pautler, SE
Peterson, J
Stolle, CA
Zbar, B
Merino, MJ
Schmidt, LS
Pinto, PA
Srinivasan, R
Pacak, K
Linehan, WM
AF Shuch, B.
Ricketts, C. J.
Vocke, C. D.
Metwalli, A. R.
Bratslavsky, G.
Middelton, L.
Yang, Y.
Wei, M-H
Pautler, S. E.
Peterson, J.
Stolle, C. A.
Zbar, B.
Merino, M. J.
Schmidt, L. S.
Pinto, P. A.
Srinivasan, R.
Pacak, K.
Linehan, W. M.
TI Succinate dehydrogenase kidney cancer (SDH-RCC): an aggressive example
of the Warburg effect in cancer
SO BJU INTERNATIONAL
LA English
DT Meeting Abstract
CT 11th International Kidney Cancer Symposium
CY OCT 05-06, 2012
CL Chicago, IL
C1 [Shuch, B.; Ricketts, C. J.; Vocke, C. D.; Metwalli, A. R.; Bratslavsky, G.; Middelton, L.; Yang, Y.; Wei, M-H; Peterson, J.; Zbar, B.; Schmidt, L. S.; Pinto, P. A.; Srinivasan, R.; Linehan, W. M.] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Pautler, S. E.] Univ Western Ontario, Dept Urol, London, ON, Canada.
[Pautler, S. E.] Univ Western Ontario, Dept Oncol, London, ON, Canada.
[Stolle, C. A.] Childrens Hosp Philadelphia, Mol Genet Lab, Dept Pathol & Lab Med, Abramson Res Ctr, Philadelphia, PA 19104 USA.
[Merino, M. J.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Schmidt, L. S.] SAIC Frederick Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Pacak, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
J9 BJU INT
JI BJU Int.
PD OCT
PY 2012
VL 110
SU 2
SI SI
MA 08
BP 4
EP 4
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 008BO
UT WOS:000308932400009
ER
PT J
AU Smeenge, M
Barentsz, J
Cosgrove, D
de la Rosette, J
de Reijke, T
Eggener, S
Frauscher, F
Kovacs, G
Matin, SF
Mischi, M
Pinto, P
Rastinehad, A
Rouviere, O
Salomon, G
Polascik, T
Walz, J
Wijkstra, H
Marberger, M
AF Smeenge, Martijn
Barentsz, Jelle
Cosgrove, David
de la Rosette, Jean
de Reijke, Theo
Eggener, Scott
Frauscher, Ferdinand
Kovacs, Gyoergy
Matin, Surena F.
Mischi, Massimo
Pinto, Peter
Rastinehad, Ardeshir
Rouviere, Olivier
Salomon, Georg
Polascik, Thomas
Walz, Jochen
Wijkstra, Hessel
Marberger, Michael
TI Role of transrectal ultrasonography (TRUS) in focal therapy of prostate
cancer: report from a Consensus Panel
SO BJU INTERNATIONAL
LA English
DT Review
DE prostate cancer; focal therapy; consensus; transrectal ultrasonography;
contrast-enhanced ultrasonography; prostate biopsies
ID REAL-TIME ELASTOGRAPHY; CONTRAST-ENHANCED ULTRASONOGRAPHY; GUIDED
BIOPSIES; ULTRASOUND; CRYOSURGERY; EXPERIENCE; ABLATION; IMPACT
AB To establish a consensus on the utility of ultrasonography (US) to select patients for focal therapy. Topics were the current status of US to determine focality of prostate cancer, to monitor and assess outcome of focal therapy and the diagnostic advantages of new US methods. In addition, the biopsy techniques required to identify focal lesions were discussed.
Urological surgeons, radiation oncologists, radiologists, and basic researchers from Europe and North America participated in a consensus meeting on the use of transrectal US (TRUS) in focal therapy of prostate cancer. The consensus process was face-to-face and specific clinical issues were raised and discussed with agreement sought when possible.
TRUS is commonly used and essential for diagnosing men with prostate cancer. It is particularly useful for targeting specific anatomical regions or visible lesions. However, it has several limitations and there is a need for improvement. Newer visualisation techniques, e.g. colour Doppler US, contrast-enhanced US and elastography, are being developed but currently there is no US technique that can accurately characterise a cancer suitable for focal therapy. Systematic biopsy is the only known procedure that allows the identification of prostate cancers suitable for focal therapy. Scarce data exist about the role of US for monitoring patients during or after ablative therapy.
Consensus was reached on all key aspects of the meeting.
US cannot reliably identify focal prostate cancer. New US methods show promising results in identifying prostate cancer focality.
Currently selecting appropriate candidates for focal therapy should be performed using dedicated protocols and biopsy schemes.
C1 [Smeenge, Martijn; de la Rosette, Jean; de Reijke, Theo; Wijkstra, Hessel] AMC Univ Hosp, Dept Urol, NL-1105 AZ Amsterdam, Netherlands.
[Barentsz, Jelle] Radboud Univ Nijmegen, Med Ctr, Dept Radiol, NL-6525 ED Nijmegen, Netherlands.
[Cosgrove, David] Univ London Imperial Coll Sci Technol & Med, Imaging Sci Dept, London, England.
[Eggener, Scott] Univ Chicago, Urol Sect, Chicago, IL 60637 USA.
[Frauscher, Ferdinand] Med Univ Innsbruck, Dept Radiol, Innsbruck, Austria.
[Kovacs, Gyoergy] Univ Lubeck, Interdisciplinary Brachytherapy Unit, Lubeck, Germany.
[Matin, Surena F.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA.
[Mischi, Massimo; Wijkstra, Hessel] Eindhoven Univ Technol, Dept Elect Engn, NL-5600 MB Eindhoven, Netherlands.
[Pinto, Peter; Rastinehad, Ardeshir] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Rouviere, Olivier] Hop Edouard Herriot, Dept Urinary & Vasc Radiol, Lyon, France.
[Salomon, Georg] Univ Hamburg Hosp, Martini Clin, Prostate Canc Ctr, Hamburg, Germany.
[Polascik, Thomas] Duke Univ, Med Ctr, Div Urol Surg, Durham, NC USA.
[Walz, Jochen] Inst J Paoli I Calmettes, Ctr Canc, Dept Urol, F-13009 Marseille, France.
[Marberger, Michael] Med Univ Vienna, Dept Urol, Vienna, Austria.
RP Smeenge, M (reprint author), AMC Univ Hosp, Dept Urol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
EM M.smeenge@amc.uva.nl
RI Barentsz, Jelle/D-3515-2009;
OI Rouviere, Olivier/0000-0002-0030-478X
FU Bracco SpA; Galil and Bracco SpA; Visualase, Inc.
FX David Cosgrove received support from Bracco SpA attending scientific
meetings. Jean de la Rosette received support from Galil and Bracco SpA
for conducting studies. Scott Eggener received funding from Visualase,
Inc. for conducting studies. Ferdinand Frauscher received support from
Bracco SpA attending scientific meetings and training.
NR 36
TC 16
Z9 17
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
J9 BJU INT
JI BJU Int.
PD OCT
PY 2012
VL 110
IS 7
BP 942
EP 948
DI 10.1111/j.1464-410X.2012.11072.x
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 009XU
UT WOS:000309059600007
PM 22462566
ER
PT J
AU Sutcliffe, S
Grubb, RL
Platz, EA
Ragard, LR
Riley, TL
Kazin, SS
Hayes, RB
Hsing, AW
Andriole, GL
AF Sutcliffe, Siobhan
Grubb, Robert L., III
Platz, Elizabeth A.
Ragard, Lawrence R.
Riley, Thomas L.
Kazin, Sally S.
Hayes, Richard B.
Hsing, Ann W.
Andriole, Gerald L.
CA Urologic Dis Amer Project
TI Non-steroidal anti-inflammatory drug use and the risk of benign
prostatic hyperplasia-related outcomes and nocturia in the Prostate,
Lung, Colorectal, and Ovarian Cancer Screening Trial
SO BJU INTERNATIONAL
LA English
DT Article
DE aspirin; benign prostatic hyperplasia; ibuprofen; lower urinary tract
symptoms; non-steroidal anti-inflammatory drugs
ID URINARY-TRACT SYMPTOMS; INFLAMMATION; MEN; ANTIGEN; ASSOCIATION;
PREDICTOR; DESIGN; VOLUME
AB OBJECTIVE
To investigate the relationship between non-steroidal anti-inflammatory drug (NSAID) use and the incidence of benign prostatic hyperplasia (BPH)-related outcomes and nocturia, a lower urinary tract symptom (LUTS) of BPH, in light of accumulating evidence suggesting a role for inflammation in BPH/LUTS development.
PATIENTS AND METHODS
At baseline, participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial completed questions on recent, regular aspirin and ibuprofen use, BPH surgery, diagnosis of an enlarged prostate/BPH, and nocturia. Participants in the intervention arm also underwent a digital rectal examination (DRE), from which prostate dimensions were estimated, as well as a prostate-specific antigen (PSA) test. Only participants in the intervention arm without BPH/LUTS at baseline were included in the analysis (n = 4771).
During follow-up, participants underwent annual DREs and PSA tests, provided annual information on finasteride use, and completed a supplemental questionnaire in 2006-2008 that included additional questions on diagnosis of an enlarged prostate/BPH and nocturia.
Information collected was used to investigate regular aspirin or ibuprofen use in relation to the incidence of six BPH/LUTS definitions: diagnosis of an enlarged prostate/BPH, nocturia (waking two or more times per night to urinate), finasteride use, any self-reported BPH/LUTS, prostate enlargement (estimated prostate volume >= 30 mL on any follow-up DRE) and elevation in PSA level (>1.4 ng/mL on any follow-up PSA test).
RESULTS
Generally, null results were observed for any recent, regular aspirin or ibuprofen use (risk ratio = 0.92-1.21, P = 0.043-0.91) and frequency of use (risk ratios for one category increase in NSAID use = 0.98-1.11, P-trends = 0.10-0.99) with incident BPH/LUTS.
CONCLUSION
The findings obtained in the present study do not support a protective role for recent NSAID use in BPH/LUTS development.
C1 [Sutcliffe, Siobhan] Washington Univ, Div Publ Hlth Sci, Sch Med, St Louis, MO 63110 USA.
[Sutcliffe, Siobhan] Washington Univ, Alvin J Siteman Canc Ctr, Sch Med, Dept Surg, St Louis, MO 63110 USA.
[Grubb, Robert L., III; Andriole, Gerald L.] Washington Univ, Div Urol Surg, Sch Med, St Louis, MO 63110 USA.
[Platz, Elizabeth A.] Johns Hopkins Med Inst, Dept Epidemiol, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Platz, Elizabeth A.] Johns Hopkins Med Inst, Brady Urol Inst, Baltimore, MD 21205 USA.
[Platz, Elizabeth A.] Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA.
[Ragard, Lawrence R.] Westat Corp, Rockville, MD USA.
[Riley, Thomas L.] Informat Management Serv Inc, Rockville, MD USA.
[Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Kazin, Sally S.] Univ Georgia, Dept Math, Athens, GA 30602 USA.
[Hayes, Richard B.] NYU, Sch Med, Div Epidemiol, Dept Environm Med, New York, NY USA.
RP Sutcliffe, S (reprint author), Washington Univ, Div Publ Hlth Sci, Sch Med, 660 S Euclid Ave,Box 8100,Room 5026, St Louis, MO 63110 USA.
EM sutcliffes@wudosis.wustl.edu
OI Sutcliffe, Siobhan/0000-0002-4613-8107; Hayes,
Richard/0000-0002-0918-661X
FU Urologic Diseases in America Project [N01-DK-70003]
FX This analysis was funded by the Urologic Diseases in America Project
(N01-DK-70003). The authors thank Drs Paul Pinsky (National Cancer
Institute) and Jennifer St Sauver (Mayo Clinic College of Medicine) for
helpful discussion relating to the manuscript, as well as Drs Christine
Berg and Philip Prorok (Division of Cancer Prevention, National Cancer
Institute), the Screening Center investigators and staff of PLCO, the
staff at Information Management Services Inc., and Barbara O ' Brien and
staff (Westat) for their contributions to PLCO.; Gerald L. Andriole is a
Consultant to Bristol Myers Squibb Co. and Viking Medical, an Investor
in Envisioneering Medical, a Consultant/Advisor to Amarex LLC, Amgen,
Augmenix, Bayer, Cambridge Endo, Caris, GlaxoSmithKline, Janssen
Biotech, Inc., Myriad Genetics, Steba Biotech, and Ortho-Clinical
Diagnostics, and declares financial compensation in relation to all
these roles.
NR 23
TC 17
Z9 19
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
J9 BJU INT
JI BJU Int.
PD OCT
PY 2012
VL 110
IS 7
BP 1050
EP 1059
DI 10.1111/j.1464-410X.2011.10867.x
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA 009XU
UT WOS:000309059600023
PM 22429766
ER
PT J
AU Torres, AR
Westover, JB
Gibbons, C
Johnson, RC
Ward, DC
AF Torres, Anthony R.
Westover, Jonna B.
Gibbons, Cole
Johnson, Randall C.
Ward, David C.
TI Activating killer-cell immunoglobulin-like receptors (KIR) and their
cognate HLA ligands are significantly increased in autism
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Article
DE Killer-cell immunoglobulin-like receptor; KIR genes; KIR haplotypes;
Human leukocyte antigen; HLA ligands; Leukocyte receptor complex;
Autism; Immune dysfunction; Natural killer cells
ID PERVASIVE DEVELOPMENTAL DISORDERS; SPECTRUM DISORDERS; INCREASED
PREVALENCE; AUTOIMMUNE-DISEASES; INCREASED FREQUENCY; DIAGNOSTIC CHANGE;
FAMILY-HISTORY; NULL ALLELE; CHILDREN; ASSOCIATION
AB Killer-cell immunoglobulin-like receptor (KIR) proteins are expressed on natural killer (NK) cells and appear important in innate and adaptive immunity. There are about 14 KIR genes on chromosome 19q13.4, composed of those that inhibit and those that activate NK cell killing. Haplotypes have different combinations of these genes meaning that not all genes are present in a subject. There are two main classes of cognate human leukocyte antigen (HLA) ligands (HLA-Bw4 and HLA-C1/C2) that bind to the inhibitory/activating receptors. As a general rule, the inhibitory state is maintained except when virally infected or tumor cells are encountered; however, both increased activation and inhibition states have been associated with susceptibility and protection against numerous disease states including cancer, arthritis, and psoriasis.
Utilizing DNA from 158 Caucasian subjects with autism and 176 KIR control subjects we show for the first time a highly significant increase in four activating KIR genes (2DS5, 3DS1, 2DS1 and 2DS4) as measured by chi square values and odds ratios. In addition, our data suggests a highly significant increase in the activating KIR gene 2DS1 and its cognate HLA-C2 ligand (2051 + C2; p = 0.00003 [Odds ratio = 2.87]). This information ties together two major immune gene complexes, the human leukocyte complex and the leukocyte receptor complex, and may partially explain immune abnormalities observed in many subjects with autism. (c) 2012 Elsevier Inc. All fights reserved.
C1 [Torres, Anthony R.; Westover, Jonna B.; Gibbons, Cole] Utah State Univ, Ctr Persons Disabil, Logan, UT 84322 USA.
[Gibbons, Cole] Utah State Univ, Dept Bioengn, Logan, UT 84322 USA.
[Johnson, Randall C.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, BSP CCR Genet Core, Frederick, MD 21702 USA.
[Johnson, Randall C.] Conservatoire Natl Arts & Metiers, Chaire Bioinformat, Paris, France.
[Ward, David C.] Utah State Univ, Ctr Adv Nutr, Logan, UT 84322 USA.
RP Torres, AR (reprint author), Utah State Univ, Ctr Persons Disabil, 6804 Old Main Hill, Logan, UT 84322 USA.
EM Anthony.Torres@usu.edu
RI Johnson, Randall/B-1517-2014
OI Johnson, Randall/0000-0001-7754-0847
FU Early Markers for Autism NIH grant [RO1-ESO16669]; Utah Science
Technology and Research (USTAR) initiative at Utah State University;
Utah Autism Foundation (SLC, Utah); Frederick National Laboratory for
Cancer Research; National Institutes of Health [HHSN261200800001E];
Intramural Research Program of NIH; Frederick National Laboratory;
Center for Cancer Research
FX We gratefully acknowledge the resources provided by the ACRE Consortium
and the participating AGRE families. Funding was provided [in part] by
the Early Markers for Autism NIH grant RO1-ESO16669, the Utah Science
Technology and Research (USTAR) initiative at Utah State University, and
the Utah Autism Foundation (SLC, Utah). This project also received
Federal funding [in part] from the Frederick National Laboratory for
Cancer Research, National Institutes of Health, under contract
HHSN261200800001E. This research was also supported [in part] by the
Intramural Research Program of NIH, Frederick National Laboratory,
Center for Cancer Research. The content of this publication does not
necessarily reflect the views of policies of the Department of Health
and Human Services, nor does its mention of trade names, commercial
products or organizations imply endorsement of the US Government.
NR 46
TC 12
Z9 12
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1591
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD OCT
PY 2012
VL 26
IS 7
BP 1122
EP 1127
DI 10.1016/j.bbi.2012.07.014
PG 6
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 007PC
UT WOS:000308899600015
PM 22884899
ER
PT J
AU Speaks, C
McGlynn, KA
Cook, MB
AF Speaks, Crystal
McGlynn, Katherine A.
Cook, Michael B.
TI Significant calendar period deviations in testicular germ cell tumors
indicate that postnatal exposures are etiologically relevant
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Testicular cancer; Age-period-cohort; Carcinoma in situ; Calendar period
deviations
ID CANCER INCIDENCE; EUROPEAN COUNTRIES; CARCINOMA-INSITU; COHORT MODELS;
UNDESCENDED TESTIS; MARIJUANA USE; TIME TRENDS; AGE; MORTALITY; RATES
AB The current working model of type II testicular germ cell tumor (TGCT) pathogenesis states that carcinoma in situ arises during embryogenesis, is a necessary precursor, and always progresses to cancer. An implicit condition of this model is that only in utero exposures affect the development of TGCT in later life. In an age-period-cohort analysis, this working model contends an absence of calendar period deviations. We tested this contention using data from the SEER registries of the United States.
We assessed age-period-cohort models of TGCTs, seminomas, and nonseminomas for the period 1973-2008. Analyses were restricted to whites diagnosed at ages 15-74 years. We tested whether calendar period deviations were significant in TGCT incidence trends adjusted for age deviations and cohort effects.
This analysis included 32,250 TGCTs (18,475 seminomas and 13,775 nonseminomas). Seminoma incidence trends have increased with an average annual percentage change in log-linear rates (net drift) of 1.25 %, relative to just 0.14 % for nonseminoma. In more recent time periods, TGCT incidence trends have plateaued and then undergone a slight decrease. Calendar period deviations were highly statistically significant in models of TGCT (p = 1.24(-9)) and seminoma (p = 3.99(-14)), after adjustment for age deviations and cohort effects; results for nonseminoma (p = 0.02) indicated that the effects of calendar period were much more muted.
Calendar period deviations play a significant role in incidence trends of TGCT, which indicates that postnatal exposures are etiologically relevant.
C1 [McGlynn, Katherine A.; Cook, Michael B.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20852 USA.
[Speaks, Crystal] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA.
RP Cook, MB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS Suite 550, Bethesda, MD 20852 USA.
EM michael.cook@nih.gov
RI Cook, Michael/A-5641-2009
OI Cook, Michael/0000-0002-0533-7302
FU National Cancer Institute, National Institutes of Health, Department of
Health and Human Services
FX The study was supported by Intramural Program of the National Cancer
Institute, National Institutes of Health, Department of Health and Human
Services.
NR 40
TC 3
Z9 3
U1 1
U2 5
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD OCT
PY 2012
VL 23
IS 10
BP 1593
EP 1598
DI 10.1007/s10552-012-0036-5
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 006JC
UT WOS:000308814400001
PM 22941667
ER
PT J
AU Kitahara, CM
Linet, MS
Freeman, LEB
Check, DP
Church, TR
Park, Y
Purdue, MP
Schairer, C
de Gonzalez, AB
AF Kitahara, Cari M.
Linet, Martha S.
Freeman, Laura E. Beane
Check, David P.
Church, Timothy R.
Park, Yikyung
Purdue, Mark P.
Schairer, Catherine
de Gonzalez, Amy Berrington
TI Cigarette smoking, alcohol intake, and thyroid cancer risk: a pooled
analysis of five prospective studies in the United States
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Thyroid neoplasms; Cigarette smoking; Alcohol intake; Prospective study;
Epidemiology
ID THYROTROPIN CONCENTRATION; HORMONE LEVELS; US MEN; WOMEN; CONSUMPTION;
METAANALYSIS; POPULATION; PREVALENCE; PAPILLARY; EXPOSURE
AB We examined the associations between cigarette smoking, alcohol intake, and thyroid cancer risk in a pooled analysis of five prospective studies.
Data from five prospective U.S. studies were standardized and then combined into one aggregate dataset (384,433 men and 361,664 women). Pooled hazard ratios (HR) and 95 % confidence intervals (CI) for thyroid cancer were estimated from mutually adjusted models of cigarette smoking and alcohol intake, which were additionally adjusted for age, sex, education, race, marital status, body mass index, and cohort.
Over follow-up, 1,003 incident thyroid cancer cases (335 men and 668 women) were identified. Compared to never smokers, current smoking was associated with reduced risk of thyroid cancer (HR = 0.68, 95 % CI 0.55-0.85); this association was slightly stronger among non-drinkers (HR = 0.46, 95 % CI 0.29-0.74). No reduction in risk was observed for former, compared to never, smokers. Greater smoking intensity, duration, and pack-years were associated with further reductions in risk among former and current smokers. Alcohol intake was also inversely associated with thyroid cancer risk (a parts per thousand yen7 drinks/week versus 0, HR = 0.72, 95 % CI 0.58-0.90, p trend = 0.002). Inverse associations with smoking and alcohol were more pronounced for papillary versus follicular tumors.
The results of this pooled analysis suggest that both cigarette smoking and alcohol consumption are associated with reduced risks of papillary thyroid cancer and, possibly, follicular thyroid cancer.
C1 [Kitahara, Cari M.; Linet, Martha S.; Freeman, Laura E. Beane; Check, David P.; Park, Yikyung; Purdue, Mark P.; Schairer, Catherine; de Gonzalez, Amy Berrington] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Church, Timothy R.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN USA.
RP Kitahara, CM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, EPS 7056,6120 Execut Blvd, Rockville, MD 20852 USA.
EM kitaharac@mail.nih.gov
RI Purdue, Mark/C-9228-2016; Beane Freeman, Laura/C-4468-2015; Kitahara,
Cari/R-8267-2016; Check, David/J-7184-2015;
OI Purdue, Mark/0000-0003-1177-3108; Beane Freeman,
Laura/0000-0003-1294-4124; Check, David/0000-0003-3887-0493; Church,
Timothy R./0000-0003-3292-5035; Park, Yikyung/0000-0002-6281-489X
FU National Institutes of Health; National Institute of Environmental
Health Sciences [Z01-ES049030]; National Cancer Institute [Z01-CP010119]
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, the National Institute of
Environmental Health Sciences (Z01-ES049030) and National Cancer
Institute (Z01-CP010119).
NR 40
TC 32
Z9 33
U1 0
U2 9
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD OCT
PY 2012
VL 23
IS 10
BP 1615
EP 1624
DI 10.1007/s10552-012-0039-2
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 006JC
UT WOS:000308814400004
PM 22843022
ER
PT J
AU Schonfeld, SJ
Curtis, RE
Anderson, WF
de Gonzalez, AB
AF Schonfeld, Sara J.
Curtis, Rochelle E.
Anderson, William F.
de Gonzalez, Amy Berrington
TI The risk of a second primary lung cancer after a first invasive breast
cancer according to estrogen receptor status
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Breast cancer; Lung cancer; Estrogen receptor status; Second primary
ID GROWTH-FACTOR RECEPTOR; CIGARETTE-SMOKING; AMERICAN-SOCIETY; WOMEN;
EPIDEMIOLOGY; SURVEILLANCE; MALIGNANCIES; RADIOTHERAPY; GUIDELINES;
TAMOXIFEN
AB Lung cancers account for 5 % of second primary cancers after breast cancer. The low overall 5-year relative survival rate of lung cancer makes it a particularly concerning new malignancy for breast cancer survivors. It is unknown whether second lung cancer risk varies by estrogen receptor (ER) expression of the first breast cancer.
We evaluated second primary lung cancer risks using standardized incidence ratios (SIRs) (95 % confidence intervals (CIs)) among 222,148 one-year breast cancer survivors in the NCI-SEER Program registry database (1992-2008). Relative risks (RRs) and 95 % CIs for lung cancer following ER- compared with ER+ breast cancer were estimated using Poisson regression, adjusted for age, year, and stage of breast cancer diagnosis, attained age, latency, and radiotherapy. We also examined the reciprocal association of second ER- and ER+ breast cancers among 28,107 1-year lung cancer survivors.
There were 418 and 1,444 second lung cancers diagnosed following 50,781 ER- and 171,367 ER+ breast cancers. Second lung cancer rates were significantly elevated after ER- (SIR = 1.20 (1.09-1.33)), but not ER+ (SIR = 0.96 (0.91-1.01)) breast cancer. The adjusted RR for a second lung cancer following ER- compared with ER+ breast cancer was 1.22 (1.10-1.37). The reciprocal adjusted RR for a second ER- compared with ER+ breast cancer following lung cancer was 1.29 (0.98-1.70).
The parallel increase for a second lung cancer following an ER- first breast cancer and for a second ER- breast cancer after a first lung cancer suggests that there may be shared etiologic factors for these cancers. Further evaluation of lung cancer risk after ER- breast cancer may identify women at high risk for this fatal malignancy.
C1 [Schonfeld, Sara J.; Curtis, Rochelle E.; Anderson, William F.; de Gonzalez, Amy Berrington] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Schonfeld, SJ (reprint author), Int Agcy Res Canc, Sect Environm & Radiat, 150 Cours Albert Thomas, F-69372 Lyon 08, France.
EM schonfelds@fellows.iarc.fr
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute
FX This research was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute.
NR 40
TC 6
Z9 7
U1 0
U2 5
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD OCT
PY 2012
VL 23
IS 10
BP 1721
EP 1728
DI 10.1007/s10552-012-0054-3
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 006JC
UT WOS:000308814400015
PM 22918549
ER
PT J
AU Brell, JM
Krishnamurthi, SS
Rath, L
Bokar, JA
Savvides, P
Gibbons, J
Cooney, MM
Meropol, NJ
Ivy, P
Dowlati, A
AF Brell, Joanna M.
Krishnamurthi, Smitha S.
Rath, Linda
Bokar, Joseph A.
Savvides, Panayiotis
Gibbons, Joseph
Cooney, Matthew M.
Meropol, Neal J.
Ivy, Percy
Dowlati, Afshin
TI Phase I trial of sunitinib and gemcitabine in patients with advanced
solid tumors
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE Phase I; Sunitinib; Gemcitabine; Pancreatic cancer
ID ADVANCED PANCREATIC-CANCER; CELL LUNG-CANCER; III TRIAL; BEVACIZUMAB;
ADENOCARCINOMA; COMBINATION; CARBOPLATIN; PACLITAXEL; INHIBITOR; PLACEBO
AB Combining cytotoxic agents with bevacizumab has yielded significant benefits in a number of solid tumors. Combining small-molecule kinase inhibitors of VEGFR with chemotherapy has yet to demonstrate clinical benefit. The dose, schedule and agents used may be critical to the development of this combinatorial therapy.
We performed a phase I trial of sunitinib and gemcitabine in patients with advanced solid tumor malignancies based on strong preclinical rationale.
Two different MTDs were determined. The schedule of gemcitabine 800 mg/m2 on days 1, 8, 15 and sunitinib 25 mg daily was considered to be a MTD. However, omission of day 15 gemcitabine was common, and thus, a second MTD of gemcitabine of 675 mg/m2 on days 1 and 8 with sunitinib 25 mg daily was determined to be the recommended phase II dose. Grade 4 neutropenia and thrombocytopenia occurred in 33 and 6 %, respectively. Grade 3/4 non-hematological toxicities were uncommon. Four of 33 patients had a partial response. Another 11 patients had stable disease ranging from 3 to 36 months. Thus, the recommended phase II dose of this combination is gemcitabine 675 mg/m2 on days 1 and 8 on an every 21-day schedule along with sunitinib 25 mg continuous daily.
This combination is well-tolerated and has significant clinical activity.
C1 [Dowlati, Afshin] Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA.
[Ivy, Percy] NCI, CTEP, Bethesda, MD 20892 USA.
[Brell, Joanna M.; Krishnamurthi, Smitha S.; Rath, Linda; Bokar, Joseph A.; Savvides, Panayiotis; Gibbons, Joseph; Cooney, Matthew M.; Meropol, Neal J.; Dowlati, Afshin] Case Western Reserve Univ, Univ Hosp Seidman Canc Ctr, Cleveland, OH 44106 USA.
[Brell, Joanna M.; Krishnamurthi, Smitha S.; Rath, Linda; Bokar, Joseph A.; Savvides, Panayiotis; Gibbons, Joseph; Cooney, Matthew M.; Meropol, Neal J.; Dowlati, Afshin] Case Western Reserve Univ, Dev Therapeut Program, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA.
RP Dowlati, A (reprint author), Univ Hosp Case Med Ctr, 11100 Euclid Ave, Cleveland, OH 44106 USA.
EM afshin.dowlati@case.edu
FU NIH [U01 CA62502]
FX Supported by NIH Grant U01 CA62502 (PI: AD).
NR 15
TC 8
Z9 8
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD OCT
PY 2012
VL 70
IS 4
BP 547
EP 553
DI 10.1007/s00280-012-1936-5
PG 7
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 011YF
UT WOS:000309201500007
PM 22868341
ER
PT J
AU Abi-Jaoudeh, N
Kruecker, J
Kadoury, S
Kobeiter, H
Venkatesan, AM
Levy, E
Wood, BJ
AF Abi-Jaoudeh, Nadine
Kruecker, Jochen
Kadoury, Samuel
Kobeiter, Hicham
Venkatesan, Aradhana M.
Levy, Elliot
Wood, Bradford J.
TI Multimodality Image Fusion-Guided Procedures: Technique, Accuracy, and
Applications
SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Review
DE Ablation; Imaging; Interventional oncology; Chemoembolization;
Endovascular aneurysm repair; Image fusion; Navigation
ID ELECTROMAGNETIC NAVIGATION BRONCHOSCOPY; NEEDLE PATH OVERLAY;
RADIOFREQUENCY ABLATION; LIVER-TUMOR; GUIDANCE; BIOPSY; CT; SYSTEMS;
SURGERY; LESIONS
AB Personalized therapies play an increasingly critical role in cancer care: Image guidance with multimodality image fusion facilitates the targeting of specific tissue for tissue characterization and plays a role in drug discovery and optimization of tailored therapies. Positron-emission tomography (PET), magnetic resonance imaging (MRI), and contrast-enhanced computed tomography (CT) may offer additional information not otherwise available to the operator during minimally invasive image-guided procedures, such as biopsy and ablation. With use of multimodality image fusion for image-guided interventions, navigation with advanced modalities does not require the physical presence of the PET, MRI, or CT imaging system. Several commercially available methods of image-fusion and device navigation are reviewed along with an explanation of common tracking hardware and software. An overview of current clinical applications for multimodality navigation is provided.
C1 [Abi-Jaoudeh, Nadine] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Kruecker, Jochen] Philips Res N Amer, Briarcliff Manor, NY USA.
[Kadoury, Samuel] Ecole Polytech, Dept Comp & Software Engn, Inst Biomed Engn, Montreal, PQ H3C 3A7, Canada.
[Kobeiter, Hicham] CHU Henri Mondor, UPEC, Dept Radiol, F-94000 Creteil, France.
[Kobeiter, Hicham] CHU Henri Mondor, UPEC, Dept Imagrie Med, F-94000 Creteil, France.
RP Abi-Jaoudeh, N (reprint author), NIH, Ctr Clin, Rm 1C365,Bldg 10,MSC 1182,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM naj@mail.nih.gov; jochen.kruecker@philips.com;
samuel.kadoury@polymtl.ca; hicham.kobeiter@gmail.com;
VenkatesanA@cc.nih.gov; levyeb@cc.nih.gov; bwood@cc.nih.gov
FU National Institutes of Health (NIH) Center for Interventional Oncology;
NIH; Philips Health Care
FX We acknowledge Peter Pinto, Peter Choyke, Baris Turkbey, Julie Locklin,
and Stacey Gates for their contributions toward the prostate fusion
biopsy section. We also acknowledge Ankur Kapoor for contributions on
the optical-tracking section. This work was supported in part by the
National Institutes of Health (NIH) Center for Interventional Oncology
and the NIH Intramural Research Program. This work was also supported by
collaborative research and development agreements (NIH and Philips
Health Care). The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the United States Government.
NR 47
TC 40
Z9 41
U1 7
U2 29
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0174-1551
J9 CARDIOVASC INTER RAD
JI Cardiovasc. Interv. Radiol.
PD OCT
PY 2012
VL 35
IS 5
BP 986
EP 998
DI 10.1007/s00270-012-0446-5
PG 13
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 008II
UT WOS:000308950200003
PM 22851166
ER
PT J
AU Kim, JH
Park, JH
Choo, K
Song, SK
Kim, JS
Park, YH
Kim, J
Chun, KJ
Han, D
Faranesh, AZ
Lederman, RJ
AF Kim, June-Hong
Park, Ju-Hyun
Choo, Kiseok
Song, Sung-Kook
Kim, Jung-Su
Park, Young-Hyun
Kim, Jun
Chun, Kook-Jin
Han, Dongcheul
Faranesh, Anthony Z.
Lederman, Robert J.
TI Pressure-wire based assessment of microvascular resistance using
calibrated upstream balloon obstruction
SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
LA English
DT Article
DE coronary artery physiology; microvascular resistance; magnetic resonance
imaging; interventional cardiology; intravascular diagnostics
ID FRACTIONAL FLOW RESERVE; MYOCARDIAL-INFARCTION; MICROCIRCULATORY
RESISTANCE; CORONARY INTERVENTION; VIABLE MYOCARDIUM; STENOSIS SEVERITY;
CATHETERIZATION; INDEX; ANGIOPLASTY; GUIDELINES
AB Objectives: We assess microvascular integrity as a marker of myocardial viability after coronary stenting, using only a pressure guidewire. Background: Microvascular integrity generally is not assessed using pressure-only guidewires because the transducer lies upstream of microvasculature. We partially inflate a balloon inside a coronary stent to achieve a specific normalized pressure drop at rest (distal coronary/aortic pressure = 0.8) and then infuse a vasodilator, to render the wire sensitive to microvascular function. We hypothesize that the further decline in pressure (?FFR0.8) predicts MRI myocardial viability. Methods: We studied 29 subjects with acute coronary syndrome including myocardial infarction. After successful culprit stenting, the resting coronary/aortic pressure was set to 0.8 using temporary balloon obstruction. ?FFR0.8 was defined as 0.8-(distal coronary/aortic pressures) during adenosine-induced hyperemia. The average transmural extent of infarction was defined as the average area of MRI late gadolinium enhancement (after 2.8 +/- 1.5 days) divided by the corresponding full thickness of the gadolinium enhanced sector in short axis slices, and was compared with ?FFR0.8. Results: ?FFR0.8 corresponded inversely and linearly with the average transmural extent of infarction (r2 = 0.65, P < 0.001). We found that a transmural extent of infarction of 0.50 corresponded to a ?FFR0.8 threshold of 0.1, and had high sensitivity and specificity (100% and 94.4%, respectively). Conclusions: Using only an upstream pressure-sensitive guidewire and a partially obstructing balloon during pharmacologic hyperemia, we were able to predict MRI myocardial viability with high accuracy after relief of epicardial stenosis. With further validation, this may prove a useful clinical prognostic tool after percutaneous intervention. (c) 2011 Wiley Periodicals, Inc.
C1 [Lederman, Robert J.] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Kim, June-Hong; Park, Ju-Hyun; Choo, Kiseok; Song, Sung-Kook; Kim, Jung-Su; Park, Young-Hyun; Kim, Jun; Chun, Kook-Jin; Han, Dongcheul] Pusan Natl Univ, Div Cardiol, Dept Internal Med, Yangsan Hosp, Pusan, South Korea.
[Kim, June-Hong; Park, Ju-Hyun; Choo, Kiseok; Song, Sung-Kook; Kim, Jung-Su; Park, Young-Hyun; Kim, Jun; Chun, Kook-Jin; Han, Dongcheul] Pusan Natl Univ, Res Inst Convergence Biomed Sci & Technol, Yangsan Hosp, Pusan, South Korea.
RP Lederman, RJ (reprint author), NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bldg 10,Room 2C713,MSC1538, Bethesda, MD 20892 USA.
EM lederman@nih.gov
OI lederman, robert/0000-0003-1202-6673
FU Korean Society of Interventional Cardiology [2009007]; Division of
Intramural Research; National Heart Lung and Blood Institute; National
Institutes of Health USA [Z01-HL006061-01]
FX Grant sponsor: Korean Society of Interventional Cardiology; grant
number: 2009007; Grant sponsors: Division of Intramural Research;
National Heart Lung and Blood Institute; Grant sponsor: National
Institutes of Health USA; grant number: Z01-HL006061-01
NR 23
TC 3
Z9 3
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1522-1946
J9 CATHETER CARDIO INTE
JI Catheter. Cardiovasc. Interv.
PD OCT 1
PY 2012
VL 80
IS 4
BP 581
EP 589
DI 10.1002/ccd.23277
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 008AN
UT WOS:000308929600016
PM 21805603
ER
PT J
AU Otto, M
AF Otto, Michael
TI MRSA virulence and spread
SO CELLULAR MICROBIOLOGY
LA English
DT Review
ID RESISTANT STAPHYLOCOCCUS-AUREUS; PANTON-VALENTINE LEUKOCIDIN;
METHICILLIN RESISTANCE; NASAL COLONIZATION; EPITHELIAL-CELLS;
UNITED-STATES; INFECTIONS; PENICILLIN; EMERGENCE; CARRIAGE
AB Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most frequent causes of hospital- and community-associated infections. Resistance to the entire class of beta-lactam antibiotics, such as methicillin and penicillin, makes MRSA infections difficult to treat. Hospital-associated MRSA strains are often multi-drug-resistant, leaving only lower efficiency drugs such as vancomycin as treatments options. Like many other S.?aureus strains, MRSA strains produce a series of virulence factors, such as toxins and adhesion proteins. Recent findings have shed some new light on the molecular events that underlie MRSA epidemic waves. Newly emerging MRSA clones appear to have acquired phenotypic traits that render them more virulent or able to colonize better, either via mobile genetic elements or via adaptation of gene expression. Acquisition of Panton-Valentine leukocidin genes and increased expression of core genome-encoded toxins are being discussed as potentially contributing to the success of the recently emerged community-associated MRSA strains. However, the molecular factors underlying the spread of hospital- and community-associated MRSA strains are still far from being completely understood, a situation calling for enhanced research efforts in that area.
C1 NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
RP Otto, M (reprint author), NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM motto@niaid.nih.gov
OI Otto, Michael/0000-0002-2222-4115
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases (NIAID), NIH
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases (NIAID), NIH.
NR 50
TC 85
Z9 89
U1 0
U2 76
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1462-5814
J9 CELL MICROBIOL
JI Cell Microbiol.
PD OCT
PY 2012
VL 14
IS 10
BP 1513
EP 1521
DI 10.1111/j.1462-5822.2012.01832.x
PG 9
WC Cell Biology; Microbiology
SC Cell Biology; Microbiology
GA 007IF
UT WOS:000308881300002
PM 22747834
ER
PT J
AU Maruvada, R
Zhu, LK
Pearce, D
Zheng, Y
Perfect, J
Kwon-Chung, KJ
Kim, KS
AF Maruvada, Ravi
Zhu, Longkun
Pearce, Donna
Zheng, Yi
Perfect, John
Kwon-Chung, Kyung J.
Kim, Kwang Sik
TI Cryptococcus neoformans phospholipase B1 activates host cell Rac1 for
traversal across the blood-brain barrier
SO CELLULAR MICROBIOLOGY
LA English
DT Article
ID MICROVASCULAR ENDOTHELIAL-CELLS; CENTRAL-NERVOUS-SYSTEM; ACTIN
CYTOSKELETON; MENINGITIS; INFECTION; INVASION; GTPASE; ADULTS;
PENETRATION; DOWNSTREAM
AB Cryptococcus neoformans penetration into the central nervous system (CNS) requires traversal of the bloodbrain barrier that is composed of a single layer of human brain microvascular endothelial cells (HBMEC), but the underlying mechanisms of C.?neoformans traversal remain incompletely understood. C.?neoformans transcytosis of HBMEC monolayer involves rearrangements of the host cell actin cytoskeleton and small GTP-binding Rho family proteins such as Rac1 are shown to regulate host cell actin cytoskeleton. We, therefore, examined whether C.?neoformans traversal of the bloodbrain barrier involves host Rac1. While the levels of activated Rac1 (GTP-Rac1) in HBMEC increased significantly upon incubation with C.?neoformans strains, pharmacological inhibition and down-modulation of Rac1 significantly decreased C.?neoformans transcytosis of HBMEC monolayer. Also, Rac1 inhibition was efficient in preventing C.?neoformans penetration into the brain. In addition, C.?neoformans phospholipase B1 (Plb1) was shown to contribute to activating host cell Rac1, andSTAT3 was observed to associate with GTP-Rac1 in HBMEC that were incubated with C.?neoformans strain but not with its ?plb1 mutant. These findings demonstrate for the first time that C.?neoformans Plb1 aids fungal traversal across the bloodbrain barrier by activating host cell Rac1 and its association with STAT3, and suggest that pharmacological intervention of hostmicrobial interaction contributing to traversal of the bloodbrain barrier may prevent C.?neoformans penetration into the brain.
C1 [Maruvada, Ravi; Zhu, Longkun; Pearce, Donna; Kim, Kwang Sik] Johns Hopkins Univ, Sch Med, Div Pediat Infect Dis, Dept Pediat, Baltimore, MD 21287 USA.
[Zheng, Yi] Childrens Hosp Res Fdn, Div Expt Hematol, Cincinnati, OH 45229 USA.
[Perfect, John] Duke Univ, Med Ctr, Div Infect Dis, Durham, NC USA.
[Kwon-Chung, Kyung J.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
RP Kim, KS (reprint author), Johns Hopkins Univ, Sch Med, Div Pediat Infect Dis, Dept Pediat, 200 N Wolfe St,Room 3157, Baltimore, MD 21287 USA.
EM kwangkim@jhmi.edu
RI Zheng, Yi/J-7235-2015
OI Zheng, Yi/0000-0001-7089-6074
FU NIH [AI84984, NS26310]; National Institute of Allergy and Infectious
Diseases, NIH, Bethesda, MD
FX This work was supported by the NIH Grants AI84984 and NS26310 (K. S.
K.). The works by K.J. Kwon-Chung were supported by funds from the
intramural programme of the National Institute of Allergy and Infectious
Diseases, NIH, Bethesda, MD. The experiments were approved by the Animal
Care and Use Committee of the Johns Hopkins University.
NR 35
TC 22
Z9 26
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1462-5814
J9 CELL MICROBIOL
JI Cell Microbiol.
PD OCT
PY 2012
VL 14
IS 10
BP 1544
EP 1553
DI 10.1111/j.1462-5822.2012.01819.x
PG 10
WC Cell Biology; Microbiology
SC Cell Biology; Microbiology
GA 007IF
UT WOS:000308881300005
PM 22646320
ER
PT J
AU Iyer, LV
Ramamoorthy, A
Rutkowska, E
Furimsky, AM
Tang, L
Catz, P
Green, CE
Jozwiak, K
Wainer, IW
AF Iyer, Lalitha V.
Ramamoorthy, Anuradha
Rutkowska, Ewelina
Furimsky, Anna M.
Tang, Liang
Catz, Paul
Green, Carol E.
Jozwiak, Krzysztof
Wainer, Irving W.
TI The Stereoselective Sulfate Conjugation of 4'-Methoxyfenoterol
Stereoisomers by Sulfotransferase Enzymes
SO CHIRALITY
LA English
DT Article
DE sulfotransferases; SULT1A1; SULT1A3; SULT1E1; stereoselective phase II
metabolism
ID MOLECULAR-FIELD ANALYSIS; HUMAN PHENOLSULFOTRANSFERASES; FENOTEROL
DERIVATIVES; RAT; METABOLISM; EXPRESSION; BINDING
AB The presystemic sulfate conjugation of the stereoisomers of 4'-methoxyfenoterol, (R,R')-MF, (S,S')-MF, (R,S')-MF, and (S,R')-MF, was investigated using commercially available human intestinal S9 fractions, a mixture of sulfotransferase (SULT) enzymes. The results indicate that the sulfation was stereospecific and that an S-configuration at the beta-OH carbon of the MF molecule enhanced the maximal formation rates with (S,R')-MF??(S,S')-MF approximate to(R,S')-MF approximate to R,R')-MF, and competition studies demonstrated that (S,R')-MF is an effective inhibitor of (R,R')-MF sulfation (IC50?=?60?mu M). In addition, the results from a cDNA-expressed human SULT isoform screen indicated that SULT1A1, SULT1A3, and SULT1E1 can mediate the sulfation of all four MF stereoisomers. Previously published molecular models of SULT1A3 and SULT1A1 were used in docking simulations of the MF stereoisomers using Molegro Virtual Docker. The models of the MF-SULT1A3 and MF-SULT1A1 complexes indicate that each of the two chiral centers of MF molecule plays a role in the observed relative stabilities. The observed stereoselectivity is the result of multiple hydrogen bonding interactions and induced conformational changes within the substrateenzyme complex. In conclusion, the results suggest that a formulation developed from a mixture of (R,R')-MF and (S,R')-MF may increase the oral bioavailability of (R,R')-MF. Chirality 24:796803, 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Wainer, Irving W.] NIA, Bioanalyt Chem & Drug Discovery Sect, Lab Clin Investigat, NIH, Baltimore, MD 21224 USA.
[Iyer, Lalitha V.; Furimsky, Anna M.; Tang, Liang; Catz, Paul; Green, Carol E.] SRI Int, Biosci Div, Menlo Pk, CA 94025 USA.
[Rutkowska, Ewelina; Jozwiak, Krzysztof] Med Univ Lublin, Lab Med Chem & Neuroengn, Lublin, Poland.
RP Wainer, IW (reprint author), NIA, Bioanalyt Chem & Drug Discovery Sect, Lab Clin Investigat, NIH, 251 Bayview Blvd,08B133, Baltimore, MD 21224 USA.
EM wainerir@grc.nia.nih.gov
FU Intramural Research Program of the National Institute on Aging, NIA
[HHSN271201000008I]; Foundation for Polish Science (TEAM programme)
FX This work was supported by the Intramural Research Program of the
National Institute on Aging, NIA, (IWW); NIA Contract No.
HHSN271201000008I (CEG); Foundation for Polish Science (TEAM programme)
(KJ) and equipment purchased within the Project "the equipment of
innovative laboratories doing research on new medicines used in the
therapy of civilization and neoplastic diseases" within the Operational
Program Development of Eastern Poland, 2007-2013 (KJ).
NR 15
TC 4
Z9 4
U1 1
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0899-0042
J9 CHIRALITY
JI Chirality
PD OCT
PY 2012
VL 24
IS 10
BP 796
EP 803
DI 10.1002/chir.22072
PG 8
WC Chemistry, Medicinal; Chemistry, Analytical; Chemistry, Organic;
Pharmacology & Pharmacy
SC Pharmacology & Pharmacy; Chemistry
GA 012MK
UT WOS:000309240200005
PM 22744891
ER
PT J
AU Ito, Y
Clary, R
Witten, JJ
Zeng, Y
AF Ito, Yoichiro
Clary, Robert
Witten, Jacob J.
