FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Kim, YB
AF Kim, Young Bae
TI Improved trimethoprim-resistance cassette for prokaryotic selections
SO JOURNAL OF BIOSCIENCE AND BIOENGINEERING
LA English
DT Article
DE Dihydrofolate reductase (dfr); Trimethoprim (Tmp); Cloning vector;
Plasmid construction; Transformation; Selectable marker; Antibiotic
resistance
ID DIHYDROFOLATE-REDUCTASE GENE; NUCLEOTIDE-SEQUENCE; VECTORS; PBR322; COPY
AB Many of the antibiotic resistance elements used in molecular biology have idiosyncratic limitations. For example, beta-lactam selections rely on. antibiotics that are unstable to hydrolysis and allow satellite colonies to form upon extended incubation, and tetracycline selections typically give rise to widely varying colony sizes and lower transformation efficiencies. Although prokaryotic Type II dihydrofolate reductase (dfr) genes have long been considered to have potential utility for the selection of plasmids and mobile elements in bacteria, practical limitations to the quality of those selections, mostly relating to background and inefficiency, have led for the most part to their underuse. I describe here the construction of a Type Ila dfr prokaryotic expression cassette that confers strong resistance against trimethoprim (Tmp), a bactericidal dfr inhibiting antibiotic. The Tmp-resistance cassette provides consistent and efficient selections and plasmid transformation frequencies equivalent to those encountered with beta-lactamases. (C) 2009, The Society for Biotechnology, Japan. All rights reserved.
C1 [Kim, Young Bae] Massachusetts Gen Hosp, CCIB, Boston, MA 02114 USA.
[Kim, Young Bae] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
RP Kim, YB (reprint author), Massachusetts Gen Hosp, CCIB, 185 Cambridge St, Boston, MA 02114 USA.
EM ykim@ccib.mgh.harvard.edu
FU Sundry Seed Lab
FX I thank Dr. Brian Seed for his support and encouragement during this
work. This work was supported by the Sundry Seed Lab Research Fund. I
also thank Dr. Eun-Kyung Suh (Harvard Medical School), Ms. Aimee Landry
(CCIB, MGH) and particularly Dr. Linda Chun (CCIB, MGH) for helpful
suggestions on the manuscript, and Seed lab members for testing and
making use of the materials.
NR 15
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PU SOC BIOSCIENCE BIOENGINEERING JAPAN
PI OSAKA
PA OSAKA UNIV, FACULTY ENGINEERING, 2-1 YAMADAOKA, SUITA, OSAKA, 565-0871,
JAPAN
SN 1389-1723
J9 J BIOSCI BIOENG
JI J. Biosci. Bioeng.
PD NOV
PY 2009
VL 108
IS 5
BP 441
EP 445
DI 10.1016/j.jbiosc.2009.05.015
PG 5
WC Biotechnology & Applied Microbiology; Food Science & Technology
SC Biotechnology & Applied Microbiology; Food Science & Technology
GA 539IN
UT WOS:000273247700017
PM 19804872
ER
PT J
AU Souer, JS
Ring, D
Jupiter, JB
Matschke, S
Audige, L
Marent-Huber, M
AF Souer, J. Sebastiaan
Ring, David
Jupiter, Jesse B.
Matschke, Stefan
Audige, Laurent
Marent-Huber, Marta
CA AOCID Prospective ORIF Distal Radi
TI Comparison of AO Type-B and Type-C Volar Shearing Fractures of the
Distal Part of the Radius
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Article
ID LUNATE FACET; FIXATION; ADULTS; SF-36
AB Background: Fractures of the volar articular margin of the distal part of the radius with volar radiocarpal subluxation (volar shearing, or Barton, fractures) can be accompanied by a fracture of the dorsal metaphyseal cortex. We tested the null hypothesis that there is no difference in wrist function or health status after open reduction and plate-and-screw fixation between volar shearing fractures with a dorsal cortical fracture (complete articular, AO Type C) and those without :I dorsal cortical fracture (partial articular, AO Type B).