Zeng, Yun
TI Vortex Counter-Current Chromatography: Performance of a New Preparative
Column
SO CHROMATOGRAPHIA
LA English
DT Article
DE Vortex counter-current chromatography; Preparative separation; DNP-amino
acids; Dipeptides; Sudan dyes
AB A new preparative column for the vortex counter-current chromatograph was fabricated by making many (966) cylindrical separation units to a high-density polyethylene disk and then threading them with 6-40 taps. The resulting column had a total capacity of 364 mL. The performance of this vortex column was examined with three different two-phase solvent systems each using a set of suitable test samples: hexane-ethyl acetate-methanol-0.1 M hydrochloric acid (1:1:1:1, v/v) for the separation of DNP-amino acids; 1-butanol-acetic acid-water (4:1:5, v/v) for the separation of dipeptides; and hexane-acetonitrile-water (20:15:2, v/v) for the separation of Sudan dyes. Most of the separations show high partition efficiency of over a thousand theoretical plates, as expected based on the results previously obtained in preliminary separations with a small column. Overall, the results of the present study suggest that further improvement of the partition efficiency can be obtained by the modifying column configuration.
C1 [Ito, Yoichiro; Witten, Jacob J.; Zeng, Yun] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Witten, Jacob J.] Amherst Coll, Amherst, MA 01002 USA.
[Zeng, Yun] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361005, Peoples R China.
RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bldg 10,Room 8N230,10 Ctr Dr, Bethesda, MD 20892 USA.
EM itoy2@mail.nih.gov
OI Witten, Jacob/0000-0003-0037-5999
FU Intramural NIH HHS [ZIA HL001060-03]
NR 10
TC 3
Z9 3
U1 1
U2 10
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0009-5893
J9 CHROMATOGRAPHIA
JI Chromatographia
PD OCT
PY 2012
VL 75
IS 19-20
BP 1091
EP 1097
DI 10.1007/s10337-012-2285-6
PG 7
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 012GK
UT WOS:000309223800001
PM 23503931
ER
PT J
AU Bous, SM
Solomon, BD
Graul-Neumann, L
Neitzel, H
Hardisty, EE
Muenke, M
AF Bous, Sophia M.
Solomon, Benjamin D.
Graul-Neumann, Luitgard
Neitzel, Heidemarie
Hardisty, Emily E.
Muenke, Maximilian
TI Holoprosencephaly-polydactyly/pseudotrisomy 13: a presentation of two
new cases and a review of the literature
SO CLINICAL DYSMORPHOLOGY
LA English
DT Review
DE holoprosencephaly; holoprosencephaly and polydactyly; polydactyly;
pseudotrisomy; pseudotrisomy 13
ID PSEUDOTRISOMY-13 SYNDROME; SONIC HEDGEHOG; PSEUDO-TRISOMY-13 SYNDROME;
MIDLINE MALFORMATION; PRENATAL-DIAGNOSIS; CANDIDATE GENES;
HEART-DEFECTS; HYPOPLASIA; MOUSE; LIMB
AB Patients with a combination of holoprosencephaly and polydactyly, but with apparently normal chromosomes, may be clinically diagnosed with holoprosencephaly-polydactyly syndrome (HPS), also termed pseudotrisomy 13. However, the criteria for HPS have been controversial since the advent of the diagnostic term, and a clear understanding of the condition lacks definitive delineation. We review the historical and current perspectives on the condition and analyze findings in 40 patients with apparent HPS, including cases from the literature and two previously unreported patients. Overall, our analysis suggests previously unrecognized trends in patients diagnosed with HPS. Specifically, there appears to be a higher prevalence of visceral anomalies, most significantly cardiac and genitourinary, but also with increased gastrointestinal, pulmonary, adrenal, skeletal, and renal abnormalities, in patients with HPS. Although these visceral anomalies may not be essential for the identification of HPS, clinicians should be aware of the presence of such characteristics in these patients to optimize management and help establish etiologies. Clin Dysmorphol 21:183-190 (c) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Bous, Sophia M.; Solomon, Benjamin D.; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Hardisty, Emily E.] Univ N Carolina Chapel Hill, Sch Med, Dept Obstet & Gynecol, Div Maternal Fetal Med Reprod Genet, Chapel Hill, NC USA.
[Bous, Sophia M.] Cincinnati Childrens Hosp Med Ctr, Dept Genet, Cincinnati, OH USA.
[Graul-Neumann, Luitgard; Neitzel, Heidemarie] Charite Campus Virchow, Berlin, Germany.
RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA.
EM mamuenke@mail.nih.gov
FU Division of Intramural Research, National Human Genome Research
Institute, National Institutes of Health, Department of Health and Human
Services, USA
FX The authors would like to thank all the patients who participated in
these studies. This research was supported by the Division of Intramural
Research, National Human Genome Research Institute, National Institutes
of Health, Department of Health and Human Services, USA.
NR 47
TC 4
Z9 5
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0962-8827
J9 CLIN DYSMORPHOL
JI Clin. Dysmorphol.
PD OCT
PY 2012
VL 21
IS 4
BP 183
EP 190
DI 10.1097/MCD.0b013e3283551fd0
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 006DA
UT WOS:000308798500001
PM 22643382
ER
PT J
AU Bartels, E
Schulz, AC
Mora, NW
Pineda-Alvarez, DE
Wijers, CHW
Marcelis, CM
Stressig, R
Ritgen, J
Schmiedeke, E
Mattheisen, M
Draaken, M
Hoffmann, P
Hilger, AC
Dworschak, GC
Baudisch, F
Ludwig, M
Bagci, S
Muller, A
Gembruch, U
Geipel, A
Berg, C
Bartmann, P
Nothen, MM
van Rooij, IALM
Solomon, BD
Reutter, HM
AF Bartels, Enrika
Schulz, Anna C.
Mora, Nicole W.
Pineda-Alvarez, Daniel E.
Wijers, Charlotte H. W.
Marcelis, Carlo M.
Stressig, Ruediger
Ritgen, Jochen
Schmiedeke, Eberhard
Mattheisen, Manuel
Draaken, Markus
Hoffmann, Per
Hilger, Alina C.
Dworschak, Gabriel C.
Baudisch, Friederike
Ludwig, Michael
Bagci, Soyhan
Mueller, Andreas
Gembruch, Ulrich
Geipel, Annegret
Berg, Christoph
Bartmann, Peter
Noethen, Markus M.
van Rooij, Iris A. L. M.
Solomon, Benjamin D.
Reutter, Heiko M.
TI VATER/VACTERL association: identification of seven new twin pairs, a
systematic review of the literature, and a classical twin analysis
SO CLINICAL DYSMORPHOLOGY
LA English
DT Article
DE concordant; discordant; dizygous; monozygous; twin study; VACTERL
association
ID VACTERL-ASSOCIATION; VATER ASSOCIATION; TRACHEOESOPHAGEAL FISTULA;
MONOAMNIOTIC TWINS; CONGENITAL-ANOMALIES; ESOPHAGEAL ATRESIA;
DISCORDANT; AGENESIS; DELETION; MALFORMATIONS
AB The VATER/VACTERL association is typically defined by the presence of at least three of the following congenital malformations: vertebral anomalies, anal atresia, cardiac malformations, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. The identification of 14 twin pairs with an initial diagnosis of VATER/VACTERL association at our clinical centers led to the performance of a classical twin study. This involved a thorough evaluation of these 14 twin pairs and a further 55 twin pairs identified from a systematic review of the literature. The zygosity, concordance, and malformation status of all 69 twin pairs were evaluated. Twenty-four twin pairs fulfilled the criteria for inclusion in a comparison of the concordance rates between monozygous (MZ) and dizygous (DZ) twin pairs. The pairwise concordance rates were 15% [95% confidence interval (CI) 4-42%] for MZ and 18% (95% CI 5-48%) for DZ twin pairs (P=0.53). The probandwise concordance rates were 27% (95% CI 11-52%) for MZ and 31% (95% CI 13-58%) for DZ twin pairs (P=0.40). Although based on a limited number of twin pairs, the findings of the present study are consistent with the low number of familial cases reported to date, and suggest that the role of inherited genetic factors in the majority of VATER/VACTERL cases is limited. Clin Dysmorphol 21:191-195 (c) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Mattheisen, Manuel; Draaken, Markus; Hoffmann, Per; Noethen, Markus M.] Brigham & Womens Hosp, Dept Genom, Life & Brain Ctr, Boston, MA 02115 USA.
[Mattheisen, Manuel] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[Mattheisen, Manuel] Harvard Univ, Sch Med, Boston, MA USA.
[Baudisch, Friederike; Ludwig, Michael] Univ Bonn, Dept Clin Chem & Clin Pharmacol, D-53127 Bonn, Germany.
[Gembruch, Ulrich; Geipel, Annegret; Berg, Christoph] Univ Hosp Bonn, Dept Obstet & Prenatal Med, Bonn, Germany.
[Stressig, Ruediger; Ritgen, Jochen] Praenatal De Partnership Private Practices Prenat, Dusseldorf, Germany.
[Schmiedeke, Eberhard] Hosp Bremen Mitte, Ctr Child & Adolescent Hlth, Dept Pediat Surg & Urol, Bremen, Germany.
[Mora, Nicole W.; Pineda-Alvarez, Daniel E.; Solomon, Benjamin D.] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
[Wijers, Charlotte H. W.; van Rooij, Iris A. L. M.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & HTA, NL-6525 ED Nijmegen, Netherlands.
[Marcelis, Carlo M.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
RP Reutter, HM (reprint author), Univ Bonn, Dept Neonatol, Sigmund Freud Str 25, D-53127 Bonn, Germany.
EM reutter@uni-bonn.de
RI Mattheisen, Manuel/B-4949-2012; Rooij, van, Iris/A-5705-2014;
OI Mattheisen, Manuel/0000-0002-8442-493X; Rooij, van,
Iris/0000-0002-9519-966X; Nothen, Markus/0000-0002-8770-2464; Hoffmann,
Per/0000-0002-6573-983X
FU German Federal Ministry of Education and Research (Bundesministerium fur
Bildung und Forschung, BMBF [01GM08107]; Division of Intramural
Research, National Human Genome Research Institute, National Institutes
of Health and Human Services, USA; Radboud University Nijmegen Medical
Centre; University of Bonn, BONFOR [O-149.0096]
FX The authors thank all the patients and their parents for their
cooperation. The authors also thank the German self-help organization
for people with anorectal malformations (SoMA e.V.). H.M.R., E.B., E.S.,
M.D., M.L., M.M., P.H., A.H., G.D., F.B., and M.M.N. are members of the
'Network for the Systematic Investigation of the Molecular Causes,
Clinical Implications, and Psychosocial Outcome of Congenital Uro-Rectal
Malformations (CURE-Net),' which is supported by a research grant
(01GM08107) from the German Federal Ministry of Education and Research
(Bundesministerium fur Bildung und Forschung, BMBF). The research
carried out at the National Institutes of Health was supported by the
Division of Intramural Research, National Human Genome Research
Institute, National Institutes of Health and Human Services, USA.
Charlotte Wijers is supported by a grant from the Radboud University
Nijmegen Medical Centre. GD is supported by the University of Bonn,
BONFOR, grant number O-149.0096.
NR 37
TC 6
Z9 6
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0962-8827
J9 CLIN DYSMORPHOL
JI Clin. Dysmorphol.
PD OCT
PY 2012
VL 21
IS 4
BP 191
EP 195
DI 10.1097/MCD.0b013e328358243c
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA 006DA
UT WOS:000308798500002
PM 22895008
ER
PT J
AU Sims, EK
Addo, OY
Gollenberg, AL
Himes, JH
Hediger, ML
Lee, PA
AF Sims, Emily K.
Addo, O. Y.
Gollenberg, Audra L.
Himes, John H.
Hediger, Mary L.
Lee, Peter A.
TI Inhibin B and luteinizing hormone levels in girls aged 6-11 years from
NHANES III, 1988-1994
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID FOLLICLE-STIMULATING-HORMONE; BODY-MASS INDEX; PUBERTAL DEVELOPMENT;
DIMERIC INHIBINS; MENSTRUAL-CYCLE; SERUM INHIBIN; YOUNG GIRLS;
ESTRADIOL; ONSET; ASSOCIATION
AB Objective To evaluate inhibin B and luteinizing hormone (LH) levels in a large, representative cross-sectional sample of US girls and characterize the relationships of these laboratory values with age, clinical signs of puberty and other correlates. Design Cross-sectional analysis of LH and inhibin B in banked serum from 720 girls aged 611 similar to years who participated in the Third National Health and Nutrition Examination Survey (NHANES III). Measurements Levels of inhibin B and LH, race, ethnicity and anthropometric measurements were compared for all girls. Visual assessment of pubertal stage was performed on girls aged 8 similar to years and older. A two-part model was used to establish normative data and Tobit regression models were used to evaluate associations with participant characteristics. Receiver operating characteristic (ROC) analysis was performed to identify optimum cut points predictive of puberty onset. Results Mean hormone levels progressively increased with age. LH levels progressively increased with pubertal stage. Inhibin B levels increased gradually from breast stage I to II, then more sharply to peak at stage III, followed by a plateau at stages IV and V. ROC curves indicated that both hormones were consistent with pubertal onset as indicated by breast stage II. Conclusions This study characterizes inhibin B and LH values in a large, representative cross-sectional sample of US girls. Inhibin B can be a useful tool in combination with other clinical and biochemical parameters to evaluate gonadal function as a reflection of pubertal progression in girls.
C1 [Sims, Emily K.; Lee, Peter A.] Indiana Univ Sch Med, Dept Pediat Endocrinol & Diabetol, Riley Hosp Children, Indianapolis, IN USA.
[Addo, O. Y.; Himes, John H.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Gollenberg, Audra L.] Shenandoah Univ, Dept Publ Hlth, Coll Arts & Sci, Winchester, VA USA.
[Hediger, Mary L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Bethesda, MD USA.
[Lee, Peter A.] Penn State Univ, Milton S Hershey Med Ctr, Dept Pediat, Penn State Coll Med, Hershey, PA 17033 USA.
RP Sims, EK (reprint author), 705 Riley Hosp Dr,Room 5960, Indianapolis, IN 46202 USA.
EM eksims@iupui.edu
OI Addo, O.Yaw/0000-0003-1269-759X
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development; NIH [T32DK065549]
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, Eunice Kennedy Shriver National
Institute of Child Health and Human Development. E.K.S. is supported by
NIH grant T32DK065549.
NR 36
TC 2
Z9 2
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-0664
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD OCT
PY 2012
VL 77
IS 4
BP 555
EP 563
DI 10.1111/j.1365-2265.2012.04393.x
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 003TZ
UT WOS:000308635600011
PM 22443272
ER
PT J
AU Morgan, DJ
Meddings, J
Saint, S
Lautenbach, E
Shardell, M
Anderson, D
Milstone, AM
Drees, M
Pineles, L
Safdar, N
Bowling, J
Henderson, D
Yokoe, D
Harris, AD
AF Morgan, Daniel J.
Meddings, Jennifer
Saint, Sanjay
Lautenbach, Ebbing
Shardell, Michelle
Anderson, Deverick
Milstone, Aaron M.
Drees, Marci
Pineles, Lisa
Safdar, Nasia
Bowling, Jason
Henderson, David
Yokoe, Deborah
Harris, Anthony D.
CA SHEA Res Network
TI Does Nonpayment for Hospital-Acquired Catheter-Associated Urinary Tract
Infections Lead to Overtesting and Increased Antimicrobial Prescribing?
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID CARE-ASSOCIATED INFECTIONS; DISEASES-SOCIETY; PATIENT SAFETY;
GUIDELINES; RESISTANCE; PNEUMONIA; DIAGNOSIS; MEDICARE; AMERICA; ADULTS
AB Background. On 1 October 2008, in an effort to stimulate efforts to prevent catheter-associated urinary tract infection (CAUTI), the Centers for Medicare & Medicaid Services (CMS) implemented a policy of not reimbursing hospitals for hospital-acquired CAUTI. Since any urinary tract infection present on admission would not fall under this initiative, concerns have been raised that the policy may encourage more testing for and treatment of asymptomatic bacteriuria.
Methods. We conducted a retrospective multicenter cohort study with time series analysis of all adults admitted to the hospital 16 months before and 16 months after policy implementation among participating Society for Healthcare Epidemiology of America Research Network hospitals. Our outcomes were frequency of urine culture on admission and antimicrobial use.
Results. A total of 39 hospitals from 22 states submitted data on 2 362 742 admissions. In 35 hospitals affected by the CMS policy, the median frequency of urine culture performance did not change after CMS policy implementation (19.2% during the prepolicy period vs 19.3% during the postpolicy period). The rate of change in urine culture performance increased minimally during the prepolicy period (0.5% per month) and decreased slightly during the postpolicy period (-0.25% per month; P < .001). In the subset of 10 hospitals providing antimicrobial use data, the median frequency of fluoroquinolone antimicrobial use did not change substantially (14.6% during the prepolicy period vs 14.0% during the postpolicy period). The rate of change in fluoroquinolone use increased during the prepolicy period (1.26% per month) and decreased during the postpolicy period (-0.60% per month; P < .001).
Conclusions. We found no evidence that CMS nonpayment policy resulted in overtesting to screen for and document a diagnosis of urinary tract infection as present on admission.
C1 [Morgan, Daniel J.; Shardell, Michelle; Pineles, Lisa; Harris, Anthony D.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Morgan, Daniel J.; Harris, Anthony D.] VA Maryland Healthcare Syst, Baltimore, MD USA.
[Milstone, Aaron M.] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA.
[Milstone, Aaron M.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Henderson, David] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Meddings, Jennifer] Univ Michigan, Sch Med, Dept Internal Med, Div Gen Med, Ann Arbor, MI USA.
[Saint, Sanjay] Univ Michigan, Sch Med, Hosp Outcomes Program Excellence HOPE VA Ann Arbo, Ann Arbor, MI USA.
[Saint, Sanjay] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA.
[Lautenbach, Ebbing] Univ Penn, Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA.
[Lautenbach, Ebbing] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Drees, Marci] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA.
[Anderson, Deverick] Duke Univ Hosp, Durham, NC USA.
[Drees, Marci] Christiana Care Hlth Syst, Dept Med, Wilmington, DE USA.
[Safdar, Nasia] Univ Wisconsin, Dept Med, Madison, WI USA.
[Safdar, Nasia] Univ Wisconsin Hosp & Clin, William S Middleton VA Med Ctr, Madison, WI 53792 USA.
[Safdar, Nasia] Univ Wisconsin Hosp & Clin, Dept Infect Control, Madison, WI 53792 USA.
[Bowling, Jason] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, Univ Hlth Syst, San Antonio, TX 78229 USA.
[Yokoe, Deborah] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Yokoe, Deborah] Harvard Univ, Sch Med, Boston, MA USA.
RP Morgan, DJ (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, 685 W Baltimore St,MSTF 334, Baltimore, MD 21201 USA.
EM dmorgan@epi.umaryland.edu
RI Morgan, Dane/B-7972-2008; Jacob, Jesse/A-8836-2009
OI Morgan, Dane/0000-0002-4911-0046;
FU Society for Hospital Epidemiology of America; Merck
FX This work was supported by the Society for Hospital Epidemiology of
America.; D. J. M. has received an unrestricted research grant from
Merck. D. A. has received an unrestricted research grant from Merck and
has served on a speakers' bureau for Merck. A. D. H. and D. A. have
received payment for contributions to UpToDate Online. All other authors
report no potential conflicts.
NR 16
TC 18
Z9 18
U1 0
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD OCT 1
PY 2012
VL 55
IS 7
BP 923
EP 929
DI 10.1093/cid/cis556
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 002JI
UT WOS:000308527500010
PM 22700826
ER
PT J
AU Cohen, C
Simonsen, L
Sample, J
Kang, JW
Miller, M
Madhi, SA
Campsmith, M
Viboud, C
AF Cohen, Cheryl
Simonsen, Lone
Sample, Jeannette
Kang, Jong-Won
Miller, Mark
Madhi, Shabir A.
Campsmith, Michael
Viboud, Cecile
TI Influenza-Related Mortality Among Adults Aged 25-54 Years With AIDS in
South Africa and the United States of America
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RESPIRATORY-TRACT INFECTIONS; PANDEMIC
PREPAREDNESS; EXCESS MORTALITY; HIV-INFECTION; VACCINATION; PNEUMONIA;
MORBIDITY; IMPACT; RECOMMENDATIONS
AB Background. Data are limited on human immunodeficiency virus (HIV)-associated influenza burden in sub-Saharan Africa and the impact of highly active antiretroviral therapy (HAART). We compared influenza-related mortality in adults with AIDS in South Africa and the United States in the pre-HAART era and evaluated mortality trends after HAART introduction in the United States.
Methods. Monthly all-cause and pneumonia and influenza (P&I) mortality rates were compiled for adults with AIDS aged 25-54 years in South Africa (1998-2005) and the United States (pre-HAART era, 1987-1994; HAART era, 1997-2005). We estimated influenza-related deaths as excess mortality above a model baseline during influenza epidemic periods. Influenza-related mortality rates in adults with AIDS were compared with rates for age peers in the general population and adults >= 65 years old.
Results. In the United States before HAART, influenza-related mortality rates in adults with AIDS were 150 (95% confidence interval [CI], 49-460) and 208 (95% CI, 74-583) times greater than in the general population for all-cause and P&I deaths, respectively, and 2.5 (95% CI, 0.9-7.2) and 4.1 (95% CI, 1.4-13) times higher than in elderly adults. After HAART introduction, influenza-related mortality in adults with AIDS dropped 3-6-fold but remained elevated compared with the general population (all-cause relative risk [RR], 44 [95% CI, 16-121]); P& I RR, 73 [95% CI, 47-113]). Influenza-related mortality in South African adults with AIDS in recent years was similar to that in the United States in the pre-HAART era.
Conclusions. Adults with AIDS experience substantially elevated influenza-associated mortality, which declines with widespread HAART introduction but does not disappear. These data support increased access to HAART and influenza vaccination for HIV-infected adults.
C1 [Cohen, Cheryl] Univ Witwatersrand, Natl Hlth Lab Serv, Natl Inst Communicable Dis, Johannesburg, South Africa.
[Cohen, Cheryl] Univ Witwatersrand, Sch Publ Hlth, Johannesburg, South Africa.
[Madhi, Shabir A.] Univ Witwatersrand, Natl Res Fdn, Dept Sci & Technol, Johannesburg, South Africa.
[Simonsen, Lone; Kang, Jong-Won; Miller, Mark; Viboud, Cecile] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Simonsen, Lone; Sample, Jeannette] George Washington Univ, Dept Global Hlth, Washington, DC USA.
[Campsmith, Michael] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Kang, Jong-Won] Chungbuk Natl Univ, Coll Med, Dept Prevent Med, Chonju, South Korea.
RP Cohen, C (reprint author), Natl Inst Communicable Dis, Epidemiol & Surveillance Unit, Private Bag X4, ZA-2131 Johannesburg, Gauteng, South Africa.
EM cherylc@nicd.ac.za
OI Simonsen, Lone/0000-0003-1535-8526
FU RAPIDD program of the Science & Technology Directorate, Department of
Homeland Security; Fogarty International Center; National Institutes of
Health; Wyeth-Pfizer; SDI Health
FX This work was supported in part by the RAPIDD program of the Science &
Technology Directorate, Department of Homeland Security, and Fogarty
International Center, National Institutes of Health (to L. S.). No other
external funding was obtained for this publication. No funding bodies
had any role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.; L. S. has received funding
for a research study from Wyeth-Pfizer and consulting fees from SDI
Health, a data warehouse business in Plymouth Meeting, Pennsylvania. All
other authors report no potential conflicts.
NR 36
TC 34
Z9 34
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD OCT 1
PY 2012
VL 55
IS 7
BP 996
EP 1003
DI 10.1093/cid/cis549
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 002JI
UT WOS:000308527500021
PM 22715173
ER
PT J
AU Harrington, W
McGready, R
Muehlenbachs, A
Fried, M
Nosten, F
Duffy, P
AF Harrington, Whitney
McGready, Rose
Muehlenbachs, Atis
Fried, Michal
Nosten, Francois
Duffy, Patrick
TI Intermittent Preventive Treatment in Pregnancy With
Sulfadoxine-Pyrimethamine: The Times They Are A-Changin'
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Letter
ID MALARIA; WOMEN; FACILITATION; PARASITES; QUEERPAM
C1 [Harrington, Whitney; Muehlenbachs, Atis] Univ Washington, Seattle, WA 98195 USA.
[McGready, Rose; Nosten, Francois] Shoklo Malaria Res Unit, Mae Sot, Thailand.
[McGready, Rose; Nosten, Francois] Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand.
[McGready, Rose; Nosten, Francois] Univ Oxford, Ctr Trop Med, Oxford OX1 2JD, England.
[Fried, Michal; Duffy, Patrick] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Bethesda, MD 20892 USA.
RP Harrington, W (reprint author), 4800 Sand Point Way NE,A5950 GME Off, Seattle, WA 98105 USA.
EM wharring@uw.edu
OI Nosten, Francois/0000-0002-7951-0745; McGready, Rose/0000-0003-1621-3257
NR 10
TC 5
Z9 5
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD OCT 1
PY 2012
VL 55
IS 7
BP 1025
EP U175
DI 10.1093/cid/cis568
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 002JI
UT WOS:000308527500027
PM 22715177
ER
PT J
AU Jia, X
Jia, L
AF Jia, Xiao
Jia, Lee
TI Nanoparticles Improve Biological Functions of Phthalocyanine
Photosensitizers Used for Photodynamic Therapy
SO CURRENT DRUG METABOLISM
LA English
DT Review
DE Photodynamic therapy; phthalocyanine photosensitizers; nanoparticles;
nanocarriers; drug delivery
ID HEXADECAFLUORO ZINC PHTHALOCYANINE; POLY(LACTIC ACID) NANOPARTICLES;
CARBON NANOTUBES; DRUG-DELIVERY; PLGA NANOPARTICLES; GOLD NANOPARTICLES;
SINGLET OXYGEN; QUANTUM DOTS; CANCER; VIVO
AB Photodynamic therapy (PDT) is a new technology using photodynamic effect for disease diagnosis and treatment. It is a two-step technique involving the uptake of a photosensitizer by cancer tissue followed by light irradiation that excites the photosensitizer to produce highly reactive oxygen species, the latter execute apoptosis of cancerous cells. As a second-generation of photosensitizers, phthalocyanine demonstrates higher absorption in the 650-800nm range and short tissue accumulation compared to their first generation. However, many potent phthalocyanine photosensitizers are hydrophobic and poorly water-soluble, which limit their therapeutic applications. As a result, advanced delivery systems and different strategies are called for to improve the effectiveness of PDT. Facts have proved that using nanoparticles as carries of photosensitizers is a very promising route. Nanoparticles have the potentials to increase photosensitizers' aqueous solubility, bioavailability and stability, and deliver photosensitizers to the target tissues. This article reviewed the commonly-used nanoparticles, including colloid gold, quantum dots, paramagnetic nanoparticles, silica-based materials, polymer-based nanoparticles, as potential delivery systems for phthalocyanine photosensitizers, and summarized the improved biological functions of phthalocyanine photosensitizers in PDT.
C1 [Jia, Xiao; Jia, Lee] Fuzhou Univ, Coll Chem & Chem Engn, Inst Res Funct Mat, Fuzhou 350002, Peoples R China.
[Jia, Lee] Natl Canc Inst, NIH, Dev Therapeut Program, Bethesda, MD 20852 USA.
RP Jia, L (reprint author), 6130 Executive Blvd,Suite 8042, Bethesda, MD 20852 USA.
EM pharmlink@gmail.com
NR 41
TC 30
Z9 30
U1 4
U2 80
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-2002
J9 CURR DRUG METAB
JI Curr. Drug Metab.
PD OCT
PY 2012
VL 13
IS 8
BP 1119
EP 1122
PG 4
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 006AO
UT WOS:000308791700009
PM 22380016
ER
PT J
AU Bowers, M
Eng, LE
Lao, ZM
Turnbull, RK
Bao, XZ
Riedel, E
Mackem, S
Joyner, AL
AF Bowers, Megan
Eng, Liane
Lao, Zhimin
Turnbull, Rowena K.
Bao, Xiaozhong
Riedel, Elyn
Mackem, Susan
Joyner, Alexandra L.
TI Limb anterior-posterior polarity integrates activator and repressor
functions of GLI2 as well as GLI3
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Digit patterning; Sonic hedgehog; Polydactyly; Gli1
ID T-BOX GENES; SONIC-HEDGEHOG; VERTEBRATE LIMB; HOMEOTIC TRANSFORMATION;
DIGIT IDENTITY; SHH; MOUSE; EXPRESSION; SPECIFICATION; BUD
AB Anterior-posterior (AP) limb patterning is directed by sonic hedgehog (SHH) signaling from the posteriorly located zone of polarizing activity (ZPA). GLI3 and GLI2 are the transcriptional mediators generally utilized in SHH signaling, and each can function as an activator (A) and repressor (R). Although GLI3R has been suggested to be the primary effector of SHH signaling during limb AP patterning, a role for GL13A or GLI2 has not been fully ruled out, nor has it been determined whether Gli3 plays distinct roles in limb development at different stages. By conditionally removing Gli3 in the limb at multiple different time points, we uncovered four Gli3-mediated functions in limb development that occur at distinct but partially over-lapping time windows: AP patterning of the proximal limb, AP patterning of the distal limb, regulation of digit number and bone differentiation. Furthermore, by removing Gli2 in Gli3 temporal conditional knock-outs, we uncovered an essential role for Gli2 in providing the remaining posterior limb patterning seen in Gli3 single mutants. To test whether GLIAs or GLIRs regulate different aspects of AP limb patterning and/or digit number, we utilized a knock-in allele in which GLI1, which functions solely as an activator, is expressed in place of the bifunctional GLI2 protein. Interestingly, we found that GLIAs contribute to AP patterning specifically in the posterior limb, whereas GLIRs predominantly regulate anterior patterning and digit number. Since GLI3 is a more effective repressor, our results explain why GLI3 is required only for anterior limb patterning and why GLI2 can compensate for GL13A in posterior limb patterning. Taken together, our data suggest that establishment of a complete range of AP positional identities in the limb requires integration of the spatial distribution, timing, and dosage of GLI2 and GLI3 activators and repressors. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Bowers, Megan; Eng, Liane; Lao, Zhimin; Turnbull, Rowena K.; Joyner, Alexandra L.] Sloan Kettering Inst, Dev Biol Program, New York, NY 10065 USA.
[Bowers, Megan] Skirball Inst Biomol Med, Dev Genet Program, New York, NY 10016 USA.
[Bao, Xiaozhong; Mackem, Susan] NCI Frederick, Canc & Dev Biol Lab, Frederick, MD 21702 USA.
[Riedel, Elyn] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
RP Joyner, AL (reprint author), Sloan Kettering Inst, Dev Biol Program, New York, NY 10065 USA.
EM joynera@mskcc.org
FU NIH [R01 CA128158, R01 DE016779]; Center for Cancer Research, National
Cancer Institute
FX We would like to thank Dr. Cindy Loomis for advice and insightful
comments throughout the studies and Dr. Sandra Wilson for critical
reading of the manuscript. We would like to thank Dr. Virginia E
Papaioannou and Dr. Cindy Loomis for generously providing the Tbx2 and
Pax9 in situ probes, respectively. This work was funded by the NIH
grants nos. R01 CA128158 and R01 DE016779 to ALJ and by the Center for
Cancer Research, National Cancer Institute to SM.
NR 62
TC 23
Z9 23
U1 0
U2 16
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD OCT 1
PY 2012
VL 370
IS 1
BP 110
EP 124
DI 10.1016/j.ydbio.2012.07.017
PG 15
WC Developmental Biology
SC Developmental Biology
GA 005DL
UT WOS:000308730600011
PM 22841643
ER
PT J
AU Towner, RA
Smith, N
Saunders, D
Henderson, M
Downum, K
Lupu, F
Silasi-Mansat, R
Ramirez, DC
Gomez-Mejiba, SE
Bonini, MG
Ehrenshaft, M
Mason, RP
AF Towner, Rheal A.
Smith, Nataliya
Saunders, Debra
Henderson, Michael
Downum, Kristen
Lupu, Florea
Silasi-Mansat, Robert
Ramirez, Dario C.
Gomez-Mejiba, Sandra E.
Bonini, Marcelo G.
Ehrenshaft, Marilyn
Mason, Ronald P.
TI In Vivo Imaging of Immuno-Spin Trapped Radicals With Molecular Magnetic
Resonance Imaging in a Diabetic Mouse Model
SO DIABETES
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; OXIDATIVE STRESS; PROTEIN RADICALS; FATTY-ACIDS;
STREPTOZOTOCIN; KIDNEY; RATS; MRI; DISEASE; INJURY
AB Oxidative stress plays a major role in diabetes. In vivo levels of membrane-bound radicals (MBRs) in a streptozotocin-induced diabetic mouse model were uniquely detected by combining molecular magnetic resonance imaging (mMRI) and immunotrapping techniques. An anti-DMPO (5,5-dimethyl-1-pyrroline N-oxide) antibody (Ab) covalently bound to an albumin (BSA)-Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)-biotin MRI contrast agent (anti-DMPO probe), and mMRI, were used to detect. in vivo levels of DMPO-MBR adducts in kidneys, livers, and lungs of diabetic mice, after DMPO administration. Magnetic resonance signal intensities, which increase in the presence of a Gd-based molecular probe, were significantly higher within the livers, kidneys, and lungs of diabetic animals administered the anti-DMPO probe compared with controls. Fluorescence images validated the location of the anti-DMPO probe in excised tissues via conjugation of streptavidin-Cy3, which targeted the probe biotin moiety, and immunohistochemistry was used to validate the presence of DMPO adducts in diabetic mouse livers. This is the first report of noninvasively imaging in vivo levels of MBRs within any disease model. This method can be specifically applied toward diabetes models for in vivo assessment of free radical levels, providing an avenue to more fully understand the role of free radicals in diabetes. Diabetes 61:2405-2413, 2012
C1 [Towner, Rheal A.; Smith, Nataliya; Saunders, Debra; Henderson, Michael; Downum, Kristen] Oklahoma Med Res Fdn, Adv Magnet Resonance Ctr, Oklahoma City, OK 73104 USA.
[Lupu, Florea; Silasi-Mansat, Robert] Oklahoma Med Res Fdn, Cardiovasc Biol Res Program, Oklahoma City, OK 73104 USA.
[Ramirez, Dario C.; Gomez-Mejiba, Sandra E.] Oklahoma Med Res Fdn, Expt Therapeut Res Lab, Oklahoma City, OK 73104 USA.
[Bonini, Marcelo G.] Univ Illinois, Dept Pharmacol, Cardiol Sect, Chicago, IL USA.
[Ehrenshaft, Marilyn; Mason, Ronald P.] NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA.
RP Towner, RA (reprint author), Oklahoma Med Res Fdn, Adv Magnet Resonance Ctr, 825 NE 13th St, Oklahoma City, OK 73104 USA.
EM rheal-towner@omrf.org
RI RAMIREZ, DARIO/K-3312-2013
OI Silasi, Robert/0000-0001-9590-6160; RAMIREZ, DARIO/0000-0001-6725-3326
FU National Institute of Environmental Health Sciences; National Institutes
of Health IDeA Networks of Biomedical Research Excellence
[P20-RR-016478-09]; OMRF
FX The OMRF, the National Institute of Environmental Health Sciences (to
R.M.), and the National Institutes of Health IDeA Networks of Biomedical
Research Excellence (Grant P20-RR-016478-09 to R.A.T.) provided funds
that contributed to this study.
NR 47
TC 11
Z9 11
U1 0
U2 7
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD OCT
PY 2012
VL 61
IS 10
BP 2405
EP 2413
DI 10.2337/db11-1540
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 013KP
UT WOS:000309304600004
PM 22698922
ER
PT J
AU Guo, TQ
Bond, ND
Jou, W
Gavrilova, O
Portas, J
McPherron, AC
AF Guo, Tingqing
Bond, Nichole D.
Jou, William
Gavrilova, Oksana
Portas, Jennifer
McPherron, Alexandra C.
TI Myostatin Inhibition Prevents Diabetes and Hyperphagia in a Mouse Model
of Lipodystrophy
SO DIABETES
LA English
DT Article
ID INDUCED INSULIN-RESISTANCE; SKELETAL-MUSCLE; ADIPOSE-TISSUE; INHERITED
LIPODYSTROPHIES; CONGENITAL LIPODYSTROPHY; ENERGY-METABOLISM;
GENE-EXPRESSION; GUT HORMONES; WEIGHT-LOSS; FOOD-INTAKE
AB Lipodystrophies are characterized by a loss of white adipose tissue, which causes ectopic lipid deposition, peripheral insulin resistance, reduced adipokine levels, and increased food intake (hyperphagia). The growth factor myostatin (MSTN) negatively regulates skeletal muscle growth, and mice with MSTN inhibition have reduced adiposity and improved insulin sensitivity. MSTN inhibition may therefore be efficacious in ameliorating diabetes. To test this hypothesis, we inhibited MSTN signaling in a diabetic model of generalized lipodystrophy to analyze its effects on glucose metabolism separate from effects on adipose mass. A-ZIP/F1 lipodystrophic mice were crossed to mice expressing a dominant-negative MSTN receptor (activin receptor type IIB) in muscle. MSTN inhibition in A-ZIP/F1 mice reduced blood glucose, serum insulin, triglyceride levels, and the rate of triglyceride synthesis, and improved insulin sensitivity. Unexpectedly, hyperphagia was normalized by MSTN inhibition in muscle. Blood glucose and hyperphagia were reduced in double mutants independent of the adipokine leptin. These results show that the effect of MSTN inhibition on insulin sensitivity is not secondary to an effect on adipose mass and that MSTN inhibition may be an effective treatment for diabetes. These results further suggest that muscle may play a heretofore unappreciated role in regulating food intake. Diabetes 61:2414-2423, 2012
C1 [Guo, Tingqing; Bond, Nichole D.; Portas, Jennifer; McPherron, Alexandra C.] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Jou, William; Gavrilova, Oksana] NIDDKD, Mouse Metab Core Lab, NIH, Bethesda, MD 20892 USA.
RP McPherron, AC (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
EM mcpherrona@niddk.nih.gov
FU NIH; NIDDK
FX This work is supported by the Intramural Research Program of the NIH,
NIDDK.
NR 50
TC 24
Z9 24
U1 1
U2 11
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD OCT
PY 2012
VL 61
IS 10
BP 2414
EP 2423
DI 10.2337/db11-0915
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 013KP
UT WOS:000309304600005
PM 22596054
ER
PT J
AU Kim, YD
Kim, YH
Tadi, S
Yu, JH
Yim, YH
Jeoung, NH
Shong, M
Hennighausen, L
Harris, RA
Lee, IK
Lee, CH
Choi, HS
AF Kim, Yong Deuk
Kim, Yong-Hoon
Tadi, Surendar
Yu, Ji Hoon
Yim, Yong-Hyeon
Jeoung, Nam Ho
Shong, Minho
Hennighausen, Lothar
Harris, Robert A.
Lee, In-Kyu
Lee, Chul-Ho
Choi, Hueng-Sik
TI Metformin Inhibits Growth Hormone-Mediated Hepatic PDK4 Gene Expression
Through Induction of Orphan Nuclear Receptor Small Heterodimer Partner
SO DIABETES
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; PYRUVATE-DEHYDROGENASE COMPLEX; SIGNAL
TRANSDUCER; GLUCOSE-PRODUCTION; TRANSCRIPTION; LIVER; MICE; MECHANISM;
TARGET; STAT5B
AB Growth hormone (GH) is a counter-regulatory hormone that plays an important role in preventing hypoglycemia during fasting. Because inhibition of the pyruvate dehydrogenase complex (PDC) by pyruvate dehydrogenase kinase 4 (PDK4) conserves substrates for gluconeogenesis, we tested whether GH increases PDK4 expression in liver by a signaling pathway sensitive to inhibition by metformin. The effects of GH and metformin were determined in the liver of wild-type, small heterodimer partner (SHP)-, PDK4-, and signal transducer and activator of transcription 5 (STAT5)-null mice. Administration of GH in vivo increased PDK4 expression via a pathway dependent on STAT5 phosphorylation. Metformin inhibited the induction of PDK4 expression by GH via a pathway dependent on AMP-activated protein kinase (AMPK) and SHP induction. The increase in PDK4 expression and PDC phosphorylation by GH was reduced in STAT5-null mice. Metformin decreased GH-mediated induction of PDK4 expression and metabolites in wildtype but not in SHP-null mice. In primary hepatocytes, dominant-negative mutant-AMPK and SHP knockdown prevented the inhibitory effect of metformin on GH-stimulated PDK4 expression. SHP directly inhibited STAT5 association on the PDK4 gene promoter. Metformin inhibits GH-induced PDK4 expression and metabolites via an AMPK-SHP-dependent pathway. The metformin-AMPK-SHP network may provide a novel therapeutic approach for the treatment of hepatic metabolic disorders induced by the GH-mediated pathway. Diabetes 61:2484-2494, 2012
C1 [Kim, Yong Deuk; Choi, Hueng-Sik] Chonnam Natl Univ, Natl Creat Res Initiat Ctr Nucl Receptor Signals, Hormone Res Ctr, Sch Biol Sci & Technol, Kwangju, South Korea.
[Kim, Yong Deuk; Harris, Robert A.] Kyungpook Natl Univ, Sch Med, Res Inst Aging & Metab, World Class Univ Program, Taegu, South Korea.
[Kim, Yong-Hoon; Lee, Chul-Ho] Univ Sci & Technol, Korea Res Inst Biosci & Biotechnol, Lab Anim Ctr, Taejon, South Korea.
[Tadi, Surendar; Shong, Minho] Chungnam Natl Univ, Dept Internal Med, Sch Med, Taejon, South Korea.
[Tadi, Surendar; Yim, Yong-Hyeon] Korea Res Inst Stand & Sci, Taejon, South Korea.
[Yu, Ji Hoon; Hennighausen, Lothar] NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
[Jeoung, Nam Ho] Catholic Univ Daegu, Dept Fundamental Med & Pharmaceut Sci, Gyongsan, South Korea.
[Hennighausen, Lothar] Dankook Univ, Dept Nanobiomed Sci, Chungnam, South Korea.
[Hennighausen, Lothar] Dankook Univ, WCU Res Ctr Nanobiomed Sci, Chungnam, South Korea.
[Harris, Robert A.; Lee, In-Kyu] Indiana Univ Sch Med, Roudebush VA Med Ctr, Indianapolis, IN USA.
[Harris, Robert A.; Lee, In-Kyu] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN USA.
[Choi, Hueng-Sik] Chonnam Natl Univ, Sch Med, Res Inst Med Sci, Dept Biomed Sci, Kwangju, South Korea.
RP Choi, HS (reprint author), Chonnam Natl Univ, Natl Creat Res Initiat Ctr Nucl Receptor Signals, Hormone Res Ctr, Sch Biol Sci & Technol, Kwangju, South Korea.
EM chullee@kribb.re.kr; hsc@chonnam.ac.kr
OI Jeoung, Nam Ho/0000-0002-7584-3761
FU National Creative Research Initiatives Center for Nuclear Receptor
Signals; Korean Ministry of Education, Science and Technology
[20110018305]; Future-based Technology Development Program (BIO Fields)
through the National Research Foundation of Korea (NRF); Ministry of
Education, Science and Technology [20100019512, R32-10064]; KRIBB
Research Initiative Program of Korea; World Class University program
through the NRF; Korea Health Technology R&D Project, Ministry of Health
Welfare [A111345]
FX This work was supported by a National Creative Research Initiatives
Center for Nuclear Receptor Signals Grant funded from the Korean
Ministry of Education, Science and Technology (20110018305),
Future-based Technology Development Program (BIO Fields) through the
National Research Foundation of Korea (NRF) funded by the Ministry of
Education, Science and Technology (20100019512 to H.-S.C.), and by the
KRIBB Research Initiative Program of Korea (to C.-H.L.), and the World
Class University program through the NRF funded by the Ministry of
Education, Science and Technology (R32-10064), a Grant of the Korea
Health Technology R&D Project, Ministry of Health & Welfare Grant
A111345 (to I.-K.L.).
NR 40
TC 8
Z9 8
U1 0
U2 4
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD OCT
PY 2012
VL 61
IS 10
BP 2484
EP 2494
DI 10.2337/db11-1665
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 013KP
UT WOS:000309304600013
PM 22698918
ER
PT J
AU Restif, O
Hayman, DTS
Pulliam, JRC
Plowright, RK
George, DB
Luis, AD
Cunningham, AA
Bowen, RA
Fooks, AR
O'Shea, TJ
Wood, JLN
Webb, CT
AF Restif, Olivier
Hayman, David T. S.
Pulliam, Juliet R. C.
Plowright, Raina K.
George, Dylan B.
Luis, Angela D.
Cunningham, Andrew A.
Bowen, Richard A.
Fooks, Anthony R.
O'Shea, Thomas J.
Wood, James L. N.
Webb, Colleen T.
TI Model-guided fieldwork: practical guidelines for multidisciplinary
research on wildlife ecological and epidemiological dynamics
SO ECOLOGY LETTERS
LA English
DT Article
DE Field ecology; infectious diseases; mathematical models; statistical
models; study design; wildlife epidemiology
ID BIG BROWN BATS; EMERGING INFECTIOUS-DISEASES; PLAGUE EPIZOOTICS;
EPTESICUS-FUSCUS; YERSINIA-PESTIS; EIDOLON HELVUM; PUBLIC-HEALTH;
PRAIRIE DOGS; POPULATION; TRANSMISSION
AB Infectious disease ecology has recently raised its public profile beyond the scientific community due to the major threats that wildlife infections pose to biological conservation, animal welfare, human health and food security. As we start unravelling the full extent of emerging infectious diseases, there is an urgent need to facilitate multidisciplinary research in this area. Even though research in ecology has always had a strong theoretical component, cultural and technical hurdles often hamper direct collaboration between theoreticians and empiricists. Building upon our collective experience of multidisciplinary research and teaching in this area, we propose practical guidelines to help with effective integration among mathematical modelling, fieldwork and laboratory work. Modelling tools can be used at all steps of a field-based research programme, from the formulation of working hypotheses to field study design and data analysis. We illustrate our model-guided fieldwork framework with two case studies we have been conducting on wildlife infectious diseases: plague transmission in prairie dogs and lyssavirus dynamics in American and African bats. These demonstrate that mechanistic models, if properly integrated in research programmes, can provide a framework for holistic approaches to complex biological systems.
C1 [Restif, Olivier; Hayman, David T. S.; Wood, James L. N.] Univ Cambridge, Dept Vet Med, Dis Dynam Unit, Cambridge CB3 0ES, England.
[Hayman, David T. S.; Luis, Angela D.; Webb, Colleen T.] Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA.
[Hayman, David T. S.; Cunningham, Andrew A.] Zool Soc London, Inst Zool, London NW1 4RY, England.
[Hayman, David T. S.; Fooks, Anthony R.] Anim Hlth & Vet Labs Agcy, Weybridge KT15 3NB, Surrey, England.
[Pulliam, Juliet R. C.; George, Dylan B.; Luis, Angela D.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Pulliam, Juliet R. C.] Univ Florida, Dept Biol, Gainesville, FL 32611 USA.
[Pulliam, Juliet R. C.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32610 USA.
[Plowright, Raina K.] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[George, Dylan B.] US Dept Def, Ft Detrick, MD 21702 USA.
[Bowen, Richard A.; O'Shea, Thomas J.] Colorado State Univ, Dept Biomed Sci, Ft Collins, CO 80523 USA.
[Fooks, Anthony R.] Univ Liverpool, Natl Ctr Zoonosis Res, Neston CH64 7TE, South Wirral, England.
RP Restif, O (reprint author), Univ Cambridge, Dept Vet Med, Dis Dynam Unit, Madingley Rd, Cambridge CB3 0ES, England.
EM or226@cam.ac.uk
RI Wood, James/A-1626-2008; APHA, Staff publications/E-6082-2010; Barley,
Kamal/F-9579-2011; Cunningham, Andrew/E-7536-2010; Fooks,
Anthony/F-5418-2010; Pulliam, Juliet/A-6516-2008;
OI Wood, James/0000-0002-0258-3188; Barley, Kamal/0000-0003-1874-9813;
Pulliam, Juliet/0000-0003-3314-8223; Restif, Olivier/0000-0001-9158-853X
FU Science and Technology Directorate, Department of Homeland Security;
Fogarty International Center, National Institutes of Health; Royal
Society; Cedar Tree Foundation; Wellcome Trust; UK Department for
Environment, Food and Rural Affairs [SEV 3500]; European Commission
under ANTIGONE [278976]; Alborada Trust
FX We thank R. Biek, T. J. McKinley and two anonymous reviewers whose
comments have greatly helped improve the manuscript. This work was made
possible by funding from the Research and Policy for Infectious Disease
Dynamics (RAPIDD) programme of the Science and Technology Directorate,
Department of Homeland Security and Fogarty International Center,
National Institutes of Health. OR is a Royal Society-funded University
Research Fellow. RKP and DTSH acknowledge support from the Cedar Tree
Foundation through David H. Smith Fellowships in Conservation Research,
and DTSH from the Wellcome Trust through a Research Training Fellowship.
AAC is supported by a Royal Society Wolfson Research Merit award. ARF
was partially funded by the UK Department for Environment, Food and
Rural Affairs (grant SEV 3500) and by the European Commission Seventh
Framework Programme under ANTIGONE (project number 278976). JLNW is
supported by the Alborada Trust. The funders had no role in the
conception or redaction of this manuscript; the views expressed are
those of the authors only.
NR 81
TC 35
Z9 35
U1 10
U2 112
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1461-023X
EI 1461-0248
J9 ECOL LETT
JI Ecol. Lett.
PD OCT
PY 2012
VL 15
IS 10
BP 1083
EP 1094
DI 10.1111/j.1461-0248.2012.01836.x
PG 12
WC Ecology
SC Environmental Sciences & Ecology
GA 000QN
UT WOS:000308402300002
PM 22809422
ER
PT J
AU Fujimoto, K
Matsuura, K
Das, B
Fu, LZ
Shi, YB
AF Fujimoto, Kenta
Matsuura, Kazuo
Das, Biswajit
Fu, Liezhen
Shi, Yun-Bo
TI Direct Activation of Xenopus Iodotyrosine Deiodinase by Thyroid Hormone
Receptor in the Remodeling Intestine during Amphibian Metamorphosis
SO ENDOCRINOLOGY
LA English
DT Article
ID POSTEMBRYONIC DEVELOPMENT; STEM-CELLS; FROG METAMORPHOSIS;
GENE-EXPRESSION; MOLECULAR-BASIS; TADPOLE TAIL; LAEVIS; RECRUITMENT;
HYPOTHYROIDISM; TRANSCRIPTION
AB Thyroid hormone (TH) plays critical roles during vertebrate postembryonic development. TH production in the thyroid involves incorporating inorganic iodide into thyroglobulin. The expression of iodotyrosine deiodinase (IYD; also known as iodotyrosine dehalogenase 1) in the thyroid gland ensures efficient recycling of iodine from the byproducts of TH biosynthesis: 3'-monoiodotyrosine and 3', 5'-diiodotyrosine. Interestingly, IYD is known to be expressed in other organs in adult mammals, suggesting iodine recycling outside the thyroid. On the other hand, the developmental role of iodine recycling has yet to be investigated. Here, using intestinal metamorphosis as a model, we discovered that the Xenopus tropicalis IYD gene is strongly up-regulated by TH during metamorphosis in the intestine but not the tail. We further demonstrated that this induction was one of the earliest events during intestinal metamorphosis, with IYD being activated directly through the binding of liganded TH receptors to a TH response element in the IYD promoter region. Because iodide is mainly taken up from the diet in the intestine and the tadpole stops feeding during metamorphosis when the intestine is being remodeled, our findings suggest that IYD transcription is activated by liganded TH receptors early during intestinal remodeling to ensure efficient iodine recycling at the climax of metamorphosis when highest levels of TH are needed for the proper transformations of different organs. (Endocrinology 153: 5082-5089, 2012)
C1 [Fujimoto, Kenta; Matsuura, Kazuo; Das, Biswajit; Fu, Liezhen; Shi, Yun-Bo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
RP Shi, YB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, Program Cellular Regulat & Metab, NIH, 18 Lib Dr, Bethesda, MD 20892 USA.
EM shi@helix.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health.
NR 53
TC 2
Z9 2
U1 0
U2 16
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD OCT
PY 2012
VL 153
IS 10
BP 5082
EP 5089
DI 10.1210/en.2012-1308
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 012BK
UT WOS:000309210200048
PM 22865369
ER
PT J
AU Zhao, L
Zhu, XG
Park, JW
Fozzatti, L
Willingham, M
Cheng, SY
AF Zhao, Li
Zhu, Xuguang
Park, Jeong Won
Fozzatti, Laura
Willingham, Mark
Cheng, Sheue-yann
TI Role of TSH in the Spontaneous Development of Asymmetrical Thyroid
Carcinoma in Mice with a Targeted Mutation in a Single Allele of the
Thyroid Hormone-beta Receptor
SO ENDOCRINOLOGY
LA English
DT Article
ID FOCAL ADHESION KINASE; MOUSE MODEL; SERUM TSH; THERAPEUTIC TARGETS;
CANCER; RESISTANCE; GENE; CARCINOGENESIS; SRC; ANGIOGENESIS
AB Mutations of the thyroid hormone receptor-beta gene (THRB) cause resistance to thyroid hormone (RTH). A mouse model of RTH harboring a homozygous thyroid hormone receptor (TR)-beta mutation known as PV (Thrb(PV/PV) mouse) spontaneously develops follicular thyroid cancer (FTC). Similar to RTH patients with mutations of two alleles of the THRB gene, the Thrb(PV/PV) mouse exhibits elevated thyroid hormones accompanied by highly nonsuppressible TSH. However, the heterozygous Thrb(PV/+) mouse with mildly elevated TSH (similar to 2-fold) does not develop FTC. The present study examined whether the mutation of a single allele of the Thrb gene is sufficient to induce FTC in Thrb(PV/+) mice under stimulation by high TSH. Thrb(PV/+) mice and wild-type siblings were treated with propylthiouracil (PTU) to elevate serum TSH. Thrb(PV/+) mice treated with PTU (Thrb(PV/+)-PTU) spontaneously developed FTC similar to human thyroid cancer, but wild-type siblings treated with PTU did not. Interestingly, approximately 33% of Thrb(PV/+)-PTU mice developed asymmetrical thyroid tumors, as is frequently observed in human thyroid cancer. Molecular analyses showed activation of the cyclin 1-cyclin-dependent kinase-4-transcription factor E2F1 pathway to increase thyroid tumor cell proliferation of Thrb(PV/+)-PTU mice. Moreover, via extranuclear signaling, the PV also activated the integrin-Src-focal adhesion kinase-AKT-metalloproteinase pathway to increase migration and invasion of tumor cells. Therefore, mutation of a single allele of the Thrb gene is sufficient to drive the TSH-simulated hyperplastic thyroid follicular cells to undergo carcinogenesis. The present study suggests that the Thrb(PV/+)-PTU mouse model potentially could be used to gain insights into the molecular basis underlying the association between thyroid cancer and RTH seen in some affected patients. (Endocrinology 153: 5090-5100, 2012)
C1 [Zhao, Li; Zhu, Xuguang; Park, Jeong Won; Fozzatti, Laura; Cheng, Sheue-yann] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Willingham, Mark] Wake Forest Univ, Dept Pathol, Winston Salem, NC 27157 USA.
RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA.
EM chengs@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 43
TC 7
Z9 7
U1 2
U2 8
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD OCT
PY 2012
VL 153
IS 10
BP 5090
EP 5100
DI 10.1210/en.2012-1600
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 012BK
UT WOS:000309210200049
PM 22919057
ER
PT J
AU Salzer, W
Seibel, N
Smith, M
AF Salzer, Wanda
Seibel, Nita
Smith, Malcolm
TI Erwinia asparaginase in pediatric acute lymphoblastic leukemia
SO EXPERT OPINION ON BIOLOGICAL THERAPY
LA English
DT Article
DE acute lymphoblastic leukemia; allergy; antibody; Erwinia asparaginase;
treatment
ID ESCHERICHIA-COLI-ASPARAGINASE; CHILDRENS ONCOLOGY GROUP; ACUTE
LYMPHOCYTIC-LEUKEMIA; PEG-ASPARAGINASE; SYNTHETASE EXPRESSION; E. COLI;
HYPERSENSITIVITY REACTIONS; INTRAMUSCULAR THERAPY; CEREBROSPINAL-FLUID;
ANTIBODY-FORMATION
AB Introduction: Asparaginase is a major a component of therapy for acute lymphoblastic leukemia (ALL) and has been used for over 40 years. Hypersensitivity reactions limit the use and efficacy of asparaginase products. However, Erwinia asparaginase gained the Food and Drug Administration (FDA) approval in November 2011, for use in patients with allergic reactions to Escherichia coli-derived asparaginase.
Areas covered: Erwinia asparaginase is an enzyme that hydrolyzes the amino acid asparagine. This review examines the properties of Erwinia asparaginase compared to the two other preparations of asparaginase available for use in the United States. Results of selected clinical trials involving Erwinia asparaginase, including the pivotal study resulting in FDA approval, are presented.
Expert opinion: Erwinia asparaginase is well tolerated, and it is effective in achieving asparaginase levels associated with efficacy in the treatment of ALL. With FDA approval of Erwinia asparagainse, oncologists now have an alternative for ALL patients who become hypersensitive to E. coli-derived asparaginase. Future studies will be needed to establish optimal dosing of Erwinia asparaginase (e.g., intravenous vs. intramuscular) and to better define the most appropriate indications for its use in patients previously treated with E. coli-derived asparaginase.
C1 [Salzer, Wanda; Seibel, Nita; Smith, Malcolm] NCI, Bethesda, MD 20892 USA.
RP Salzer, W (reprint author), NCI, Bethesda, MD 20892 USA.
EM wanda.salzer@us.army.mil
NR 80
TC 10
Z9 12
U1 2
U2 4
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1471-2598
J9 EXPERT OPIN BIOL TH
JI Expert Opin. Biol. Ther.
PD OCT
PY 2012
VL 12
IS 10
BP 1407
EP 1414
DI 10.1517/14712598.2012.718327
PG 8
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA 004EQ
UT WOS:000308663600010
PM 22946493
ER
PT J
AU Jin, G
Mizutani, A
Fukuda, T
Chen, L
Nakanishi, K
Yan, T
Kudoh, T
Hirohata, S
Kasai, T
Murakami, H
Salomon, DS
Seno, M
AF Jin, Guoliang
Mizutani, Akifumi
Fukuda, Takayuki
Chen, Ling
Nakanishi, Keisuke
Yan, Ting
Kudoh, Takayuki
Hirohata, Satoshi
Kasai, Tomonari
Murakami, Hiroshi
Salomon, David S.
Seno, Masaharu
TI Eosinophil cationic protein enhances cardiomyocyte differentiation of
P19CL6 embryonal carcinoma cells by stimulating the FGF receptor
signaling pathway
SO GROWTH FACTORS
LA English
DT Article
DE Eosinophil cationic protein; cardiomyocyte differentiation; P19CL6 cells
ID STEM-CELLS; MESODERM DIFFERENTIATION; CARDIAC DIFFERENTIATION;
GROWTH-FACTOR; CARDIOMYOGENESIS; EXPRESSION; WNT; INHIBITION; TAK1
AB We investigated the functional role of eosinophil cationic protein (ECP) in regulating cardiomyogenesis using mouse P19CL6 embryonic carcinoma cells. ECP was confirmed to accelerate the cardiomyocyte differentiation of P19CL6 cells by enhancing the rate and area size of beating of cardiomyocyte and by facilitating the expression of cardiomyocyte-specific genes, such as GATA4 and alpha-MHC. Since cardiomyocyte differentiation in vivo is considered to follow mesoderm induction, the induction of Brachyury, a marker of mesoderm, was assessed. Brachyury expression was found to be enhanced after the addition of ECP. This enhancement was due to the stimulation of extracellular signal-regulated kinase (ERK) 1/2 phosphorylation by ECP. In this context, treatment with SU5402, an inhibitor of fibroblast growth factor (FGF) receptor 1, suppressed Brachyury expression, phosphorylation of ERK1/2, and cardiomyocyte differentiation induced by ECP. We concluded that ECP might induce mesoderm differentiation through FGF signaling pathway and enhance subsequent cardiomyocyte differentiation in concert with dimethyl sulfoxide in P19CL6 cells. ECP may be a novel factor for cardiomyocyte differentiation, which should be very useful to prepare adequate numbers of cardiomyocytes for therapeutic cell transplantation.
C1 [Jin, Guoliang; Mizutani, Akifumi; Fukuda, Takayuki; Chen, Ling; Nakanishi, Keisuke; Yan, Ting; Kudoh, Takayuki; Kasai, Tomonari; Murakami, Hiroshi; Seno, Masaharu] Okayama Univ, Grad Sch Nat Sci & Technol, Dept Med Bioengn Sci, Lab Nanobiotechnol, Okayama 7008530, Japan.
[Hirohata, Satoshi] Okayama Univ, Grad Sch Med Dent & Pharmacol, Dept Mol Biol & Biochem, Okayama 7008558, Japan.
[Salomon, David S.] NCI, Lab Canc Prevent, Frederick, MD 21702 USA.
RP Seno, M (reprint author), Okayama Univ, Grad Sch Nat Sci & Technol, Dept Med Bioengn Sci, Lab Nanobiotechnol, Okayama 7008530, Japan.
EM mseno@cc.okayama-u.ac.jp
RI Hirohata, Satoshi/B-2253-2011; SENO, Masaharu /B-2092-2011
OI Hirohata, Satoshi/0000-0002-4815-5891; SENO, Masaharu
/0000-0001-8547-6259
FU Ministry of Education, Culture, Sports, Science, and Technology; Japan
Science and Technology Agency (JST); Chugoku Industrial Innovation
Center
FX This research was supported in part by the Ministry of Education,
Culture, Sports, Science, and Technology Grant-in-Aid for Scientific
Research, by Japan Science and Technology Agency (JST), and by Chugoku
Industrial Innovation Center. The authors report no conflicts of
interest. The authors alone are responsible for the content and writing
of the paper.
NR 32
TC 2
Z9 2
U1 0
U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0897-7194
J9 GROWTH FACTORS
JI Growth Factors
PD OCT
PY 2012
VL 30
IS 5
BP 344
EP 355
DI 10.3109/08977194.2012.709852
PG 12
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 013FP
UT WOS:000309291600008
PM 22845717
ER
PT J
AU Sinner, MF
Porthan, K
Noseworthy, PA
Havulinna, AS
Tikkanen, JT
Muller-Nurasyid, M
Peloso, G
Ulivi, S
Beckmann, BM
Brockhaus, AC
Cooper, RR
Gasparini, P
Hengstenberg, C
Hwang, SJ
Iorio, A
Junttila, MJ
Klopp, N
Kahonen, M
Laaksonen, MA
Lehtimaki, T
Lichtner, P
Lyytikainen, LP
Martens, E
Meisinger, C
Meitinger, T
Merchant, FM
Nieminen, MS
Peters, A
Pietila, A
Perz, S
Oikarinen, L
Raitakari, O
Reinhard, W
Silander, K
Thorand, B
Wichmann, HE
Sinagra, G
Viikari, J
O'Donnell, CJ
Ellinor, PT
Huikuri, HV
Kaab, S
Newton-Cheh, C
Salomaa, V
AF Sinner, Moritz F.
Porthan, Kimmo
Noseworthy, Peter A.
Havulinna, Aki S.
Tikkanen, Jani T.
Mueller-Nurasyid, Martina
Peloso, Gina
Ulivi, Sheila
Beckmann, Britt Maria
Brockhaus, A. Catharina
Cooper, Rebecca R.
Gasparini, Paolo
Hengstenberg, Christian
Hwang, Shih-Jen
Iorio, Annamaria
Junttila, M. Juhani
Klopp, Norman
Kahonen, Mika
Laaksonen, Maarit A.
Lehtimaki, Terho
Lichtner, Peter
Lyytikainen, Leo-Pekka
Martens, Eimo
Meisinger, Christa
Meitinger, Thomas
Merchant, Faisal M.
Nieminen, Markku S.
Peters, Annette
Pietila, Arto
Perz, Siegfried
Oikarinen, Lasse
Raitakari, Olli
Reinhard, Wibke
Silander, Kaisa
Thorand, Barbara
Wichmann, H. -Erich
Sinagra, Gianfranco
Viikari, Jorma
O'Donnell, Christopher J.
Ellinor, Patrick T.
Huikuri, Heikki V.
Kaeaeb, Stefan
Newton-Cheh, Christopher
Salomaa, Veikko
TI A meta-analysis of genome-wide association studies of the
electrocardiographic early repolarization pattern
SO HEART RHYTHM
LA English
DT Article
DE Early repolarization; Sudden cardiac death; Arrhythmia; GWAS;
Meta-analysis; Electrocardiogram
ID TRANSIENT OUTWARD CURRENT; QT INTERVAL DURATION; J-POINT ELEVATION;
J-WAVE SYNDROMES; ATRIAL-FIBRILLATION; COMMON VARIANTS;
VENTRICULAR-FIBRILLATION; CHANNEL; KV4.3; MUTATIONS
AB BACKGROUND The early repolarization pattern (ERP) is common and associated with risk of sudden cardiac death. ERP is heritable, and mutations have been described in syndromatic cases.
OBJECTIVE To conduct a meta-analysis of genome-wide association studies to identify common genetic variants influencing ERP.
METHODS We ascertained ERP on the basis of electrocardiograms in 3 large community-based cohorts from Europe and the United States: the Framingham Heart Study, the Health 2000 Study, and the KORA F4 Study. We analyzed genome-wide association studies in participants with and without ERP by logistic regression assuming an additive genetic model and meta-analyzed individual cohort results. We then sought to strengthen support for findings that reached P <= 1 x 10(-5) in independent individuals by direct genotyping or in-silico analysis of genome-wide data. We meta-analyzed the results from both stages.
RESULTS Of 7482 individuals in the discovery stage, 452 showed ERP (ERP positive: mean age 46.9 +/- 8.9 years, 30.3% women; ERP negative: 47.5 +/- 9.4 years, 54.2% women). After meta-analysis, 8 single nucleotide polymorphisms reached P <= 1 x 10(-5): The most significant finding was intergenic rs11653989 (odds ratio 0.47; 95% confidence interval 0.36-0.61; P = 6.9 x 10(-9)). The most biologically relevant finding was intronic to KCND3: rs17029069 (odds ratio 1.46; 95% confidence interval 1.25-1.69; P = 8.5 x 10(-7)). In the replication step (7151 individuals), none of the 8 variants replicated, and combined meta-analysis results failed to reach genome-wide significance.
CONCLUSIONS In a genome-wide association study, we were not able to reliably identify genetic variants predisposing to ERP, presumably due to insufficient statistical power and phenotype heterogeneity. The reported heritability of ERP warrants continued investigation in larger well-phenotyped populations.
C1 [Sinner, Moritz F.; Noseworthy, Peter A.; Cooper, Rebecca R.; Merchant, Faisal M.; Ellinor, Patrick T.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Peloso, Gina; Ellinor, Patrick T.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Charlestown, MA USA.
[Sinner, Moritz F.; Noseworthy, Peter A.; Peloso, Gina; Hwang, Shih-Jen; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Sinner, Moritz F.; Noseworthy, Peter A.; Peloso, Gina; Hwang, Shih-Jen; O'Donnell, Christopher J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Sinner, Moritz F.; Mueller-Nurasyid, Martina; Beckmann, Britt Maria; Brockhaus, A. Catharina; Martens, Eimo; Kaeaeb, Stefan] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany.
[Porthan, Kimmo; Nieminen, Markku S.; Oikarinen, Lasse] Univ Helsinki, Cent Hosp, Div Cardiol, Dept Med, Helsinki, Finland.
[Havulinna, Aki S.; Pietila, Arto; Silander, Kaisa; Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Laaksonen, Maarit A.] Natl Inst Hlth & Welf, Dept Hlth Funct Capac & Welf, Helsinki, Finland.
[Tikkanen, Jani T.; Junttila, M. Juhani; Huikuri, Heikki V.] Univ Oulu, Dept Internal Med, Inst Clin Med, SF-90220 Oulu, Finland.
[Mueller-Nurasyid, Martina; Brockhaus, A. Catharina] German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Klopp, Norman] German Res Ctr Environm Hlth, Inst Mol Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Meisinger, Christa; Wichmann, H. -Erich] German Res Ctr Environm Hlth, Inst Epidemiol 1, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Peters, Annette; Thorand, Barbara] German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Perz, Siegfried] German Res Ctr Environm Hlth, Inst Biol & Med Imaging, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Mueller-Nurasyid, Martina; Wichmann, H. -Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, Munich, Germany.
[Mueller-Nurasyid, Martina] Univ Munich, Chair Genet Epidemiol, Munich, Germany.
[Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.
[Kahonen, Mika] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[Lehtimaki, Terho; Lyytikainen, Leo-Pekka] Univ Tampere, Dept Clin Chem, Fimlab Ltd, FIN-33101 Tampere, Finland.
[Ulivi, Sheila; Gasparini, Paolo] IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy.
[Hengstenberg, Christian; Reinhard, Wibke] Univ Klinikum Regensburg, Klin & Poliklin Innere Med 2, Regensburg, Germany.
[Lichtner, Peter; Meitinger, Thomas] German Res Ctr Environm Hlth, Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Meitinger, Thomas; Peters, Annette; Kaeaeb, Stefan] Munich Heart Alliance, Munich, Germany.
[Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland.
[Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Silander, Kaisa] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Wichmann, H. -Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Viikari, Jorma] Turku Univ Hosp, Dept Med, FIN-20520 Turku, Finland.
[Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Cardiovasc Res Ctr, Div Cardiol, Boston, MA 02114 USA.
[Iorio, Annamaria; Sinagra, Gianfranco] Azienda Osped Univ Univ Trieste, Cardiovasc Dept, Trieste, Italy.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
RP Newton-Cheh, C (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Cardiovasc Res Ctr, Div Cardiol, 185 Cambridge St,CPZN 5-242, Boston, MA 02114 USA.
EM cnewtoncheh@partners.org
RI Kaab, Stefan/H-3915-2012; Ulivi, Sheila/H-3700-2013; Meisinger,
Christine/B-5358-2014; Thorand, Barbara/B-5349-2014; Meitinger,
Thomas/O-1318-2015; Peters, Annette/A-6117-2011; Lyytikainen,
Leo-Pekka/C-8544-2016;
OI Ulivi, Sheila/0000-0003-3606-835X; Thorand, Barbara/0000-0002-8416-6440;
Lyytikainen, Leo-Pekka/0000-0002-7200-5455; Meisinger,
Christa/0000-0002-9026-6544; SINAGRA, GIANFRANCO/0000-0003-2700-8478
FU German Heart Foundation; Finnish Foundation for Cardiovascular Research;
Orion-Farmos Research Foundation; Max Schaldach Fellowship in Cardiac
Pacing and Electrophysiology; National Institutes of Health
[RO1HL092577, 5R21DA027021, 1RO1HL104156, 1K24HL10578]; German National
Genome Research Network NGFN-Plus [01GS0838]; German Federal Ministry
for Education and Research (BMBF)/French Agence National de la Recherche
(ANR) [SCD-Gene: 01KU0907]; BMBF cluster of excellence "personalized
medicine M4"; National Institutes of Health; Burroughs Wellcome Fund;
Academy of Finland [129494, 139635, 134309, 126925, 121584, 124282,
129378, 117787, 41071]; Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson
Evans Endowment of the Department of Medicine at Boston University
School of Medicine; Boston Medical Center; NHLBI Division of Intramural
Research; National Institute for Health and Welfare; Finnish Centre for
Pensions; Social Insurance Institution of Finland; Local Government
Pensions Institution; Wellcome Trust Sanger Institute; BMBF; state of
Bavaria; BMBF in the context of NGFN plus [01GS0838]; LMU Excellence
Initiative; Munich Center of Health Sciences (MC Health) as part of
LMUinnovativ; Social Insurance Institution of Finland, Kuopio, Tampere;
Turku University Hospital Medical Funds [9M048, 9N035]; Juho Vainio
Foundation; Paavo Nurmi Foundation; Finnish Foundation of Cardiovascular
Research; Finnish Cultural Foundation; Tampere Tuberculosis Foundation;
Emil Aaltonen Foundation; project of "Genetic Park of FVG"; Regione FVG
[L.26.2008]; Associazione Amici del Cuore
FX This study was supported by the German Heart Foundation (to Dr Sinner),
the Finnish Foundation for Cardiovascular Research (to Dr Porthan and Dr
Oikarinen), the Orion-Farmos Research Foundation (to Dr Porthan), the
Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology (to Dr
Noseworthy), National Institutes of Health grants RO1HL092577,
5R21DA027021, 1RO1HL104156, and 1K24HL10578 (to Dr Ellinor), the German
National Genome Research Network NGFN-Plus (01GS0838) (to Dr Kaab), the
German Federal Ministry for Education and Research (BMBF)/French Agence
National de la Recherche (ANR) (SCD-Gene: 01KU0907) (to Dr Kaab), the
BMBF cluster of excellence "personalized medicine M4" (to Dr Kaab), the
National Institutes of Health and the Burroughs Wellcome Fund (to Dr
Newton-Cheh), and the Academy of Finland grants 129494 and 139635 (to Dr
Salomaa). This research used data and resources from the NHLBI's and
Boston University School of Public Health's Framingham Heart Study
(N01-HC-25195), its contract with Affymetrix, Inc, for genotyping
services (contract number N02-HL-6-4278), and involved researchers
participating in the SNP Health Association Resource (SHARe) project
utilizing the Linux Cluster for Genetic Analysis (LinGA-II) funded by
the Robert Dawson Evans Endowment of the Department of Medicine at
Boston University School of Medicine and Boston Medical Center. Funding
for analyses was provided by the NHLBI Division of Intramural Research
(to Dr. O'Donnell, Dr Peloso, and Dr Hwang). The Health 2000 Study was
funded by the National Institute for Health and Welfare (THL), the
Finnish Centre for Pensions (ETK), The Social Insurance Institution of
Finland (KELA), The Local Government Pensions Institution (KEVA), and
other organizations listed on the Web site of the survey
(http://www.terveys2000.fi). GWAS genotyping was supported by the
Wellcome Trust Sanger Institute. The MONICA/KORA Augsburg studies were
financed by the Helmholtz Zentrum Munchen, German Research Center for
Environmental Health, Neuherberg, Germany, and supported by grants from
the BMBF and the state of Bavaria. Additional support was provided from
the BMBF in the context of NGFN plus (01GS0838), the LMU Excellence
Initiative, and the Munich Center of Health Sciences (MC Health) as part
of LMUinnovativ. The Young Finns Study was financed by the Academy of
Finland: grants 134309 (Eye), 126925, 121584, 124282, and 129378
(Salve), 117787 (Gendi), and 41071 (Skidi), the Social Insurance
Institution of Finland, Kuopio, Tampere, and Turku University Hospital
Medical Funds (grants 9M048 and 9N035 for TeLeht), Juho Vainio
Foundation, Paavo Nurmi Foundation, Finnish Foundation of Cardiovascular
Research and Finnish Cultural Foundation, Tampere Tuberculosis
Foundation, and Emil Aaltonen Foundation (TL). The project of "Genetic
Park of FVG" was supported by Regione FVG (L.26.2008) and the
Associazione Amici del Cuore. Dr Newton-Cheh reports to be on the
scientific advisory board of Merck, Inc. Address for reprint requests
and correspondence: Dr Christopher Newton-Cheh, MD, MPH, Center for
Human Genetic Research, Cardiovascular Research Center, Massachusetts
General Hospital, 185 Cambridge St, CPZN 5.242, Boston, MA 02114. E-mail
address: cnewtoncheh@partners.org.
NR 32
TC 20
Z9 21
U1 1
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1547-5271
J9 HEART RHYTHM
JI Heart Rhythm
PD OCT
PY 2012
VL 9
IS 10
BP 1627
EP 1634
DI 10.1016/j.hrthm.2012.06.008
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 013FZ
UT WOS:000309292600011
PM 22683750
ER
PT J
AU Turkbey, EB
Gai, N
Lima, JAC
van der Geest, RJ
Wagner, KR
Tomaselli, GF
Bluemke, DA
Nazarian, S
AF Turkbey, Evrim B.
Gai, Neville
Lima, Joao A. C.
van der Geest, Rob J.
Wagner, Kathryn R.
Tomaselli, Gordon F.
Bluemke, David A.
Nazarian, Saman
TI Assessment of cardiac involvement in myotonic muscular dystrophy by T1
mapping on magnetic resonance imaging
SO HEART RHYTHM
LA English
DT Article
DE Myotonic muscular dystrophy; MRI; T1 mapping; Ventricular function
ID DIFFUSE MYOCARDIAL FIBROSIS; HEART-DISEASE; ABNORMALITIES; INFARCTION;
TYPE-1; SIZE
AB BACKGROUND Patients with myotonic muscular dystrophy (DM) are at risk for atrioventricular block and left ventricular (LV) dysfunction. Noninvasive detection of diffuse myocardial fibrosis may improve disease management in this population.
OBJECTIVE To define functional and postcontrast myocardial T1 time cardiac magnetic resonance characteristics in patients with DM.
METHODS Thirty-three patients with DM (24 with type 1 and 9 with type 2) and 13 healthy volunteers underwent cardiac magnetic resonance for the assessment of LV indices and the evaluation of diffuse myocardial fibrosis by T1 mapping. The association of myocardial T1 time with electrocardiogram abnormalities and LV indices was examined among patients with DM.
RESULTS Patients with DM had lower end-diastolic volume index (68.9 mL/m(2) vs 60.3 mL/m(2); P = .045) and cardiac index (2.7 L/min/m(2) vs 2.33 L/min/m(2); P = .005) and shorter myocardial T1 time (394.5 ms vs 441.4 ms; P < .0001) than did control subjects. Among patients with DM, there was a positive association between higher T1 time and LV mass index (2.2 ms longer per g/m(2); P = .006), LV end-diastolic volume index (1.3 ms longer per mL/m(2); P = .026), filtered QRS duration (1.2 ms longer per unit; P = .005), and low-amplitude (<40 mcV) late-potential duration (0.9 ms longer per unit; P = .01). Using multivariate random effects regression, each 10-ms increase in myocardial T1 time of patients with type 1 DM was independently associated with 1.3-ms increase in longitudinal PR and QRS intervals during follow-up.
CONCLUSIONS DM is associated with structural alterations on cardiac magnetic resonance. Postcontrast myocardial T1 time was shorter in patients with DM than in controls, likely reflecting the presence of diffuse myocardial fibrosis.
C1 [Lima, Joao A. C.; Tomaselli, Gordon F.; Nazarian, Saman] Johns Hopkins Univ, Div Cardiol, Dept Med, Sch Med, Baltimore, MD 21287 USA.
[Turkbey, Evrim B.; Gai, Neville; Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
[Turkbey, Evrim B.; Gai, Neville; Bluemke, David A.] Ctr Clin, Bethesda, MD USA.
[Turkbey, Evrim B.; Lima, Joao A. C.; Bluemke, David A.] Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA.
[van der Geest, Rob J.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands.
[Wagner, Kathryn R.] Kennedy Krieger Inst, Dept Neurol & Neurosci, Baltimore, MD USA.
RP Nazarian, S (reprint author), Johns Hopkins Univ, Div Cardiol, Dept Med, Sch Med, Carnegie 592C,600 N Wolfe St, Baltimore, MD 21287 USA.
EM snazarian@jhmi.edu
RI van der Geest, Rob/J-8193-2015;
OI van der Geest, Rob/0000-0002-9084-5597; Bluemke,
David/0000-0002-8323-8086
FU National Institutes of Health [K23-HL089333]; P.J. Schafer Memorial
Research Award; intramural National Institutes of Health research
program
FX The study was funded by National Institutes of Health (grant no.
K23-HL089333) and the P.J. Schafer Memorial Research Award to Dr
Nazarian, and the intramural National Institutes of Health research
program. Dr van der Geest is a consultant for Medis Medical Imaging
Systems. Dr Nazarian has received honoraria for lectures (not speakers'
bureau) from St Jude Medical, Biotronic, and Boston Scientific, Inc. He
is also on the MRI advisory panel (unpaid) for Medtronic. Address for
reprint requests and correspondence: Dr Saman Nazarian, MD, Division of
Cardiology, Department of Medicine, School of Medicine, Johns Hopkins
University, Carnegie 592C, 600 N Wolfe St, Baltimore, MD 21287. E-mail
address: snazarian@jhmi.edu.
NR 23
TC 10
Z9 10
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1547-5271
J9 HEART RHYTHM
JI Heart Rhythm
PD OCT
PY 2012
VL 9
IS 10
BP 1691
EP 1697
DI 10.1016/j.hrthm.2012.06.032
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 013FZ
UT WOS:000309292600026
PM 22710483
ER
PT J
AU Murray, EA
Wise, SP
AF Murray, Elisabeth A.
Wise, Steven P.
TI Why is there a special issue on perirhinal cortex in a journal called
hippocampus? The perirhinal cortex in historical perspective
SO HIPPOCAMPUS
LA English
DT Editorial Material
DE medial temporal lobe; memory systems; prefrontal cortex; ventral stream
ID MEDIAL TEMPORAL-LOBE; RESOLVES FEATURE AMBIGUITY; VISUAL RECOGNITION
MEMORY; OBJECT RECOGNITION; CORTICAL AFFERENTS; RHESUS-MONKEYS; RHINAL
CORTEX; AREA TE; PARAHIPPOCAMPAL REGION; ENTORHINAL CORTICES
AB Despite its small size, the perirhinal cortex (PRh) plays a central role in understanding the cerebral cortex, vision, and memory; it figures in discussions of cognitive capacities as diverse as object perception, semantic knowledge, feelings of familiarity, and conscious recollection. Two conceptual constructs have encompassed PRh. The current orthodoxy incorporates PRh within the medial temporal lobe (MTL) as a memory area; an alternative considers PRh to be a sensory area with a role in both perception and memory. A historical perspective provides insight into both these ideas. PRh came to be included in the MTL because of two accidents of history. In evolutionary history, the hippocampus migrated from its ancestral situation as medial cortex into the temporal lobe; in the history of neuropsychology, a memory system that originally consisted of the amygdala and hippocampus came to include PRh. These two histories explain why a part of the sensory neocortex, PRh, entered into the conceptual construct called the MTL. They also explain why some experimental results seem to exclude a perceptual function for this sensory area, while others embrace perception. The exclusion of perceptual functions results from a history of categorizing tasks as perceptual or mnemonic, often on inadequate grounds. By exploring the role of PRh in encoding, representing, and retrieving stimulus information, it can be understood as a part of the sensory neocortex, one that has the same relationship with the hippocampus as do other parts of the neocortex that evolved at about the same time. (C) 2012 Wiley Periodicals, Inc.
C1 [Murray, Elisabeth A.] NIMH, Neuropsychol Lab, Sect Neurobiol Learning & Memory, NIH, Bethesda, MD 20892 USA.
RP Murray, EA (reprint author), NIMH, Neuropsychol Lab, Sect Neurobiol Learning & Memory, NIH, Bldg 49,Room 1B80,MSC 4415,49 Convent Dr, Bethesda, MD 20892 USA.
EM murraye@mail.nih.gov
OI Murray, Elisabeth/0000-0003-1450-1642
FU Intramural NIH HHS [ZIA MH002736-18]
NR 78
TC 17
Z9 17
U1 2
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1050-9631
J9 HIPPOCAMPUS
JI Hippocampus
PD OCT
PY 2012
VL 22
IS 10
SI SI
BP 1941
EP 1951
DI 10.1002/hipo.22055
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 007GF
UT WOS:000308876100001
PM 22987673
ER
PT J
AU Johnson, G
MacLehose, RF
Baird, DD
Laughlin-Tommaso, SK
Hartmann, KE
AF Johnson, Gayle
MacLehose, Richard F.
Baird, Donna D.
Laughlin-Tommaso, Shannon K.
Hartmann, Katherine E.
TI Uterine leiomyomata and fecundability in the Right from the Start study
SO HUMAN REPRODUCTION
LA English
DT Article
DE leiomyoma; pregnancy; epidemiology
ID ASSISTED CONCEPTION; FIBROIDS; PREGNANCY; INFERTILITY; TRIMESTER;
OUTCOMES; MYOMAS; IMPACT; WOMEN
AB Previous research suggests the removal of uterine leiomyomata may improve ability to conceive. Most of this previous research was conducted in infertility clinics. We investigated the association between leiomyoma characteristics on time to pregnancy among women enrolled from the general population.
We enrolled a cohort study of women in early pregnancy. Participants retrospectively reported their time to conception. Leiomyomata characteristics were determined by first-trimester ultrasound. We used discrete time hazard models to estimate the effects of uterine leiomyomata on time to pregnancy.
In this population of 3000 women, 11 (324) with one or more leiomyomata, we found no association between leiomyomata presence, type, location, segment or size on time to pregnancy.
These results suggest that leiomyomata have little effect on time to pregnancy in this cohort of women. The study excluded women who had been treated for infertility, and this may have resulted in underestimation of the association. However, differences between our study and previous studies in specialty clinics may be, in part, attributable to differences between our community-recruited population of women and women receiving fertility care, as well as difference in leiomyomata size or type in women having myomectomies to treat infertility.
C1 [Johnson, Gayle; MacLehose, Richard F.] Univ Minnesota, Div Biostat, Minneapolis, MN 55455 USA.
[MacLehose, Richard F.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA.
[Baird, Donna D.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Laughlin-Tommaso, Shannon K.] Mayo Clin, Ctr Uterine Fibroids, Rochester, MN USA.
[Hartmann, Katherine E.] Vanderbilt Univ, Inst Med & Publ Hlth, Nashville, TN USA.
[Hartmann, Katherine E.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
RP MacLehose, RF (reprint author), Univ Minnesota, Div Biostat, 420 Delaware St SE,Box 303, Minneapolis, MN 55455 USA.
EM macl0029@umn.edu
RI Baird, Donna/D-5214-2017
OI Baird, Donna/0000-0002-5544-2653
FU National Institute of Environmental Health Sciences, NIH; American Water
Works Association Research Foundation [2579]; National Institute of
Child Health and Human Development [R01 HD043883-04, HD049675];
Vanderbilt CTSA from NCRR/NIH [UL1 RR024975-01]
FX This research was supported in part (D. D. B. salary) by the National
Institute of Environmental Health Sciences, NIH. The work was conducted
as part of the Right from the Start study. The parent study received
support from the American Water Works Association Research Foundation
under contract no. 2579; National Institute of Child Health and Human
Development Grants R01 HD043883-04 and HD049675: 'Consequences and
Course of Uterine Fibroids in Pregnancy'. Recruitment was also supported
in part by Vanderbilt CTSA grant UL1 RR024975-01 from NCRR/NIH.
NR 25
TC 3
Z9 3
U1 2
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
J9 HUM REPROD
JI Hum. Reprod.
PD OCT
PY 2012
VL 27
IS 10
BP 2991
EP 2997
DI 10.1093/humrep/des263
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 007JS
UT WOS:000308885200015
PM 22811308
ER
PT J
AU Fadlallah, B
Seth, S
Keil, A
Principe, J
AF Fadlallah, Bilal
Seth, Sohan
Keil, Andreas
Principe, Jose
TI Quantifying Cognitive State From EEG Using Dependence Measures
SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
LA English
DT Article
DE Brain connectivity; correlation; electroencephalogram (EEG); finite
impulse response (FIR) least-square filter; generalized measure of
association (GMA); mutual information (MI); steady-state visual evoked
potential (ssVEP)
ID MUTUAL INFORMATION ANALYSIS; VISUAL-CORTEX; FUNCTIONAL CONNECTIVITY;
MOTIVATED ATTENTION; NATURAL SCENES; TIME-SCALES; NETWORKS; COHERENCE;
EMOTION; BRAIN
AB The exquisite human ability to perceive facial features has been explained by the activity of neurons particularly responsive to faces, found in the fusiform gyrus and the anterior part of the superior temporal sulcus. This study hypothesizes and demonstrates that it is possible to automatically discriminate face processing from processing of a simple control stimulus based on processed EEGs in an online fashion with high temporal resolution using measures of statistical dependence applied on steady-state visual evoked potentials. Correlation, mutual information, and a novel measure of association, referred to as generalized measure of association (GMA), were applied on filtered current source density data. Dependences between channel locations were assessed for two separate conditions elicited by distinct pictures (a face and a Gabor grating) flickering at a rate of 17.5 Hz. Filter settings were chosen to minimize the distortion produced by bandpassing parameters on dependence estimation. Statistical analysis was performed for automated stimulus classification using the Kolmogorov-Smirnov test. Results show active regions in the occipito-parietal part of the brain for both conditions with a greater dependence between occipital and inferotemporal sites for the face stimulus. GMA achieved a higher performance in discriminating the two conditions. Because no additional face-like stimuli were examined, this study established a basic difference between one particular face and one nonface stimulus. Future work may use additional stimuli and experimental manipulations to determine the specificity of the current connectivity results.
C1 [Fadlallah, Bilal; Principe, Jose] Univ Florida, Dept Elect & Comp Engn, Gainesville, FL 32611 USA.
[Fadlallah, Bilal; Principe, Jose] Univ Florida, Computat NeuroEngn Lab, Gainesville, FL 32611 USA.
[Seth, Sohan] Aalto Univ, Dept Informat & Comp Sci, FI-00076 Aalto, Finland.
[Seth, Sohan] Helsinki Inst Informat Technol, FI-00014 Helsinki, Finland.
[Keil, Andreas] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA.
[Keil, Andreas] Univ Florida, NIMH Ctr Study Emot & Attent, Gainesville, FL 32611 USA.
RP Fadlallah, B (reprint author), Univ Florida, Dept Elect & Comp Engn, Gainesville, FL 32611 USA.
EM bhf@cnel.ufl.edu; sohan.seth@hiit.fi; akeil@ufl.edu;
principe@cnel.ufl.edu
RI Keil, Andreas/F-9427-2011
OI Keil, Andreas/0000-0002-4064-1924
FU National Science Foundation [IIS-0964197]; Lebanese Center for
Scientific Research
FX This work was supported by the National Science Foundation under Grant
IIS-0964197 and the Lebanese Center for Scientific Research. Asterisk
indicates corresponding author.
NR 53
TC 11
Z9 11
U1 2
U2 10
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9294
EI 1558-2531
J9 IEEE T BIO-MED ENG
JI IEEE Trans. Biomed. Eng.
PD OCT
PY 2012
VL 59
IS 10
BP 2773
EP 2781
DI 10.1109/TBME.2012.2210283
PG 9
WC Engineering, Biomedical
SC Engineering
GA 008XD
UT WOS:000308989000010
PM 22851234
ER
PT J
AU Bestor, A
Rego, ROM
Tilly, K
Rosa, PA
AF Bestor, Aaron
Rego, Ryan O. M.
Tilly, Kit
Rosa, Patricia A.
TI Competitive Advantage of Borrelia burgdorferi with Outer Surface Protein
BBA03 during Tick-Mediated Infection of the Mammalian Host
SO INFECTION AND IMMUNITY
LA English
DT Article
ID LYME-DISEASE SPIROCHETE; IXODES-SCAPULARIS TICKS; SENSU-STRICTO;
BABESIA-MICROTI; GENE-EXPRESSION; ANAPLASMA-PHAGOCYTOPHILUM;
SIMULTANEOUS TRANSMISSION; EXTRACHROMOSOMAL DNAS; LINEAR PLASMIDS;
STRAIN B31
AB Linear plasmid lp54 is one of the most highly conserved and differentially expressed elements of the segmented genome of the Lyme disease spirochete Borrelia burgdorferi. We previously reported that deletion of a 4.1-kb region of lp54 (bba01 to bba07 [bba01-bba07]) led to a slight attenuation of tick-transmitted infection in mice following challenge with a large number of infected ticks. In the current study, we reduced the number of ticks in the challenge to more closely mimic the natural dose and found a profound defect in tick-transmitted infection of the bba01-bba07 mutant relative to wild-type B. burgdorferi. We next focused on deletion of bba03 as the most likely cause of this mutant phenotype, as previous studies have shown that expression of bba03 is increased by culture conditions that simulate tick feeding. Consistent with this hypothesis, we demonstrated increased expression of bba03 by spirochetes in fed relative to unfed ticks. We also observed that a bba03 deletion mutant, although fully competent by itself, did not efficiently infect mice when transmitted by ticks that were simultaneously coinfected with wild-type B. burgdorferi. These results suggest that BBA03 provides a competitive advantage to spirochetes carrying this protein during tick transmission to a mammalian host in the natural infectious cycle.
C1 [Bestor, Aaron; Rego, Ryan O. M.; Tilly, Kit; Rosa, Patricia A.] NIAID, Lab Zoonot Pathogens, NIH, Rocky Mt Labs, Hamilton, MT USA.
RP Bestor, A (reprint author), NIAID, Lab Zoonot Pathogens, NIH, Rocky Mt Labs, Hamilton, MT USA.
EM bestora@niaid.nih.gov
RI Rego, Ryan/G-9773-2014
OI Rego, Ryan/0000-0001-6932-0940
FU NIH, NIAID
FX This research was supported by the intramural research program of the
NIH, NIAID.
NR 58
TC 20
Z9 20
U1 0
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD OCT
PY 2012
VL 80
IS 10
BP 3501
EP 3511
DI 10.1128/IAI.00521-12
PG 11
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 006EB
UT WOS:000308801200016
PM 22851744
ER
PT J
AU Seo, KS
Kim, JW
Park, JY
Viall, AK
Minnich, SS
Rohde, HN
Schnider, DR
Lim, SY
Hong, JB
Hinnebusch, BJ
O'Loughlin, JL
Deobald, CF
Bohach, GA
Hovde, CJ
Minnich, SA
AF Seo, Keun Seok
Kim, Jong Wan
Park, Joo Youn
Viall, Austin K.
Minnich, Scott S.
Rohde, Harold N.
Schnider, Darren R.
Lim, Seung Yong
Hong, Joon Bae
Hinnebusch, B. Joseph
O'Loughlin, Jason L.
Deobald, Claudia F.
Bohach, Gregory A.
Hovde, Carolyn J.
Minnich, Scott A.
TI Role of a New Intimin/Invasin-Like Protein in Yersinia pestis Virulence
SO INFECTION AND IMMUNITY
LA English
DT Article
ID PRIMARY PNEUMONIC PLAGUE; EPITHELIAL-CELLS; MOUSE MODEL; GENE; PLASMID;
PSEUDOTUBERCULOSIS; ENTEROCOLITICA; INVASIN; GENOME; FLEA
AB A comprehensive TnphoA mutant library was constructed in Yersinia pestis KIM6 to identify surface proteins involved in Y. pestis host cell invasion and bacterial virulence. Insertion site analysis of the library repeatedly identified a 9,042-bp chromosomal gene (YPO3944), intimin/invasin-like protein (Ilp), similar to the Gram-negative intimin/invasin family of surface proteins. Deletion mutants of ilp were generated in Y. pestis strains KIM5(pCD1(+)) Pgm(-) (pigmentation negative)/, KIM6(pCD1(-)) Pgm(+), and CO92. Comparative analyses were done with the deletions and the parental wild type for bacterial adhesion to and internalization by HEp-2 cells in vitro, infectivity and maintenance in the flea vector, and lethality in murine models of systemic and pneumonic plague. Deletion of ilp had no effect on bacterial blockage of flea blood feeding or colonization. The Y. pestis KIM5 Delta ilp strain had reduced adhesion to and internalization by HEp-2 cells compared to the parental wild-type strain (P<0.05). Following intravenous challenge with Y. pestis KIM5 Delta ilp, mice had a delayed time to death and reduced dissemination to the lungs, livers, and kidneys as monitored by in vivo imaging using a lux reporter system (in vivo imaging system [IVIS]) and bacterial counts. Intranasal challenge in mice with Y. pestis CO92 Delta ilp had a 55-fold increase in the 50% lethal dose ([LD50] 1.64 x 10(4) CFU) compared to the parental wild-type strain LD50 (2.98 x 10(2) CFU). These findings identified Ilp as a novel virulence factor of Y. pestis.
C1 [Kim, Jong Wan; Viall, Austin K.; Minnich, Scott S.; Rohde, Harold N.; Schnider, Darren R.; Lim, Seung Yong; Hong, Joon Bae; O'Loughlin, Jason L.; Deobald, Claudia F.; Hovde, Carolyn J.; Minnich, Scott A.] Univ Idaho, Sch Food Sci, Moscow, ID 83843 USA.
[Seo, Keun Seok; Park, Joo Youn; Bohach, Gregory A.] Mississippi State Univ, Dept Basic Sci, Mississippi State, MS 39762 USA.
[Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
RP Minnich, SA (reprint author), Univ Idaho, Sch Food Sci, Moscow, ID 83843 USA.