Methods: In a multicenter cohort study, fifty-seven patients with a volar marginal shearing fracture of the distal part of the radius and volar radiocarpal subluxation were followed for at least one year following plate-and-screw fixation. Thirty-seven patients who also had a dorsal metaphyseal cortical fracture (Type-C fracture) were compared with twenty patients who had a partial articular (Type-B) fracture. The two cohorts were analyzed for differences in wrist and forearm motion,; grip strength, pain, and the Gartland and Werley, Disabilities of the Arm, Shoulder and Hand (DASH), and Short Form-36 (SF-36) scores at six, twelve, and twenty-four months postoperatively. Differences in mean values and their change over time were determined.
Results: There were no significant differences between patients with a Type-B fracture and those with a Type-C fracture with respect to motion, grip strength, or the Gartland and Werley or DASH score at any time point. At six months after the surgery, the patients with a Type-B volar shearing fracture reported a mean score for pain in motion of 0.5 point on a 10-point visual analogue scale compared with 2.2 points for patients with a Type-C fracture (difference in means, 1.7 points [95% confidence interval, 0.7 to 2.6 points]; p < 0.001), but no significant difference was seen at twelve or twenty-four months.
Conclusions: Volar shearing fractures are usually complete articular, Type-C injuries. Patients with a Type-C volar shearing fracture experience more pain during early recovery, but ultimately their outcome is comparable with that for patients with a Type-B (partial articular) volar shearing fracture.
C1 [Souer, J. Sebastiaan] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Souer, JS (reprint author), Massachusetts Gen Hosp, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
RI AOCID, AO Foundation/R-6455-2016
FU AO Clinical Investigation and Documentation (AOCID); Small Bone
Innovations; Smith and Nephew Richards; Wright Medical; Tornier; Acumed;
Joint Active Systems; Biomet; Stryker; DePuy; Hand Innovations; Skeletal
Dynamics; Illuminos; Mimedex
FX In support of their research for or preparation of this work, one or
more of the authors received, in any one year, outside funding or grants
in excess of $10,000 from AO Clinical Investigation and Documentation
(AOCID). In addition, one or more of the authors or a member of his or
her immediate family received, in any one year, payments or other
benefits in excess of $10,000 (in total) or a commitment or agreement to
provide such benefits from commercial entities (Small Bone Innovations,
Smith and Nephew Richards, Wright Medical, Tornier, Acumed, Joint Active
Systems, Biomet, Stryker, DePuy, Hand Innovations, Skeletal Dynamics,
Illuminos, and Mimedex).
NR 16
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U1 0
U2 1
PU JOURNAL BONE JOINT SURGERY INC
PI NEEDHAM
PA 20 PICKERING ST, NEEDHAM, MA 02192 USA
SN 0021-9355
J9 J BONE JOINT SURG AM
JI J. Bone Joint Surg.-Am. Vol.
PD NOV
PY 2009
VL 91A
IS 11
BP 2605
EP 2611
DI 10.2106/JBJS.H.01479
PG 7
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 518DZ
UT WOS:000271671800011
PM 19884434
ER
PT J
AU Jupiter, JB
Fernandez, DL
Levin, LS
Wysocki, RW
AF Jupiter, Jesse B.
Fernandez, Diego L.
Levin, L. Scott
Wysocki, Robert W.
TI Reconstruction of Posttraumatic Disorders of the Forearm
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Article
ID VASCULARIZED FIBULAR GRAFT; ULNAR TORSION PROFILES; DONOR-SITE
MORBIDITY; ONE-BONE FOREARM; SEGMENTAL DEFECTS; PLATE FIXATION;
INTEROSSEOUS MEMBRANE; MALUNITED FRACTURES; LONG BONES; ANTERIOR
DISLOCATION
RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Hand & Upper Limb Serv, Yawkey Bldg,Suite 2100,55 Parknian St, Boston, MA 02114 USA.