EM sminnich@uidaho.edu
OI Seo, Keun Seok/0000-0001-9280-9680
FU National Institutes of Health [P20 RR15587, P20 RR16454, P20 GM103408];
Idaho Agricultural Experimental Station
FX This study was supported by National Institutes of Health grants P20
RR15587, P20 RR16454, and P20 GM103408 and the Idaho Agricultural
Experimental Station.
NR 33
TC 8
Z9 8
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD OCT
PY 2012
VL 80
IS 10
BP 3559
EP 3569
DI 10.1128/IAI.00294-12
PG 11
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 006EB
UT WOS:000308801200021
PM 22851752
ER
PT J
AU Le Foll, B
Chakraborty-Chatterjee, M
Lev-Ran, S
Barnes, C
Pushparaj, A
Gamaleddin, I
Yan, YJ
Khaled, M
Goldberg, SR
AF Le Foll, Bernard
Chakraborty-Chatterjee, Munmun
Lev-Ran, Shaul
Barnes, Chanel
Pushparaj, Abhiram
Gamaleddin, Islam
Yan, Yijin
Khaled, Maram
Goldberg, Steven R.
TI Varenicline decreases nicotine self-administration and cue-induced
reinstatement of nicotine-seeking behaviour in rats when a long
pretreatment time is used
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Cue-induced reinstatement; drug discrimination; nicotine; progressive
ratio schedule; varenicline
ID PARTIAL AGONIST VARENICLINE; DISCRIMINATIVE-STIMULUS; DEPENDENCE;
ADDICTION; SCHEDULE; ACCESS
AB Effects of varenicline (Champix), a nicotinic partial agonist, were evaluated on subjective effects of nicotine (drug discrimination), motivation for nicotine taking (progressive-ratio schedule of intravenous nicotine self-administration) and reinstatement (cue-induced reinstatement of previously extinguished nicotine-seeking behaviour). Effects on motor performance were assessed in rats trained to discriminate nicotine (0.4 mg/kg) from saline under a fixed-ratio (FR 10) schedule of food delivery and in rats trained to respond for food under a progressive-ratio schedule. At short pretreatment times (5-40 mm), varenicline produced full or high levels of partial generalization to nicotine's discriminative-stimulus effects and disrupted responding for food, while there were low levels of partial generalization and no disruption of responding for food at 2- or 4-h pretreatment times. Varenicline (1 and 3 mg/kg, 2-h pretreatment time) enhanced discrimination of low doses of nicotine and to a small extent decreased discrimination of the training dose of nicotine. It also dose-dependently decreased nicotine-taking behaviour, but had no effect on food-taking behaviour under progressive-ratio schedules. Finally, varenicline significantly reduced the ability of a nicotine-associated cue to reinstate extinguished nicotine-seeking behaviour. The ability of varenicline to reduce both nicotine-taking and nicotine-seeking behaviour can contribute to its relatively high efficacy in treating human smokers.
C1 [Le Foll, Bernard; Chakraborty-Chatterjee, Munmun; Lev-Ran, Shaul; Pushparaj, Abhiram; Gamaleddin, Islam; Yan, Yijin; Khaled, Maram] Ctr Addict & Mental Hlth, Translat Addict Res Lab, Toronto, ON M5S 2S1, Canada.
[Le Foll, Bernard] Univ Toronto, Inst Med Sci, Dept Family Med, Toronto, ON M5S 1A1, Canada.
[Le Foll, Bernard] Univ Toronto, Inst Med Sci, Dept Community Med, Toronto, ON M5S 1A1, Canada.
[Le Foll, Bernard; Lev-Ran, Shaul] Ctr Addict & Mental Hlth, Addict Program, Toronto, ON M5S 2S1, Canada.
[Barnes, Chanel; Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD USA.
RP Le Foll, B (reprint author), Ctr Addict & Mental Hlth, Translat Addict Res Lab, 33 Russell St, Toronto, ON M5S 2S1, Canada.
EM bernard_lefoll@camh.net
RI Le Foll, Bernard/K-2952-2014;
OI Le Foll, Bernard/0000-0002-6406-4973; Pushparaj,
Abhiram/0000-0002-7109-9795
FU Intramural Research Program of the National Institute on Drug Abuse,
NIH, DHHS, Baltimore, Maryland, USA; Pfizer
FX The varenicline utilized in this study was a gift from Pfizer. This
research was supported in part by the Intramural Research Program of the
National Institute on Drug Abuse, NIH, DHHS, Baltimore, Maryland, USA.
We thank Dr Zuzana Justinova for her help with the revision of this
manuscript.; Dr Bernard Le Foll has received speaking fees and research
grants from Pfizer.
NR 21
TC 21
Z9 21
U1 0
U2 1
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1461-1457
J9 INT J NEUROPSYCHOPH
JI Int. J. Neuropsychopharmacol.
PD OCT
PY 2012
VL 15
IS 9
BP 1265
EP 1274
DI 10.1017/S1461145711001398
PG 10
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 006TW
UT WOS:000308842900008
PM 21939589
ER
PT J
AU Rance, B
Doughty, E
Demner-Fushman, D
Kann, MG
Bodenreider, O
AF Rance, Bastien
Doughty, Emily
Demner-Fushman, Dina
Kann, Maricel G.
Bodenreider, Olivier
TI A mutation-centric approach to identifying pharmacogenomic relations in
text
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Pharmacogenomics; Mutation extraction; Biocuration
ID WARFARIN; KNOWLEDGE; MENTIONS; GENOMICS; PROGRESS; SYSTEM
AB Objectives: To explore the notion of mutation-centric pharmacogenomic relation extraction and to evaluate our approach against reference pharmacogenomic relations.
Methods: From a corpus of MEDLINE abstracts relevant to genetic variation, we identify co-occurrences between drug mentions extracted using MetaMap and RxNorm, and genetic variants extracted by EMU. The recall of our approach is evaluated against reference relations curated manually in PharmGKB. We also reviewed a random sample of 180 relations in order to evaluate its precision.
Results: One crucial aspect of our strategy is the use of biological knowledge for identifying specific genetic variants in text, not simply gene mentions. On the 104 reference abstracts from PharmGKB, the recall of our mutation-centric approach is 33-46%. Applied to 282,000 abstracts from MEDLINE, our approach identifies pharmacogenomic relations in 4534 abstracts, with a precision of 65%.
Conclusions: Compared to a relation-centric approach, our mutation-centric approach shows similar recall, but slightly lower precision. We show that both approaches have limited overlap in their results, but are complementary and can be used in combination. Rather than a solution for the automatic curation of pharmacogenomic knowledge, we see these high-throughput approaches as tools to assist biocurators in the identification of pharmacogenomic relations of interest from the published literature. This investigation also identified three challenging aspects of the extraction of pharmacogenomic relations, namely processing full-text articles, sequence validation of DNA variants and resolution of genetic variants to reference databases, such as dbSNP. Published by Elsevier Inc.
C1 [Rance, Bastien; Demner-Fushman, Dina; Bodenreider, Olivier] Natl Lib Med, Bethesda, MD 20894 USA.
[Doughty, Emily; Kann, Maricel G.] Univ Maryland Baltimore Cty, Baltimore, MD 21250 USA.
RP Bodenreider, O (reprint author), Natl Lib Med, 8600 Rockville Pike,MS 3841,Bldg 38A,Rm 9S904, Bethesda, MD 20894 USA.
EM olivier@nlm.nih.gov
OI Rance, Bastien/0000-0003-4417-1197
FU National Institutes of Health (NIH) [1K22CA143148]; NIH, National
Library of Medicine
FX The authors want to thank Adrien Coulet, Nigam H. Shah, Yael Garten,
Mark Musen and Russ B. Altman (Stanford University) for sharing with us
the list of MEDLINE abstracts in which they have identified
pharmacogenomic relations using the relation-centric method reported in
[7]. We would also like to thank Jim Mork for his help in the
preparation of the MEDLINE dataset. This work was supported by the
National Institutes of Health (NIH) through grant 1K22CA143148 (MGK,
ED), and by the Intramural Research Program of the NIH, National Library
of Medicine (O.B., B.R., D.D.-F.).
NR 27
TC 5
Z9 5
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD OCT
PY 2012
VL 45
IS 5
BP 835
EP 841
DI 10.1016/j.jbi.2012.05.003
PG 7
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 011DZ
UT WOS:000309146200003
PM 22683993
ER
PT J
AU Li, J
Lu, ZY
AF Li, Jiao
Lu, Zhiyong
TI Systematic identification of pharmacogenomics information from clinical
trials
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Text mining; Clinical outcome; Pharmacogenomics; Clinical trial
ID DRUG DISCOVERY; TEXT; REGISTRATION; DESIGN; GENE
AB Recent progress in high-throughput genomic technologies has shifted pharmacogenomic research from candidate gene pharmacogenetics to clinical pharmacogenomics (PGx). Many clinical related questions may be asked such as 'what drug should be prescribed for a patient with mutant alleles?' Typically, answers to such questions can be found in publications mentioning the relationships of the gene-drug-disease of interest. In this work, we hypothesize that ClinicalTrials.gov is a comparable source rich in PGx related information. In this regard, we developed a systematic approach to automatically identify PGx relationships between genes, drugs and diseases from trial records in ClinicalTrials.gov. In our evaluation, we found that our extracted relationships overlap significantly with the curated factual knowledge through the literature in a PGx database and that most relationships appear on average 5 years earlier in clinical trials than in their corresponding publications, suggesting that clinical trials may be valuable for both validating known and capturing new PGx related information in a more timely manner. Furthermore, two human reviewers judged a portion of computer-generated relationships and found an overall accuracy of 74% for our text-mining approach. This work has practical implications in enriching our existing knowledge on PGx gene-drug-disease relationships as well as suggesting crosslinks between ClinicalTrials.gov and other PGx knowledge bases. Published by Elsevier Inc.
C1 [Li, Jiao; Lu, Zhiyong] Natl Lib Med, NIH, Bethesda, MD 20894 USA.
RP Lu, ZY (reprint author), Natl Lib Med, NIH, Bethesda, MD 20894 USA.
EM zhiyong.lu@nih.gov
FU National Institutes of Health, National Library of Medicine
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Library of Medicine. The authors
would like to thank Dr. John Wilbur for his helpful comments on this
manuscript and Dr. Bastien Rance for his valuable discussion on the
related work. The authors would also like to thank the PharmGKB team for
clarifying their curation scope and discussing the usefulness of our
work.
NR 38
TC 7
Z9 7
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD OCT
PY 2012
VL 45
IS 5
BP 870
EP 878
DI 10.1016/j.jpi.2012.04.005
PG 9
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 011DZ
UT WOS:000309146200007
PM 22546622
ER
PT J
AU Maltsev, AS
Ying, JF
Bax, A
AF Maltsev, Alexander S.
Ying, Jinfa
Bax, Ad
TI Deuterium isotope shifts for backbone H-1, N-15 and C-13 nuclei in
intrinsically disordered protein alpha-synuclein
SO JOURNAL OF BIOMOLECULAR NMR
LA English
DT Article
DE Chemical shift; IDP; IUP; Protein NMR; H-2; Random coil; Triple
resonance NMR
ID NMR CHEMICAL-SHIFTS; SECONDARY STRUCTURE; MULTIDIMENSIONAL NMR; RANDOM
COIL; CONFORMATIONAL PROPERTIES; SEQUENCE HOMOLOGY; TORSION ANGLES;
IDENTIFICATION; RESOLUTION; RECONSTRUCTION
AB Intrinsically disordered proteins (IDPs) are abundant in nature and characterization of their potential structural propensities remains a widely pursued but challenging task. Analysis of NMR secondary chemical shifts plays an important role in such studies, but the output of such analyses depends on the accuracy of reference random coil chemical shifts. Although uniform perdeuteration of IDPs can dramatically increase spectral resolution, a feature particularly important for the poorly dispersed IDP spectra, the impact of deuterium isotope shifts on random coil values has not yet been fully characterized. Very precise H-2 isotope shift measurements for C-13(alpha), C-13(beta), C-13', N-15, and H-1(N) have been obtained by using a mixed sample of protonated and uniformly perdeuterated alpha-synuclein, a protein with chemical shifts exceptionally close to random coil values. Decomposition of these isotope shifts into one-bond, two-bond and three-bond effects as well as intra- and sequential residue contributions shows that such an analysis, which ignores conformational dependence, is meaningful but does not fully describe the total isotope shift to within the precision of the measurements. Random coil H-2 isotope shifts provide an important starting point for analysis of such shifts in structural terms in folded proteins, where they are known to depend strongly on local geometry.
C1 [Maltsev, Alexander S.; Ying, Jinfa; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, 5 Mem Dr, Bethesda, MD 20892 USA.
EM bax@nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health (NIH);
Intramural AIDS-Targeted Antiviral Program of the Office of the
Director, NIH
FX We thank James L. Baber for experimental support. This work was funded
by the Intramural Research Program of the National Institute of Diabetes
and Digestive and Kidney Diseases, National Institutes of Health (NIH)
and the Intramural AIDS-Targeted Antiviral Program of the Office of the
Director, NIH.
NR 49
TC 15
Z9 15
U1 1
U2 22
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0925-2738
J9 J BIOMOL NMR
JI J. Biomol. NMR
PD OCT
PY 2012
VL 54
IS 2
BP 181
EP 191
DI 10.1007/s10858-012-9666-x
PG 11
WC Biochemistry & Molecular Biology; Spectroscopy
SC Biochemistry & Molecular Biology; Spectroscopy
GA 012KT
UT WOS:000309235800007
PM 22960996
ER
PT J
AU Mathews, LA
Keller, JM
Goodwin, BL
Guha, R
Shinn, P
Mull, R
Thomas, CJ
de Kluyver, RL
Sayers, TJ
Ferrer, M
AF Mathews, Lesley A.
Keller, Jonathan M.
Goodwin, Bonnie L.
Guha, Rajarshi
Shinn, Paul
Mull, Rebecca
Thomas, Craig J.
de Kluyver, Rachel L.
Sayers, Thomas J.
Ferrer, Marc
TI A 1536-Well Quantitative High-Throughput Screen to Identify Compounds
Targeting Cancer Stem Cells
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE qHTS; cancer stem cells; pancreatic cancer; prostate cancer
ID EPITHELIAL-MESENCHYMAL TRANSITION; PANCREATIC-CANCER; SELF-RENEWAL;
MODEL; SALINOMYCIN; PROPAGATION; EXPRESSION
AB Tumor cell subpopulations called cancer stem cells (CSCs) or tumor-initiating cells (TICs) have self-renewal potential and are thought to drive metastasis and tumor formation. Data suggest that these cells are resistant to current chemotherapy and radiation therapy treatments, leading to cancer recurrence. Therefore, finding new drugs and/or drug combinations that cause death of both the differentiated tumor cells as well as CSC populations is a critical unmet medical need. Here, we describe how cancer-derived CSCs are generated from cancer cell lines using stem cell growth media and nonadherent conditions in quantities that enable high-throughput screening (HTS). A cell growth assay in a 1536-well microplate format was developed with these CSCs and used to screen a focused collection of oncology drugs and clinical candidates to find compounds that are cytotoxic against these highly aggressive cells. A hit selection process that included potency and efficacy measurements during the primary screen allowed us to efficiently identify compounds with potent cytotoxic effects against spheroid-derived CSCs. Overall, this research demonstrates one of the first miniaturized HTS assays using CSCs. The procedures described here should enable further testing of the effect of compounds on CSCs and help determine which pathways need to be targeted to kill them.
C1 [Mathews, Lesley A.; Keller, Jonathan M.; Goodwin, Bonnie L.; Guha, Rajarshi; Shinn, Paul; Mull, Rebecca; Thomas, Craig J.; Ferrer, Marc] NIH, Div Preclin Innovat, NCATS, Rockville, MD 20850 USA.
[de Kluyver, Rachel L.] Univ Sydney, No Clin Sch, Kolling Inst Med Res, Sydney, NSW 2006, Australia.
[Sayers, Thomas J.] SAIC Frederick Inc, Basic Sci Program, NCI Canc, Frederick, MD USA.
[Sayers, Thomas J.] Frederick Natl Lab, Inflammat Program, Frederick, MD USA.
RP Mathews, LA (reprint author), NIH, Div Preclin Innovat, NCATS, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
EM mathewsla@mail.nih.gov
RI Sayers, Thomas/G-4859-2015
FU NIH Common Fund Molecular Libraries and Imaging Program [U54 MH084681];
Frederick National Laboratory for Cancer Research, National Institutes
of Health [HHSN261200800001E]
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This research
was partly supported by the NIH Common Fund Molecular Libraries and
Imaging Program, grant U54 MH084681. In addition, this project has been
funded in part with federal funds from the Frederick National Laboratory
for Cancer Research, National Institutes of Health, under contract
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. government.
NR 35
TC 15
Z9 15
U1 0
U2 13
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD OCT
PY 2012
VL 17
IS 9
SI SI
BP 1231
EP 1242
DI 10.1177/1087057112458152
PG 12
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA 014CG
UT WOS:000309352100013
PM 22927676
ER
PT J
AU Swaroop, M
Thorne, N
Rao, MS
Austin, CP
McKew, JC
Zheng, W
AF Swaroop, Manju
Thorne, Natasha
Rao, Mahendra S.
Austin, Christopher P.
McKew, John C.
Zheng, Wei
TI Evaluation of Cholesterol Reduction Activity of Methyl-beta-cyclodextrin
Using Differentiated Human Neurons and Astrocytes
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE induced pluripotent stem cells; neural stem cells; human neurons;
astrocytes; skin fibroblasts; methyl-beta-cyclodextrin
ID EMBRYONIC STEM-CELLS; DISEASE; TRANSPORT; TOXICITY; STORAGE; MODEL
AB Recent advances in stem cell technology have enabled large-scale production of human cells such as cardiomyocytes, hepatocytes, and neurons for evaluation of pharmacologic effect and toxicity of drug candidates. The assessment of compound efficacy and toxicity using human cells should lower the high clinical attrition rates of drug candidates by reducing the impact of species differences on drug efficacy and toxicity from animal studies. Methyl-beta-cyclodextrin (MBCD) has been shown to reduce lysosomal cholesterol accumulation in skin fibroblasts derived from patients with Niemann Pick type C disease and in the NPC1-/- mouse model. However, the compound has never been tested in human differentiated neurons. We have determined the cholesterol reduction effect of MBCD in neurons differentiated from human neural stem cells (NSCs) and commercially available astrocytes. The use of NSCs for producing differentiated neurons in large quantities can significantly reduce the production time and enhance the reproducibility of screening results. The EC50 values of MBCD on cholesterol reduction in human neurons and astrocytes were 66.9 and 110.7 mu M, respectively. The results indicate that human neurons differentiated from the NSCs and human astrocytes are useful tools for evaluating pharmacologic activity and toxicity of drug candidates to predict their clinical efficacy.
C1 [Zheng, Wei] NIH, Natl Ctr Advancing Translat Sci, Bethesda, MD 20892 USA.
[Rao, Mahendra S.] NIAMSD, Ctr Regenerat Med, NIH, Bethesda, MD 20892 USA.
RP Zheng, W (reprint author), NIH, Natl Ctr Advancing Translat Sci, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA.
EM wzheng@mail.nih.gov
OI Zheng, Wei/0000-0003-1034-0757
FU Intramural Research Program of the Therapeutics for Rare and Neglected
Diseases, National Center for Advancing Translational Sciences, National
Institutes of Health
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This work was
supported by the Intramural Research Program of the Therapeutics for
Rare and Neglected Diseases, National Center for Advancing Translational
Sciences, National Institutes of Health. We would also like to thank Dr.
Anand Swaroop for comments on the manuscript.
NR 23
TC 9
Z9 9
U1 0
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
EI 1552-454X
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD OCT
PY 2012
VL 17
IS 9
SI SI
BP 1243
EP 1251
DI 10.1177/1087057112456877
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA 014CG
UT WOS:000309352100014
PM 22923786
ER
PT J
AU Liu, CT
Estrada, K
Yerges-Armstrong, LM
Amin, N
Evangelou, E
Li, G
Minster, RL
Carless, MA
Kammerer, CM
Oei, L
Zhou, YH
Alonso, N
Dailiana, Z
Eriksson, J
Garcia-Giralt, N
Giroux, S
Husted, LB
Khusainova, RI
Koromila, T
Kung, AW
Lewis, JR
Masi, L
Mencej-Bedrac, S
Nogues, X
Patel, MS
Prezelj, J
Richards, JB
Sham, PC
Spector, T
Vandenput, L
Xiao, SM
Zheng, HF
Zhu, K
Balcells, S
Brandi, ML
Frost, M
Goltzman, D
Gonzalez-Macias, J
Karlsson, M
Khusnutdinova, EK
Kollia, P
Langdahl, BL
Ljunggren, O
Lorentzon, M
Marc, J
Mellstroem, D
Ohlsson, C
Olmos, JM
Ralston, SH
Riancho, JA
Rousseau, F
Urreizti, R
Van Hul, W
Zarrabeitia, MT
Castano-Betancourt, M
Demissie, S
Grundberg, E
Herrera, L
Kwan, T
Medina-Gomez, C
Pastinen, T
Sigurdsson, G
Thorleifsson, G
VanMeurs, JBJ
Blangero, J
Hofman, A
Liu, YM
Mitchell, BD
O'Connell, JR
Oostra, BA
Rotter, JI
Stefansson, K
Streeten, EA
Styrkarsdottir, U
Thorsteinsdottir, U
Tylavsky, FA
Uitterlinden, A
Cauley, JA
Harris, TB
Ioannidis, JPA
Psaty, BM
Robbins, JA
Zillikens, MC
VanDuijn, CM
Prince, RL
Karasik, D
Rivadeneira, F
Kiel, DP
Cupples, LA
Hsu, YH
AF Liu, Ching-Ti
Estrada, Karol
Yerges-Armstrong, Laura M.
Amin, Najaf
Evangelou, Evangelos
Li, Guo
Minster, Ryan L.
Carless, Melanie A.
Kammerer, Candace M.
Oei, Ling
Zhou, Yanhua
Alonso, Nerea
Dailiana, Zoe
Eriksson, Joel
Garcia-Giralt, Natalia
Giroux, Sylvie
Husted, Lise Bjerre
Khusainova, Rita I.
Koromila, Theodora
Kung, Annie WaiChee
Lewis, Joshua R.
Masi, Laura
Mencej-Bedrac, Simona
Nogues, Xavier
Patel, Millan S.
Prezelj, Janez
Richards, J. Brent
Sham, Pak Chung
Spector, Timothy
Vandenput, Liesbeth
Xiao, Su-Mei
Zheng, Hou-Feng
Zhu, Kun
Balcells, Susana
Brandi, Maria Luisa
Frost, Morten
Goltzman, David
Gonzalez-Macias, Jesus
Karlsson, Magnus
Khusnutdinova, Elza K.
Kollia, Panagoula
Langdahl, Bente Lomholt
Ljunggren, Oesten
Lorentzon, Mattias
Marc, Janja
Mellstroem, Dan
Ohlsson, Claes
Olmos, Jose M.
Ralston, Stuart H.
Riancho, Jose A.
Rousseau, Francois
Urreizti, Roser
Van Hul, Wim
Zarrabeitia, Maria T.
Castano-Betancourt, Martha
Demissie, Serkalem
Grundberg, Elin
Herrera, Lizbeth
Kwan, Tony
Medina-Gomez, Carolina
Pastinen, Tomi
Sigurdsson, Gunnar
Thorleifsson, Gudmar
VanMeurs, Joyce B. J.
Blangero, John
Hofman, Albert
Liu, Yongmei
Mitchell, Braxton D.
O'Connell, Jeffrey R.
Oostra, Ben A.
Rotter, Jerome I.
Stefansson, Kari
Streeten, Elizabeth A.
Styrkarsdottir, Unnur
Thorsteinsdottir, Unnur
Tylavsky, Frances A.
Uitterlinden, Andre
Cauley, Jane A.
Harris, Tamara B.
Ioannidis, John P. A.
Psaty, Bruce M.
Robbins, John A.
Zillikens, M. Carola
VanDuijn, Cornelia M.
Prince, Richard L.
Karasik, David
Rivadeneira, Fernando
Kiel, Douglas P.
Cupples, L. Adrienne
Hsu, Yi-Hsiang
TI Assessment of gene-by-sex interaction effect on bone mineral density
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE GENE-BY-SEX INTERACTION; BMD; ASSOCIATION; AGING
ID GENOME-WIDE ASSOCIATION; QUANTITATIVE TRAIT LOCI; GENOTYPE IMPUTATION;
GENDER; MASS; OSTEOPOROSIS; CELLS; BMD; SUSCEPTIBILITY; DETERMINANTS
AB Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p?1?X?10-5) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect?=?0.02 and p?=?3.0?X?10-5; female effect?=?-0.007 and p?=?3.3?X?10-2), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p?5?X?10-8) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. (c) 2012 American Society for Bone and Mineral Research.
C1 [Liu, Ching-Ti; Zhou, Yanhua; Demissie, Serkalem; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Estrada, Karol; Oei, Ling; Castano-Betancourt, Martha; Herrera, Lizbeth; Medina-Gomez, Carolina; VanMeurs, Joyce B. J.; Uitterlinden, Andre; Zillikens, M. Carola; Rivadeneira, Fernando] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Estrada, Karol; Amin, Najaf; Oei, Ling; Castano-Betancourt, Martha; Medina-Gomez, Carolina; VanMeurs, Joyce B. J.; Hofman, Albert; Uitterlinden, Andre; VanDuijn, Cornelia M.; Rivadeneira, Fernando] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Estrada, Karol; Oei, Ling; Castano-Betancourt, Martha; Medina-Gomez, Carolina; VanMeurs, Joyce B. J.; Uitterlinden, Andre; Rivadeneira, Fernando] Netherlands Genom Initiat NGI Sponsored Netherlan, Leiden, Netherlands.
[Yerges-Armstrong, Laura M.; Mitchell, Braxton D.; O'Connell, Jeffrey R.; Streeten, Elizabeth A.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Evangelou, Evangelos] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.
[Li, Guo] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Minster, Ryan L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
[Carless, Melanie A.; Blangero, John] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA.
[Alonso, Nerea; Ralston, Stuart H.] Univ Edinburgh, Rheumat Dis Unit, Ctr Mol Med, MRC IGMM, Edinburgh, Midlothian, Scotland.
[Dailiana, Zoe] Univ Thessalia, Sch Med, Dept Orthopaed Surg, Larisa, Greece.
[Eriksson, Joel; Vandenput, Liesbeth; Ljunggren, Oesten; Mellstroem, Dan; Ohlsson, Claes] Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Inst Med, Gothenburg, Sweden.
[Garcia-Giralt, Natalia] Hosp del Mar, IMIM, URFOA, Barcelona, Spain.
[Giroux, Sylvie; Rousseau, Francois] URGHM, Ctr Rech CHUQ HSFA, Quebec City, PQ, Canada.
[Husted, Lise Bjerre; Langdahl, Bente Lomholt] Aarhus Univ Hosp, Dept Endocrinol & Internal Med, DK-8000 Aarhus, Denmark.
[Khusainova, Rita I.; Khusnutdinova, Elza K.] Ufa Sci Ctr RAS, Inst Biochem & Genet, Ufa, Russia.
[Khusainova, Rita I.; Khusnutdinova, Elza K.] Bashkir State Univ, Dept Biol, Ufa 450074, Russia.
[Koromila, Theodora; Kollia, Panagoula] Univ Athens, Dept Human Genet, Sch Biol, Athens, Greece.
[Kung, Annie WaiChee; Xiao, Su-Mei] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China.
[Kung, Annie WaiChee; Xiao, Su-Mei] Univ Hong Kong, Res Ctr Heart Brain Hormone & Healthy Aging, Hong Kong, Hong Kong, Peoples R China.
[Lewis, Joshua R.; Zhu, Kun; Prince, Richard L.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.
[Lewis, Joshua R.; Zhu, Kun; Prince, Richard L.] Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Perth, WA, Australia.
[Masi, Laura; Brandi, Maria Luisa] Univ Florence, Dept Internal Med, Florence, Italy.
[Mencej-Bedrac, Simona; Marc, Janja] Univ Ljubljana, Dept Clin Biochem, Ljubljana, Slovenia.
[Nogues, Xavier] UAB, Hosp del Mar, IMIM, Dept Internal Med, Barcelona, Spain.
[Patel, Millan S.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada.
[Prezelj, Janez] Univ Med Ctr, Dept Endocrinol Diabet & Metab Dis, Ljubljana, Slovenia.
[Richards, J. Brent; Zheng, Hou-Feng] McGill Univ, Jewish Gen Hosp, Dept Med Human Genet & Epidemiol & Biostat, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada.
[Richards, J. Brent; Spector, Timothy] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Sham, Pak Chung] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China.
[Sham, Pak Chung] Univ Hong Kong, Ctr Reprod Dev & Growth, Hong Kong, Hong Kong, Peoples R China.
[Balcells, Susana; Urreizti, Roser] Univ Barcelona, Dept Genet, CIBERER, IBUB, Barcelona, Spain.
[Frost, Morten] Odense Univ Hosp, Dept Endocrinol, DK-5000 Odense, Denmark.
[Frost, Morten] Univ So Denmark, Inst Clin, Odense, Denmark.
[Goltzman, David] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Gonzalez-Macias, Jesus; Riancho, Jose A.] Univ Cantabria, Dept Med, E-39005 Santander, Spain.
[Gonzalez-Macias, Jesus; Olmos, Jose M.] Hosp UM Valdecilla IFIMAV, Dept Internal Med, RETICEF, Santander, Spain.
[Karlsson, Magnus] Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden.
[Karlsson, Magnus] Lund Univ, Dept Orthopaed, Malmo, Sweden.
[Oostra, Ben A.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
[Oostra, Ben A.; VanDuijn, Cornelia M.] Ctr Med Syst Biol, Leiden, Netherlands.
[Oostra, Ben A.; VanDuijn, Cornelia M.] Netherlands Consortium Healthy Aging, Leiden, Netherlands.
[Oostra, Ben A.; VanDuijn, Cornelia M.] Netherlands Genom Initiat, The Hague, Netherlands.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Sigurdsson, Gunnar; Stefansson, Kari; Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Thorleifsson, Gudmar; Stefansson, Kari; Styrkarsdottir, Unnur; Thorsteinsdottir, Unnur] DeCODE Genet, Reykjavik, Iceland.
[Streeten, Elizabeth A.] Vet Adm Med Ctr, GRECC, Baltimore, MD 21218 USA.
[Tylavsky, Frances A.] Univ Tennessee, Dept Prevent Med, Coll Med, Memphis, TN USA.
[Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Ioannidis, John P. A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.
[Ioannidis, John P. A.] Stanford Univ, Dept Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA.
[Ioannidis, John P. A.] Univ Washington, Dept Hlth Res & Policy, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Robbins, John A.] Univ Calif Davis, Dept Med, Sacramento, CA USA.
[Karasik, David; Kiel, Douglas P.; Hsu, Yi-Hsiang] Inst Aging Res, Hebrew SeniorLife, Boston, MA USA.
[Karasik, David; Kiel, Douglas P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Cupples, L. Adrienne] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Hsu, Yi-Hsiang] Harvard Univ, Sch Publ Hlth, Mol & Integrat Physiol Sci Program, Boston, MA 02115 USA.
[Rousseau, Francois] Univ Laval, Dept Mol Biol Med Biochem & Pathol, Fac Med, Quebec City, PQ, Canada.
[Rousseau, Francois] Univ Laval, APOGEE Net CanGeneTest Network Genet Hlth Serv, Quebec City, PQ, Canada.
[Van Hul, Wim] Univ Antwerp, Dept Med Genet, B-2020 Antwerp, Belgium.
[Zarrabeitia, Maria T.] Univ Cantabria, Dept Legal Med, E-39005 Santander, Spain.
[Grundberg, Elin] Wellcome Trust Sanger Inst, Cambridge, England.
[Kwan, Tony; Pastinen, Tomi] McGill Univ, Dept Human Genet, Genome Quebec Innovat Ctr, Montreal, PQ, Canada.
[Liu, Yongmei] Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC USA.
RP Liu, CT (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, 801 Massachusetts Ave CT3, Boston, MA 02118 USA.
EM ctliu@bu.edu; kiel@hsl.harvard.edu; adrienne@bu.edu;
YiHsiangHsu@hsl.harvard.edu
RI Zheng, Houfeng/K-4424-2012; Balcells, Susana/C-5222-2017; Evangelou,
Evangelos/C-3033-2013; Oei, Ling/E-8163-2013; Dzhemileva,
Lilya/K-8636-2013; Zhu, Kun/L-2208-2013; Lewis, Joshua/D-5077-2013;
Urreizti, Roser/M-6402-2014; Rivadeneira, Fernando/O-5385-2015; Frost,
Morten/G-9410-2011; Khusnutdinova, Elza/A-4810-2013
OI Kiel, Douglas/0000-0001-8474-0310; Karasik, David/0000-0002-8826-0530;
Vandenput, Liesbeth/0000-0002-1712-6131; Medina-Gomez,
Carolina/0000-0001-7999-5538; Mitchell, Braxton/0000-0003-4920-4744;
Evangelou, Evangelos/0000-0002-5488-2999; Cauley, Jane
A/0000-0003-0752-4408; Zheng, Houfeng/0000-0002-5684-8313; Balcells,
Susana/0000-0003-1211-1907; Cupples, L. Adrienne/0000-0003-0273-7965;
Oei, Ling/0000-0003-3523-458X; Dzhemileva, Lilya/0000-0003-3315-4746;
Zhu, Kun/0000-0002-8723-7574; Lewis, Joshua/0000-0003-1003-8443;
Urreizti, Roser/0000-0003-3617-7134; Rivadeneira,
Fernando/0000-0001-9435-9441; Frost, Morten/0000-0002-5608-1589;
FU Medtronic; NIH [R01 AG18728, R01HL088119, R01AR046838, U01 HL084756, R01
AR43351, P01-HL45522, R01-MH-078111, R01-MH-083824]; Nutrition and
Obesity Research Center of Maryland [P30DK072488]; NIAMS/NIH
[F32AR059469]; Instituto de Salud Carlos III-FIS (Spanish Health
Ministry) [PI 06/0034, PI08/0183]; Canadian Institutes of Health
Research (CIHR); NHLBI [HHSN268201200036C, N01-HC-85239, N01-HC-85079,
N01-HC-85086, N01-HC-35129, N01 HC15103, N01 HC-55222, N01-HC-75150,
N01-HC-45133, HL080295, HL087652, HL105756]; NIA [AG-023629, AG-15928,
AG-20098, AG-027058, N01AG62101, N01AG62103, N01AG62106,
1R01AG032098-01A1]; National Center of Advancing Translational
Technologies CTSI [UL1TR000124]; National Institute of Diabetes and
Digestive and Kidney Diseases [DK063491]; EUROSPAN (European Special
Populations Research Network); European Commission FP6 STRP grant
[018947, LSHG-CT-2006-01947]; Netherlands Organisation for Scientific
Research; Erasmus MC; Centre for Medical Systems Biology (CMSB);
Netherlands Brain Foundation (HersenStichting Nederland); US National
Institute for Arthritis, Musculoskeletal and Skin Diseases; National
Institute on Aging [R01 AR/AG41398, R01 AR050066, R21 AR056405];
National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278]; Canadian Institutes of
Health Research from Institute of Aging [165446]; Institute of Genetics
[179433]; Institute of Musculoskeletal health [221765]; Intramural
Research Program of the NIH, National Institute on Aging; National
Institutes of Health [HHSN268200782096C]; Hong Kong Research Grant
Council [HKU 768610M]; Bone Health Fund of HKU Foundation; KC Wong
Education Foundation; Small Project Funding [201007176237]; Matching
Grant; CRCG Grant; Osteoporosis and Endocrine Research Fund; Genomics
Strategic Research Theme of The University of Hong Kong; Netherlands
Organisation of Scientific Research NWO Investments [175.010.2005.011,
911-03-012]; Research Institute for Diseases in the Elderly
[014-93-015]; Netherlands Genomics Initiative (NGI)/Netherlands
Consortium for Healthy Aging (NCHA) [050-060-810]; Erasmus Medical
Center and Erasmus University, Rotterdam; Netherlands Organization for
the Health Research and Development (ZonMw); Research Institute for
Diseases in the Elderly (RIDE); Ministry of Education, Culture and
Science; Ministry for Health, Welfare and Sports; European Commission
(DG XII); Municipality of Rotterdam; German Bundesministerium fur
Forschung und Technology [01 AK 803 A-H, 01 IG 07015 G]
FX KS, UT, US, and GT are employed by deCODE Genetics. BMP serves on a Data
Safety Monitoring Board for a clinical trial of a device (Zoll Lifecor)
and on a Steering Committee for the Yale Open Data Access Project funded
by Medtronic. These are unrelated to the article and not likely to be
conflicts, but he wanted to disclose them. All other authors state that
they have no conflicts of interest.; Amish: The Old Order Amish Study
was supported by NIH research grants R01 AG18728, R01HL088119,
R01AR046838, and U01 HL084756. Partial funding was also provided by the
Nutrition and Obesity Research Center of Maryland (P30DK072488). LMY-A
was supported by F32AR059469 from NIAMS/NIH.; CABRIO: Supported by
grants from Instituto de Salud Carlos III-FIS (Spanish Health Ministry)
PI 06/0034 and PI08/0183.; The Canadian Multicentre Osteoporosis Study
(CaMos) was supported by a grant from the Canadian Institutes of Health
Research (CIHR).; Cardiovascular Health Study: This CHS research was
supported by NHLBI contracts HHSN268201200036C, N01-HC-85239,
N01-HC-85079 through N01-HC-85086; N01-HC-35129, N01 HC15103, N01
HC-55222, N01-HC-75150, N01-HC-45133, and NHLBI grants HL080295,
HL087652, HL105756 with additional contribution from NINDS. Additional
support was provided through AG-023629, AG-15928, AG-20098, and
AG-027058 from the NIA. See also http://www.chs-nhlbi.org/pi.htm. DNA
handling and genotyping was supported in part by National Center of
Advancing Translational Technologies CTSI grant UL1TR000124 and National
Institute of Diabetes and Digestive and Kidney Diseases grant DK063491
to the Southern California Diabetes Endocrinology Research Center.;
Erasmus Rucphen Family Study (ERF): The genotyping for the ERF study was
supported by EUROSPAN (European Special Populations Research Network)
and the European Commission FP6 STRP grant (018947; LSHG-CT-2006-01947).
The ERF study was further supported by grants from the Netherlands
Organisation for Scientific Research, Erasmus MC, the Centre for Medical
Systems Biology (CMSB), and the Netherlands Brain Foundation
(HersenStichting Nederland). We are grateful to all patients and their
relatives, general practitioners and neurologists for their
contributions and to P Veraart for her help in genealogy, Jeannette
Vergeer for the supervision of the laboratory work, and P Snijders for
his help in data collection. We also acknowledge Internationale
Stichting Alzheimer Onderzoek (ISAO) and Hersenstichting Netherlands.;
Framingham Osteoporosis Study (FOS): The study was funded by grants from
the US National Institute for Arthritis, Musculoskeletal and Skin
Diseases and National Institute on Aging (DPK: R01 AR/AG41398; DK: R01
AR050066; YHH: R21 AR056405). The Framingham Heart Study of the National
Heart, Lung, and Blood Institute of the National Institutes of Health
and Boston University School of Medicine were supported by the National
Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195)
and its contract with Affymetrix, Inc. for genotyping services
(N02-HL-6-4278). Analyses reflect intellectual input and resource
development from the Framingham Heart Study investigators participating
in the SNP Health Association Resource (SHARe) project. A portion of
this research was conducted using the Linux Cluster for Genetic Analysis
(LinGA-II) funded by the Robert Dawson Evans Endowment of the Department
of Medicine at Boston University School of Medicine and Boston Medical
Center.; GEOS: The Genetics of Osteoporosis Study was funded in part by
the Canadian Institutes of Health Research from Institute of Aging
(#165446), Institute of Genetics (#179433), and Institute of
Musculoskeletal health (#221765).; Health ABC: This research was
supported by NIA contracts N01AG62101, N01AG62103, and N01AG62106 and in
part by the Intramural Research Program of the NIH, National Institute
on Aging. The genome-wide association study was funded by NIA grant
1R01AG032098-01A1 to Wake Forest University Health Sciences, and
genotyping services were provided by the Center for Inherited Disease
Research (CIDR). CIDR is fully funded through a federal contract from
the National Institutes of Health to The Johns Hopkins University
(HHSN268200782096C).; HKOS: This project is supported by Hong Kong
Research Grant Council (HKU 768610M); The Bone Health Fund of HKU
Foundation; The KC Wong Education Foundation; Small Project Funding
(201007176237); Matching Grant, CRCG Grant and Osteoporosis and
Endocrine Research Fund; and the Genomics Strategic Research Theme of
The University of Hong Kong. The authors are grateful to the
participants and clinical staff at the Queen Mary Hospital of The
University of Hong Kong. RSI, RSII, RSIII: The GWA study was funded by
the Netherlands Organisation of Scientific Research NWO Investments
(175.010.2005.011, 911-03-012), the Research Institute for Diseases in
the Elderly (014-93-015; RIDE2), and the Netherlands Genomics Initiative
(NGI)/Netherlands Consortium for Healthy Aging (NCHA) (050-060-810). We
thank Pascal Arp, Mila Jhamai, Dr Michael Moorhouse, Marijn Verkerk, and
Sander Bervoets for their help in creating the GWAS database. The
Rotterdam Study is funded by Erasmus Medical Center and Erasmus
University, Rotterdam; Netherlands Organization for the Health Research
and Development (ZonMw); the Research Institute for Diseases in the
Elderly (RIDE); the Ministry of Education, Culture and Science; the
Ministry for Health, Welfare and Sports; the European Commission (DG
XII); and the Municipality of Rotterdam. The authors are grateful to the
participants and staff from the Rotterdam Study, the participating
general practitioners, and the pharmacists. We thank Dr Tobias A Knoch,
Luc V de Zeeuw, Anis Abuseiris, and Rob de Graaf, as well as their
institutions, the Erasmus Computing Grid, Rotterdam, The Netherlands,
and especially the national German MediGRID and Services@MediGRID part
of the German D-Grid, both funded by the German Bundesministerium fur
Forschung und Technology under grants #01 AK 803 A-H and #01 IG 07015 G
for access to their grid resources.; San Antonio Family Osteoporosis
Study: The SAFOS was supported by NIH research grants R01 AR43351,
P01-HL45522, R01-MH-078111, and R01-MH-083824.
NR 43
TC 17
Z9 19
U1 2
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD OCT
PY 2012
VL 27
IS 10
BP 2051
EP 2064
DI 10.1002/jbmr.1679
PG 14
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 007ZB
UT WOS:000308925800003
PM 22692763
ER
PT J
AU Lee, NR
Wallace, GL
Adeyemi, EI
Lopez, KC
Blumenthal, JD
Clasen, LS
Giedd, JN
AF Lee, Nancy Raitano
Wallace, Gregory L.
Adeyemi, Elizabeth I.
Lopez, Katherine C.
Blumenthal, Jonathan D.
Clasen, Liv S.
Giedd, Jay N.
TI Dosage effects of X and Y chromosomes on language and social functioning
in children with supernumerary sex chromosome aneuploidies: implications
for idiopathic language impairment and autism spectrum disorders
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Article
DE Chromosome anomalies; social cognition; language disorder; autistic
disorder; sex differences
ID KLINEFELTER-SYNDROME; TRAITS; 47,XXY; BOYS; XXY; ABNORMALITIES;
VALIDATION; EXPRESSION; SPEECH; XYY
AB Background: Supernumerary sex chromosome aneuploidies (X/Y-aneuploidies), the presence of extra X and/or Y chromosomes, are associated with heightened rates of language impairments and social difficulties. However, no single study has examined different language domains and social functioning in the same sample of children with tri-, tetra-, and pentasomy X/Y-aneuploidy. The current research sought to fill this gap in the literature and to examine dosage effects of X and Y chromosomes on language and social functioning. Methods: Participants included 110 youth with X/Y-aneuploidies (32 female) and 52 with typical development (25 female) matched on age (mean similar to 12 years; range 422) and maternal education. Participants completed the Wechsler intelligence scales, and parents completed the Childrens Communication Checklist-2 and the Social Responsiveness Scale to assess language skills and autistic traits, respectively. Results: Both supernumerary X and Y chromosomes were related to depressed structural and pragmatic language skills and increased autistic traits. The addition of a Y chromosome had a disproportionately greater impact on pragmatic language; the addition of one or more X chromosomes had a disproportionately greater impact on structural language. Conclusions: Given that we link extra X chromosomes with structural language impairments and an extra Y chromosome with pragmatic language impairments, X/Y-aneuploidies may provide clues to genetic mechanisms contributing to idiopathic language impairment and autism spectrum disorders.
C1 [Lee, Nancy Raitano; Wallace, Gregory L.; Adeyemi, Elizabeth I.; Lopez, Katherine C.; Blumenthal, Jonathan D.; Clasen, Liv S.; Giedd, Jay N.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
[Wallace, Gregory L.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Lee, NR (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10,MSC 1367, Bethesda, MD 20892 USA.
EM lnancy@mail.nih.gov
RI Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; Lee, Nancy/M-7492-2016;
OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Lee,
Nancy/0000-0002-6663-0713; Wallace, Gregory/0000-0003-0329-5054
FU NIH, National Institute of Mental Health
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Mental Health. We thank the families for
their participation.
NR 34
TC 20
Z9 21
U1 2
U2 26
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9630
J9 J CHILD PSYCHOL PSYC
JI J. Child Psychol. Psychiatry
PD OCT
PY 2012
VL 53
IS 10
BP 1072
EP 1081
DI 10.1111/j.1469-7610.2012.02573.x
PG 10
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 012LQ
UT WOS:000309238100009
PM 22827287
ER
PT J
AU Mullin, PM
Bray, A
Vu, V
Schoenberg-Paik, F
MacGibbon, K
Romero, R
Goodwin, TM
Fejzo, MS
AF Mullin, P. M.
Bray, A.
Vu, V.
Schoenberg-Paik, F.
MacGibbon, K.
Romero, R.
Goodwin, T. M.
Fejzo, M. S.
TI No increased risk of psychological/behavioral disorders in siblings of
women with hyperemesis gravidarum (HG) unless their mother had HG
SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE
LA English
DT Article
DE anxiety; bipolar; depression; hyperemesis gravidarum; outcome
ID PRENATAL EXPOSURE; PREGNANCY; ADULTHOOD; OUTCOMES; COHORT; NAUSEA
AB Hyperemesis gravidarum (HG), severe nausea and vomiting of pregnancy, is characterized by prolonged maternal stress, undernutrition and dehydration. Maternal stress and malnutrition of pregnancy are linked to poor neonatal outcome and associated with poor adult health, and we recently showed that in utero exposure to HG may lead to increased risks of psychological and behavioral disorders in the offspring. In addition, we have shown familial aggregation of HG, which is strong evidence for a genetic component to the disease. In this study, we compare the rates of psychological and behavioral disorders in 172 adults with and 101 adults without a sibling with HG. The rate of emotional/behavioral disorders is identical (15%) in both groups. The results suggest that the etiology of HG is not likely to include genetic factors associated with emotional and behavioral disorders. In addition, this study provides evidence that the increased incidence of psychological/behavioral disorders among offspring of women with HG is attributable to the HG pregnancy itself, rather than to confounding genetic factors linked to HG.
C1 [Mullin, P. M.; Goodwin, T. M.; Fejzo, M. S.] Univ So Calif, Keck Sch Med, Dept Maternal Fetal Med, Los Angeles, CA 90033 USA.
[Bray, A.; Schoenberg-Paik, F.] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA USA.
[MacGibbon, K.] Hyperemesis Educ & Res Fdn, Leesburg, VA USA.
[Romero, R.] NICHD, Dept Hlth & Human Serv, NIH, DHHS,Perinatol Res Branch, Bethesda, MD USA.
[Romero, R.] NICHD, Dept Hlth & Human Serv, NIH, DHHS,Perinatol Res Branch, Detroit, MI USA.
[Vu, V.; Fejzo, M. S.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
RP Fejzo, MS (reprint author), UCLA Sch Med, 5535 MRL Bldg,675 Charles E Young Dr S, Los Angeles, CA 90095 USA.
EM mfejzo@mednet.ucla.edu
FU National Institute of Child Health and Human Development, National
Institute of Health, Department of Health and Human Services
FX This research was supported in part by the Intramural Research Program
of the National Institute of Child Health and Human Development,
National Institute of Health, Department of Health and Human Services.
NR 25
TC 1
Z9 1
U1 0
U2 3
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 2040-1744
J9 J DEV ORIG HLTH DIS
JI J. Dev. Orig. Health Dis.
PD OCT
PY 2012
VL 3
IS 5
BP 375
EP 379
DI 10.1017/S2040174412000220
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 999JQ
UT WOS:000308307800011
PM 25102267
ER
PT J
AU Dudley, ME
AF Dudley, Mark E.
TI A Major Player "Gets in the Act"
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Editorial Material
ID TUMOR-INFILTRATING LYMPHOCYTES; CELL TRANSFER THERAPY; ADOPTIVE TRANSFER
THERAPY; METASTATIC MELANOMA; T-CELLS; TRANSFER IMMUNOTHERAPY; CANCER
REGRESSION; PERSISTENCE; CHEMOTHERAPY; EXPANSION
C1 NCI, Bethesda, MD 20892 USA.
RP Dudley, ME (reprint author), NCI, Bethesda, MD 20892 USA.
EM med@nih.gov
NR 31
TC 0
Z9 0
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD OCT
PY 2012
VL 35
IS 8
BP 595
EP 597
DI 10.1097/CJI.0b013e3182725602
PG 3
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 012FR
UT WOS:000309221600001
PM 22996364
ER
PT J
AU Davis, M
Conlon, K
Bohac, GC
Barcenas, J
Leslie, W
Watkins, L
Lamzabi, I
Deng, YP
Li, Y
Plate, JMD
AF Davis, Marcherie
Conlon, Kevin
Bohac, Gerald C.
Barcenas, John
Leslie, William
Watkins, LaTanja
Lamzabi, Ihab
Deng, Youping
Li, Yan
Plate, Janet M. D.
TI Effect of Pemetrexed on Innate Immune Killer Cells and Adaptive Immune T
Cells in Subjects With Adenocarcinoma of the Pancreas
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE pancreatic cancer; innate immunity; NK cells; pemetrexed; interferon
gamma (IFN gamma); interleukin-2 (IL-2); B7-H3
ID INTERFERON-GAMMA; COSTIMULATORY MOLECULE; CLINICAL BENEFIT; CANCER;
GEMCITABINE; TRIAL; DEFICIENCY; INDUCTION; CARCINOMA; RESPONSES
AB Baseline levels of innate and adaptive immune cell functions were studied in patients with pancreatic cancer. The effects of pemetrexed were measured at 7 and 14 days after initial therapy then 14 days after combination therapy with gemcitabine. Pretherapy levels of absolute numbers of natural killer (NK) cells positively correlated with survival. Cytolytic units of NK activity correlated positively with NK cell numbers. Pemetrexed decreased NK cytolytic units to significance when combined with gemcitabine. Pemetrexed increased intracellular accumulation of interferon gamma (IFN gamma) in NK cells that correlated negatively with survival. Addition of gemcitabine decreased IFN gamma-producing NK cells to baseline. Memory (CD45RO(+)) T cells enumerated at baseline correlated negatively with survival but were decreased by pemetrexed therapy. Memory T cells were increased in subjects with greater B7-H3 expression in tumor tissue, whereas OX40(+)-activated total T cells and helper T-cell subset were decreased. FoxP3(+), CD8(+) T cells correlated positively with progression-free interval and survival. In conclusion, innate NK-cell immunity and FoxP3(+), CD8(+) T cells seemed beneficial to pancreatic cancer patients. Higher levels of B7-H3 expression in pancreatic tumors were detrimental to effective immunity. Although pemetrexed therapy increased activation of a subset of NK cells to produce IFN gamma, addition of gemcitabine abated those responses, decreasing IFN gamma-producing NK cells, whereas NK cells producing interleukin-2 without IFN gamma at this timepoint positively correlated with survival. Innate immunity and adaptive immunity thus are important in defense against pancreatic cancer. Progression-free interval and survival were longer than observed in a phase III trial where gemcitabine preceded pemetrexed suggesting that a larger trial of pemetrexed preceding gemcitabine is warranted.
C1 [Plate, Janet M. D.] Rush Univ, Med Ctr, Sect Med Oncol, Div Oncol Hematol & Stem Cell Transplantat, Chicago, IL 60612 USA.
[Deng, Youping; Li, Yan] Rush Univ, Med Ctr, Rush Canc Ctr, Div Bioinformat,Dept Med, Chicago, IL 60612 USA.
[Watkins, LaTanja; Lamzabi, Ihab] Rush Univ, Med Ctr, Dept Pathol, Chicago, IL 60612 USA.
[Conlon, Kevin] NCI, Canc Therapy & Evaluat Program, Bethesda, MD 20892 USA.
[Bohac, Gerald C.] Amgen Corp, Thousand Oaks, CA 91320 USA.
RP Plate, JMD (reprint author), Rush Univ, Med Ctr, Sect Med Oncol, Div Oncol Hematol & Stem Cell Transplantat, 1725 W Harrison St, Chicago, IL 60612 USA.
EM jplate@rush.edu
FU Lilly Oncology; George W. and Lessie K. Wadsworth Memorial fund
FX The work was supported by grants from Lilly Oncology and the George W.
and Lessie K. Wadsworth Memorial fund.
NR 38
TC 14
Z9 15
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD OCT
PY 2012
VL 35
IS 8
BP 629
EP 640
DI 10.1097/CJI.0b013e31826c8a4f
PG 12
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 012FR
UT WOS:000309221600006
PM 22996369
ER
PT J
AU Lee, W
Riggs, T
Koo, W
Deter, RL
Yeo, L
Romero, R
AF Lee, Wesley
Riggs, Thomas
Koo, Winston
Deter, Russell L.
Yeo, Lami
Romero, Roberto
TI The relationship of newborn adiposity to fetal growth outcome based on
birth weight or the modified neonatal growth assessment score
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Air displacement plethysmography; body composition; body fat; fetus;
malnutrition; ultrasound
ID AIR-DISPLACEMENT PLETHYSMOGRAPHY; FRACTIONAL THIGH VOLUME; X-RAY
ABSORPTIOMETRY; BODY-COMPOSITION ASSESSMENT; FULL-TERM NEWBORNS;
BREAST-FED INFANTS; MENSTRUAL AGE; GESTATIONAL-AGE; 3-DIMENSIONAL
ULTRASONOGRAPHY; EVOLUTIONARY PERSPECTIVE
AB Objectives: (1) Develop reference ranges of neonatal adiposity using air displacement plethysmography. (2) Use new reference ranges for neonatal adiposity to compare two different methods of evaluating neonatal nutritional status. Methods: Three hundred and twenty-four normal neonates (35-41 weeks post-menstrual age) had body fat (%BF) and total fat mass (FM, g) measured using air displacement plethysmography shortly after delivery. Results were stratified for 92 of these neonates with corresponding fetal biometry using two methods for classifying nutritional status: (1) population-based weight percentiles; and (2) a modified neonatal growth assessment score (m(3)NGAS(51)). Results: At the 50th percentile, %BF varied from 7.7% (35 weeks) to 11.8% (41 weeks), while the corresponding 50th percentiles for total FM were 186-436 g. Among the subset of 92 neonates, no significant differences in adiposity were found between small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA) groups using population-based weight standards. Classification of the same neonates using m(3)NGAS(51) showed significant differences in mean %BF between corresponding groups. Conclusions: Population-based weight criteria for neonatal nutritional status can lead to misclassifications on the basis of adiposity. A neonatal growth assessment score, that considers the growth potential of several anatomic parameters, appears to more effectively classify under- and over-nourished newborns.
C1 [Lee, Wesley; Deter, Russell L.] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA.
[Lee, Wesley] Oakland Univ, Dept Obstet & Gynecol, William Beaumont Sch Med, Rochester, MI 48063 USA.
[Lee, Wesley] Oakland Univ, Dept Pediat, William Beaumont Sch Med, Rochester, MI 48063 USA.
[Riggs, Thomas] Beaumont Hosp, Res Inst, Royal Oak, MI USA.
[Lee, Wesley; Yeo, Lami; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Koo, Winston] Louisiana State Univ, Dept Pediat, Div Neonatol, Hlth Sci Ctr, Shreveport, LA 71105 USA.
[Lee, Wesley; Yeo, Lami] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
RP Lee, W (reprint author), Baylor Coll Med, Dept Obstet & Gynecol, 6651 Main St,Suite 1020, Houston, TX 77030 USA.
EM wesley.lee@bcm.edu
OI Riggs, Thomas/0000-0001-5049-422X
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX This research was supported (in part) by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS. R. Romero
contributed to this work as part of his official duties as an employee
of the United States Federal Government. None of the other authors have
disclosed a conflict of interest.
NR 68
TC 6
Z9 6
U1 0
U2 9
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD OCT
PY 2012
VL 25
IS 10
BP 1933
EP 1940
DI 10.3109/14767058.2012.683084
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 008JM
UT WOS:000308953200021
PM 22494346
ER
PT J
AU Gervasi, MT
Romero, R
Bracalente, G
Chaiworapongsa, T
Erez, O
Dong, Z
Hassan, SS
Yeo, L
Yoon, BH
Mor, G
Barzon, L
Franchin, E
Militello, V
Palu, G
AF Gervasi, Maria-Teresa
Romero, Roberto
Bracalente, Gabriella
Chaiworapongsa, Tinnakorn
Erez, Offer
Dong, Zhong
Hassan, Sonia S.
Yeo, Lami
Yoon, Bo Hyun
Mor, Gil
Barzon, Luisa
Franchin, Elisa
Militello, Valentina
Palu, Giorgio
TI Viral invasion of the amniotic cavity (VIAC) in the midtrimester of
pregnancy
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Midtrimester AF; neonatal outcome; prevalence; pregnancy outcome; viral
DNA
ID POLYMERASE-CHAIN-REACTION; PRETERM PREMATURE RUPTURE;
HUMAN-IMMUNODEFICIENCY-VIRUS; CONGENITAL CYTOMEGALOVIRUS-INFECTION; 2009
H1N1 INFLUENZA; FETAL INFLAMMATORY RESPONSE; PARVOVIRUS B19 INFECTION;
HEPATITIS-B-VIRUS; HUMAN-PAPILLOMAVIRUS INFECTIONS;
RESPIRATORY-DISTRESS-SYNDROME
AB Introduction: The prevalence of viral infections in the amniotic fluid (AF) has not yet been ascertained. The aim of this study was to determine the prevalence of specific viral nucleic acids in the AF and its relationship to pregnancy outcome. Study design: From a cohort of 847 consecutive women undergoing midtrimester amniocentesis, 729 cases were included in this study after exclusion of documented fetal anomalies, chromosomal abnormalities, unavailability of AF specimens and clinical outcomes. AF specimens were tested by quantitative real-time PCR for the presence of genome sequences of the following viruses: adenoviruses, herpes simplex virus (HSV), varicella zoster virus (VZV), human herpesvirus 6 (HHV6), human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), parvovirus B19 and enteroviruses. Viral nucleic acid testing was also performed in maternal blood and cord blood in the population of women in whom AF was positive for viruses and in a control group of 29 women with AF negative for viral nucleic acids. The relationship between the presence of viruses and pregnancy and neonatal outcome was examined. The correlation between the presence of nucleic acids of viruses in the AF and the concentration of the cytokine interleukin-6 (IL-6) and the T cell chemokine CXCL-10 (or IP-10) in AF and maternal blood were analyzed. Results: Viral genome sequences were found in 16 of 729 (2.2%) AF samples. HHV6 was the most commonly detected virus (7 cases, 1.0%), followed by HCMV (6 cases, 0.8%), parvovirus B19 (2 cases, 0.3%) and EBV (1 case, 0.1%), while HSV, VZV, enteroviruses and adenoviruses were not found in this cohort. Corresponding viral DNA was also detected in maternal blood of six out of seven women with HHV6-positive AF and in the umbilical cord plasma, which was available in one case. In contrast, viral DNA was not detected in maternal blood of women with AF positive for parvovirus B19, HCMV, EBV or of women with AF negative for viruses. HHV6 genome copy number in AF and maternal blood was consistent with genomic integration of viral DNA and genetic infection in all women. There was no significant difference in the AF concentration of IL-6 and IP-10 between patients with and without VIAC. However, for HCMV, there was a significant relationship between viral copy number and IP-10 concentration in maternal blood and AF. The group of women with AF positive for viral DNA delivered at term healthy neonates without complications in 14 out of 16 cases. In one case of HHV6 infection in the AF, the patient developed gestational hypertension at term, and in another case of HHV6 infection in the AF, the patient delivered at 33 weeks after preterm premature rupture of membranes (PPROM). Conclusion: Viral nucleic acids are detectable in 2.2% of AF samples obtained from asymptomatic women in the midtrimester. HHV6 was the most frequently detected virus in AF. Adenoviruses were not detected. Vertical transmission of HHV6 was demonstrated in one case.
C1 [Gervasi, Maria-Teresa] Azienda Osped, Dept Hlth Mothers & Children, Ob Gyn Unit, Padua, Italy.
[Romero, Roberto; Chaiworapongsa, Tinnakorn; Dong, Zhong; Hassan, Sonia S.; Yeo, Lami] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Romero, Roberto; Chaiworapongsa, Tinnakorn; Dong, Zhong; Hassan, Sonia S.; Yeo, Lami] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Bracalente, Gabriella; Hassan, Sonia S.; Yeo, Lami] Dept Hlth Mothers & Children, Ob Gyn Unit, Treviso, Italy.
[Chaiworapongsa, Tinnakorn] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Erez, Offer] Ben Gurion Univ Negev, Soroka Univ, Med Ctr, Dept Obstet & Gynecol,Fac Hlth Sci,Sch Med, IL-84105 Beer Sheva, Israel.
[Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea.
[Mor, Gil] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod Immunol Unit, New Haven, CT USA.
[Barzon, Luisa; Franchin, Elisa; Militello, Valentina; Palu, Giorgio] Univ Padua, Dept Mol Med, Padua, Italy.
RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
RI Yoon, Bo Hyun/H-6344-2011
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX This research was supported, in part, by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS.
NR 276
TC 25
Z9 26
U1 0
U2 6
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD OCT
PY 2012
VL 25
IS 10
BP 2002
EP 2013
DI 10.3109/14767058.2012.683899
PG 12
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 008JM
UT WOS:000308953200035
PM 22524157
ER
PT J
AU Teng, J
Chang, T
Reyes, C
Nelson, KB
AF Teng, Jennifer
Chang, Taeun
Reyes, Christine
Nelson, Karin B.
TI Placental weight and neurologic outcome in the infant: a review
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Review
DE Cerebral palsy; fetoplacental ratio; neonatal encephalopathy; normative
weight; placenta; placentomegaly
ID CEREBRAL-PALSY; REFERENCE VALUES; CLINICAL-SIGNIFICANCE; PERCENTILE
CURVES; BIRTH; SINGLETON; GROWTH; RATIOS; FETAL; ANTECEDENTS
AB Objective: To review the agreement of published standards on placental weights (PW) and fetal-placental (F/P) ratios, examine factors contributing to PW and ask whether aberrant placental weight is associated with adverse neurologic outcome. Methods: We conducted a literature search for standards of PW, F/P ratio and the relationship of PW to perinatal death, neonatal encephalopathy or cerebral palsy. We reviewed 17 studies of normative PW and 10 of F/P ratios. Since 1990, seven studies compared mean and extreme percentile bounds between 35 and 42 weeks of gestation. Nine publications examined PW and neurologic outcome. Results: Untrimmed placentas were heavier by 131-193 g. F/P ratios differed by 0.2-2.34 between trimmed and untrimmed placentas. Fresh, frozen or fixed preparation prior to weighing had minimal effect on weight. Gender and race had negligible affect. Placentas from caesarean sections averaged 75 g heavier than vaginal deliveries. There were no consistent associations of aberrant PW and neurologic outcome. Conclusions: Reference standards of recent studies on trimmed placentas were largely in agreement. Current findings relating aberrant PW and adverse neurologic outcome are inconclusive. Further study of the relationship between placental weight and neonatal encephalopathy or cerebral palsy is warranted, in representative populations using within-study controls.
C1 [Teng, Jennifer; Chang, Taeun; Reyes, Christine; Nelson, Karin B.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Nelson, Karin B.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
RP Teng, J (reprint author), Childrens Natl Med Ctr, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM jteng@childrensnational.org
NR 30
TC 9
Z9 10
U1 0
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD OCT
PY 2012
VL 25
IS 10
BP 2082
EP 2087
DI 10.3109/14767058.2012.671871
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 008JM
UT WOS:000308953200051
PM 22394270
ER
PT J
AU Hughes, RC
AF Hughes, Robert C.
TI Individual risk and community benefit in international research
SO JOURNAL OF MEDICAL ETHICS
LA English
DT Article
ID PROTECTING COMMUNITIES; JUSTICE; GLOBALIZATION
AB It is widely agreed that medical researchers who conduct studies in low- and middle-income countries (LMICs) are morally required to ensure that their research benefits the broader host community, not only the subjects. The justification for this moral requirement has not been adequately examined. Most attempts to justify this requirement focus on researchers' interaction with the community as a whole, not on their relationship with their subjects. This paper argues that in some cases, research must benefit the broader host community for researchers to treat subjects and prospective subjects ethically. If research presents substantial net risks to subjects, researchers can ethically ask LMIC citizens to participate only if people in LMICs, normally including people in the host community, stand to benefit.
C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Hughes, RC (reprint author), NIH, Dept Bioeth, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM hughesrc@cc.nih.gov
FU Intramural Research Program of the NIH, Clinical Center
FX I am grateful to Benjamin Chan, Joseph Millum, Seema Shah, Seana
Shiffrin, David Wendler and Alan Wertheimer for helpful comments on
previous drafts of this manuscript. This work was completed as part of
the author's duties as a fellow of the U.S. National Institutes of
Health and was supported by the Intramural Research Program of the NIH,
Clinical Center. The views expressed here are the author's and do not
reflect the policies and positions of the NIH, the U.S. Public Health
Service, or the U.S. Department of Health and Human Services.
NR 22
TC 3
Z9 3
U1 0
U2 7
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0306-6800
J9 J MED ETHICS
JI J. Med. Ethics
PD OCT
PY 2012
VL 38
IS 10
BP 626
EP 629
DI 10.1136/medethics-2011-100171
PG 4
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 012VU
UT WOS:000309265500013
PM 22562945
ER
PT J
AU Lynch, SK
Liu, C
Morgan, NY
Xiao, X
Gomella, AA
Mazilu, D
Bennett, EE
Assoufid, L
de Carlo, F
Wen, H
AF Lynch, S. K.
Liu, C.
Morgan, N. Y.
Xiao, X.
Gomella, A. A.
Mazilu, D.
Bennett, E. E.
Assoufid, L.
de Carlo, F.
Wen, H.
TI Fabrication of 200 nm period centimeter area hard x-ray absorption
gratings by multilayer deposition
SO JOURNAL OF MICROMECHANICS AND MICROENGINEERING
LA English
DT Article
ID SHEARING INTERFEROMETER; TALBOT INTERFEROMETRY; PHASE GRATINGS;
LITHOGRAPHY; TOMOGRAPHY; TISSUE; BEAM
AB We describe the design and fabrication trials of x-ray absorption gratings of 200 nm period and up to 100:1 depth-to-period ratios for full-field hard x-ray imaging applications. Hard x-ray phase-contrast imaging relies on gratings of ultra-small periods and sufficient depth to achieve high sensitivity. Current grating designs utilize lithographic processes to produce periodic vertical structures, where grating periods below 2.0 mu m are difficult due to the extreme aspect ratios of the structures. In our design, multiple bilayers of x-ray transparent and opaque materials are deposited on a staircase substrate, and mostly on the floor surfaces of the steps only. When illuminated by an x-ray beam horizontally, the multilayer stack on each step functions as a micro-grating whose grating period is the thickness of a bilayer. The array of micro-gratings over the length of the staircase works as a single grating over a large area when continuity conditions are met. Since the layers can be nanometers thick and many microns wide, this design allows sub-micron grating periods and sufficient grating depth to modulate hard x-rays. We present the details of the fabrication process and diffraction profiles and contact radiography images showing successful intensity modulation of a 25 keV x-ray beam.
C1 [Lynch, S. K.; Gomella, A. A.; Mazilu, D.; Bennett, E. E.; Wen, H.] NHLBI, Imaging Phys Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Liu, C.; Xiao, X.; Assoufid, L.; de Carlo, F.] Argonne Natl Lab Argonne, Adv Photon Source, Xray Sci Div, Argonne, IL 60439 USA.
[Morgan, N. Y.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
RP Lynch, SK (reprint author), NHLBI, Imaging Phys Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
EM wenh@nhlbi.nih.gov
RI Bennett, Eric/A-2551-2013; Wen, Han/G-3081-2010
OI Wen, Han/0000-0001-6844-2997
FU Division of Intramural Research, National Heart, Lung and Blood
Institute, NIH [HL006143-01]; US Department of Energy, Office of
Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]
FX We thank Dr Jon C Geist and Dr Craig D McGray of the Physical
Measurement Laboratory at the National Institute of Standards and
Technology for assistance with KOH etching, and Dr Maria Aronova of
NIBIB/NIH for assistance with scanning electron microscopy. The work was
funded by the Division of Intramural Research, National Heart, Lung and
Blood Institute, NIH, under project no HL006143-01. Use of the Advanced
Photon Source at Argonne National Laboratory was supported by the US
Department of Energy, Office of Science, Office of Basic Energy
Sciences, under contract no DE-AC02-06CH11357.
NR 38
TC 13
Z9 13
U1 5
U2 31
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0960-1317
EI 1361-6439
J9 J MICROMECH MICROENG
JI J. Micromech. Microeng.
PD OCT
PY 2012
VL 22
IS 10
AR 105007
DI 10.1088/0960-1317/22/10/105007
PG 10
WC Engineering, Electrical & Electronic; Nanoscience & Nanotechnology;
Instruments & Instrumentation; Physics, Applied
SC Engineering; Science & Technology - Other Topics; Instruments &
Instrumentation; Physics
GA 012EY
UT WOS:000309219500007
PM 23066175
ER
PT J
AU Loh, YP
Zhou, ZA
Kao, LS
AF Loh, Y. Peng
Zhou, Zhuan
Kao, Lung-Sen
TI Proceedings of the 16th International Symposium on Chromaffin Cell
Biology
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Editorial Material
C1 [Loh, Y. Peng] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Zhou, Zhuan] Peking Univ, Inst Mol Med, State Key Lab Biomembrane Engn, Beijing 100871, Peoples R China.
[Zhou, Zhuan] Peking Univ, Inst Mol Med, Ctr Life Sci, Beijing 100871, Peoples R China.
[Kao, Lung-Sen] Natl Yang Ming Univ, Brain Res Ctr, Dept Life Sci, Taipei 112, Taiwan.
[Kao, Lung-Sen] Natl Yang Ming Univ, Brain Res Ctr, Inst Genome Sci, Taipei 112, Taiwan.
RP Loh, YP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
EM lohp@mail.nih.gov; zzhou@pku.edu.cn; lskao@ym.edu.tw
NR 0
TC 0
Z9 0
U1 0
U2 5
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD OCT
PY 2012
VL 48
IS 2
BP 313
EP 314
DI 10.1007/s12031-012-9798-1
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 008LO
UT WOS:000308958700001
PM 22588979
ER
PT J
AU Loh, YP
Corti, A
AF Loh, Y. Peng
Corti, Angelo
TI Commentary: Granins, Secretory Granule Biogenesis, and Transport
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Editorial Material
C1 [Loh, Y. Peng] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Corti, Angelo] Ist Sci San Raffaele, Tumor Biol & Vasc Targeting Unit, DIBIT Div Mol Oncol, I-20132 Milan, Italy.
RP Loh, YP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
EM lohp@mail.nih.gov
RI Corti, Angelo/F-7046-2012;
OI Corti, Angelo/0000-0002-0893-6191; Subba, Rajkrishna/0000-0003-0051-0062
NR 0
TC 0
Z9 0
U1 0
U2 1
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD OCT
PY 2012
VL 48
IS 2
BP 315
EP 316
DI 10.1007/s12031-012-9797-2
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 008LO
UT WOS:000308958700002
PM 22614097
ER
PT J
AU Loh, YP
Cheng, Y
Mahata, SK
Corti, A
Tota, B
AF Loh, Y. Peng
Cheng, Yong
Mahata, Sushil K.
Corti, Angelo
Tota, Bruno
TI Chromogranin A and Derived Peptides in Health and Disease
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Article; Proceedings Paper
CT 16th International Symposium on Chromaffin Cell Biology (ISCCB)
CY JUL 11-15, 2011
CL Beijing, PEOPLES R CHINA
DE Chromogranin A; Catestatin; Vasostatin; Serpinin; Cancer; Hypertension;
Diabetes
ID TUMOR-NECROSIS-FACTOR; CATECHOLAMINE RELEASE; IN-VIVO;
INSULIN-SECRETION; ENDOTHELIAL-CELLS; TARGETED ABLATION; DRUG
PENETRATION; CATESTATIN ACTS; FACTOR-ALPHA; PANCREASTATIN
AB Chromogranin A (CgA) is a member of the granins, a family of acidic proteins found in abundance in (neuro) endocrine cells (e.g., in chromaffin cells) and in some tumors. Like other granins, CgA has a granulogenic role in secretory granule biogenesis and is stored in these organelles. CgA is partially processed differentially in various cell types to yield biologically active peptides, such as vasostatin, pancreastatin, catestatin, and serpinins. In this review, we describe the roles of CgA and several of its derived peptides. CgA, which is elevated in the blood of cancer patients, inhibits angiogenesis and exerts protective effects on the endothelial barrier function in tumors, thus affecting response to chemotherapy. Recent studies indicate that the serpinins promote cell survival and myocardial contractility and relaxation. Other peptides such as pancreastatin were found to have significant effects on inhibition of glucose-stimulated insulin secretion and glucose uptake, induction of glycogenolysis in hepatocytes, and inhibition of lipogenesis. In contrast, catestatin has opposite effects to that of pancreastatin in glucose metabolism and lipogenesis. Catestatin appears to also play a significant role in cardiac function, blood pressure regulation, and mutations in the catestatin domain of the CgA gene are associated with hypertension in humans.
C1 [Loh, Y. Peng] NIH, Bethesda, MD 20892 USA.
[Loh, Y. Peng; Cheng, Yong] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Mahata, Sushil K.] VA San Diego Healthcare Syst, San Diego, CA 92161 USA.
[Mahata, Sushil K.] Univ Calif San Diego, Dept Med 0838, La Jolla, CA 92093 USA.
[Corti, Angelo] Ist Sci San Raffaele, Tumor Biol & Vasc Targeting Unit, DIBIT Div Mol Oncol, I-20132 Milan, Italy.
[Tota, Bruno] Univ Calabria, Dept Cell Biol, I-87030 Arcavacata Di Rende, CS, Italy.
RP Loh, YP (reprint author), NIH, Bldg 49,Room 5A22, Bethesda, MD 20892 USA.
EM lohp@mail.nih.gov
RI Corti, Angelo/F-7046-2012;
OI Corti, Angelo/0000-0002-0893-6191; Subba,
Rajkrishna/0000-0003-0051-0062; Cheng, Yong/0000-0002-7529-4408
FU Intramural NIH HHS [ZIA HD000056-36]
NR 53
TC 23
Z9 26
U1 0
U2 5
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD OCT
PY 2012
VL 48
IS 2
BP 347
EP 356
DI 10.1007/s12031-012-9728-2
PG 10
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 008LO
UT WOS:000308958700007
PM 22388654
ER
PT J
AU Carbone, E
Guerineau, NC
Loh, YP
Zhou, ZA
AF Carbone, Emilio
Guerineau, Nathalie C.
Loh, Y. Peng
Zhou, Zhuan
TI Commentary: Ion Channels, Fusion Pores and Exocytosis
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Editorial Material
C1 [Loh, Y. Peng] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Carbone, Emilio] Univ Turin, Natl Inst Neurosci, NIS Ctr, Dept Neurosci, I-10125 Turin, Italy.
[Guerineau, Nathalie C.] Univ Angers, CNRS, UMR6214, UFR Sci Med,INSERM,U1083, F-49045 Angers 01, France.
[Zhou, Zhuan] Peking Univ, Inst Mol Med, State Key Lab Biomembrane Engn, Beijing 100871, Peoples R China.
[Zhou, Zhuan] Peking Univ, Inst Mol Med, Ctr Life Sci, Beijing 100871, Peoples R China.
RP Loh, YP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
EM nathalie.guerineau@univ-angers.fr; lohp@mail.nih.gov; zzhou@pku.edu.cn
OI Carbone, Emilio/0000-0003-2239-6280; Guerineau,
Nathalie/0000-0003-2517-4210
NR 0
TC 1
Z9 1
U1 0
U2 4
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD OCT
PY 2012
VL 48
IS 2
BP 357
EP 359
DI 10.1007/s12031-012-9794-5
PG 3
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 008LO
UT WOS:000308958700008
PM 22588977
ER
PT J
AU Smith, CB
Eiden, LE
AF Smith, Corey B.
Eiden, Lee E.
TI Is PACAP the Major Neurotransmitter for Stress Transduction at the
Adrenomedullary Synapse?
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Article; Proceedings Paper
CT 16th International Symposium on Chromaffin Cell Biology (ISCCB)
CY JUL 11-15, 2011
CL Beijing, PEOPLES R CHINA
DE Chromaffin cell; Neurotransmission; PACAP; Splanchnic-adrenal synapse;
Stress
ID CYCLASE-ACTIVATING POLYPEPTIDE; ADRENAL CHROMAFFIN CELLS; SPLANCHNIC
NERVE-STIMULATION; SUPERIOR CERVICAL-GANGLION; CATECHOLAMINE
BIOSYNTHETIC-ENZYMES; ADENYLATE-CYCLASE; NEUROPEPTIDE-Y; SIGNALING
PATHWAYS; TRANSSYNAPTIC REGULATION; TYROSINE-HYDROXYLASE
AB It has been known for more than a decade that the neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) is co-stored with acetylcholine in the splanchnic nerve terminals innervating the adrenal medulla. Both transmitters are robust secretagogues for catecholamine release from chromaffin cells. Here, we review the unique contribution of PACAP to the functioning of the splanchnic-adrenal synapse in stress. While acetylcholine is released across a wide range of firing frequencies, PACAP is released only at high frequencies of stimulation, and its role in the regulation of epinephrine secretion and biosynthesis is highly specialized. PACAP is responsible for long-term catecholamine secretion using secretory mechanisms different from the rapidly desensitizing depolarization evoked by acetylcholine through nicotinic receptor activation. PACAP signaling also maintains catecholamine synthesis required for sustained secretion during prolonged stress via induction of the enzymes TH and PNMT, and enhances transcription of additional secreted molecules found in chromaffin cells that alter further secretion through both autocrine and paracrine mechanisms. PACAP thus mediates chromaffin cell plasticity via functional encoding of cellular experience. These features of PACAP action at the splanchnic-adrenal synapse may be paradigmatic for the general actions of neuropeptides as effectors of stimulus-secretion-synthesis coupling in stress.
C1 [Eiden, Lee E.] NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA.
[Smith, Corey B.] Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA.
RP Eiden, LE (reprint author), NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bldg 49,Room 5A-38,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM eidenl@mail.nih.gov
OI Eiden, Lee/0000-0001-7524-944X
FU Intramural NIH HHS [ZIA MH002386-27, ZIA MH002386-25, Z99 MH999999, ZIA
MH002386-24, ZIA MH002386-26, ZIA MH002386-28]; NHLBI NIH HHS [TS
HL07653, T32 HL007653]; NIMH NIH HHS [Z01 MH002386, 1Z01MH002386]; NINDS
NIH HHS [R01 NS052123, NS-052123]
NR 76
TC 18
Z9 18
U1 0
U2 9
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD OCT
PY 2012
VL 48
IS 2
BP 403
EP 412
DI 10.1007/s12031-012-9749-x
PG 10
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 008LO
UT WOS:000308958700014
PM 22610912
ER
PT J
AU Bunn, SJ
Ait-Ali, D
Eiden, LE
AF Bunn, Stephen J.
Ait-Ali, Djida
Eiden, Lee E.
TI Immune-Neuroendocrine Integration at the Adrenal Gland: Cytokine Control
of the Adrenomedullary Transcriptome
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Article; Proceedings Paper
CT 16th International Symposium on Chromaffin Cell Biology (ISCCB)
CY JUL 11-15, 2011
CL Beijing, PEOPLES R CHINA
DE Adrenal medulla; Chromaffin cell; Cytokine; IFN; IL-1; IL-6;
Inflammation; PACAP; Stress; TNF
ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; CHROMAFFIN CELLS; TNF RECEPTOR;
CATECHOLAMINE RELEASE; INTERFERON-ALPHA; MEDULLARY CELLS;
NEUROPEPTIDE-Y; SECRETION; INTERLEUKIN-1
AB The bovine chromaffin cell represents an ideal model for the study of cell signaling to gene expression by first messengers. An abundance of GPCR, ionotropic, and growth factor receptors are expressed on these cells, and they can be obtained and studied as an abundant highly enriched cell population; importantly, this is true of no other postmitotic neuroendocrine or neuronal cell type. Chromaffin cells have now been shown to bear receptors for cytokines whose expression in the circulation is highly elevated in inflammation, including tumor necrosis factor, interferon, interleukin-1, and interleukin-6. The use of bovine-specific microarrays, and various biochemical measurements in this highly homogenous cell preparation reveals unique cohorts of distinct genes regulated by cytokines in chromaffin cells, via signaling pathways that are in some cases uniquely neuroendocrine. The transcriptomic signatures of cytokine signaling in chromaffin cells suggest that the adrenal medulla may integrate neuronal, hormonal, and immune signaling during inflammation, through induction of paracrine factors that signal to both adrenal cortex and sensory afferents of the adrenal gland, and autocrine factors, which determine the duration and type of paracrine secretory signaling that occurs in either acute or chronic inflammatory conditions.
C1 [Bunn, Stephen J.] Univ Otago, Sch Med Sci, Dept Anat, Ctr Neuroendocrinol, Dunedin, New Zealand.
[Ait-Ali, Djida; Eiden, Lee E.] NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA.
RP Bunn, SJ (reprint author), Univ Otago, Sch Med Sci, Dept Anat, Ctr Neuroendocrinol, POB 913, Dunedin, New Zealand.
EM stephen.bunn@anatomy.otago.ac.nz; eidenl@mail.nih.gov
OI Eiden, Lee/0000-0001-7524-944X
FU Intramural NIH HHS [ZIA MH002386-26, ZIA MH002386-25]
NR 36
TC 2
Z9 3
U1 0
U2 6
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD OCT
PY 2012
VL 48
IS 2
BP 413
EP 419
DI 10.1007/s12031-012-9745-1
PG 7
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 008LO
UT WOS:000308958700015
PM 22421803
ER
PT J
AU Kao, LS
Loh, YP
AF Kao, Lung-Sen
Loh, Y. Peng
TI Commentary: Neurotransmitter Secretion and Cell Signaling
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Editorial Material
C1 [Loh, Y. Peng] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Kao, Lung-Sen] Natl Yang Ming Univ, Brain Res Ctr, Dept Life Sci, Taipei 112, Taiwan.
[Kao, Lung-Sen] Natl Yang Ming Univ, Brain Res Ctr, Inst Genome Sci, Taipei 112, Taiwan.
RP Loh, YP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
EM lskao@ym.edu.tw; lohp@mail.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD OCT
PY 2012
VL 48
IS 2
BP 427
EP 428
DI 10.1007/s12031-012-9796-3
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 008LO
UT WOS:000308958700017
PM 22588978
ER
PT J
AU Shen, H
Banerjee, AA
Mlynarska, P
Hautman, M
Hong, S
Kapetanovic, IM
Lyubimov, AV
Liu, Y
AF Shen, Hao
Banerjee, Aryamitra A.
Mlynarska, Paulina
Hautman, Mathew
Hong, Seungpyo
Kapetanovic, Izet M.
Lyubimov, Alexander V.
Liu, Ying
TI Enhanced oral bioavailability of a cancer preventive agent (SR13668) by
employing polymeric nanoparticles with high drug loading
SO JOURNAL OF PHARMACEUTICAL SCIENCES
LA English
DT Article
DE bioavailability; nanoparticles; stability; scalable; nanoprecipitation;
spray drying; cancer chemoprevention
ID DELIVERY-SYSTEMS; BLOCK-COPOLYMERS; VORTEX MIXER; DESIGN;
NANOPRECIPITATION; INDOLE-3-CARBINOL; DERIVATIVES; MECHANISMS;
PARTICLES; RELEASE
AB SR13668 [2,10-Dicarbethoxy-6-methoxy-5,7-dihydro-indolo-(2,3-b)carbazole] has been proven effective in cancer prevention, but the limited bioavailability has hindered its clinical translation. In this study, we have developed a continuous, scalable process to form stable poly(lactic-co-glycolic acid) nanoparticles encapsulating SR13668, based on understanding of the competitive kinetics of nanoprecipitation and spray drying. The optimized formulation achieved high drug loading (33.3?wt %) and small particles (150?nm) with narrow size distribution. The prepared nanoparticle suspensions through flash nanoprecipitation were spray dried to achieve long-term stability and to conveniently adjust the nanoparticle concentration before use. In vitro release of SR13668 from the nanosuspensions was measured in a solution with separated organic and aqueous phases to overcome the limit of SR13668 low water solubility. Higher oral bioavailability of SR13668 by employing polymeric nanoparticles compared with the Labrasol (R) formulation was demonstrated in a mouse model.(C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:38773885, 2012
C1 [Shen, Hao; Mlynarska, Paulina; Liu, Ying] Univ Illinois, Dept Chem Engn, Chicago, IL 60607 USA.
[Banerjee, Aryamitra A.; Lyubimov, Alexander V.] Univ Illinois, Dept Pharmacol, Chicago, IL 60612 USA.
[Hautman, Mathew] Ctr Biomed Testing, Chicago, IL 60612 USA.
[Hong, Seungpyo; Liu, Ying] Univ Illinois, Dept Biopharmaceut Sci, Chicago, IL 60612 USA.
[Kapetanovic, Izet M.] NCI, Bethesda, MD 20892 USA.
RP Liu, Y (reprint author), Univ Illinois, Dept Chem Engn, Chicago, IL 60607 USA.
EM lyubimov@uic.edu; liuying@uic.edu
RI Banerjee, Aryamitra/A-1364-2013
FU National Cancer Institute, Department of Health and Human Services
[N01-CN-43306]
FX The study was supported by National Cancer Institute, Department of
Health and Human Services (contract number N01-CN-43306). The authors
are grateful to Dr. Yoon Yeo at Purdue University for the access of the
spray dryer in her laboratory.
NR 38
TC 6
Z9 6
U1 0
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3549
J9 J PHARM SCI-US
JI J. Pharm. Sci.
PD OCT
PY 2012
VL 101
IS 10
BP 3877
EP 3885
DI 10.1002/jps.23269
PG 9
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology &
Pharmacy
SC Pharmacology & Pharmacy; Chemistry
GA 994XA
UT WOS:000307966600032
PM 22821759
ER
PT J
AU Paul, RK
Ramamoorthy, A
Scheers, J
Wersto, RP
Toll, L
Jimenez, L
Bernier, M
Wainer, IW
AF Paul, Rajib K.
Ramamoorthy, Anuradha
Scheers, Jade
Wersto, Robert P.
Toll, Lawrence
Jimenez, Lucita
Bernier, Michel
Wainer, Irving W.
TI Cannabinoid Receptor Activation Correlates with the Proapoptotic Action
of the beta(2)-Adrenergic Agonist (R,R ')-4-Methoxy-1-Naphthylfenoterol
in HepG2 Hepatocarcinoma Cells
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID MOLECULAR-FIELD ANALYSIS; BETA-2-ADRENERGIC RECEPTOR; PROTEIN-KINASE;
FENOTEROL DERIVATIVES; BETA-ADRENOCEPTORS; ERK1/2 ACTIVATION;
ADENYLATE-CYCLASE; CANCER; LIGANDS; HETERODIMERIZATION
AB Inhibition of cell proliferation by fenoterol and fenoterol derivatives in 1321N1 astrocytoma cells is consistent with beta(2)-adrenergic receptor (beta(2)-AR) stimulation. However, the events that result in fenoterol-mediated control of cell proliferation in other cell types are not clear. Here, we compare the effect of the beta(2)-AR agonists (R,R')-fenoterol (Fen) and (R,R')-4-methoxy-1-naphthylfenoterol (MNF) on signaling and cell proliferation in HepG2 hepatocarcinoma cells by using Western blotting and [H-3]thymidine incorporation assays. Despite the expression of beta(2)-AR, no cAMP accumulation was observed when cells were stimulated with isoproterenol or Fen, although the treatment elicited both mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt activation. Unexpectedly, isoproterenol and Fen promoted HepG2 cell growth, but MNF reduced proliferation together with increased apoptosis. The mitogenic responses of Fen were attenuated by 3-(isopropylamino)-1-[(7-methyl-4-indanyl) oxy]butan-2-ol (ICI 118,551), a beta(2)-AR antagonist, whereas those of MNF were unaffected. Because of the coexpression of beta(2)-AR and cannabinoid receptors (CBRs) and their impact on HepG2 cell proliferation, these G alpha(i)/G alpha(o)-linked receptors may be implicated in MNF signaling. Cell treatment with (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-napthalenylmethanone (WIN 55,212-2), a synthetic agonist of CB1R and CB2R, led to growth inhibition, whereas inverse agonists of these receptors blocked MNF mitogenic responses without affecting Fen signaling. MNF responses were sensitive to pertussis toxin. The beta(2)-AR-deficient U87MG cells were refractory to Fen, but responsive to the antiproliferative actions of MNF and WIN 55,212-2. The data indicate that the presence of the naphthyl moiety in MNF results in functional coupling to the CBR pathway, providing one of the first examples of a dually acting beta(2)-AR-CBR ligand.
C1 [Paul, Rajib K.; Ramamoorthy, Anuradha; Bernier, Michel; Wainer, Irving W.] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA.
[Scheers, Jade; Wersto, Robert P.] NIA, Flow Cytometry Unit, Res Resources Branch, NIH, Baltimore, MD 21224 USA.
[Jimenez, Lucita] SRI Int, Menlo Pk, CA 94025 USA.
[Toll, Lawrence] Torrey Pines Inst Mol Studies, Port St Lucie, FL USA.
RP Bernier, M (reprint author), NIA, Clin Invest Lab, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM bernierm@mail.nih.gov
OI Bernier, Michel/0000-0002-5948-368X
FU Intramural Research Program of the National Institutes of Health;
National Institutes of Health National Institute on Aging [N01AG-3-1009]
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health and the National Institutes of
Health National Institute on Aging under Contract N01AG-3-1009.
NR 46
TC 7
Z9 8
U1 0
U2 11
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD OCT
PY 2012
VL 343
IS 1
BP 157
EP 166
DI 10.1124/jpet.112.195206
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 009AK
UT WOS:000308997500017
PM 22776956
ER
PT J
AU Tae, HJ
Marshall, S
Zhang, J
Wang, MY
Briest, W
Talan, MI
AF Tae, Hyun-Jin
Marshall, Shannon
Zhang, Jing
Wang, Mingyi
Briest, Wilfried
Talan, Mark I.
TI Chronic Treatment with a Broad-Spectrum Metalloproteinase Inhibitor,
Doxycycline, Prevents the Development of Spontaneous Aortic Lesions in a
Mouse Model of Vascular Ehlers-Danlos Syndrome
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID SYNDROME TYPE-IV; MATRIX METALLOPROTEINASES; MARFAN-SYNDROME; GENETIC
FEATURES; GROWTH-RATE; ANEURYSM; COLLAGEN; CELLS; TRIAL;
MATRIX-METALLOPROTEINASE-9
AB There is no proven therapy or prevention for vascular Ehlers-Danlos syndrome (vEDS), a genetic disorder associated with the mutation of procollagen type III and characterized by increased fragility of vascular and hollow organ walls. Heterozygous COL3A1-deficient (HT) mice recapitulate a mild presentation of one of the variants of vEDS: haploinsufficiency for collagen III. Adult HT mice are characterized by increased metalloproteinase (MMP) activity, reduced collagen content in the arterial walls, and spontaneous development of various severity lesions in aorta. We hypothesized that chronic treatment with a MMP inhibitor would increase collagen content and prevent the development of spontaneous aortic lesions. HT mice were treated since weaning with the broad-spectrum MMP inhibitor doxycycline added to food. At the age of 9 months MMP-9 expression was twice as high in the tunica media of aorta in untreated HT mice, whereas total collagen content was 30% lower (p < 0.01) and the cumulative score of aortic lesions was eight times higher than in wild-type (WT) mice (p < 0.01). After 9 months of doxycycline treatment, MMP-9 activity, collagen content, and lesions in the aortas of HT mice were at the level of those of WT mice (p > 0.05). In the mouse model of collagen III haploinsufficiency treatment with broad-spectrum MMP inhibitor that was started early in life normalized increased MMP activity, reduced aortic collagen content in adults, and prevented the development of spontaneous aortic lesions. Our findings provide experimental justification for the clinical evaluation of the benefit of doxycycline at least in the haploinsufficient variety of vEDS.
C1 [Tae, Hyun-Jin; Marshall, Shannon; Zhang, Jing; Wang, Mingyi; Talan, Mark I.] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA.
[Briest, Wilfried] Fritz Lipmann Inst, Leibniz Inst Age Res, Jena, Germany.
RP Talan, MI (reprint author), NIA, Cardiovasc Sci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM talanm@mail.nih.gov
OI Briest, Wilfried/0000-0003-4556-4849
FU National Institutes of Health National Institute on Aging
FX This work was fully supported by the Intramural Research Program of the
National Institutes of Health National Institute on Aging.
NR 37
TC 8
Z9 8
U1 1
U2 2
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD OCT
PY 2012
VL 343
IS 1
BP 246
EP 251
DI 10.1124/jpet.112.197020
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 009AK
UT WOS:000308997500026
PM 22815532
ER
PT J
AU Tabbutt, S
Ghanayem, N
Ravishankar, C
Sleeper, LA
Cooper, DS
Frank, DU
Lu, MM
Pizarro, C
Frommelt, P
Goldberg, CS
Graham, EM
Krawczeski, CD
Lai, WW
Lewis, A
Kirsh, JA
Mahony, L
Ohye, RG
Simsic, J
Lodge, AJ
Spurrier, E
Stylianou, M
Laussen, P
AF Tabbutt, Sarah
Ghanayem, Nancy
Ravishankar, Chitra
Sleeper, Lynn A.
Cooper, David S.
Frank, Deborah U.
Lu, Minmin
Pizarro, Christian
Frommelt, Peter
Goldberg, Caren S.
Graham, Eric M.
Krawczeski, Catherine Dent
Lai, Wyman W.
Lewis, Alan
Kirsh, Joel A.
Mahony, Lynn
Ohye, Richard G.
Simsic, Janet
Lodge, Andrew J.
Spurrier, Ellen
Stylianou, Mario
Laussen, Peter
CA Pediatric Heart Network
TI Risk factors for hospital morbidity and mortality after the Norwood
procedure: A report from the Pediatric Heart Network Single Ventricle
Reconstruction trial
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID PULMONARY-ARTERY CONDUIT; EXTRACORPOREAL MEMBRANE-OXYGENATION; STAGE-I
RECONSTRUCTION; BLALOCK-TAUSSIG SHUNT; OPERATION; OUTCOMES; PALLIATION;
EXPERIENCE; STENOSIS; INFANTS
AB Objectives: We sought to identify risk factors for mortality and morbidity during the Norwood hospitalization in newborn infants with hypoplastic left heart syndrome and other single right ventricle anomalies enrolled in the Single Ventricle Reconstruction trial.
Methods: Potential predictors for outcome included patient- and procedure-related variables and center volume and surgeon volume. Outcome variables occurring during the Norwood procedure and before hospital discharge or stage II procedure included mortality, end-organ complications, length of ventilation, and hospital length of stay. Univariate and multivariable Cox regression analyses were performed with bootstrapping to estimate reliability for mortality.
Results: Analysis included 549 subjects prospectively enrolled from 15 centers; 30-day and hospital mortality were 11.5% (63/549) and 16.0% (88/549), respectively. Independent risk factors for both 30-day and hospital mortality included lower birth weight, genetic abnormality, extracorporeal membrane oxygenation (ECMO) and open sternum on the day of the Norwood procedure. In addition, longer duration of deep hypothermic circulatory arrest was a risk factor for 30-day mortality. Shunt type at the end of the Norwood procedure was not a significant risk factor for 30-day or hospital mortality. Independent risk factors for postoperative renal failure (n = 46), sepsis (n = 93), increased length of ventilation, and hospital length of stay among survivors included genetic abnormality, lower center/surgeon volume, open sternum, and post-Norwood operations.
Conclusions: Innate patient factors, ECMO, open sternum, and lower center/surgeon volume are important risk factors for postoperative mortality and/or morbidity during the Norwood hospitalization. (J Thorac Cardiovasc Surg 2012; 144: 882-95)
C1 [Tabbutt, Sarah; Ravishankar, Chitra] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Ghanayem, Nancy; Frommelt, Peter] Med Coll Wisconsin, Childrens Hosp Wisconsin, Milwaukee, WI 53226 USA.
[Sleeper, Lynn A.; Lu, Minmin] New England Res Inst, Watertown, MA 02172 USA.
[Cooper, David S.] Congenital Heart Inst Florida, St Petersburg, FL USA.
[Frank, Deborah U.] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA.
[Frank, Deborah U.] Univ Utah, Salt Lake City, UT USA.
[Pizarro, Christian; Spurrier, Ellen] Nemours Cardiac Ctr, Wilmington, DE USA.
[Goldberg, Caren S.; Ohye, Richard G.] Univ Michigan, Sch Med, Ann Arbor, MI USA.
[Graham, Eric M.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Krawczeski, Catherine Dent] Cincinnati Childrens Med Ctr, Cincinnati, OH USA.
[Lai, Wyman W.] Morgan Stanley Childrens Hosp New York Presbyteri, New York, NY USA.
[Lewis, Alan] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Kirsh, Joel A.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Mahony, Lynn] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Simsic, Janet] Emory Univ, Atlanta, GA 30322 USA.
[Lodge, Andrew J.] Duke Univ, N Carolina Consortium, Durham, NC USA.
[Stylianou, Mario] NHLBI, Bethesda, MD 20892 USA.
[Laussen, Peter] Childrens Hosp, Boston, MA 02115 USA.
RP Tabbutt, S (reprint author), Univ Calif San Francisco, Benioff Childrens Hosp, Moffitt 680,555 Parnassus Ave, San Francisco, CA 94143 USA.
EM tabbutts@peds.ucsf.edu
RI gaynor, James william/E-5194-2013
OI gaynor, James william/0000-0001-7955-5604
FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279,
HL068281, HL068285, HL068292, HL068290, HL068288, HL085057]
FX Supported by grants from the National Heart, Lung, and Blood Institute
(HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290,
HL068288, HL085057). This work is solely the responsibility of the
authors and does not necessarily represent the official views of the
NHLBI.
NR 25
TC 75
Z9 77
U1 1
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD OCT
PY 2012
VL 144
IS 4
BP 882
EP 895
DI 10.1016/j.jtcvs.2012.05.019
PG 14
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 010RK
UT WOS:000309111600024
PM 22704284
ER
PT J
AU Ghanayem, NS
Allen, KR
Tabbutt, S
Atz, AM
Clabby, ML
Cooper, DS
Eghtesady, P
Frommelt, PC
Gruber, PJ
Hill, KD
Kaltman, JR
Laussen, PC
Lewis, AB
Lurito, KJ
Minich, LL
Ohye, RG
Schonbeck, JV
Schwartz, SM
Singh, RK
Goldberg, CS
AF Ghanayem, Nancy S.
Allen, Kerstin R.
Tabbutt, Sarah
Atz, Andrew M.
Clabby, Martha L.
Cooper, David S.
Eghtesady, Pirooz
Frommelt, Peter C.
Gruber, Peter J.
Hill, Kevin D.
Kaltman, Jonathan R.
Laussen, Peter C.
Lewis, Alan B.
Lurito, Karen J.
Minich, L. LuAnn
Ohye, Richard G.
Schonbeck, Julie V.
Schwartz, Steven M.
Singh, Rakesh K.
Goldberg, Caren S.
CA Pediatric Heart Network
TI Interstage mortality after the Norwood procedure: Results of the
multicenter Single Ventricle Reconstruction trial
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID LEFT-HEART SYNDROME; BLALOCK-TAUSSIG SHUNT; PULMONARY-ARTERY CONDUIT;
STAGE-I PALLIATION; RISK-FACTORS; OUTCOMES; DEATH; OPERATION; INFANTS;
DISEASE
AB Objective: For infants with single ventricle malformations undergoing staged repair, interstage mortality is reported at 2% to 20%. The Single Ventricle Reconstruction trial randomized subjects with a single morphologic right ventricle undergoing a Norwood procedure to a modified Blalock-Taussig shunt (MBTS) or a right ventricle-to-pulmonary artery shunt (RVPAS). The aim of this analysis was to explore the associations of interstage mortality and shunt type, and demographic, anatomic, and perioperative factors.
Methods: Participants in the Single Ventricle Reconstruction trial who survived to discharge after the Norwood procedure were included (n = 426). Interstage mortality was defined as death postdischarge after the Norwood procedure and before the stage II procedure. Univariate analysis and multivariable logistic regression were performed adjusting for site.
Results: Overall interstage mortality was 50 of 426 (12%)-13 of 225 (6%) for RVPAS and 37 of 201 (18%) for MBTS (odds ratio [OR] for MBTS, 3.4; P < .001). When moderate to severe postoperative atrioventricular valve regurgitation (AVVR) was present, interstage mortality was similar between shunt types. Interstage mortality was independently associated with gestational age less than 37 weeks (OR, 3.9; P = .008), Hispanic ethnicity (OR, 2.6; P = .04), aortic atresia/mitral atresia (OR, 2.3; P = .03), greater number of post-Norwood complications (OR, 1.2; P = .006), census block poverty level (P = .003), and MBTS in subjects with no or mild postoperative AVVR (OR, 9.7; P < .001).
Conclusions: Interstage mortality remains high at 12% and is increased with the MBTS compared with the RVPAS if postoperative AVVR is absent or mild. Preterm delivery, anatomic, and socioeconomic factors are also important. Avoiding preterm delivery when possible and close surveillance after Norwood hospitalization for infants with identified risk factors may reduce interstage mortality. (J Thorac Cardiovasc Surg 2012; 144: 896-906)
C1 [Ghanayem, Nancy S.; Frommelt, Peter C.] Med Coll Wisconsin, Childrens Hosp Wisconsin, Milwaukee, WI 53226 USA.
[Allen, Kerstin R.; Schonbeck, Julie V.] New England Res Inst, Watertown, MA 02172 USA.
[Tabbutt, Sarah; Gruber, Peter J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Atz, Andrew M.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Clabby, Martha L.] Emory Univ, Atlanta, GA 30322 USA.
[Cooper, David S.] Congenital Heart Inst Florida, St Petersburg, FL USA.
[Eghtesady, Pirooz] Cincinnati Childrens Med Ctr, Cincinnati, OH USA.
[Hill, Kevin D.] Duke Univ, Durham, NC USA.
[Kaltman, Jonathan R.] NHLBI, N Carolina Consortium, Bethesda, MD 20892 USA.
[Laussen, Peter C.] Childrens Hosp, Boston, MA 02115 USA.
[Lewis, Alan B.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Lurito, Karen J.] E Carolina Univ, Greenville, NC USA.
[Minich, L. LuAnn] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA.
[Minich, L. LuAnn] Univ Utah, Salt Lake City, UT USA.
[Ohye, Richard G.; Goldberg, Caren S.] Univ Michigan, Sch Med, Ann Arbor, MI USA.
[Schwartz, Steven M.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Singh, Rakesh K.] Columbia Univ, New York, NY USA.
RP Ghanayem, NS (reprint author), Med Coll Wisconsin, Childrens Hosp Wisconsin, 9000 W Wisconsin Ave,POB 1997, Milwaukee, WI 53226 USA.
EM nancyg@mcw.edu
OI Eghtesady, Pirooz/0000-0001-7161-8391
FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279,
HL068281, HL068285, HL068288, HL068290, HL068292, HL085057]
FX Supported by Grants HL068269, HL068270, HL068279, HL068281, HL068285,
HL068288, HL068290, HL068292, and HL085057 from the National Heart,
Lung, and Blood Institute. This work is solely the responsibility of the
authors and does not necessarily represent the official views of the
National Heart, Lung, and Blood Institute.
NR 26
TC 80
Z9 83
U1 2
U2 13
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD OCT
PY 2012
VL 144
IS 4
BP 896
EP 906
DI 10.1016/j.jtcvs.2012.05.020
PG 11
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 010RK
UT WOS:000309111600025
PM 22795436
ER
PT J
AU Ohye, RG
Schonbeck, JV
Eghtesady, P
Laussen, PC
Pizarro, C
Shrader, P
Frank, DU
Graham, EM
Hill, KD
Jacobs, JP
Kanter, KR
Kirsh, JA
Lambert, LM
Lewis, AB
Ravishankar, C
Tweddell, JS
Williams, IA
Pearson, GD
AF Ohye, Richard G.
Schonbeck, Julie V.
Eghtesady, Pirooz
Laussen, Peter C.
Pizarro, Christian
Shrader, Peter
Frank, Deborah U.
Graham, Eric M.
Hill, Kevin D.
Jacobs, Jeffrey P.
Kanter, Kirk R.
Kirsh, Joel A.
Lambert, Linda M.
Lewis, Alan B.
Ravishankar, Chitra
Tweddell, James S.
Williams, Ismee A.
Pearson, Gail D.
CA Pediat Heart Network Investigators
TI Cause, timing, and location of death in the Single Ventricle
Reconstruction trial
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID LEFT-HEART SYNDROME; PULMONARY-ARTERY CONDUIT; BLALOCK-TAUSSIG SHUNT;
NORWOOD PROCEDURE; STAGED RECONSTRUCTION; 1ST-STAGE PALLIATION;
RISK-FACTORS; OUTCOMES; OPERATION; INFANTS
AB Objectives: The Single Ventricle Reconstruction trial randomized 555 subjects with a single right ventricle undergoing the Norwood procedure at 15 North American centers to receive either a modified Blalock-Taussig shunt or right ventricle-to-pulmonary artery shunt. Results demonstrated a rate of death or cardiac transplantation by 12 months postrandomization of 36% for the modified Blalock-Taussig shunt and 26% for the right ventricle-to-pulmonary artery shunt, consistent with other publications. Despite this high mortality rate, little is known about the circumstances surrounding these deaths.
Methods: There were 164 deaths within 12 months postrandomization. A committee adjudicated all deaths for cause and recorded the timing, location, and other factors for each event.
Results: The most common cause of death was cardiovascular (42%), followed by unknown cause (24%) and multisystem organ failure (7%). The median age at death for subjects dying during the 12 months was 1.6 months (interquartile range, 0.6 to 3.7 months), with the highest number of deaths occurring during hospitalization related to the Norwood procedure. The most common location of death was at a Single Ventricle Reconstruction trial hospital (74%), followed by home (13%). There were 29 sudden, unexpected deaths (18%), although in retrospect, 12 were preceded by a prodrome.
Conclusions: In infants with a single right ventricle undergoing staged repair, the majority of deaths within 12 months of the procedure are due to cardiovascular causes, occur in a hospital, and within the first few months of life. Increased understanding of the circumstances surrounding the deaths of these single ventricle patients may reduce the high mortality rate. (J Thorac Cardiovasc Surg 2012; 144: 907-14)
C1 [Ohye, Richard G.] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA.
[Schonbeck, Julie V.; Shrader, Peter] New England Res Inst, Watertown, MA 02172 USA.
[Eghtesady, Pirooz] Cincinnati Childrens Med Ctr, Cincinnati, OH USA.
[Laussen, Peter C.] Childrens Hosp, Boston, MA 02115 USA.
[Pizarro, Christian] Alfred I duPont Hosp Children, Wilmington, DE USA.
[Frank, Deborah U.; Lambert, Linda M.] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Graham, Eric M.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Hill, Kevin D.] Duke Univ, Med Ctr, Durham, NC USA.
[Jacobs, Jeffrey P.] Congenital Heart Inst Florida, St Petersburg, FL USA.
[Kanter, Kirk R.] Emory Univ, Sch Med, Atlanta, GA USA.
[Kirsh, Joel A.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Lewis, Alan B.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Ravishankar, Chitra] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Tweddell, James S.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA.
[Williams, Ismee A.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
[Pearson, Gail D.] NHLBI, Bethesda, MD 20892 USA.
RP Ohye, RG (reprint author), Univ Michigan, Sch Med, 5144 CVC,1500 E Med Ctr Dr,SPC 5864, Ann Arbor, MI 48109 USA.
EM ohye@umich.edu
OI Eghtesady, Pirooz/0000-0001-7161-8391
FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279,
HL068281, HL068285, HL068292, HL068290, HL068288, HL085057]
FX This study was supported by U01 grants from the National Heart, Lung,
and Blood Institute (Nos. HL068269, HL068270, HL068279, HL068281,
HL068285, HL068292, HL068290, HL068288, and HL085057).
NR 24
TC 32
Z9 32
U1 1
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD OCT
PY 2012
VL 144
IS 4
BP 907
EP 914
DI 10.1016/j.jtcvs.2012.04.028
PG 8
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 010RK
UT WOS:000309111600026
PM 22901498
ER
PT J
AU Pasquali, SK
Ohye, RG
Lu, MM
Kaltman, J
Caldarone, CA
Pizarro, C
Dunbar-Masterson, C
Gaynor, JW
Jacobs, JP
Kaza, AK
Newburger, J
Rhodes, JF
Scheurer, M
Silver, E
Sleeper, LA
Tabbutt, S
Tweddell, J
Uzark, K
Wells, W
Mahle, WT
Pearson, GD
AF Pasquali, Sara K.
Ohye, Richard G.
Lu, Minmin
Kaltman, Jonathan
Caldarone, Christopher A.
Pizarro, Christian
Dunbar-Masterson, Carolyn
Gaynor, J. William
Jacobs, Jeffrey P.
Kaza, Aditya K.
Newburger, Jane
Rhodes, John F.
Scheurer, Mark
Silver, Eric
Sleeper, Lynn A.
Tabbutt, Sarah
Tweddell, James
Uzark, Karen
Wells, Winfield
Mahle, William T.
Pearson, Gail D.
CA Pediat Heart Network Investigators
TI Variation in perioperative care across centers for infants undergoing
the Norwood procedure
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID CONGENITAL HEART-SURGERY; JOINT COUNCIL; OUTCOMES; DISEASE; PALLIATION;
OPERATIONS; DATABASE
AB Objectives: In the Single Ventricle Reconstruction trial, infants undergoing the Norwood procedure were randomly allocated to undergo a right ventricle-to-pulmonary artery shunt or a modified Blalock-Taussig shunt. Apart from shunt type, subjects received the local standard of care. We evaluated variation in perioperative care during the Norwood hospitalization across 14 trial sites.
Methods: Data on preoperative, operative, and postoperative variables for 546 enrolled subjects who underwent the Norwood procedure were collected prospectively on standardized case report forms, and variation across the centers was described.
Results: Gestational age, birth weight, and proportion with hypoplastic left heart syndrome were similar across sites. In contrast, all recorded variables related to preoperative care varied across centers, including fetal diagnosis (range, 55%-85%), preoperative intubation (range, 29%-91%), and enteral feeding. Perioperative and operative factors were also variable across sites, including median total support time (range, 74-189 minutes) and other perfusion variables, arch reconstruction technique, intraoperative medication use, and use of modified ultrafiltration (range, 48%-100%). Additional variation across centers was seen in variables related to postoperative care, including proportion with an open sternum (range, 35%-100%), median intensive care unit stay (range, 9-44 days), type of feeding at discharge, and enrollment in a home monitoring program (range, 1%-100%; 5 sites did not have a program). Overall, in-hospital death or transplant occurred in 18% (range across sites, 7%-39%).
Conclusions: Perioperative care during the Norwood hospitalization varies across centers. Further analysis evaluating the underlying causes and relationship of this variation to outcome is needed to inform future studies and quality improvement efforts. (J Thorac Cardiovasc Surg 2012; 144: 915-21)
C1 [Pasquali, Sara K.] Duke Univ, Med Ctr, Dept Pediat, Div Cardiol,Duke Clin Res Inst, Durham, NC 27715 USA.
[Ohye, Richard G.] Univ Michigan, Sect Pediat Cardiovasc Surg, Ann Arbor, MI 48109 USA.
[Lu, Minmin; Sleeper, Lynn A.] New England Res Inst, Watertown, MA 02172 USA.
[Kaltman, Jonathan; Pearson, Gail D.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Caldarone, Christopher A.] Toronto Hosp Sick Children, Dept Surg, Toronto, ON, Canada.
[Pizarro, Christian] Alfred I duPont Hosp Children, Nemours Cardiac Ctr, Wilmington, DE USA.
[Dunbar-Masterson, Carolyn; Newburger, Jane] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA.
[Gaynor, J. William] Childrens Hosp Philadelphia, Div Cardiothorac Surg, Philadelphia, PA 19104 USA.
[Jacobs, Jeffrey P.] Congenital Heart Inst Florida, St Petersburg, FL USA.
[Kaza, Aditya K.] Primary Childrens Med Ctr, Div Pediat Cardiothorac Surg, Salt Lake City, UT 84103 USA.
[Scheurer, Mark] Med Univ S Carolina, Div Pediat Cardiol, Charleston, SC 29425 USA.
[Silver, Eric] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA.
[Tabbutt, Sarah] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[Tweddell, James] Childrens Hosp Wisconsin, Div Cardiothorac Surg, Milwaukee, WI 53201 USA.
[Uzark, Karen] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH USA.
[Wells, Winfield] Childrens Hosp Los Angeles, Div Cardiothorac Surg, Los Angeles, CA 90027 USA.
[Mahle, William T.] Emory Univ, Sch Med, Childrens Healthcare Atlanta, Atlanta, GA USA.
RP Pasquali, SK (reprint author), Duke Univ, Med Ctr, Dept Pediat, Div Cardiol,Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA.
EM sara.pasquali@duke.edu
RI gaynor, James william/E-5194-2013
OI gaynor, James william/0000-0001-7955-5604
FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279,
HL068281, HL068285, HL068288, HL068290, HL068292, HL085057,
1K08HL103631-01]; American Heart Association
FX Supported by grants HL068269, HL068270, HL068279, HL068281, HL068285,
HL068288, HL068290, HL068292, and HL085057 from the National Heart,
Lung, and Blood Institute. S. K. P. receives grant support from the
National Heart, Lung, and Blood Institute (1K08HL103631-01) and from the
American Heart Association Mid-Atlantic Affiliate Clinical Research
Program. The contents of this work are solely the responsibility of the
authors and do not necessarily represent the official views of the
National Institutes of Health and National Heart, Lung, and Blood
Institute. ClinicalTrials.gov number, NCT00115934.
NR 20
TC 30
Z9 30
U1 1
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD OCT
PY 2012
VL 144
IS 4
BP 915
EP 921
DI 10.1016/j.jtcvs.2012.05.021
PG 7
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 010RK
UT WOS:000309111600027
PM 22698562
ER
PT J
AU Battisti, AJ
Yoder, JD
Plevka, P
Winkler, DC
Prasad, VM
Kuhn, RJ
Frey, TK
Steven, AC
Rossmann, MG
AF Battisti, Anthony J.
Yoder, Joshua D.
Plevka, Pavel
Winkler, Dennis C.
Prasad, Vidya Mangala
Kuhn, Richard J.
Frey, Teryl K.
Steven, Alasdair C.
Rossmann, Michael G.
TI Cryo-Electron Tomography of Rubella Virus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CAPSID PROTEIN; ELECTRON-MICROSCOPY; SINDBIS VIRUS; NONSTRUCTURAL
POLYPROTEIN; 3-DIMENSIONAL STRUCTURE; GLYCOPROTEIN; SEQUENCE; PARTICLES;
E2; ALPHAVIRUSES
AB Rubella virus is the only member of the Rubivirus genus within the Togaviridae family and is the causative agent of the childhood disease known as rubella or German measles. Here, we report the use of cryo-electron tomography to examine the three-dimensional structure of rubella virions and compare their structure to that of Ross River virus, a togavirus belonging the genus Alphavirus. The ectodomains of the rubella virus glycoproteins, E1 and E2, are shown to be organized into extended rows of density, separated by 9 nm on the viral surface. We also show that the rubella virus nucleocapsid structure often forms a roughly spherical shell which lacks high density at its center. While many rubella virions are approximately spherical and have dimensions similar to that of the icosahedral Ross River virus, the present results indicate that rubella exhibits a large degree of pleo-morphy. In addition, we used rotation function calculations and other analyses to show that approximately spherical rubella virions lack the icosahedral organization which characterizes Ross River and other alphaviruses. The present results indicate that the assembly mechanism of rubella virus, which has previously been shown to differ from that of the alphavirus assembly pathway, leads to an organization of the rubella virus structural proteins that is different from that of alphaviruses.
C1 [Battisti, Anthony J.; Yoder, Joshua D.; Plevka, Pavel; Prasad, Vidya Mangala; Kuhn, Richard J.; Rossmann, Michael G.] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
[Winkler, Dennis C.; Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA.
[Frey, Teryl K.] Georgia State Univ, Dept Biol, Atlanta, GA USA.
RP Rossmann, MG (reprint author), Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
EM mr@purdue.edu
RI Plevka, Pavel/H-8661-2014
OI Plevka, Pavel/0000-0003-4215-3315
FU National Institutes of Health (NIH) [AI095366, AI21389]; NIH/General
Medicine for the Biophysics training grant [T32 GM008296-20]; National
Science Foundation [MCB-1014547]; Intramural Research Program of the
National Institute of Arthritis, Musculoskeletal, and Skin Diseases
FX We acknowledge support provided by National Institutes of Health (NIH)
grants AI095366 to M. G. R. and AI21389 to T. K. F. and by NIH/General
Medicine for the Biophysics training grant T32 GM008296-20 in support of
A.J.B. (C. V. Stauffacher, P. I.). Support to M. G. R. was also provided
by the National Science Foundation (MCB-1014547) for technical
developments. A. C. S. was supported in part by the Intramural Research
Program of the National Institute of Arthritis, Musculoskeletal, and
Skin Diseases.
NR 49
TC 15
Z9 16
U1 0
U2 13
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2012
VL 86
IS 20
BP 11078
EP 11085
DI 10.1128/JVI.01390-12
PG 8
WC Virology
SC Virology
GA 010SR
UT WOS:000309114900015
PM 22855483
ER
PT J
AU Li, YX
O'Dell, S
Wilson, R
Wu, XL
Schmidt, SD
Hogerkorp, CM
Louder, MK
Longo, NS
Poulsen, C
Guenaga, J
Chakrabarti, BK
Doria-Rose, N
Roederer, M
Connors, M
Mascola, JR
Wyatt, RT
AF Li, Yuxing
O'Dell, Sijy
Wilson, Richard
Wu, Xueling
Schmidt, Stephen D.
Hogerkorp, Carl-Magnus
Louder, Mark K.
Longo, Nancy S.
Poulsen, Christian
Guenaga, Javier
Chakrabarti, Bimal K.
Doria-Rose, Nicole
Roederer, Mario
Connors, Mark
Mascola, John R.
Wyatt, Richard T.
TI HIV-1 Neutralizing Antibodies Display Dual Recognition of the Primary
and Coreceptor Binding Sites and Preferential Binding to Fully Cleaved
Envelope Glycoproteins
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODIES; CD4 BINDING;
TYROSINE SULFATION; GP120 GLYCOPROTEIN; CD4-BINDING SITE; B-CELLS;
ENTRY; BROAD; INDIVIDUALS
AB The gp120 CD4 binding site (CD4bs) and coreceptor binding site (CoRbs) are two functionally conserved elements of the HIV-1 envelope glycoproteins (Env). We previously defined the presence of CD4bs-neutralizing antibodies in the serum of an HIV-1-infected individual and subsequently isolated the CD4bs-specific monoclonal antibodies (MAbs) VRC01 and VRC03 from the memory B cell population. Since this donor's serum also appeared to contain neutralizing antibodies to the CoRbs, we employed a differential fluorescence-activated cell sorter (FACS)-based sorting strategy using an Env trimer possessing a CoRbs knockout mutation (I420R) to isolate specific B cells. The MAb VRC06 was recovered from these cells, and its genetic sequence allowed us to identify a clonal relative termed VRC06b, which was isolated from a prior cell sort using a resurfaced core gp120 probe and its cognate CD4bs knockout mutant. VRC06 and VRC06b neutralized 22% and 44% of viruses tested, respectively. Epitope mapping studies revealed that the two MAbs were sensitive to mutations in both the gp120 CoRbs and the CD4bs and could cross-block binding of both CD4bs and CoRbs MAbs to gp120. Fine mapping indicated contacts within the gp120 bridging sheet and the base of the third major variable region (V3), which are elements of the CoRbs. Cell surface binding assays demonstrated preferential recognition of fully cleaved Env trimers over uncleaved trimers. Thus, VRC06 and VRC06b are Env trimer precursor cleavage-sensitive neutralizing MAbs that bind to a region of gp120 that overlaps both the primary and the secondary HIV-1 receptor binding sites.
C1 [Li, Yuxing; Wilson, Richard; Poulsen, Christian; Guenaga, Javier; Chakrabarti, Bimal K.; Wyatt, Richard T.] Scripps Res Inst, IAVI Ctr Neutralizing Antibodies, TSRI, La Jolla, CA 92037 USA.
[Li, Yuxing; O'Dell, Sijy; Wu, Xueling; Schmidt, Stephen D.; Hogerkorp, Carl-Magnus; Louder, Mark K.; Longo, Nancy S.; Roederer, Mario; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Doria-Rose, Nicole; Connors, Mark] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Li, Yuxing; Chakrabarti, Bimal K.; Wyatt, Richard T.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
RP Wyatt, RT (reprint author), Scripps Res Inst, IAVI Ctr Neutralizing Antibodies, TSRI, La Jolla, CA 92037 USA.
EM yuxingli@scripps.edu; wyatt@scripps.edu
RI Schmidt, Stephen/B-5398-2012; Poulsen, Christian/M-4638-2014
FU International AIDS Vaccine Initiative; Vaccine Research Center, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health
FX This study was supported by the International AIDS Vaccine Initiative
and the Intramural Research Program of the Vaccine Research Center,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 54
TC 31
Z9 32
U1 0
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2012
VL 86
IS 20
BP 11231
EP 11241
DI 10.1128/JVI.01543-12
PG 11
WC Virology
SC Virology
GA 010SR
UT WOS:000309114900029
PM 22875963
ER
PT J
AU Schmitz, JE
Ma, ZM
Hagan, EA
Wilks, AB
Furr, KL
Linde, CH
Zahn, RC
Brenchley, JM
Miller, CJ
Permar, SR
AF Schmitz, Joern E.
Ma, Zhong-Min
Hagan, Emily A.
Wilks, Andrew B.
Furr, Kathryn L.
Linde, Caitlyn H.
Zahn, Roland C.
Brenchley, Jason M.
Miller, Christopher J.
Permar, Sallie R.
TI Memory CD4(+) T Lymphocytes in the Gastrointestinal Tract Are a Major
Source of Cell-Associated Simian Immunodeficiency Virus in Chronic
Nonpathogenic Infection of African Green Monkeys
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SOOTY MANGABEYS; SIV INFECTION; NATURAL HOSTS; IMMUNE ACTIVATION;
IN-VIVO; DEPLETION; PATHOGENESIS; RESPONSES; VIREMIA; AIDS
AB Simian immunodeficiency virus (SIV) infection of natural hosts is characterized by nonpathogenic chronic viremia, maintenance of gastrointestinal epithelial barrier integrity, and low numbers of target cells. Assessment of cell-associated virus load in T cell subsets in multiple anatomic compartments of chronically SIV-infected sabeus African green monkeys (AGMs) revealed that gastrointestinal memory CD4(+) T lymphocytes are a major source of cell-associated virus and a significant contributor to SIV viremia in AGMs.
C1 [Permar, Sallie R.] Duke Univ, Med Ctr, Human Vaccine Inst, Durham, NC 27706 USA.
[Schmitz, Joern E.; Hagan, Emily A.; Wilks, Andrew B.; Furr, Kathryn L.; Linde, Caitlyn H.; Zahn, Roland C.] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA.
[Ma, Zhong-Min; Miller, Christopher J.] Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA.
[Ma, Zhong-Min; Miller, Christopher J.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA.
[Brenchley, Jason M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Brenchley, Jason M.] NIAID, Program Barrier Immun & Repair, NIH, Bethesda, MD 20892 USA.
RP Permar, SR (reprint author), Duke Univ, Med Ctr, Human Vaccine Inst, Durham, NC 27706 USA.
EM sallie.permar@duke.edu
FU Center for HIV/AIDS Vaccine Immunology (CHAVI) Early Career NHP
Investigator Award [AI067854]; NIH [K08AI087992, AI065335]
FX This work was supported by the Center for HIV/AIDS Vaccine Immunology
(CHAVI) Early Career NHP Investigator Award (AI067854) (S. R. P.) and
NIH grants K08AI087992 (S. R. P.) and AI065335 (J.E.S.).
NR 28
TC 7
Z9 7
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2012
VL 86
IS 20
BP 11380
EP 11385
DI 10.1128/JVI.01556-12
PG 6
WC Virology
SC Virology
GA 010SR
UT WOS:000309114900043
PM 22896600
ER
PT J
AU Kim, SH
Nayak, S
Paldurai, A
Nayak, B
Samuel, A
Aplogan, GL
Awoume, KA
Webby, RJ
Ducatez, MF
Collins, PL
Samal, SK
AF Kim, Shin-Hee
Nayak, Subhashree
Paldurai, Anandan
Nayak, Baibaswata
Samuel, Arthur
Aplogan, Gilbert L.
Awoume, Kodzo A.
Webby, Richard J.
Ducatez, Mariette F.
Collins, Peter L.
Samal, Siba K.
TI Complete Genome Sequence of a Novel Newcastle Disease Virus Strain
Isolated from a Chicken in West Africa
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID LINEAGE
AB The complete genome sequence of an African Newcastle disease virus (NDV) strain isolated from a chicken in Togo in 2009 was determined. The genome is 15,198 nucleotides (nt) in length and is classified in genotype VII in the class II cluster. Compared to common vaccine strains, the African strain contains a previously described 6-nt insert in the downstream untranslated region of the N gene and a novel 6-nt insert in the HN-L intergenic region. Genome length differences are a marker of the natural history of NDV. This is the first description of a class II NDV strain with a genome of 15,198 nt and a 6-nt insert in the HN-L intergenic region. Sequence divergence relative to vaccine strains was substantial, likely contributes to outbreaks, and illustrates the continued evolution of new NDV strains in West Africa.
C1 [Kim, Shin-Hee; Nayak, Subhashree; Paldurai, Anandan; Nayak, Baibaswata; Samuel, Arthur; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Aplogan, Gilbert L.] LADISERO, Lab Diagnost Vet & Serosurveillance, Parakou, Benin.
[Awoume, Kodzo A.] Lab Vet Lome, Lome, Togo.
[Webby, Richard J.] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA.
[Ducatez, Mariette F.] Ecole Natl Vet Toulouse, INRA, UMR 1225, IHAP, Toulouse, France.
[Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
EM ssamal@umd.edu
RI Nayak, Baibaswata/L-6156-2016
FU NIAID [N01A060009]; NIAID, NIH; National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Department of Health
and Human Services [HHSN266200700005C]; American Lebanese Syrian
Associated Charities (ALSAC)
FX This work was supported by NIAID contract N01A060009 (85% support) and
the NIAID, NIH, Intramural Research Program (15% support). R. J. Webby
and M. F. Ducatez were supported by the National Institute of Allergy
and Infectious Diseases, National Institutes of Health, Department of
Health and Human Services, under contract no. HHSN266200700005C and by
the American Lebanese Syrian Associated Charities (ALSAC).
NR 11
TC 16
Z9 20
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2012
VL 86
IS 20
BP 11394
EP 11395
DI 10.1128/JVI.01922-12
PG 2
WC Virology
SC Virology
GA 010SR
UT WOS:000309114900046
PM 22997417
ER
PT J
AU Liu, H
Qin, J
Shen, Y
AF Liu, Hao
Qin, Jing
Shen, Yu
TI Imputation for semiparametric transformation models with biased-sampling
data
SO LIFETIME DATA ANALYSIS
LA English
DT Article
DE Biased sampling; Estimating equation; Imputation; Transformation models
ID MAXIMUM-LIKELIHOOD-ESTIMATION; PREVALENT COHORT DATA; CENSORED-DATA;
LENGTH-BIAS; NONPARAMETRIC-ESTIMATION; REGRESSION-ANALYSIS;
SURVIVAL-DATA; DENSITY
AB Widely recognized in many fields including economics, engineering, epidemiology, health sciences, technology and wildlife management, length-biased sampling generates biased and right-censored data but often provide the best information available for statistical inference. Different from traditional right-censored data, length-biased data have unique aspects resulting from their sampling procedures. We exploit these unique aspects and propose a general imputation-based estimation method for analyzing length-biased data under a class of flexible semiparametric transformation models. We present new computational algorithms that can jointly estimate the regression coefficients and the baseline function semiparametrically. The imputation-based method under the transformation model provides an unbiased estimator regardless whether the censoring is independent or not on the covariates. We establish large-sample properties using the empirical processes method. Simulation studies show that under small to moderate sample sizes, the proposed procedure has smaller mean square errors than two existing estimation procedures. Finally, we demonstrate the estimation procedure by a real data example.
C1 [Liu, Hao] Baylor Coll Med, Div Biostat, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[Qin, Jing] NIAID, Biostat Res Branch, Natl Inst Hlth Bethesda, Bethesda, MD 20892 USA.
[Shen, Yu] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
RP Liu, H (reprint author), Baylor Coll Med, Div Biostat, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
EM haol@bcm.edu; jingqin@niaid.nih.gov; yshen@mdanderson.org
OI Shen, Yu/0000-0002-3899-7868
FU U.S. NIH [CA079466, CA016672, CA058183]; Seniors' Independence Research
Program, through the National Health Research and Development Program
(NHRDP) of Health Canada Project [6606-3954-MC(S)]; Pfizer Canada
Incorporated through the Medical Research Council/Pharmaceutical
Manufacturers Association of Canada [6603-1417-302(R)]; Bayer
Incorporated; British Columbia Health Research Foundation [38 (93-2), 34
(96-1)]
FX The work was supported in part by the U.S. NIH grants CA079466, CA016672
and CA058183. The authors thank one referee for his/her constructive
comments. The authors also thank Professor Asgharian and the
investigators from the Canadian Study of Health and Aging for generously
sharing the dementia data. The data reported in this article were
collected as part of the Canadian Study of Health and Aging. The core
study was funded by the Seniors' Independence Research Program, through
the National Health Research and Development Program (NHRDP) of Health
Canada Project 6606-3954-MC(S). Additional funding was provided by
Pfizer Canada Incorporated through the Medical Research
Council/Pharmaceutical Manufacturers Association of Canada Health
Activity Program, NHRDP Project 6603-1417-302(R), Bayer Incorporated,
and the British Columbia Health Research Foundation Projects 38 (93-2)
and 34 (96-1). The study was coordinated through the University of
Ottawa and the Division of Aging and Seniors, Health Canada.
NR 47
TC 1
Z9 1
U1 0
U2 9
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1380-7870
J9 LIFETIME DATA ANAL
JI Lifetime Data Anal.
PD OCT
PY 2012
VL 18
IS 4
BP 470
EP 503
DI 10.1007/s10985-012-9225-5
PG 34
WC Mathematics, Interdisciplinary Applications; Statistics & Probability
SC Mathematics
GA 004CD
UT WOS:000308656800005
PM 22903245
ER
PT J
AU Todd, JR
King, JW
Oberle, A
Matsumoto, T
Odaka, Y
Fowler, M
Pore, RS
Shahan, TA
Yin, LJ
Sanusi, ID
AF Todd, John R.
King, John W.
Oberle, Arnold
Matsumoto, Tadahiko
Odaka, Yoshinobu
Fowler, Marjorie
Pore, R. Scott
Shahan, Tracy Allan
Yin, Lijia
Sanusi, Irwan D.
TI Protothecosis: report of a case with 20-year follow-up, and review of
previously published cases
SO MEDICAL MYCOLOGY
LA English
DT Review
DE Prototheca; protothecosis; review; treatment; azoles; amphotericin-B;
immunosuppression; immunocompetent; infection
ID AMBULATORY PERITONEAL-DIALYSIS; CUTANEOUS-PROTOTHECOSIS; OLECRANON
BURSITIS; GENUS PROTOTHECA; AMPHOTERICIN-B; IMMUNOCOMPROMISED HOST;
WICKERHAMII ALGAEMIA; ANTIFUNGAL THERAPY; ALGAL INFECTION; ACHLORIC
ALGAE
AB We present a Prototheca wickerhamii wound infection case that failed treatment with ketoconazole but was cured with amphotericin-B plus tetracycline. The patient was immunocompetent but had had local steroid injections. We reviewed another 159 cases from the literature. Prototheca has infected many areas of the human body, but most often skin, olecranon bursa, or wounds. Prior treatment with steroids and immune deficiencies are contributing factors. Itraconazole and fluconazole are reasonable initial treatments for patients with mild infections. For serious infections, or for infections that have failed azole treatment, amphotericin-B is the treatment of choice.
C1 [Todd, John R.; King, John W.] LSU Hlth Sci Ctr, Infect Dis Sect, Shreveport, LA 71130 USA.
[Oberle, Arnold; Fowler, Marjorie; Sanusi, Irwan D.] LSU Hlth Sci Ctr, Dept Pathol, Shreveport, LA 71130 USA.
[Odaka, Yoshinobu] LSU Hlth Sci Ctr, Dept Biochem & Mol Biol, Shreveport, LA 71130 USA.
[Matsumoto, Tadahiko] Yamada Inst Hlth & Med, Dept Dermatol, Tokyo, Japan.
[Pore, R. Scott] W Virginia Univ, Dept Microbiol & Immunol, Morgantown, WV 26506 USA.
[Shahan, Tracy Allan] NIAID, NIH, Bethesda, MD 20892 USA.
[Yin, Lijia] Sierra Pathol Lab, Mol Diagnost Div, Clovis, CA USA.
RP Todd, JR (reprint author), LSU Hlth Sci Ctr, Infect Dis Sect, 1501 Kings Highway, Shreveport, LA 71130 USA.
EM jtodd@lsuhsc.edu
NR 207
TC 20
Z9 25
U1 0
U2 18
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1369-3786
EI 1460-2709
J9 MED MYCOL
JI Med. Mycol.
PD OCT
PY 2012
VL 50
IS 7
BP 673
EP 689
DI 10.3109/13693786.2012.677862
PG 17
WC Infectious Diseases; Mycology; Veterinary Sciences
SC Infectious Diseases; Mycology; Veterinary Sciences
GA 008HV
UT WOS:000308948900001
PM 22571772
ER
PT J
AU Gawrisch, K
AF Gawrisch, Klaus
TI Tafazzin senses curvature
SO NATURE CHEMICAL BIOLOGY
LA English
DT News Item
ID BARTH-SYNDROME; CARDIOLIPIN; DEFICIENCY
C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.
RP Gawrisch, K (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.
EM gawrisch@helix.nih.gov
FU Intramural NIH HHS [Z01 AA000003-15]
NR 10
TC 5
Z9 5
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD OCT
PY 2012
VL 8
IS 10
BP 811
EP 812
DI 10.1038/nchembio.1068
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 009WN
UT WOS:000309056200003
PM 22987008
ER
PT J
AU You, CJ
Dai, XX
Yuan, BF
Wang, J
Wang, JS
Brooks, PJ
Niedernhofer, LJ
Wang, YS
AF You, Changjun
Dai, Xiaoxia
Yuan, Bifeng
Wang, Jin
Wang, Jianshuang
Brooks, Philip J.
Niedernhofer, Laura J.
Wang, Yinsheng
TI A quantitative assay for assessing the effects of DNA lesions on
transcription
SO NATURE CHEMICAL BIOLOGY
LA English
DT Article
ID NUCLEOTIDE EXCISION-REPAIR; ESCHERICHIA-COLI; MAMMALIAN-CELLS;
RNA-POLYMERASE; IN-VIVO; TRANSLESION SYNTHESIS; MUTAGENESIS CAUSES;
BYPASS; DAMAGE; 8,5'-CYCLOPURINE-2'-DEOXYNUCLEOSIDES
AB Most mammalian cells in nature are quiescent but actively transcribing mRNA for normal physiological processes; thus, it is important to investigate how endogenous and exogenous DNA damage compromises transcription in cells. Here we describe a new competitive transcription and adduct bypass (CTAB) assay to determine the effects of DNA lesions on the fidelity and efficiency of transcription. Using this strategy, we demonstrate that the oxidatively induced lesions 8,5'-cyclo-2'-deoxyadenosine (cdA) and 8,5'-cyclo-2'-deoxyguanosine (cdG) and the methylglyoxal-induced lesion N-2-(1-carboxyethyl)-2'-deoxyguanosine (N-2-CEdG) strongly inhibited transcription in vitro and in mammalian cells. In addition, cdA and cdG, but not N-2-CEdG, induced transcriptional mutagenesis in vitro and in vivo. Furthermore, when located on the template DNA strand, all examined lesions were primarily repaired by transcription-coupled nucleotide excision repair in mammalian cells. This newly developed CTAB assay should be generally applicable for quantitatively assessing how other DNA lesions affect DNA transcription in vitro and in cells.
C1 [You, Changjun; Dai, Xiaoxia; Yuan, Bifeng; Wang, Jin; Wang, Jianshuang; Wang, Yinsheng] Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA.
[Brooks, Philip J.] NIAAA, Lab Neurogenet, Rockville, MD 20852 USA.
[Niedernhofer, Laura J.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA USA.
RP You, CJ (reprint author), Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA.
EM Yinsheng.Wang@ucr.edu
RI Yuan, Bi-Feng/K-5803-2013
OI Yuan, Bi-Feng/0000-0001-5223-4659
FU NCI NIH HHS [R01 CA101864]; NIDDK NIH HHS [R01 DK082779]; NIEHS NIH HHS
[R01 ES016114, R01 ES019873]
NR 47
TC 34
Z9 34
U1 1
U2 19
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD OCT
PY 2012
VL 8
IS 10
BP 817
EP 822
DI 10.1038/NCHEMBIO.1046
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 009WN
UT WOS:000309056200006
PM 22902614
ER
PT J
AU Anastasiou, D
Yu, YM
Israelsen, WJ
Jiang, JK
Boxer, MB
Hong, BS
Tempel, W
Dimov, S
Shen, M
Jha, A
Yang, H
Mattaini, KR
Metallo, CM
Fiske, BP
Courtney, KD
Malstrom, S
Khan, TM
Kung, C
Skoumbourdis, AP
Veith, H
Southall, N
Walsh, MJ
Brimacombe, KR
Leister, W
Lunt, SY
Johnson, ZR
Yen, KE
Kunii, K
Davidson, SM
Christofk, HR
Austin, CP
Inglese, J
Harris, MH
Asara, JM
Stephanopoulos, G
Salituro, FG
Jin, SF
Dang, L
Auld, DS
Park, HW
Cantley, LC
Thomas, CJ
Heiden, MGV
AF Anastasiou, Dimitrios
Yu, Yimin
Israelsen, William J.
Jiang, Jian-Kang
Boxer, Matthew B.
Hong, Bum Soo
Tempel, Wolfram
Dimov, Svetoslav
Shen, Min
Jha, Abhishek
Yang, Hua
Mattaini, Katherine R.
Metallo, Christian M.
Fiske, Brian P.
Courtney, Kevin D.
Malstrom, Scott
Khan, Tahsin M.
Kung, Charles
Skoumbourdis, Amanda P.
Veith, Henrike
Southall, Noel
Walsh, Martin J.
Brimacombe, Kyle R.
Leister, William
Lunt, Sophia Y.
Johnson, Zachary R.
Yen, Katharine E.
Kunii, Kaiko
Davidson, Shawn M.
Christofk, Heather R.
Austin, Christopher P.
Inglese, James
Harris, Marian H.
Asara, John M.
Stephanopoulos, Gregory
Salituro, Francesco G.
Jin, Shengfang
Dang, Lenny
Auld, Douglas S.
Park, Hee-Won
Cantley, Lewis C.
Thomas, Craig J.
Heiden, Matthew G. Vander
TI Pyruvate kinase M2 activators promote tetramer formation and suppress
tumorigenesis
SO NATURE CHEMICAL BIOLOGY
LA English
DT Article
ID CANCER-CELL METABOLISM; TUMOR-GROWTH; NUCLEAR TRANSLOCATION;
THYROID-HORMONE; BINDING PROTEIN; ISOFORM; FRUCTOSE-1,6-BISPHOSPHATE;
ISOZYME; INHIBITION; CONVERSION
AB Cancer cells engage in a metabolic program to enhance biosynthesis and support cell proliferation. The regulatory properties of pyruvate kinase M2 (PKM2) influence altered glucose metabolism in cancer. The interaction of PKM2 with phosphotyrosine-containing proteins inhibits enzyme activity and increases the availability of glycolytic metabolites to support cell proliferation. This suggests that high pyruvate kinase activity may suppress tumor growth. We show that expression of PKM1, the pyruvate kinase isoform with high constitutive activity, or exposure to published small-molecule PKM2 activators inhibits the growth of xenograft tumors. Structural studies reveal that small-molecule activators bind PKM2 at the subunit interaction interface, a site that is distinct from that of the endogenous activator fructose-1,6-bisphosphate (FBP). However, unlike FBP, binding of activators to PKM2 promotes a constitutively active enzyme state that is resistant to inhibition by tyrosine-phosphorylated proteins. These data support the notion that small-molecule activation of PKM2 can interfere with anabolic metabolism.
C1 [Anastasiou, Dimitrios; Courtney, Kevin D.; Christofk, Heather R.; Asara, John M.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Dept Med, Div Signal Transduct, Boston, MA 02215 USA.
[Anastasiou, Dimitrios; Courtney, Kevin D.; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA.
[Yu, Yimin; Israelsen, William J.; Mattaini, Katherine R.; Fiske, Brian P.; Malstrom, Scott; Khan, Tahsin M.; Lunt, Sophia Y.; Johnson, Zachary R.; Davidson, Shawn M.; Heiden, Matthew G. Vander] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Jiang, Jian-Kang; Boxer, Matthew B.; Shen, Min; Skoumbourdis, Amanda P.; Veith, Henrike; Southall, Noel; Walsh, Martin J.; Brimacombe, Kyle R.; Leister, William; Austin, Christopher P.; Inglese, James; Auld, Douglas S.; Thomas, Craig J.] Natl Ctr Adv Translat Sci, NIH, Chem Genom Ctr, Bethesda, MD USA.
[Hong, Bum Soo; Tempel, Wolfram; Dimov, Svetoslav; Park, Hee-Won] Univ Toronto, Struct Genom Consortium, Toronto, ON, Canada.
[Jha, Abhishek; Stephanopoulos, Gregory] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[Yang, Hua; Kung, Charles; Yen, Katharine E.; Kunii, Kaiko; Salituro, Francesco G.; Jin, Shengfang; Dang, Lenny] Agios Pharmaceut, Cambridge, MA USA.
[Metallo, Christian M.] Univ Calif San Diego, Dept Bioengn, San Diego, CA 92103 USA.
[Courtney, Kevin D.; Heiden, Matthew G. Vander] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Harris, Marian H.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Asara, John M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Park, Hee-Won] Univ Toronto, Dept Pharmacol, Toronto, ON, Canada.
RP Anastasiou, D (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Signal Transduct, Boston, MA 02215 USA.
EM mvh@mit.edu
RI Cantley, Lewis/D-1800-2014; Southall, Noel/H-8991-2012;
OI Cantley, Lewis/0000-0002-1298-7653; Southall, Noel/0000-0003-4500-880X;
Lunt, Sophia/0000-0003-4522-6065
FU Canadian Institutes of Health Research; Howard Hughes Medical Institute;
Intramural NIH HHS; NCI NIH HHS [5P01CA120964, 5P30CA006516,
5P30CA1405141, P01 CA120964, P30 CA006516]; NIGMS NIH HHS [R01 GM056203,
R01 GM56203, T32 GM007287]; NIMH NIH HHS [R03 MH085679, R03MH085679];
Wellcome Trust
NR 43
TC 177
Z9 180
U1 5
U2 59
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
EI 1552-4469
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD OCT
PY 2012
VL 8
IS 10
BP 839
EP 847
DI 10.1038/NCHEMBIO.1060
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 009WN
UT WOS:000309056200009
PM 22922757
ER
PT J
AU Germain, RN
AF Germain, Ronald N.
TI Maintaining system homeostasis: the third law of Newtonian immunology
SO NATURE IMMUNOLOGY
LA English
DT Article
ID REGULATORY T-CELLS; ADAPTIVE IMMUNE-SYSTEM; NETWORK MOTIFS; REACTIVE
OXYGEN; INNATE IMMUNITY; TGF-BETA; TOLERANCE; EFFECTOR; AUTOIMMUNITY;
RESPONSES
AB Because of the potent effector mechanisms of the immune system, the potential for self-destructive immune responses is especially high and many negative regulatory modalities exist to prevent excessive tissue damage. This Commentary places such regulatory mechanisms in the larger context of system organization on many scales. The sometimes counterintuitive nature of feedback control is discussed and a case is made for greater attention to quantitative spatiotemporal aspects of regulation, rather than limiting the discussion to the qualitative descriptions of pathways that dominate at present.
C1 NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rgermain@nih.gov
FU Intramural NIH HHS [ZIA AI000403-29, ZIA AI000545-24, ZIA AI000758-15]
NR 50
TC 34
Z9 34
U1 1
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD OCT
PY 2012
VL 13
IS 10
BP 902
EP 906
PG 5
WC Immunology
SC Immunology
GA 009PV
UT WOS:000309038600002
PM 22990887
ER
PT J
AU Goldszmid, RS
Trinchieri, G
AF Goldszmid, Romina S.
Trinchieri, Giorgio
TI The price of immunity
SO NATURE IMMUNOLOGY
LA English
DT Review
ID INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; T-CELL RESPONSES;
DENDRITIC CELLS; TOXOPLASMA-GONDII; INTERFERON-GAMMA; HIV-INFECTION;
MICROBIAL TRANSLOCATION; INTESTINAL MICROBIOTA; VIRUS-INFECTION
AB Resistance mechanisms of the innate and adaptive immune responses prevent the colonization of foreign organisms in unwanted anatomical sites and participate in tissue repair and restoration of homeostasis after damage induced either by the invasion of pathogenic microbes or by the organism's response to them. The intensity of the response is controlled and limited by positive and negative feedback circuits that aim at preventing collateral tissue damage. In this Review we will discuss the protective and pathogenic effects of host-commensal microbiota mutualism on the immune response and illustrate some examples of collateral tissue and systemic damage caused by immunity to pathogens.
C1 [Goldszmid, Romina S.; Trinchieri, Giorgio] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res,US Natl Inst Hlth, Frederick, MD 21701 USA.
RP Trinchieri, G (reprint author), NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res,US Natl Inst Hlth, Frederick, MD 21701 USA.
EM trinchig@mail.nih.gov
NR 117
TC 48
Z9 50
U1 3
U2 47
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
EI 1529-2916
J9 NAT IMMUNOL
JI Nat. Immunol.
PD OCT
PY 2012
VL 13
IS 10
BP 932
EP 938
DI 10.1038/ni.2422
PG 7
WC Immunology
SC Immunology
GA 009PV
UT WOS:000309038600006
PM 22990891
ER
PT J
AU Gattinoni, L
Klebanoff, CA
Restifo, NP
AF Gattinoni, Luca
Klebanoff, Christopher A.
Restifo, Nicholas P.
TI Paths to stemness: building the ultimate antitumour T cell
SO NATURE REVIEWS CANCER
LA English
DT Review
ID TUMOR-INFILTRATING LYMPHOCYTES; ADAPTIVE IMMUNE-RESPONSES; CHRONIC
VIRAL-INFECTION; HUMAN PERIPHERAL-BLOOD; GRAFT-VERSUS-LEUKEMIA;
SELF-RENEWAL; BETA-CATENIN; TRANSCRIPTION-FACTOR; CENTRAL MEMORY;
IN-VITRO
AB Stem cells are defined by the ability to self-renew and to generate differentiated progeny, qualities that are maintained by evolutionarily conserved pathways that can lead to cancer when deregulated. There is now evidence that these stem cell-like attributes and signalling pathways are also shared among subsets of mature memory T lymphocytes. We discuss how using stem cell-like T cells can overcome the limitations of current adoptive T cell therapies, including inefficient T cell engraftment, persistence and ability to mediate prolonged immune attack. Conferring stemness to antitumour T cells might unleash the full potential of cellular therapies.
C1 [Gattinoni, Luca; Klebanoff, Christopher A.; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Gattinoni, L (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM gattinol@mail.nih.gov; restifo@nih.gov
RI Gattinoni, Luca/A-2281-2008; Restifo, Nicholas/A-5713-2008;
OI Gattinoni, Luca/0000-0003-2239-3282; Restifo, Nicholas
P./0000-0003-4229-4580
FU National Institutes of Health, Center for Regenerative Medicine
(NIH-CRM); Center for Cancer Research (CCR) by the US National Cancer
Institute (Bethesda, Maryland)
FX This work was supported by the National Institutes of Health, Center for
Regenerative Medicine (NIH-CRM) and by the Center for Cancer Research
(CCR) by the US National Cancer Institute (Bethesda, Maryland). The
authors would like to thank M. Rao for helpful discussions about
regenerative medicine. M. Bachinski copyedited the manuscript during
construction. J. Crompton, R. Roychoudhuri, P. Muranski, D. Palmer, Y.
Ji, M. Sukumar, J. Pan, A. Leonardi, Z. Franco, Z. Yu and D. Clever
provided a lively sounding board for concepts presented here. J. C.
Yang, U. S. Kammula, R. A. Morgan, S. A. Feldman, P. F. Robbins, R. M.
Sherry, M. Parkhurst, M. Hughes and G. Phan made many valuable
suggestions regarding the clinical translation of the work described.
The authors would especially like to thank our longtime stalwart ally in
all of these efforts S. A. Rosenberg.
NR 197
TC 141
Z9 141
U1 4
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-175X
EI 1474-1768
J9 NAT REV CANCER
JI Nat. Rev. Cancer
PD OCT
PY 2012
VL 12
IS 10
BP 671
EP 684
DI 10.1038/nrc3322
PG 14
WC Oncology
SC Oncology
GA 012SP
UT WOS:000309257200012
PM 22996603
ER
PT J
AU Schiller, JT
Lowy, DR
AF Schiller, John T.
Lowy, Douglas R.
TI Understanding and learning from the success of prophylactic human
papillomavirus vaccines
SO NATURE REVIEWS MICROBIOLOGY
LA English
DT Review
ID VIRUS-LIKE PARTICLES; (HPV)-16/18 AS04-ADJUVANTED VACCINE; COTTONTAIL
RABBIT PAPILLOMAVIRUS; QUADRIVALENT HPV VACCINE; AGED 18-45 YEARS;
CERVICAL-CANCER; YOUNG-WOMEN; L1 PROTEIN; IN-VIVO; INTRAEPITHELIAL
NEOPLASIA
AB An estimated 5% of human cancers are caused by human papillomavirus (HPV) infections, and most of these cancers are of the cervix. Two prophylactic HPV vaccines that target the two most oncogenic virus types, HPV16 and HPV18, are now commercially available. In controlled clinical trials, the vaccines proved to be effective at preventing incident anogenital infection and the associated neoplastic disease that is induced by these virus types. Here, we highlight the specific aspects of HPV biology and vaccine composition that are likely to contribute to the efficacy of these vaccines, and we discuss how these particular features might or might not be relevant for the development of effective vaccines against other sexually transmitted viruses such as HIV and herpes simplex virus (HSV).
C1 [Schiller, John T.; Lowy, Douglas R.] NCI, NIH, Bethesda, MD 20892 USA.
RP Schiller, JT (reprint author), NCI, NIH, Bldg 37,Room 4106, Bethesda, MD 20892 USA.
EM schillej@dc37a.nci.nih.gov
FU Intramural Research Program, Center for Cancer Research, National Cancer
Institute, US National Institutes of Health
FX The authors' research was supported by the Intramural Research Program,
Center for Cancer Research, National Cancer Institute, US National
Institutes of Health.
NR 102
TC 61
Z9 64
U1 0
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1740-1526
J9 NAT REV MICROBIOL
JI Nat. Rev. Microbiol.
PD OCT
PY 2012
VL 10
IS 10
BP 681
EP 692
DI 10.1038/nrmicro2872
PG 12
WC Microbiology
SC Microbiology
GA 009XE
UT WOS:000309057900011
PM 22961341
ER
PT J
AU Sun, MY
Peipert, JF
Zhao, QH
Wilson, TE
Weber, KM
Sanchez-Keeland, L
D'Souza, G
Young, M
Watts, DH
Keller, MJ
Cohan, D
Massad, LS
AF Sun, Mengyang
Peipert, Jeffrey F.
Zhao, Qiuhong
Wilson, Tracey E.
Weber, Kathleen M.
Sanchez-Keeland, Lorraine
D'Souza, Gypsyamber
Young, Mary
Watts, D. Heather
Keller, Marla J.
Cohan, Deborah
Massad, L. Stewart
TI Trends in Contraceptive Use Among Women With Human Immunodeficiency
Virus
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID ACTING REVERSIBLE CONTRACEPTION; INTERAGENCY HIV; ANTIRETROVIRAL
THERAPY; INTRAUTERINE-DEVICES; HIV-1-INFECTED WOMEN; PREGNANCY;
PREDICTORS; INFECTION; CHOICE; COHORT
AB OBJECTIVE: To estimate trends in contraceptive use, especially long-acting reversible contraceptives (LARCs) and condoms, among human immunodeficiency virus (HIV)-seropositive and HIV-seronegative women.
METHODS: Human immunodeficiency virus-seropositive and HIV-seronegative women in a multicenter longitudinal cohort were interviewed semiannually between 1998 and 2010 about sexual behaviors and contraceptive use. Trends in contraceptive use by women aged 18-45 years who were at risk for unintended pregnancy but not trying to conceive were analyzed using generalized estimating equations.
RESULTS: Condoms were the dominant form of contraception for HIV-seropositive women and showed little change across time. Less than 15% of these women used no contraception. Between 1998 and 2010, LARC use increased among HIV-seronegative women from 4.8% (6 of 126) to 13.5% (19 of 141, P=.02), but not significantly among seropositive women (0.9% [4 of 438] to 2.8% [6 of 213], P=.09). Use of highly effective contraceptives, including pills, patches, rings, injectable progestin, implants, and intrauterine devices, ranged from 15.2% (53 of 348) in 1998 to 17.4% (37 of 213) in 2010 (P=.55). Human immunodeficiency virus-seronegative but not HIV-seropositive LARC users were less likely than nonusers to use condoms consistently (hazard ratio 0.51, 95% confidence interval [CI] 0.32-0.81, P=.004 for seronegative women; hazard ratio 1.09, 95% CI 0.96-1.23 for seropositive women).
CONCLUSION: Although most HIV-seropositive women use contraception, they rely primarily on condoms and have not experienced the increase in LARC use seen among seronegative women. Strategies to improve simultaneous use of condoms and LARC are needed to minimize risk of unintended pregnancy as well as HIV transmission and acquisition of sexually transmitted infections. (Obstet Gynecol 2012; 120: 783-90) DOI:http://10.1097/AOG.0b013e318269c8bb
C1 [Massad, L. Stewart] Washington Univ, Sch Med, Div Gynecol, St Louis, MO 63110 USA.
Suny Downstate Med Ctr, Sch Publ Hlth, Brooklyn, NY 11203 USA.
Univ So Calif, PA C, Los Angeles, CA USA.
John H Stroger Hosp Cook Cty, Hektoen Inst Med, Chicago, IL USA.
John H Stroger Hosp Cook Cty, CORE Ctr, Chicago, IL USA.
Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
Georgetown Univ, Washington, DC USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
Albert Einstein Coll Med, Bronx, NY USA.
RP Massad, LS (reprint author), Washington Univ, Sch Med, Div Gynecol, Campus Box 8064, St Louis, MO 63110 USA.
EM massadl@wudosis.wustl.edu
FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004,
UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590];
Eunice Kennedy Shriver National Institute of Child Health and Human
Development [UO1-HD-32632]; National Cancer Institute; National
Institute on Drug Abuse; National Institute on Deafness and Other
Communication Disorders; National Center for Research Resources [UL1
RR024131]
FX The Women's Interagency HIV Study is funded by the National Institute of
Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834,
UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (UO1-HD-32632). The study is co-funded by the National
Cancer Institute, the National Institute on Drug Abuse, and the National
Institute on Deafness and Other Communication Disorders. Funding is also
provided by the National Center for Research Resources (UCSF-CTSI grant
UL1 RR024131). The contents of this publication are solely the
responsibility of the authors and do not necessarily represent the
official views of the National Institutes of Health.
NR 31
TC 11
Z9 11
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD OCT
PY 2012
VL 120
IS 4
BP 783
EP 790
DI 10.1097/AOG.0b013e318269c8bb
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 012FN
UT WOS:000309221200008
PM 22996095
ER
PT J
AU Massad, LS
D'Souza, G
Tian, F
Minkoff, H
Cohen, M
Wright, RL
Colie, C
Hessol, NA
AF Massad, L. Stewart
D'Souza, Gypsyamber
Tian, Fang
Minkoff, Howard
Cohen, Mardge
Wright, Rodney L.
Colie, Christine
Hessol, Nancy A.
TI Negative Predictive Value of Pap Testing Implications for Screening
Intervals for Women With Human Immunodeficiency Virus
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID 2006 CONSENSUS GUIDELINES; CERVICAL-CANCER; INTERAGENCY HIV; PREVENTION;
RISK; MANAGEMENT; SOCIETY; LESIONS
AB OBJECTIVE: To estimate the accuracy of Pap testing for women who are human immunodeficiency virus (HIV)-seropositive, with a focus on negative predictive value.
METHODS: Participants in the Women's Interagency HIV Study were monitored with conventional Pap tests every 6 months. After excluding those with abnormal Pap test results before study, cervical disease, or hysterectomy, women with negative enrollment Pap test results were monitored for development of precancer within 15 or 39 months, defined as a Pap test result read as high-grade squamous intraepithelial lesion, atypical glandular cells favor neoplasia, or adenocarcinoma in situ, or a cervical biopsy read as cervical intraepithelial neoplasia 2 or worse. Correlations between one or more consecutive negative Pap test results and subsequent precancer were assessed using Cox proportional hazards models.
RESULTS: Among 942 HIV-infected women with negative baseline Pap test results, eight (1%) developed precancer within 15 months and 40 (4%) within 39 months. After three consecutive negative Pap test results, precancer was rare, with no cases within 15 months and 10 of 539 (2%) within 39 months. No women developed precancer or cancer within 39 months after 10 consecutive negative Pap test results. Risks for precancer within 15 months after negative Pap test result included current smoking (adjusted hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.2-2.0 compared with nonsmokers), younger age (adjusted HR 1.5, 95% CI 1.1-2.1 for women aged younger than 31 years compared with older than 45 years), and lower CD4 count (adjusted HR 11.8, 95% CI 1.3-2.3 for CD4 200-500/microliter, adjusted HR 2.2, 95% CI 1.6-2.9 for CD4 less than 200/microliter, compared with CD4 more than 500/microliter).
CONCLUSION: Annual Pap testing appears safe for women infected with HIV; for those with serial negative tests, longer intervals are appropriate. (Obstet Gynecol 2012; 120: 791-7) DOI:http://10.1097/AOG.0b013e31826a8bbd
C1 [Massad, L. Stewart] Washington Univ, Sch Med, Div Gynecol Oncol, St Louis, MO 63110 USA.
Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
Suny Downstate Med Ctr, Maimonides Med Ctr, Brooklyn, NY 11203 USA.
Albert Einstein Coll Med, Bronx, NY 10467 USA.
Rush Med Coll, Chicago, IL 60612 USA.
Cook Cty Bur Hlth Serv, Chicago, IL USA.
Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
Georgetown Univ, Sch Med, Washington, DC USA.
RP Massad, LS (reprint author), Washington Univ, Sch Med, Div Gynecol Oncol, 4911 Barnes Jewish Hosp Plaza, St Louis, MO 63110 USA.
EM massadl@wudosis.wustl.edu
FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004,
UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590];
Eunice Kennedy Shriver National Institute of Child Health and Human
Development [UO1-HD-32632]; National Cancer Institute, the National
Institute on Drug Abuse, and the National Institute on Deafness and
Other Communication Disorders; National Center for Research Resources
[UL1 RR024131]
FX The WIHS is funded by the National Institute of Allergy and Infectious
Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989,
UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (UO1-HD-32632).
The study is co-funded by the National Cancer Institute, the National
Institute on Drug Abuse, and the National Institute on Deafness and
Other Communication Disorders. Funding is also provided by the National
Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). The
contents of this publication are solely the responsibility of the
authors and do not necessarily represent the official views of the
National Institutes of Health.
NR 15
TC 5
Z9 5
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD OCT
PY 2012
VL 120
IS 4
BP 791
EP 797
DI 10.1097/AOG.0b013e31826a8bbd
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 012FN
UT WOS:000309221200009
PM 22996096
ER
PT J
AU Myatt, L
Clifton, RG
Roberts, JM
Spong, CY
Hauth, JC
Varner, MW
Wapner, RJ
Thorp, JM
Mercer, BM
Grobman, WA
Ramin, SM
Carpenter, MW
Samuels, P
Sciscione, A
Harper, M
Tolosa, JE
Saade, G
Sorokin, Y
Anderson, GD
AF Myatt, Leslie
Clifton, Rebecca G.
Roberts, James M.
Spong, Catherine Y.
Hauth, John C.
Varner, Michael W.
Wapner, Ronald J.
Thorp, John M., Jr.
Mercer, Brian M.
Grobman, William A.
Ramin, Susan M.
Carpenter, Marshall W.
Samuels, Philip
Sciscione, Anthony
Harper, Margaret
Tolosa, Jorge E.
Saade, George
Sorokin, Yoram
Anderson, Garland D.
CA Eunice Kennedy Shriver Natl Ins
Maternal-Fetal Med Units Network M
TI The Utility of Uterine Artery Doppler Velocimetry in Prediction of
Preeclampsia in a Low-Risk Population
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID UTEROPLACENTAL BLOOD-FLOW; FETAL GROWTH RESTRICTION; WOMEN;
METAANALYSIS; HYPERTENSION; GESTATION; MARKERS; DISEASE
AB OBJECTIVE: The underlying pathophysiology of pre-eclampsia is thought to be abnormal trophoblast invasion of the spiral arteries leading to maldevelopment of uteroplacental perfusion. We estimated whether uterine artery Doppler measurements made in the early second trimester would predict the subsequent development of preeclampsia.
METHODS: Uterine artery Doppler measurements before 21 weeks of gestation (median 16.6 weeks) were correlated with subsequent development of preeclampsia in a cohort of 2,188 low-risk nulliparous women in a randomized control trial of antioxidant supplementation for prevention of preeclampsia. Preeclampsia developed in 165 (7.5%) women.
RESULTS: Development of preeclampsia overall was associated with increased resistance index, pulsatility index, a pulsatility index or resistance index multiple of the median at or above the 75th percentile but not the presence of a notch or a bilateral notch before 21 weeks of gestation. The sensitivity was 43% (95% confidence interval [CI] 35-51) and specificity 67% (95% CI 65-69) for prediction of preeclampsia overall. The presence of a notch or bilateral notch, resistance index, and pulsatility index multiple of the median was significantly associated with early onset (before 34 weeks of gestation) compared with late onset or no preeclampsia (odds ratio [OR] 6.9, 95% CI 2.3-20.9; sensitivity 78%, 95% CI 52-94; specificity 66%, 95% CI 64-68). The presence of a notch or resistance index multiple of the median at or above the 75th percentile increased the odds of developing severe compared with mild or no preeclampsia (OR 2.2, 95% CI 1.4-3.7; sensitivity 53%, 95% CI 40-65; specificity 66%, 95% CI 64-68).
CONCLUSION: Our data show poor sensitivity of second-trimester Doppler ultrasound measurements for prediction of preeclampsia overall in a well-characterized, low-risk, nulliparous population. The technique has utility in identifying poor trophoblast invasion of spiral arteries of a magnitude that severely compromises utero-placental blood flow and gives early-onset disease. (Obstet Gynecol 2012; 120: 815-22) DOI:http://10.1097/AOG.0b013e31826af7fb
C1 Univ Cincinnati, Dept Obstet, Cincinnati, OH USA.
Univ Cincinnati, Dept Gynecol, Cincinnati, OH USA.
Univ Pittsburgh, Pittsburgh, PA USA.
Univ Alabama Birmingham, Birmingham, AL USA.
Univ Utah, Salt Lake City, UT USA.
Columbia Univ, New York, NY USA.
Univ N Carolina, Chapel Hill, NC USA.
Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA.
Northwestern Univ, Chicago, IL 60611 USA.
Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
Brown Univ, Providence, RI 02912 USA.
Ohio State Univ, Columbus, OH 43210 USA.
Drexel Univ, Philadelphia, PA 19104 USA.
Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
Univ Texas Med Branch, Galveston, TX USA.
Wayne State Univ, Detroit, MI USA.
George Washington Univ, Biostat Ctr, Washington, DC USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Myatt, L (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Mail Code 7836,7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM Myattl@uthscsa.edu
RI Samuels, Philip/E-4011-2011; Varner, Michael/K-9890-2013
OI Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [HD34208, HD27869, HD40485, HD40560, HD40544,
HD34116, HD40512, HD21410, HD40545, HD40500, HD27915, HD34136, HD27860,
HD53118, HD53097, HD27917, HD36801]; National Heart, Lung, and Blood
Institute; National Center for Research Resources [M01 RR00080, UL1
RR024153, UL1 RR024989]
FX The project described was supported by grants from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development (NICHD)
(HD34208, HD27869, HD40485, HD40560, HD40544, HD34116, HD40512, HD21410,
HD40545, HD40500, HD27915, HD34136, HD27860, HD53118, HD53097, HD27917,
and HD36801); the National Heart, Lung, and Blood Institute; and the
National Center for Research Resources (M01 RR00080, UL1 RR024153, UL1
RR024989) and its contents do not necessarily represent the official
view of NICHD, National Heart, Lung and Blood Institute, National Center
for Research Resources, or the National Institutes of Health.
NR 21
TC 25
Z9 28
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD OCT
PY 2012
VL 120
IS 4
BP 815
EP 822
DI 10.1097/AOG.0b013e31826af7fb
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 012FN
UT WOS:000309221200013
PM 22996099
ER
PT J
AU Brown, J
Blank, K
AF Brown, Jill
Blank, Ken
TI Minimally Invasive Endometrial Ablation Device Complications and Use
Outside of the Manufacturers' Instructions
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID ROLLERBALL ELECTROABLATION; MENORRHAGIA; SAFETY; TRIAL
AB OBJECTIVE: To review the U. S. Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience database for reports describing serious adverse events and adverse events reports describing use outside of the manufacturers' labeled instructions for the five FDA-approved minimally invasive endometrial ablation devices.
METHODS: We queried the Manufacturer and User Facility Device Experience database for reports of device malfunction, patient injury, or death reported for each device from January 1, 2005 to December 31, 2011. We reviewed U. S. reports individually for annotations of patient injury or death and tabulated the reports by type of injury and device. We identified nine categories of serious injury (death, sepsis or bacteremia, intra-abdominal abscess, uterine rupture, thermal bowel injury, mechanical bowel injury, transmural uterine thermal injury, urologic injury, and lower genital tract or skin burns) and noted all reports citing device use outside of the manufacturers' labeled instructions. We also identified reports of hysterectomy or bowel resection attributable to an adverse event.
RESULTS: Serious adverse events, including bowel injury (n=128), sepsis or bacteremia (n=47), intra-abdominal abscess (n=18), urologic injury (n=2), and uterine rupture (n=1) were reported. Death was also reported (n=4). Eight percent (66 of 829) of serious adverse events reports cited use outside of the manufacturers' labeled instructions, as did 7.3% (6 of 82) of reports citing need for hysterectomy and 8.7% (9 of 103) of reports of bowel resection.
CONCLUSION: The findings from the Manufacturer and User Facility Device Experience database highlight the potential risk of serious complications related to endometrial ablation and underscore the importance of training in correct device use and familiarity with the manufacturer's labeled instructions. (Obstet Gynecol 2012; 120:865-70) DOI:http://10.1097/AOG.0b013e31826af4fe
C1 [Brown, Jill] NIAID, NIH, DMID, STDB, Bethesda, MD 20892 USA.
George Washington Univ, Sch Med, Washington, DC USA.
RP Brown, J (reprint author), NIAID, NIH, DMID, STDB, 6610 Rockledge Dr,Room 3106, Bethesda, MD 20892 USA.
EM jill.brown@nih.gov
NR 12
TC 5
Z9 6
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD OCT
PY 2012
VL 120
IS 4
BP 865
EP 870
DI 10.1097/AOG.0b013e31826af4fe
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 012FN
UT WOS:000309221200018
PM 22996104
ER
PT J
AU Pronk, A
Stewart, PA
Coble, JB
Katki, HA
Wheeler, DC
Colt, JS
Baris, D
Schwenn, M
Karagas, MR
Johnson, A
Waddell, R
Verrill, C
Cherala, S
Silverman, DT
Friesen, MC
AF Pronk, Anjoeka
Stewart, Patricia A.
Coble, Joseph B.
Katki, Hormuzd A.
Wheeler, David C.
Colt, Joanne S.
Baris, Dalsu
Schwenn, Molly
Karagas, Margaret R.
Johnson, Alison
Waddell, Richard
Verrill, Castine
Cherala, Sai
Silverman, Debra T.
Friesen, Melissa C.
TI Comparison of two expert-based assessments of diesel exhaust exposure in
a case-control study: programmable decision rules versus expert review
of individual jobs
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Review
ID ADULT BRAIN-TUMORS; OCCUPATIONAL-EXPOSURE; RETROSPECTIVE EVALUATION;
GENETIC SUSCEPTIBILITY; SUBJECTIVE ASSESSMENT; INTERRATER AGREEMENT;
INDUSTRIAL-HYGIENE; LUNG-CANCER; MATRIX; VALIDATION
AB Objectives Professional judgment is necessary to assess occupational exposure in population-based case-control studies; however, the assessments lack transparency and are time-consuming to perform. To improve transparency and efficiency, we systematically applied decision rules to questionnaire responses to assess diesel exhaust exposure in the population-based case-control New England Bladder Cancer Study.
Methods 2631 participants reported 14 983 jobs; 2749 jobs were administered questionnaires ('modules') with diesel-relevant questions. We applied decision rules to assign exposure metrics based either on the occupational history (OH) responses (OH estimates) or on the module responses (module estimates); we then combined the separate OH and module estimates (OH/module estimates). Each job was also reviewed individually to assign exposure (one-by-one review estimates). We evaluated the agreement between the OH, OH/module and one-by-one review estimates.
Results The proportion of exposed jobs was 20-25% for all jobs, depending on approach, and 54-60% for jobs with diesel-relevant modules. The OH/module and one-by-one review estimates had moderately high agreement for all jobs (kappa(w)=0.68-0.81) and for jobs with diesel-relevant modules (kappa(w)=0.62-0.78) for the probability, intensity and frequency metrics. For exposed subjects, the Spearman correlation statistic was 0.72 between the cumulative OH/module and one-by-one review estimates.
Conclusions The agreement seen here may represent an upper level of agreement because the algorithm and one-by-one review estimates were not fully independent. This study shows that applying decision-based rules can reproduce a one-by-one review, increase transparency and efficiency, and provide a mechanism to replicate exposure decisions in other studies.
C1 [Pronk, Anjoeka; Stewart, Patricia A.; Coble, Joseph B.; Wheeler, David C.; Colt, Joanne S.; Baris, Dalsu; Silverman, Debra T.; Friesen, Melissa C.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Pronk, Anjoeka] TNO Qual & Safety, Zeist, Netherlands.
[Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA USA.
[Katki, Hormuzd A.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Wheeler, David C.] Virginia Commonwealth Univ, Dept Biostat, Richmond, VA USA.
[Schwenn, Molly; Verrill, Castine] Maine Canc Registry, Augusta, ME USA.
[Karagas, Margaret R.; Waddell, Richard] Dartmouth Med Sch, Dept Community & Family Med, Lebanon, NH USA.
[Johnson, Alison] Vermont Canc Registry, Burlington, VT USA.
[Cherala, Sai] New Hampshire Dept Hlth & Human Serv, Concord, NH 03301 USA.
RP Friesen, MC (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8106,MSC 7240, Bethesda, MD 20892 USA.
EM friesenmc@mail.nih.gov
RI Katki, Hormuzd/B-4003-2015; Friesen, Melissa/A-5362-2009
FU National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics
FX The research was funded by the Intramural Research Programme of the
National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics.
NR 40
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Z9 14
U1 1
U2 20
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1351-0711
J9 OCCUP ENVIRON MED
JI Occup. Environ. Med.
PD OCT
PY 2012
VL 69
IS 10
BP 752
EP 758
DI 10.1136/oemed-2011-100524
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 004OS
UT WOS:000308691600009
PM 22843440
ER
PT J
AU Turk, DC
O'Connor, AB
Dworkin, RH
Chaudhry, A
Katz, NP
Adams, EH
Brownstein, JS
Comer, SD
Dart, R
Dasgupta, N
Denisco, RA
Klein, M
Leiderman, DB
Lubran, R
Rappaport, BA
Zacny, JP
Ahdieh, H
Burke, LB
Cowan, P
Jacobs, P
Malamut, R
Markman, J
Michna, E
Palmer, P
Peirce-Sandner, S
Potter, JS
Raja, SN
Rauschkolb, C
Roland, CL
Webster, LR
Weiss, RD
Wolf, K
AF Turk, Dennis C.
O'Connor, Alec B.
Dworkin, Robert H.
Chaudhry, Amina
Katz, Nathaniel P.
Adams, Edgar H.
Brownstein, John S.
Comer, Sandra D.
Dart, Richard
Dasgupta, Nabarun
Denisco, Richard A.
Klein, Michael
Leiderman, Deborah B.
Lubran, Robert
Rappaport, Bob A.
Zacny, James P.
Ahdieh, Harry
Burke, Laurie B.
Cowan, Penney
Jacobs, Petra
Malamut, Richard
Markman, John
Michna, Edward
Palmer, Pamela
Peirce-Sandner, Sarah
Potter, Jennifer S.
Raja, Srinivasa N.
Rauschkolb, Christine
Roland, Carl L.
Webster, Lynn R.
Weiss, Roger D.
Wolf, Kerry
TI Research design considerations for clinical studies of abuse-deterrent
opioid analgesics: IMMPACT recommendations
SO PAIN
LA English
DT Review
DE Abuse; Abuse deterrent formulation; Abuse liability; Opioids; Risk of
abuse; Study design
ID INJECTION-DRUG USERS; CHRONIC NONCANCER PAIN; UNITED-STATES;
ANTIRETROVIRAL TREATMENT; TEMAZEPAM CAPSULES; PROSPECTIVE COHORT;
PRESCRIPTION; MISUSE; LIABILITY; TRIALS
AB Opioids are essential to the management of pain in many patients, but they also are associated with potential risks for abuse, overdose, and diversion. A number of efforts have been devoted to the development of abuse-deterrent formulations of opioids to reduce these risks. This article summarizes a consensus meeting that was organized to propose recommendations for the types of clinical studies that can be used to assess the abuse deterrence of different opioid formulations. Because of the many types of individuals who may be exposed to opioids, an opioid formulation will need to be studied in several populations using various study designs to determine its abuse-deterrent capabilities. It is recommended that the research conducted to evaluate abuse deterrence should include studies assessing: (1) abuse liability, (2) the likelihood that opioid abusers will find methods to circumvent the deterrent properties of the formulation, (3) measures of misuse and abuse in randomized clinical trials involving pain patients with both low risk and high risk of abuse, and (4) postmarketing epidemiological studies. (C) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
C1 [Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA.
[O'Connor, Alec B.; Dworkin, Robert H.; Markman, John; Peirce-Sandner, Sarah] Univ Rochester, Rochester, NY USA.
[Chaudhry, Amina; Lubran, Robert; Raja, Srinivasa N.] Johns Hopkins Univ, Baltimore, MD USA.
[Katz, Nathaniel P.] Tufts Univ, Boston, MA 02111 USA.
[Katz, Nathaniel P.] Analges Solut, Boston, MA 02111 USA.
[Adams, Edgar H.] Covance, Conshohocken, PA USA.
[Brownstein, John S.; Weiss, Roger D.] Harvard Univ, Sch Med, Boston, MA USA.
[Comer, Sandra D.] Columbia Univ, New York, NY USA.
[Dart, Richard] Rocky Mt Poison & Drug Ctr, Denver, CO USA.
[Dart, Richard] Denver Hlth Author, Denver, CO USA.
[Dasgupta, Nabarun] Univ N Carolina, Chapel Hill, NC USA.
[Denisco, Richard A.; Jacobs, Petra] NIDA, Bethesda, MD 20892 USA.
[Klein, Michael; Rappaport, Bob A.; Burke, Laurie B.] US FDA, Silver Spring, MD USA.
[Leiderman, Deborah B.] CNS Drug Consulting, Mclean, VA USA.
[Zacny, James P.] Univ Chicago, Chicago, IL 60637 USA.
[Ahdieh, Harry] Endo Pharmaceut, Chadds Ford, PA USA.
[Cowan, Penney] Amer Chron Pain Assoc, Rocklin, CA USA.
[Malamut, Richard] AstraZeneca, Wilmington, DE USA.
[Michna, Edward] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Palmer, Pamela] AcelRx Pharmaceut, Redwood City, CA USA.
[Potter, Jennifer S.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Rauschkolb, Christine] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA.
[Roland, Carl L.] Pfizer, New Brunswick, NJ USA.
[Webster, Lynn R.] Clin Res & Pain Clin, Salt Lake City, UT USA.
[Wolf, Kerry] NAMA Recovery, Cedar Pk, TX USA.
RP Turk, DC (reprint author), Univ Washington, Dept Anesthesiol & Pain Med, Box 356540, Seattle, WA 98195 USA.
EM turkdc@uw.edu
RI Potter, Jennifer/C-6720-2008;
OI Potter, Jennifer/0000-0002-7250-4422; Lubran,
Robert/0000-0003-1235-5207; Yang, Shuman/0000-0002-9638-0890
FU NIDA NIH HHS [K24 DA022288, R01 DA016759, R01 DA031022]
NR 77
TC 11
Z9 11
U1 6
U2 19
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD OCT
PY 2012
VL 153
IS 10
BP 1997
EP 2008
DI 10.1016/j.pain.2012.05.029
PG 12
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 009WG
UT WOS:000309055500007
PM 22770841
ER
PT J
AU Ruparel, S
Henry, MA
Akopian, A
Patil, M
Zeldin, DC
Roman, L
Hargreaves, KM
AF Ruparel, Shivani
Henry, Michael A.
Akopian, Armen
Patil, Mayur
Zeldin, Darryl C.
Roman, Linda
Hargreaves, Kenneth M.
TI Plasticity of cytochrome P450 isozyme expression in rat trigeminal
ganglia neurons during inflammation
SO PAIN
LA English
DT Article
DE Cytochrome P450; TRPV1; Sensory neurons
ID LINOLEIC-ACID METABOLITES; HUMAN DENTAL-PULP; INFRAORBITAL NERVE;
SENSORY NEURONS; MESSENGER-RNA; CELLS; BRAIN; TRPV1; LIPOXYGENASE;
EPOXYGENASE
AB Recently, specific oxidized linoleic acid metabolites (OLAMs) have been identified as transient receptor potential vanilloid 1 (TRPV1) channel agonists that contribute to inflammatory and heat hyperalgesia mechanisms, yet the specific mechanism responsible for OLAM synthesis in sensory neurons is unknown. Here, we use molecular, anatomical, calcium imaging, and perforated patch electrophysiology methods to demonstrate the specific involvement of cytochrome P450 enzymes (CYPs) in the oxidation of linoleic acid leading to neuronal activation and show that this is enhanced under inflammatory conditions. Additional studies evaluated CYP expressions in the native rat trigeminal ganglia (TG) tissue and cultures as well as changes in their expression pattern following the induction of peripheral inflammation. Fourteen of 20 candidate transcripts were detected in native TG, and 7 of these displayed altered expression under cultured conditions. Moreover, complete Freund's adjuvant-induced inflammation of vibrissal pad selectively increased expression of CYP3A23/3A1 and CYP2J4 transcripts in TG. In situ hybridization studies demonstrated broad expression pattern of CYP3A23/3A1 and CYP2J4 within TG neurons. Anatomical studies characterized the expression of CYP3A1 and the CYP2J families within TG sensory neurons, including those with TRPV1, with about half of all TRPV1-positive neurons showing more prominent CYP3A1 and CYP2J expression. Together, these findings show that CYP enzymes play a primary role in mediating linoleic acid-evoked activation of sensory neurons and furthermore, implicate the involvement of specific CYPs as contributing to the formation of OLAMs that act as TRPV1 agonists within this subpopulation of nociceptors. (C) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
C1 [Ruparel, Shivani; Henry, Michael A.; Akopian, Armen; Patil, Mayur; Hargreaves, Kenneth M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Endodont, San Antonio, TX 78229 USA.
[Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
[Roman, Linda] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA.
RP Hargreaves, KM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Endodont, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM Hargreaves@uthscsa.edu
OI Ruparel, Shivani/0000-0002-8232-3780
FU National Institutes of Health (NIH) [R01NS72890, R01DA019585]; National
Center for Research Resources [U54RR02438]; American Pain Society Pain
Future Leader's Grant; NIH, National Institute of Environmental Health
Sciences [Z01 ES025034]
FX We would like to thank Gabriella Helesic, Mei Li, and Paul Chen for
their technical assistance. We would also like to thank Dr. Anibal
Diogenes for providing access to his Affymetrix data for selection of
the CYPs. We are also grateful to Dr. Amol Patwardhan for his valuable
input that he provided for this study, and his preliminary work in this
area. The study was supported by the National Institutes of Health
(NIH), R01NS72890, R01DA019585, National Center for Research Resources
U54RR02438, and the American Pain Society Pain 2010 Future Leader's
Grant (S.R.). This study was also supported, in part, by the intramural
research program of the NIH, National Institute of Environmental Health
Sciences (Z01 ES025034 to D.C.Z.). The University of Texas has claimed
intellectual property related to this discovery.
NR 44
TC 15
Z9 15
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD OCT
PY 2012
VL 153
IS 10
BP 2031
EP 2039
DI 10.1016/j.pain.2012.04.027
PG 9
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 009WG
UT WOS:000309055500010
PM 22633978
ER
PT J
AU Mollan, TL
Abraham, B
Strader, MB
Jia, YP
Lozier, JN
Olson, JS
Alayash, AI
AF Mollan, Todd L.
Abraham, Bindu
Strader, Michael Brad
Jia, Yiping
Lozier, Jay N.
Olson, John S.
Alayash, Abdu I.
TI Familial secondary erythrocytosis due to increased oxygen affinity is
caused by destabilization of the T state of hemoglobin Brigham (a2 ss
2Pro100Leu)
SO PROTEIN SCIENCE
LA English
DT Article
DE hemoglobin; allostery; kinetics; ligand binding
ID INOSITOL HEXAPHOSPHATE; R-STATE; SURFACE HYDROPHOBICITY; SUBUNIT
DISSOCIATION; LIGAND-BINDING; RATE CONSTANTS; CO BINDING; AMINO-ACID; G
GEORGIA; AUTOXIDATION
AB Hemoglobin Brigham (beta Pro100 to Leu) was first reported in a patient with familial erythrocytosis. Erythrocytes of an affected individual from the same family contain both HbA and Hb Brigham and exhibit elevated O2 affinity compared with normal cells (P50 = 23 mm Hg vs. 31 mmHg at pH 7.4 at 37 degrees C). O2 affinities measured for hemolysates were sensitive to changes in pH or chloride concentrations, indicating little change in the Bohr and Chloride effects. Hb Brigham was separated from normal HbA by nondenaturing cation exchange liquid chromatography, and the amino acid substitution was verified by mass spectrometry. The properties of Hb Brigham isolated from the patient's blood were then compared with those of recombinant Hb Brigham expressed in Escherichia coli. Kinetic experiments suggest that the rate constants for ligand binding and release in the high (R) and low (T) affinity quaternary states of Hb Brigham are similar to those of native hemoglobin. However, the Brigham mutation decreases the T to R equilibrium constant (L) which accelerates the switch to the R state during ligand binding to deoxy-Hb, increasing the rate of association by approximately twofold, and decelerates the switch during ligand dissociation from HbO2, decreasing the rate approximately twofold. These kinetic data help explain the high O2 affinity characteristics of Hb Brigham and provide further evidence for the importance of the contribution of Pro100 to intersubunit contacts and stabilization of the T quaternary structure.
C1 [Lozier, Jay N.; Alayash, Abdu I.] NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Mollan, Todd L.; Abraham, Bindu; Strader, Michael Brad; Jia, Yiping; Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Olson, John S.] Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77251 USA.
RP Alayash, AI (reprint author), NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, 8800 Rockville Pike,Bldg 29,Room 112, Bethesda, MD 20892 USA.
EM abdu.alayash@fda.hhs.gov
FU Food and Drug Administration (MODSCI); Oak Ridge Institute for Science
Education; National Institutes of Health [HL47020, GM35649]; Welch
[C-0612]
FX Grant sponsors: Food and Drug Administration (MODSCI) and Oak Ridge
Institute for Science Education (to T. L. M.); Grant sponsor: National
Institutes of Health; Grant numbers: HL47020 and GM35649 (to J.S.O.);
Grant sponsor: Welch; Grant number: C-0612 (to J.S.O.).
NR 56
TC 2
Z9 2
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD OCT
PY 2012
VL 21
IS 10
BP 1444
EP 1455
DI 10.1002/pro.2130
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 008ZE
UT WOS:000308994300004
PM 22821886
ER
PT J
AU Kepka, D
Berkowitz, Z
Yabroff, KR
Roland, K
Saraiya, M
AF Kepka, Deanna
Berkowitz, Zahava
Yabroff, K. Robin
Roland, Katherine
Saraiya, Mona
TI Human papillomavirus vaccine practices in the USA: do primary care
providers use sexual history and cervical cancer screening results to
make HPV vaccine recommendations?
SO SEXUALLY TRANSMITTED INFECTIONS
LA English
DT Article
AB Objectives Guidelines recommend against the use of Papanicolaou (Pap) or human papillomavirus (HPV) testing when determining eligibility for the HPV vaccine. Optimally, the HPV vaccine should be administered before sexual initiation. Guidelines recommend that age-eligible women with past exposure to HPV should still be vaccinated. Little is known about how primary care providers (PCPs) use sexual history and HPV and Pap tests in their HPV vaccine recommendations.
Methods Data from the 2007 Cervical Cancer Screening Supplement (CCSS) administered with the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS) were used to assess HPV vaccination recommendations. The CCSS investigates cervical cancer screening practices, HPV testing and HPV vaccine recommendations among PCPs. A summary measure of compliance with guidelines was defined as rarely or never using the number of sexual partners and HPV tests and Pap tests to determine vaccine receipt. A total of 421 PCPs completed the CCSS in 2007.
Results Among NAMCS and NHAMCS providers who recommend the HPV vaccine, only 53% (95% CI 42% to 63%) reported making guideline-consistent recommendations. The majority reported sometimes to always recommending the HPV vaccine to women with a history of an abnormal Pap result (85%; 95% CI 75% to 91%) and a positive HPV test (79%; 95% CI 70% to 86%).
Conclusions A large proportion of providers report practices that are inconsistent with guidelines. Providers may also be recommending the vaccine to women who may receive little benefit from the vaccine. Provider and system-level efforts to improve guideline-consistent practices are needed.
C1 [Kepka, Deanna] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Berkowitz, Zahava; Roland, Katherine; Saraiya, Mona] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA.
RP Kepka, D (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Execut Plaza N,Room 4017,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA.
EM deanna.kepka@nih.gov
OI Yabroff, K. Robin/0000-0003-0644-5572
FU Center for Cancer Training; Health Services and Economics Branch,
Applied Research Program, Division of Cancer Control and Population
Sciences of the National Cancer Institute, Bethesda, MD
FX DLK acknowledges support from the Cancer Prevention Fellowship Program,
Center for Cancer Training and the Health Services and Economics Branch,
Applied Research Program, Division of Cancer Control and Population
Sciences of the National Cancer Institute, Bethesda, MD.
NR 9
TC 13
Z9 13
U1 0
U2 11
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1368-4973
J9 SEX TRANSM INFECT
JI Sex. Transm. Infect.
PD OCT
PY 2012
VL 88
IS 6
BP 433
EP 435
DI 10.1136/sextrans-2011-050437
PG 3
WC Infectious Diseases
SC Infectious Diseases
GA 012VX
UT WOS:000309265800010
PM 22522751
ER
PT J
AU Padmanabhan, R
Chen, KG
Gillet, JP
Handley, M
Mallon, BS
Hamilton, RS
Park, K
Varma, S
Mehaffey, MG
Robey, PG
McKay, RDG
Gottesman, MM
AF Padmanabhan, Raji
Chen, Kevin G.
Gillet, Jean-Pierre
Handley, Misty
Mallon, Barbara S.
Hamilton, Rebecca S.
Park, Kyeyoon
Varma, Sudhir
Mehaffey, Michele G.
Robey, Pamela G.
McKay, Ronald D. G.
Gottesman, Michael M.
TI Regulation and Expression of the ATP-Binding Cassette Transporter ABCG2
in Human Embryonic Stem Cells
SO STEM CELLS
LA English
DT Article
DE Human embryonic stem cells; ATP-binding cassette; ABCG2; BMP-4;
Differentiation
ID MULTIDRUG-RESISTANCE; SELF-RENEWAL; FUNCTIONAL EXPRESSION; DRUG
TRANSPORTER; CANCER-CELLS; RNA-SEQ; DIFFERENTIATION; PROTEIN;
HOECHST-33342; GROWTH
AB The expression and function of several multidrug transporters (including ABCB1 and ABCG2) have been studied in human cancer cells and in mouse and human adult stem cells. However, the expression of ABCG2 in human embryonic stem cells (hESCs) remains unclear. Limited and contradictory results in the literature from two research groups have raised questions regarding its expression and function. In this study, we used quantitative real-time PCR, Northern blots, whole genome RNA sequencing, Western blots, and immunofluorescence microscopy to study ABCG2 expression in hESCs. We found that full-length ABCG2 mRNA transcripts are expressed in undifferentiated hESC lines. However, ABCG2 protein was undetectable even under embryoid body differentiation or cytotoxic drug induction. Moreover, surface ABCG2 protein was coexpressed with the differentiation marker stage-specific embryonic antigen-1 of hESCs, following constant BMP-4 signaling at days 4 and 6. This expression was tightly correlated with the downregulation of two microRNAs (miRNAs) (i.e., hsa-miR-519c and hsa-miR-520h). Transfection of miRNA mimics and inhibitors of these two miRNAs confirmed their direct involvement in the regulation ABCG2 translation. Our findings clarify the controversy regarding the expression of the ABCG2 gene and also provide new insights into translational control of the expression of membrane transporter mRNAs by miRNAs in hESCs. STEM Cells2012;30:21752187
C1 [Padmanabhan, Raji; Gillet, Jean-Pierre; Handley, Misty; Gottesman, Michael M.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Chen, Kevin G.; Mallon, Barbara S.; Hamilton, Rebecca S.; Park, Kyeyoon; Robey, Pamela G.; McKay, Ronald D. G.] NINDS, NIH Stem Cell Unit, NIH, Bethesda, MD 20892 USA.
[Varma, Sudhir] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA.
[Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
[McKay, Ronald D. G.] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Mehaffey, Michele G.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM mgottesman@nih.gov
RI Robey, Pamela/H-1429-2011; Varma, Sudhir/N-8763-2014; Chen,
Kevin/D-6769-2011
OI Robey, Pamela/0000-0002-5316-5576; Varma, Sudhir/0000-0002-4096-4782;
Chen, Kevin/0000-0003-2983-6330
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research; NIH
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research. The NIH Stem Cell Unit is supported by NIH funds. We
thank George Leiman for editorial assistance. R. D. G. M. is currently
affiliated with the Lieber Institute for Brain Development, Johns
Hopkins School of Medicine, Baltimore, MD.
NR 33
TC 20
Z9 21
U1 0
U2 23
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD OCT
PY 2012
VL 30
IS 10
BP 2175
EP 2187
DI 10.1002/stem.1195
PG 13
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 008AA
UT WOS:000308928300010
PM 22887864
ER
PT J
AU Fiorella, D
Derdeyn, CP
Lynn, MJ
Barnwell, SL
Hoh, BL
Levy, EI
Harrigan, MR
Klucznik, RP
McDougall, CG
Pride, GL
Zaidat, OO
Lutsep, HL
Waters, MF
Hourihane, JM
Alexandrov, AV
Chiu, D
Clark, JM
Johnson, MD
Torbey, MT
Rumboldt, Z
Cloft, HJ
Turan, TN
Lane, BF
Janis, LS
Chimowitz, MI
AF Fiorella, David
Derdeyn, Colin P.
Lynn, Michael J.
Barnwell, Stanley L.
Hoh, Brian L.
Levy, Elad I.
Harrigan, Mark R.
Klucznik, Richard P.
McDougall, Cameron G.
Pride, G. Lee, Jr.
Zaidat, Osama O.
Lutsep, Helmi L.
Waters, Michael F.
Hourihane, J. Maurice
Alexandrov, Andrei V.
Chiu, David
Clark, Joni M.
Johnson, Mark D.
Torbey, Michel T.
Rumboldt, Zoran
Cloft, Harry J.
Turan, Tanya N.
Lane, Bethany F.
Janis, L. Scott
Chimowitz, Marc I.
CA SAMMPRIS Trial Investigators
TI Detailed Analysis of Periprocedural Strokes in Patients Undergoing
Intracranial Stenting in Stenting and Aggressive Medical Management for
Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS)
SO STROKE
LA English
DT Article
DE angioplasty and stenting; clinical trial; intracranial stenosis
ID ACUTE MYOCARDIAL-INFARCTION; ARTERIAL-STENOSIS; WINGSPAN STENT; SMOKING;
THERAPY; ANGIOPLASTY; ASSOCIATION; CLOPIDOGREL; EVENTS; TRIAL
AB Background and Purpose-Enrollment in the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial was halted due to the high risk of stroke or death within 30 days of enrollment in the percutaneous transluminal angioplasty and stenting arm relative to the medical arm. This analysis focuses on the patient and procedural factors that may have been associated with periprocedural cerebrovascular events in the trial.
Methods-Bivariate and multivariate analyses were performed to evaluate whether patient and procedural variables were associated with cerebral ischemic or hemorrhagic events occurring within 30 days of enrollment (termed periprocedural) in the percutaneous transluminal angioplasty and stenting arm.
Results-Of 224 patients randomized to percutaneous transluminal angioplasty and stenting, 213 underwent angioplasty alone (n=5) or with stenting (n=208). Of these, 13 had hemorrhagic strokes (7 parenchymal, 6 subarachnoid), 19 had ischemic stroke, and 2 had cerebral infarcts with temporary signs within the periprocedural period. Ischemic events were categorized as perforator occlusions (13), embolic (4), mixed perforator and embolic (2), and delayed stent occlusion (2). Multivariate analyses showed that higher percent stenosis, lower modified Rankin score, and clopidogrel load associated with an activated clotting time above the target range were associated (P <= 0.05) with hemorrhagic stroke. Nonsmoking, basilar artery stenosis, diabetes, and older age were associated (P <= 0.05) with ischemic events.
Conclusions-Periprocedural strokes in SAMMPRIS had multiple causes with the most common being perforator occlusion. Although risk factors for periprocedural strokes could be identified, excluding patients with these features from undergoing percutaneous transluminal angioplasty and stenting to lower the procedural risk would limit percutaneous transluminal angioplasty and stenting to a small subset of patients. Moreover, given the small number of events, the present data should be used for hypothesis generation rather than to guide patient selection in clinical practice.
C1 [Fiorella, David] SUNY Stony Brook, Hlth Sci Ctr, Dept Neurosurg, Stony Brook, NY 11794 USA.
[Derdeyn, Colin P.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA.
[Derdeyn, Colin P.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Derdeyn, Colin P.] Washington Univ, Sch Med, Dept Neurosurg, St Louis, MO 63110 USA.
[Lynn, Michael J.; Lane, Bethany F.] Emory Univ, Dept Biostat & Bioinformat, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Barnwell, Stanley L.] Oregon Hlth & Sci Univ, Dept Neurol Surg, Portland, OR USA.
[Barnwell, Stanley L.] Oregon Hlth & Sci Univ, Dotter Intervent Inst, Portland, OR USA.
[Lutsep, Helmi L.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR USA.
[Hoh, Brian L.] Univ Florida, Dept Neurosurg, Gainesville, FL USA.
[Waters, Michael F.] Univ Florida, Dept Neurol & Neurosci, Gainesville, FL USA.
[Levy, Elad I.] SUNY Buffalo, Dept Neurosurg, Buffalo, NY 14260 USA.
[Harrigan, Mark R.] Univ Alabama Birmingham, Dept Neurosurg, Birmingham, AL USA.
[Alexandrov, Andrei V.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA.
[Klucznik, Richard P.] Methodist Hosp, Dept Radiol, Houston, TX 77030 USA.
[Chiu, David] Methodist Hosp, Dept Neurol, Houston, TX 77030 USA.
[McDougall, Cameron G.] Barrow Neurol Inst, Dept Neurosurg, Phoenix, AZ 85013 USA.
[Clark, Joni M.] Barrow Neurol Inst, Dept Neurol, Phoenix, AZ 85013 USA.
[Pride, G. Lee, Jr.] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA.
[Pride, G. Lee, Jr.] Univ Texas SW Med Ctr Dallas, Dept Neurosurg, Dallas, TX 75390 USA.
[Zaidat, Osama O.; Torbey, Michel T.] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA.
[Zaidat, Osama O.] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA.
[Zaidat, Osama O.] Med Coll Wisconsin, Dept Neurosurg, Milwaukee, WI 53226 USA.
[Johnson, Mark D.] Univ Texas SW, Dept Neurol & Neurotherapeut, Dallas, TX USA.
[Hourihane, J. Maurice] Dent Neurol Inst, Buffalo, NY USA.
[Rumboldt, Zoran] Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA.
[Turan, Tanya N.; Chimowitz, Marc I.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Cloft, Harry J.] Mayo Clin, Dept Radiol, Rochester, MN USA.
[Janis, L. Scott] NINDS, NIH, Bethesda, MD 20892 USA.
RP Fiorella, D (reprint author), SUNY Stony Brook, Hlth Sci Ctr, Dept Neurosurg, T-12 080, Stony Brook, NY 11794 USA.
EM fiorella.SAMMPRIS@gmail.com
OI Alexandrov, Andrei V/0000-0001-8871-1023; Turan,
Tanya/0000-0001-5399-8845; Derdeyn, Colin/0000-0002-5932-2683
FU US Public Health Service National Institute of Neurological Disorders
and Stroke (NINDS) [U01 NS058728]; National Institutes of Health;
Medical University of South Carolina [UL1RR029882]; University of
Florida [UL1RR029889]; University of Cincinnati [UL1RR029890];
University of California, San Francisco [UL1RR024131]; AstraZeneca;
National Institute of Neurological Disorders and Stroke (NINDS) [U01
NS058728]; SAMMPRIS; Siemens Medical Imaging and Microvention;
Codman/Johnson and Johnson; NFocus; W.L. Gore and Associates;
EV3/Covidien; NINDS [P50 55977, R01 NS051631, 1 R01 NS36643, 1 K24
NS050307, 1 R01 NS051688]; National Eye Institute; National Institutes
of Health (NIH) [1K08NS067058-01]; Boston Scientific Corporation; Codman
Shurtleff Inc; Abbott Vascular; NIH [K23]; NIH Challenge Grant; NINDS
for the Specialized Programs of Translational Research in Acute Stroke
(SPORTRIAS) trial; Microvention Terumo; American Academy of Neurology
(AAN) Foundation Clinical Research Training Fellowship; NIH/NINDS [1 K23
NS069668-01A1]
FX The SAMMPRIS trial was funded by a research grant (U01 NS058728) from
the US Public Health Service National Institute of Neurological
Disorders and Stroke (NINDS). In addition, the following Clinical and
Translational Science Awards, funded by the National Institutes of
Health, provided local support for the evaluation of patients in the
trial: Medical University of South Carolina (UL1RR029882), University of
Florida (UL1RR029889), University of Cincinnati (UL1RR029890), and
University of California, San Francisco (UL1RR024131). Stryker
Neurovascular (formerly Boston Scientific Neurovascular) provided study
devices and supplemental funding for third party device distribution,
site monitoring, and study auditing. This research is also supported by
the Investigator-Sponsored Study Program of AstraZeneca that donates
rosuvastatin (Crestor) to study patients.; Drs Fiorella, Derdeyn, Turan,
Janis, and Chimowitz, Michael Lynn, MS, and Bethany Lane, RN, serve on
the Executive Committee of the SAMMPRIS trial, which is funded by the
National Institute of Neurological Disorders and Stroke (NINDS; grant
number U01 NS058728). All receive salary support from the SAMMPRIS
grant. All other authors were investigators in SAMMPRIS and were
reimbursed from the SAMMPRIS grant for their effort. The following
investigators report additional support: David Fiorella, MD, PhD, has
received institutional research support from Siemens Medical Imaging and
Microvention; consulting fees from Codman/Johnson and Johnson, NFocus,
W.L. Gore and Associates, and EV3/Covidien; and royalties from
Codman/Johnson and Johnson. He has received honoraria from Scientia and
has ownership interest in CVSL and Vascular Simulations. Colin Derdeyn,
MD, receives grant support from the NINDS (P50 55977; R01 NS051631). He
is also on the Scientific Advisory Board for W.L Gore and Associates and
is the Chair of the Scientific Advisory Board for Pulse Therapeutics.
Michael J. Lynn, MS, receives grant support from the National Eye
Institute. He is the principal investigator of the Coordinating Center
for Infant Aphakia Treatment Study (EY013287) and a coinvestigator on
the Core Grant for Vision Research (EY006360). Stanley L. Barnwell, MD,
PhD, has been a consultant for Stryker Corporation. Brian L. Hoh, MD,
has received research support from National Institutes of Health (NIH)
grant number 1K08NS067058-01. Dr Hoh has served as an expert witness for
several medical defense cases including 2 cases on an arteriovenous
malformation embolism, one on a venous stent, and one on a subarachnoid
hemorrhage. Elad I. Levy, MD, has received research support from Boston
Scientific Corporation, Codman & Shurtleff Inc, and EV3/Covidien. Dr
Levy has shareholder/ownership interest in Intratech Medical Ltd and
Mynx/Access Closure. Dr Levy has acted as a consultant for Codman &
Shurtleff Inc, TheraSyn Sensors Inc, and EV3/Covidien. He has received
honoraria payment from Boston Scientific Corporation. Dr Levy has also
received other financial/material support from Abbott Vascular and
EV3/Covidien. Dr Levy has provided expertise in a legal review. Richard
P. Klucznik, MD, has received payment for speakers' bureau appointments
from EV3/Covidien and Microvention. Cameron G. McDougall, MD, has served
on medical advisory boards for Covidien and W. L. Gore & Associates. G.
Lee Pride, Jr, MD, has received research support for the ACES and LVIS
trials. Dr Pride has received honoraria payment from the Texas
Neurological Society (invited speaker) and ACOR (invited speaker). Osama
O. Zaidat, MD, MS, has acted as a consultant for EV3/Covidien, Codman
Neurovascular, Stryker Corporation, and Microvention. Michael F. Waters,
MD, PhD, has received research support from an NIH K23 grant and an NIH
Challenge Grant. Dr Waters has provided expertise in a legal review. J.
Maurice Hourihane, MD, has served as an expert witness in a medical
defense case. Andrei V. Alexandrov, MD, has received research support
from NINDS for the Specialized Programs of Translational Research in
Acute Stroke (SPORTRIAS) trial. Dr Alexandrov has received honoraria
payment for CME lectures. He has ownership interest with Cerevast
Therapeutics and has also been involved with their consultant/advisory
board. Mark D.; Johnson, MD, has received research support for the
Insulin Resistance after Stroke Trial (IRIS), Randomized Evaluation of
Recurrent Stroke Comparing PFO Closure to Established Current Standard
of Care Treatment (RESPECT), Platelet-Oriented Inhibition in New TIA and
Minor Ischemic Stroke Trial (POINT) trials. Harry J. Cloft, MD, PhD, has
received research support for the Stenting and Angioplasty With
Protection in Patients at High Risk for Endarterectomy (SAPPHIRE)
Carotid Stent registry. Bethany F. Lane, RN, has received consulting
fees from Microvention Terumo. Tanya N. Turan, MD, is a past recipient
of funding from the American Academy of Neurology (AAN) Foundation
Clinical Research Training Fellowship and is the current recipient of a
K23 grant from NIH/NINDS (1 K23 NS069668-01A1). She has also served as
an expert witness in medical legal cases. Scott Janis, PhD, is a program
director at the NINDS. Marc Chimowitz, MBChB, has received research
grants from NINDS to fund the Aspirin Or Warfarin To Prevent Stroke (Dr
WASID) trial (1 R01 NS36643) and to fund other research on intracranial
stenosis (1 K24 NS050307 and 1 R01 NS051688). He currently serves on the
stroke adjudication committee of an industry-funded osteoporosis drug
trial (Merck and Co, Inc) and on the Data Safety Monitoring Board of
another industry-funded patent foramen ovale closure trial (W.L Gore and
Associates) and is compensated for those activities. He has also served
as an expert witness in medical legal cases.
NR 20
TC 57
Z9 60
U1 1
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD OCT
PY 2012
VL 43
IS 10
BP 2682
EP +
DI 10.1161/STROKEAHA.112.661173
PG 11
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 012TG
UT WOS:000309258900035
PM 22984008
ER
PT J
AU Chimowitz, MI
Fiorella, D
Derdeyn, CP
Turan, TN
Lane, BF
Janis, LS
Lynn, MJ
AF Chimowitz, Marc I.
Fiorella, David
Derdeyn, Colin P.
Turan, Tanya N.
Lane, Bethany F.
Janis, L. Scott
Lynn, Michael J.
TI Response to Critique of the Stenting and Aggressive Medical Management
for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS)
Trial by Abou-Chebl and Steinmetz
SO STROKE
LA English
DT Editorial Material
DE angioplasty and stenting; clinical trial; intracranial stenosis
ID ARTERIAL-STENOSIS; WINGSPAN STENT; THERAPY; DISEASE; END
C1 [Chimowitz, Marc I.] Med Univ S Carolina, Stroke Program, Dept Neurosci, Charleston, SC 29425 USA.
[Fiorella, David] SUNY Stony Brook, Dept Neurosurg, Stony Brook, NY 11794 USA.
[Derdeyn, Colin P.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Derdeyn, Colin P.] Washington Univ, Sch Med, Dept Neurosurg, St Louis, MO USA.
[Derdeyn, Colin P.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA.
[Lane, Bethany F.; Lynn, Michael J.] Emory Univ, Rollins Sch Publ, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA.
[Janis, L. Scott] NINDS, NIH, Bethesda, MD 20892 USA.
RP Chimowitz, MI (reprint author), Med Univ S Carolina, Stroke Program, Dept Neurosci, 19 Hagood Ave,Harborview Off Tower,Suite 501, Charleston, SC 29425 USA.
EM mchimow@musc.edu
OI Turan, Tanya/0000-0001-5399-8845; Derdeyn, Colin/0000-0002-5932-2683
FU NCRR NIH HHS [TL1 RR029889, UL1 RR024131, UL1 RR029882, UL1 RR029890,
UL1RR024131, UL1RR029882, UL1RR029889, UL1RR029890]; NEI NIH HHS [P30
EY006360, U10 EY013287, UG1 EY013287]; NINDS NIH HHS [K23 NS069668, K24
NS050307, R01 NS036643, R01 NS051631, R01 NS051688, U01 NS058728,
U01NS058728]
NR 19
TC 3
Z9 3
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD OCT
PY 2012
VL 43
IS 10
BP 2806
EP 2809
DI 10.1161/STROKEAHA.112.661041
PG 4
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 012TG
UT WOS:000309258900056
PM 23180490
ER
PT J
AU Dinse, GE
Umbach, DM
AF Dinse, Gregg E.
Umbach, David M.
TI Parameterizing Dose-Response Models to Estimate Relative Potency
Functions Directly
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE dose response; Hill model; PeCDF; relative potency; TCDD
ID CURVES; BIOASSAY; FAMILIES
AB Many comparative analyses of toxicity assume that the potency of a test chemical relative to a reference chemical is constant, but employing such a restrictive assumption uncritically may generate misleading conclusions. Recent efforts to characterize non-constant relative potency rely on relative potency functions and estimate them secondarily after fitting dose-response models for the test and reference chemicals. We study an alternative approach of specifying a relative potency model a priori and estimating it directly using the dose-response data from both chemicals. We consider a power function in dose as a relative potency model and find that it keeps the two chemicals' dose-response functions within the same family of models for families typically used in toxicology. When differences in the response limits for the test and reference chemicals are attributable to the chemicals themselves, the older two-stage approach is the more convenient. When differences in response limits are attributable to other features of the experimental protocol or when response limits do not differ, the direct approach is straightforward to apply with nonlinear regression methods and simplifies calculation of simultaneous confidence bands. We illustrate the proposed approach using Hill models with dose-response data from U.S. National Toxicology Program bioassays. Though not universally applicable, this method of estimating relative potency functions directly can be profitably applied to a broad family of dose-response models commonly used in toxicology.
C1 [Dinse, Gregg E.; Umbach, David M.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Dinse, GE (reprint author), NIEHS, Biostat Branch, Bldg 101,Room A-349,Mail Drop A3-03,111 Alexander, Res Triangle Pk, NC 27709 USA.
EM dinse@niehs.nih.gov
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [Z01-ES-102685]
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences
(Z01-ES-102685).
NR 11
TC 1
Z9 1
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD OCT
PY 2012
VL 129
IS 2
BP 447
EP 455
DI 10.1093/toxsci/kfs209
PG 9
WC Toxicology
SC Toxicology
GA 009PM
UT WOS:000309037700019
PM 22700543
ER
PT J
AU Cheng, J
Krausz, KW
Tanaka, N
Frank, JG
AF Cheng, Jie
Krausz, Kristopher W.
Tanaka, Naoki
Frank, J. Gonzalez
TI Chronic Exposure to Rifaximin Causes Hepatic Steatosis in Pregnane X
Receptor-Humanized Mice
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE rifaximin; hepatotoxicity; human pregnane X receptor; steatosis
ID INFLAMMATORY-BOWEL-DISEASE; FATTY LIVER-DISEASE; LIPOGENIC PATHWAY;
LIPID ABSORPTION; MOUSE MODELS; PXR; METABOLISM; HOMEOSTASIS;
EXPRESSION; CELLS
AB Rifaximin, a nonsystemic antibiotic that exhibits low gastrointestinal absorption, is a potent agonist of human pregnane X receptor (PXR), which contributes to its therapeutic efficacy in inflammatory bowel disease. To investigate the effects of long-term administration of rifaximin on the liver, PXR-humanized mice were administered rifaximin for 6 months; wild-type and Pxr-null mice were treated in parallel as controls. Histological analysis revealed time-dependent intense hepatocellular fatty degeneration and increased hepatic triglycerides in PXR-humanized mice and not in wild-type and Pxr-null mice. After long-term treatment, PXR target genes were induced in small intestine and liver, with significant up-regulation in the expression of hepatic genes related to triglyceride synthesis and lipid accumulation. However, no significant hepatic accumulation of rifaximin was found, even after 6 months of treatment, in PXR-humanized mice. Genes in the small intestine that are involved in the uptake of fatty acids and triglycerides were induced along with increased triglyceride accumulation in intestinal epithelial cells of PXR-humanized mice; this was not observed in wild-type and Pxr-null mice. These findings suggest that long-term administration of rifaximin could lead to PXR-dependent hepatocellular fatty degeneration as a result of activation of genes involved in lipid uptake, thus indicating a potential adverse effect of rifaximin on liver function after long-term exposure.
C1 [Cheng, Jie; Krausz, Kristopher W.; Tanaka, Naoki; Frank, J. Gonzalez] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Frank, JG (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA.
EM fjgonz@helix.nih.gov
FU National Cancer Institute Intramural Research Program
FX National Cancer Institute Intramural Research Program.
NR 45
TC 12
Z9 13
U1 0
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD OCT
PY 2012
VL 129
IS 2
BP 456
EP 468
DI 10.1093/toxsci/kfs211
PG 13
WC Toxicology
SC Toxicology
GA 009PM
UT WOS:000309037700020
PM 22790967
ER
PT J
AU Kleinman, S
King, MR
Busch, MP
Murphy, EL
Glynn, SA
AF Kleinman, Steven
King, Melissa R.
Busch, Michael P.
Murphy, Edward L.
Glynn, Simone A.
CA Natl Heart Lung Blood Inst Retrovi
TI The National Heart, Lung, and Blood Institute Retrovirus Epidemiology
Donor Studies (Retrovirus Epidemiology Donor Study and Retrovirus
Epidemiology Donor Study-II): Twenty Years of Research to Advance Blood
Product Safety and Availability
SO TRANSFUSION MEDICINE REVIEWS
LA English
DT Review
ID HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSMISSIBLE
VIRAL-INFECTIONS; STATUS EVALUATION RISE; UNITED-STATES; HTLV-II;
DISEASE MARKERS; WHOLE-BLOOD; IRON STATUS; SAO-PAULO
AB The Retrovirus Epidemiology Donor Study (REDS), conducted from 1989 to 2001, and the REDS-II, conducted from 2004 to 2012, were National Heart, Lung, and Blood Institute funded, multicenter programs focused on improving blood safety and availability in the United States. The REDS-II also included international study sites in Brazil and China. The 3 major research domains of REDS/REDS-II have been infectious disease risk evaluation, blood donation availability, and blood donor characterization. Both programs have made significant contributions to transfusion medicine research methodology by the use of mathematical modeling, large-scale donor surveys, innovative methods of repository sample storage, and establishing an infrastructure that responded to potential emerging blood safety threats such as xenotropic murine leukemia virus related virus. Blood safety studies have included protocols evaluating epidemiologic and/or laboratory aspects of human immunodeficiency virus, human T-lymphotropic virus 112, hepatitis C virus, hepatitis B virus, West Nile virus, cytomegalovirus, human herpesvirus 8, parvovirus B19, malaria, Creutzfeldt-Jakob disease, influenza, and Trypanosoma cruzi infections. Other analyses have characterized blood donor demographics, motivations to donate, factors influencing donor return, behavioral risk factors, donors' perception of the blood donation screening process, and aspects of donor deferral. In REDS-II, 2 large-scale blood donor protocols examined iron deficiency in donors and the prevalence of leukocyte antibodies. This review describes the major study results from over 150 peer-reviewed articles published by these 2 REDS programs. In 2011, a new 7-year program, the Recipient Epidemiology and Donor Evaluation Study-III, was launched. The Recipient Epidemiology and Donor Evaluation Study-III expands beyond donor-based research to include studies of blood transfusion recipients in the hospital setting and adds a third country, South Africa, to the international program. (C) 2012 Elsevier Inc. All rights reserved.
C1 Univ British Columbia, Dept Pathol, Victoria, BC, Canada.
Westat Corp, Hlth Studies, Rockville, MD USA.
Blood Syst Res Inst, San Francisco, CA USA.
Univ Calif San Francisco, Lab Med, San Francisco, CA 94143 USA.
Univ Calif San Francisco, Lab Med & Epidemiol Biostat, San Francisco, CA 94143 USA.
NHLBI, Transfus Med & Cellular Therapeut Branch, Bethesda, MD 20892 USA.
RP Kleinman, S (reprint author), 1281 Rockcrest Ave, Victoria, BC V9A 4W4, Canada.
EM skleinman@shaw.ca
FU National Heart, Lung, and Blood Institute [N01-HB-97077, N01-HB-47114,
N01-HB-97078, N01-HB-97079, N01-HB-97080, N01-HB-97081, N01-HB-97082,
N01-HB-47168, N01-HB-47172, N01-HB-47175, N01-HB-57181]
FX The Retro virus Epidemiology Donor Snub, was supported by the National
Heart, Lung, and Blood Institute contracts N01-HB-97077 (superseded by
N01-HB-47114), -97078, -97079, -97080, -97081, and -97082. The
Retrovirus Epidemiology Donor Study-II was supported by the National
Heart, Lung, and Blood Institute contracts N01-HB-47168, -47172, -47175,
and -57181.
NR 163
TC 19
Z9 22
U1 2
U2 10
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0887-7963
J9 TRANSFUS MED REV
JI Transf. Med. Rev.
PD OCT
PY 2012
VL 26
IS 4
BP 281
EP 304
DI 10.1016/j.tmrv.2012.04.004
PG 24
WC Hematology
SC Hematology
GA 013GY
UT WOS:000309295100001
PM 22633182
ER
PT J
AU Sinha, D
Valapala, M
Bhutto, I
Patek, B
Zhang, C
Hose, S
Yang, F
Cano, M
Stark, WJ
Lutty, GA
Zigler, JS
Wawrousek, EF
AF Sinha, Debasish
Valapala, Mallika
Bhutto, Imran
Patek, Bonnie
Zhang, Cheng
Hose, Stacey
Yang, Fang
Cano, Marisol
Stark, Walter J.
Lutty, Gerard A.
Zigler, J. Samuel
Wawrousek, Eric F.
TI beta A3/A1-crystallin is required for proper astrocyte template
formation and vascular remodeling in the retina
SO TRANSGENIC RESEARCH
LA English
DT Article
DE beta A3-A1-crystallin; Astrocyte; Retina; Transgenic mice; Hyaloid and
retinal vasculature
ID ALPHA-B-CRYSTALLIN; NERVE HEAD ASTROCYTES; SPONTANEOUS MUTATION; FETAL
VASCULATURE; TRANSGENIC MICE; BLOOD-VESSELS; CELL-DEATH; EXPRESSION;
GENE; EYE
AB Nuc1 is a spontaneous rat mutant resulting from a mutation in the Cryba1 gene, coding for beta A3/A1-crystallin. Our earlier studies with Nuc1 provided novel evidence that astrocytes, which express beta A3/A1-crystallin, have a pivotal role in retinal remodeling. The role of astrocytes in the retina is only beginning to be explored. One of the limitations in the field is the lack of appropriate animal models to better investigate the function of astrocytes in retinal health and disease. We have now established transgenic mice that overexpress the Nuc1 mutant form of Cryba1, specifically in astrocytes. Astrocytes in wild type mice show normal compact stellate structure, producing a honeycomb-like network. In contrast, in transgenics over-expressing the mutant (Nuc1) Cryba1 in astrocytes, bundle-like structures with abnormal patterns and morphology were observed. In the nerve fiber layer of the transgenic mice, an additional layer of astrocytes adjacent to the vitreous is evident. This abnormal organization of astrocytes affects both the superficial and deep retinal vascular density and remodeling. Fluorescein angiography showed increased venous dilation and tortuosity of branches in the transgenic retina, as compared to wild type. Moreover, there appear to be fewer interactions between astrocytes and endothelial cells in the transgenic retina than in normal mouse retina. Further, astrocytes overexpressing the mutant beta A3/A1-crystallin migrate into the vitreous, and ensheath the hyaloid artery, in a manner similar to that seen in the Nuc1 rat. Together, these data demonstrate that developmental abnormalities of astrocytes can affect the normal remodeling process of both fetal and retinal vessels of the eye and that beta A3/A1-crystallin is essential for normal astrocyte function in the retina.
C1 [Sinha, Debasish] Johns Hopkins Univ, Wilmer Eye Inst, Sch Med, Baltimore, MD 21287 USA.
[Sinha, Debasish; Valapala, Mallika; Bhutto, Imran; Patek, Bonnie; Zhang, Cheng; Hose, Stacey; Yang, Fang; Cano, Marisol; Stark, Walter J.; Lutty, Gerard A.; Zigler, J. Samuel] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21231 USA.
[Wawrousek, Eric F.] NEI, NIH, Bethesda, MD 20892 USA.
RP Sinha, D (reprint author), Johns Hopkins Univ, Wilmer Eye Inst, Sch Med, 400 N Broadway,Smith Bldg,Room M035, Baltimore, MD 21287 USA.
EM Debasish@jhmi.edu
FU National Institutes of Health [EY018636, EY019037, EY019037-S]; Wilmer
Pooled Professors Fund; Helena Rubinstein Foundation; National Eye
Institute; Research to Prevent Blindness; Norman Raab Foundation;
[EY01765]
FX DS is thankful to the National Eye Institute for support of his IPA.
This work was also supported by National Institutes of Health: EY018636
(DS), EY019037 (DS), EY019037-S (DS), Wilmer Pooled Professors Fund
(DS), Helena Rubinstein Foundation (DS), EY01765 (Wilmer Imaging Core),
Intramural Research Program, National Eye Institute (EFW and JSZ), and
Research to Prevent Blindness (an unrestricted grant to The Wilmer Eye
Institute). We also wish to thank the Norman Raab Foundation and the
Wilmer Pooled Professors Fund for purchasing the Micron III imaging
system. We thank Steven Lee and Carl Haugen for their technical help
with the transgenic mouse production and to the Staff Members at Spring
Valley Laboratories, Woodbine, MD, for taking care of the experimental
animals. We thank Drs. Morton F. Goldberg and Bhaja K. Padhi for
critical reading and discussion regarding this manuscript.
NR 35
TC 14
Z9 15
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-8819
J9 TRANSGENIC RES
JI Transgenic Res.
PD OCT
PY 2012
VL 21
IS 5
BP 1033
EP 1042
DI 10.1007/s11248-012-9608-0
PG 10
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 999XO
UT WOS:000308349200009
PM 22427112
ER
PT J
AU Tomblyn, M
Chen, M
Kukreja, M
Aljurf, MD
Al Mohareb, F
Bolwell, BJ
Cahn, JY
Carabasi, MH
Gale, RP
Gress, RE
Gupta, V
Hale, GA
Ljungman, P
Maziarz, RT
Storek, J
Wingard, JR
Young, JAH
Horowitz, MM
Ballen, KK
AF Tomblyn, M.
Chen, M.
Kukreja, M.
Aljurf, M. D.
Al Mohareb, F.
Bolwell, B. J.
Cahn, J. -Y.
Carabasi, M. H.
Gale, R. P.
Gress, R. E.
Gupta, V.
Hale, G. A.
Ljungman, P.
Maziarz, R. T.
Storek, J.
Wingard, J. R.
Young, J. -A. H.
Horowitz, M. M.
Ballen, K. K.
TI No increased mortality from donor or recipient hepatitis B- and/or
hepatitis C-positive serostatus after related-donor allogeneic
hematopoietic cell transplantation
SO TRANSPLANT INFECTIOUS DISEASE
LA English
DT Article
DE allogeneic transplantation; hepatitis B; hepatitis C
ID BONE-MARROW-TRANSPLANTATION; VIRUS-INFECTION; SURFACE-ANTIGEN; VIRAL
REACTIVATION; HOST DISEASE; FOLLOW-UP; LAMIVUDINE; LIVER; RISK; THERAPY
AB Limited data exist on allogeneic transplant outcomes in recipients receiving hematopoietic cells from donors with prior or current hepatitis B (HBV) or C virus (HCV) infection (seropositive donors), or for recipients with prior or current HBV or HCV infection (seropositive recipients). Transplant outcomes are reported for 416 recipients from 121 centers, who received a human leukocyte antigen-identical related-donor allogeneic transplant for hematologic malignancies between 1995 and 2003. Of these, 33 seronegative recipients received grafts from seropositive donors and 128 recipients were seropositive. The remaining 256 patients served as controls. With comparable median follow-up (cases, 5.9 years; controls, 6.7 years), the incidence of treatment-related mortality, survival, graft-versus-host disease, and hepatic toxicity, appears similar in all cohorts. The frequencies of hepatic toxicities as well as causes of death between cases and controls were similar. Prior exposure to HBV or HCV in either the donor or the recipient should not be considered an absolute contraindication to transplant.
C1 [Tomblyn, M.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Tomblyn, M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplantat, Milwaukee, WI 53226 USA.
[Chen, M.; Kukreja, M.; Horowitz, M. M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Aljurf, M. D.; Al Mohareb, F.] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia.
[Bolwell, B. J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Cahn, J. -Y.] CHU Grenoble, Hop A Michallon, Serv Hematol, F-38043 Grenoble, France.
[Carabasi, M. H.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA.
[Gale, R. P.] Celgene Corp, Clin Res, Summit, NJ USA.
[Gress, R. E.] NIH, Bethesda, MD 20892 USA.
[Gupta, V.] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada.
[Hale, G. A.] Univ S Florida, All Childrens Hosp, Blood & Marrow Transplant Program, St Petersburg, FL 33701 USA.
[Ljungman, P.] Karolinska Univ Hosp, Karolinska Inst, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden.
[Maziarz, R. T.] Oregon Hlth & Sci Univ, Ctr Hematol Malignancies, Portland, OR 97201 USA.
[Storek, J.] Univ Calgary, Tom Baker Canc Ctr, Bone Marrow Transplant Program, Calgary, AB T2N 1N4, Canada.
[Wingard, J. R.] Univ Florida, Shands Hosp, Gainesville, FL USA.
[Young, J. -A. H.] Univ Minnesota, Masonic Canc Ctr, Clin Trials Off, Minneapolis, MN USA.
[Ballen, K. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Tomblyn, M (reprint author), 12902 Magnolia Dr,FOB 3, Tampa, FL 33612 USA.
EM marcie.tomblyn@moffitt.org
RI Young, Jo-Anne/G-2617-2013; Cahn, Jean-Yves/M-6493-2014
OI Young, Jo-Anne/0000-0003-4182-341X;
FU Public Health Service from the National Cancer Institute (NCI)
[U24-CA76518]; National Heart, Lung and Blood Institute (NHLBI);
National Institute of Allergy and Infectious Diseases (NIAID); NHLBI
[5U01HL069294]; NCI; Health Resources and Services Administration
(HRSA/DHHS); Office of Naval Research [N00014-06-1-0704,
N00014-08-1-0058]; AABB; Aetna; American Society for Blood and Marrow
Transplantation; Amgen, Inc.; Anonymous donation to the Medical College
of Wisconsin; Astellas Pharma US, Inc.; Baxter International, Inc.;
Bayer HealthCare Pharmaceuticals; Be the Match Foundation; Biogen IDEC;
BioMarin Pharmaceutical, Inc.; Biovitrum AB; Blood-Center of Wisconsin;
Blue Cross and Blue Shield Association; Bone Marrow Foundation; Buchanan
Family Foundation; Canadian Blood and Marrow Transplant Group;
CaridianBCT; Celgene Corporation; CellGenix, GmbH; Centers for Disease
Control and Prevention; Children's Leukemia Research Association;
ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist
Pharmaceuticals; Cylex Inc.; CytoTherm; DOR BioPharma, Inc.; Dynal
Biotech; Invitrogen Company; Eisai, Inc.; Enzon Pharmaceuticals, Inc.;
European Group for Blood and Marrow Transplantation; Gamida Cell, Ltd.;
GE Healthcare; Genentech, Inc.; Genzyme Corporation; Histogenetics,
Inc.; HKS Medical Information Systems; Hospira, Inc.; Infectious
Diseases Society of America; Kiadis Pharma; Kirin Brewery Co., Ltd.;
Leukemia & Lymphoma Society; Merck Company; Medical College of
Wisconsin; MGI Pharma, Inc.; Michigan Community Blood Centers;
Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA,
Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Nature
Publishing Group; New York Blood Center; Novartis Oncology; Oncology
Nursing Society; Osiris Therapeutics, Inc.; Otsuka America
Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc; Saladax
Biomedical, Inc.; Schering Corporation; Society for Healthcare
Epidemiology of America; Soligenix, Inc.; StemCyte, Inc.; StemSoft
Software, Inc.; Sysmex America, Inc.; THER-AKOS, Inc.; Thermogenesis
Corporation; Vidacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor
Laboratories; ViroPharma, Inc.; Wellpoint, Inc.; [HHSH234200637015C]
FX The CIBMTR is supported by Public Health Service Grant/Cooperative
Agreement U24-CA76518 from the National Cancer Institute (NCI), the
National Heart, Lung and Blood Institute (NHLBI), and the National
Institute of Allergy and Infectious Diseases (NIAID); a
Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract
HHSH234200637015C with Health Resources and Services Administration
(HRSA/DHHS); two Grants N00014-06-1-0704 and N00014-08-1-0058 from the
Office of Naval Research; and grants from AABB; Aetna; American Society
for Blood and Marrow Transplantation; Amgen, Inc.; Anonymous donation to
the Medical College of Wisconsin; Astellas Pharma US, Inc.; Baxter
International, Inc.; Bayer HealthCare Pharmaceuticals; Be the Match
Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB;
Blood-Center of Wisconsin; Blue Cross and Blue Shield Association; Bone
Marrow Foundation; Buchanan Family Foundation; Canadian Blood and Marrow
Transplant Group; CaridianBCT; Celgene Corporation; CellGenix, GmbH;
Centers for Disease Control and Prevention; Children's Leukemia Research
Association; ClinImmune Labs; CTI Clinical Trial and Consulting
Services; Cubist Pharmaceuticals; Cylex Inc.; CytoTherm; DOR BioPharma,
Inc.; Dynal Biotech, an Invitrogen Company; Eisai, Inc.; Enzon
Pharmaceuticals, Inc.; European Group for Blood and Marrow
Transplantation; Gamida Cell, Ltd.; GE Healthcare; Genentech, Inc.;
Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information
Systems; Hospira, Inc.; Infectious Diseases Society of America; Kiadis
Pharma; Kirin Brewery Co., Ltd.; The Leukemia & Lymphoma Society; Merck
& Company; The Medical College of Wisconsin; MGI Pharma, Inc.; Michigan
Community Blood Centers; Millennium Pharmaceuticals, Inc.; Miller
Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National
Marrow Donor Program; Nature Publishing Group; New York Blood Center;
Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.;
Otsuka America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc;
Saladax Biomedical, Inc.; Schering Corporation; Society for Healthcare
Epidemiology of America; Soligenix, Inc.; StemCyte, Inc.; StemSoft
Software, Inc.; Sysmex America, Inc.; THER-AKOS, Inc.; Thermogenesis
Corporation; Vidacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor
Laboratories; ViroPharma, Inc.; and Wellpoint, Inc.
NR 30
TC 5
Z9 6
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-2273
J9 TRANSPL INFECT DIS
JI Transpl. Infect. Dis.
PD OCT
PY 2012
VL 14
IS 5
BP 468
EP 478
DI 10.1111/j.1399-3062.2012.00732.x
PG 11
WC Immunology; Infectious Diseases; Transplantation
SC Immunology; Infectious Diseases; Transplantation
GA 012ME
UT WOS:000309239500020
PM 22548788
ER
PT J
AU Burns, KA
Korach, KS
AF Burns, Katherine A.
Korach, Kenneth S.
TI Estrogen receptors and human disease: an update
SO ARCHIVES OF TOXICOLOGY
LA English
DT Review
DE Estrogen; Estrogen receptors; Human disease; Cancer; Endometriosis;
Fibroids; Ovary
ID POSITIVE BREAST-CANCER; BETA ER-BETA; PERITONEAL-FLUID MACROPHAGES;
EPITHELIAL OVARIAN-CARCINOMA; STEROID-HORMONE RECEPTORS; ALPHA GENE
POLYMORPHISM; VARIANT MESSENGER-RNAS; ENDOMETRIAL CANCER; POSTMENOPAUSAL
WOMEN; PROSTATE-CANCER
AB A myriad of physiological processes in mammals are influenced by estrogens and the estrogen receptors (ERs), ER alpha and ER beta. As we reviewed previously, given the widespread role for estrogen in normal human physiology, it is not surprising that estrogen is implicated in the development or progression of a number of diseases. In this review, we are giving a 5-year update of the literature regarding the influence of estrogens on a number of human cancers (breast, ovarian, colorectal, prostate, and endometrial), endometriosis, fibroids, and cardiovascular disease. A large number of sophisticated experimental studies have provided insights into human disease, but for this review, the literature citations were limited to articles published after our previous review (Deroo and Korach in J Clin Invest 116(3):561-570, 2006) and will focus in most cases on human data and clinical trials. We will describe the influence in which estrogen's action, through one of or both of the ERs, mediates the aforementioned human disease states.
C1 [Burns, Katherine A.; Korach, Kenneth S.] NIEHS, Receptor Biol Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
RP Korach, KS (reprint author), NIEHS, Receptor Biol Sect, Lab Reprod & Dev Toxicol, NIH, B3-02,POB 12233, Res Triangle Pk, NC 27709 USA.
EM korach@niehs.nih.gov
OI Korach, Kenneth/0000-0002-7765-418X
FU NIH, National Institute of Environmental Health Sciences [Z01ES70065]
FX This research was supported by Z01ES70065 to KSK by the Intramural
Research Program of the NIH, National Institute of Environmental Health
Sciences.
NR 183
TC 74
Z9 76
U1 5
U2 51
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5761
J9 ARCH TOXICOL
JI Arch. Toxicol.
PD OCT
PY 2012
VL 86
IS 10
BP 1491
EP 1504
DI 10.1007/s00204-012-0868-5
PG 14
WC Toxicology
SC Toxicology
GA 003VW
UT WOS:000308640500002
PM 22648069
ER
PT J
AU Bible, KC
Peethambaram, PP
Oberg, AL
Maples, W
Groteluschen, DL
Boente, M
Burton, JK
Dahl, LCG
Tibodeau, JD
Isham, CR
Maguire, JL
Shridhar, V
Kukla, AK
Voll, KJ
Mauer, MJ
Colevas, AD
Wright, J
Doyle, LA
Erlichman, C
AF Bible, Keith C.
Peethambaram, Prema P.
Oberg, Ann L.
Maples, William
Groteluschen, David L.
Boente, Matthew
Burton, Jill K.
Dahl, Leigh C. Gomez
Tibodeau, Jennifer D.
Isham, Crescent R.
Maguire, Jacie L.
Shridhar, Viji
Kukla, Andrea K.
Voll, Kalli J.
Mauer, Mathew J.
Colevas, Alexander D.
Wright, John
Doyle, L. Austin
Erlichman, Charles
CA Mayo Phase 2 Consortium P2C
NCCTG
TI A Phase 2 Trial of Flavopiridol (Alvocidib) and Cisplatin in
Platin-Resistant Ovarian and Primary Peritoneal Carcinoma: MC0261
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Cyclin dependent kinase; CDK; Stat-3
ID PEGYLATED LIPOSOMAL DOXORUBICIN; II TRIAL; ONCOLOGY-GROUP; EPITHELIAL
OVARIAN; CYTOTOXIC SYNERGY; IMATINIB MESYLATE; CANCER; RECURRENT;
TRANSCRIPTION; MALIGNANCIES
AB Purpose. Based upon promising preclinical and phase 1 trial results, combined flavopiridol and cisplatin therapy was evaluated in patients with ovarian and primary peritoneal cancers.
Methods. A two cohort phase 2 trial of cisplatin (60 mg/m(2) IV) immediately followed by flavopiridol (100 mg/m(2) IV, 24 h infusion; 21 day cycles) was undertaken in patients with recurrent platin-sensitive or platin-resistant disease (progression > vs. <= 6 months following prior platin-based therapy). Measurable disease (RECIST) - or evaluable disease plus CA125 > 2X post-treatment nadir - and ECOG performance <= 2 were required.
Results. Forty-five patients were enrolled between December 23, 2004 and February 25, 2010: 40 platin-resistant (Group 1), and 5 platin-sensitive (Group 2). ill Group 1, the median number of treatment cycles was 3 (range 2-12). Only 10% of patients incurred grade 4 toxicities, but grade 3 toxicities were common (65%): neutropenia (17.5%); nausea (12.5%); vomiting, fatigue, thrombosis, anemia (10% each). Seven patients (17.5%) achieved a confirmed response (1 CR, 6 PR; median duration 118 days); ten additional patients (25%) attained maintained stable disease. Median time to progression was 4.3 months; overall survival was 16.1 months. Pilot translational studies assessed ascites flavopiridol level: surrogate marker studies were uninformative. In Group 2, although 4 of 5 patients responded (2 confirmed PRs with median time to progression, 10.8 months and median overall survival 20.6 months) the cohort was closed due to poor accrual.
Conclusions. The assessed flavopiridol and cisplatin regimen displayed clinical activity in platin resistant and sensitive ovarian/primary peritoneal cancers, meriting further study. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Bible, Keith C.; Peethambaram, Prema P.; Burton, Jill K.; Tibodeau, Jennifer D.; Isham, Crescent R.; Kukla, Andrea K.; Voll, Kalli J.; Erlichman, Charles] Mayo Clin, Div Med Oncol, Rochester, MN 55905 USA.
[Oberg, Ann L.; Dahl, Leigh C. Gomez; Mauer, Mathew J.] Mayo Clin, Canc Ctr Stat, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Maples, William] Mayo Clin Jacksonville, Div Med Oncol, Jacksonville, FL 32224 USA.
[Groteluschen, David L.] Green Bay Oncol, Green Bay, WI USA.
[Boente, Matthew] Metro Minnesota CCOP, St Louis Pk, MN USA.
[Maguire, Jacie L.; Shridhar, Viji] Mayo Clin, Dept Expt Pathol, Rochester, MN 55905 USA.
[Colevas, Alexander D.; Wright, John; Doyle, L. Austin] NCI, CTEP, Bethesda, MD 20892 USA.
RP Bible, KC (reprint author), Mayo Clin, Div Med Oncol, 200 1st St SW, Rochester, MN 55905 USA.
EM bible.keith@mayo.edu
FU National Cancer Institute [CM17104, CA097129, CA15083, CM62205]
FX This work was supported by National Cancer Institute CM17104, CA097129,
CA15083 and CM62205; Clinicaltrials.gov identifier: NCT00083122.
NR 31
TC 26
Z9 28
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD OCT
PY 2012
VL 127
IS 1
BP 55
EP 62
DI 10.1016/j.ygyno.2012.05.030
PG 8
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 005XQ
UT WOS:000308783800012
PM 22664059
ER
PT J
AU Tettelin, H
Sampaio, EP
Daugherty, SC
Hine, E
Riley, DR
Sadzewicz, L
Sengamalay, N
Shefchek, K
Su, Q
Tallon, LJ
Conville, P
Olivier, KN
Holland, SM
Fraser, CM
Zelazny, AM
AF Tettelin, Herve
Sampaio, Elizabeth P.
Daugherty, Sean C.
Hine, Erin
Riley, David R.
Sadzewicz, Lisa
Sengamalay, Naomi
Shefchek, Kent
Su, Qi
Tallon, Luke J.
Conville, Patricia
Olivier, Kenneth N.
Holland, Steven M.
Fraser, Claire M.
Zelazny, Adrian M.
TI Genomic Insights into the Emerging Human Pathogen Mycobacterium
massiliense
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID ABSCESSUS; SEQUENCE
AB Mycobacterium massiliense (Mycobacterium abscessus group) is an emerging pathogen causing pulmonary disease and skin and soft tissue infections. We report the genome sequence of the type strain CCUG 48898.
C1 [Tettelin, Herve; Daugherty, Sean C.; Hine, Erin; Riley, David R.; Sadzewicz, Lisa; Sengamalay, Naomi; Shefchek, Kent; Su, Qi; Tallon, Luke J.; Fraser, Claire M.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Inst Genome Sci, Baltimore, MD 21201 USA.
[Sampaio, Elizabeth P.; Olivier, Kenneth N.; Holland, Steven M.; Zelazny, Adrian M.] NIAID, Lab Clin Infect Dis, LCID, NIH, Bethesda, MD 20892 USA.
[Sampaio, Elizabeth P.] Fiocruz MS, Inst Oswaldo Cruz, Leprosy Lab, BR-21045900 Rio De Janeiro, Brazil.
[Conville, Patricia; Zelazny, Adrian M.] NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Tettelin, H (reprint author), Univ Maryland, Sch Med, Dept Microbiol & Immunol, Inst Genome Sci, Baltimore, MD 21201 USA.
EM tettelin@som.umaryland.edu
OI Fraser, Claire/0000-0003-1462-2428
FU federal funds from the National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Department of Health and Human
Services [HHSN272200900007C]
FX This project has been funded in part with federal funds from the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services, under
contract number HHSN272200900007C.
NR 6
TC 9
Z9 10
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD OCT
PY 2012
VL 194
IS 19
BP 5450
EP 5450
DI 10.1128/JB.01200-12
PG 1
WC Microbiology
SC Microbiology
GA 005KQ
UT WOS:000308749700034
PM 22965080
ER
EF