EM jjupiter1@partners.org; diegof@bluewin.ch; scott.levin@uphs.upenn.edu;
robertwysocki@mac.com
NR 86
TC 4
Z9 5
U1 0
U2 1
PU JOURNAL BONE JOINT SURGERY INC
PI NEEDHAM
PA 20 PICKERING ST, NEEDHAM, MA 02192 USA
SN 0021-9355
J9 J BONE JOINT SURG AM
JI J. Bone Joint Surg.-Am. Vol.
PD NOV
PY 2009
VL 91A
IS 11
BP 2730
EP 2739
PG 10
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 518DZ
UT WOS:000271671800027
PM 19884450
ER
PT J
AU Friedman, DJ
Afkarian, M
Tamez, H
Bhan, I
Isakova, T
Wolf, M
Ankers, E
Ye, J
Tonelli, M
Zoccali, C
Kuro-o, M
Moe, O
Karumanchi, SA
Thadhani, R
AF Friedman, David J.
Afkarian, Maryam
Tamez, Hector
Bhan, Ishir
Isakova, Tamara
Wolf, Myles
Ankers, Elizabeth
Ye, Jun
Tonelli, Marcello
Zoccali, Carmine
Kuro-o, Makoto
Moe, Orson
Karumanchi, S. Ananth
Thadhani, Ravi
TI Klotho Variants and Chronic Hemodialysis Mortality
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE Klotho; hemodialysis; mortality; vitamin D; fibroblast growth factor-23;
HapMap; end-stage renal disease; polymorphism
ID POSTMENOPAUSAL WOMEN; FUNCTIONAL VARIANT; GENE-EXPRESSION; TRPV5
CHANNEL; BONE-DENSITY; ASSOCIATION; MICE; POLYMORPHISMS; MUTATION;
RECEPTOR
AB Patients with end-stage renal disease (ESRD) suffer exceptionally high mortality rates in their first year of chronic hemodialysis. Both vitamin D and fibroblast growth factor (FGF)-23 levels correlate with survival in these patients. Klotho is a protein in the vitamin D/FGF-23 signaling pathway that has been linked with accelerated aging and early mortality in animal models. We therefore hypothesized that genetic variation in the Klotho gene might be associated with survival in subjects with ESRD. We tested the association between 12 single nucleotide polymorphisms (SNPs) in the Klotho gene and mortality in a cohort of ESRD patients during their first year on hemodialysis (n =1307 white and Asian). We found a significant association between the CC genotype of one tag SNP, rs577912, and increased risk for 1-yr mortality (RR, 1.76; 95% CI, 1.19-2.59; p = 0.003). This effect was even more marked among patients who were not treated with activated vitamin D supplementation (HR, 2.51; 95% CI, 1.18-5.34; p = 0.005). In lymphoblastoid cell lines derived from HapMap subjects, the CC genotype was associated with a 16-21% lower Klotho expression compared with the AA/AC genotype. Our data suggest that a specific Klotho variant (rs577912) is linked to survival in ESRD patients initiating chronic hemodialysis and that therapy with activated vitamin D may modify this risk. J Bone Miner Res 2009;24:1847-1855. Published online on May 4, 2009; doi: 10.1359/JBMR.090516
C1 [Afkarian, Maryam; Tamez, Hector; Bhan, Ishir; Isakova, Tamara; Ankers, Elizabeth; Ye, Jun; Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Friedman, David J.; Karumanchi, S. Ananth] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr,Ctr Vasc Biol Res, Boston, MA 02114 USA.
[Wolf, Myles] Univ Miami, Sch Med, Miami, FL USA.
[Tonelli, Marcello] Univ Alberta, Dept Med, Edmonton, AB, Canada.
[Zoccali, Carmine] Osped Riuniti, CNR, IBIM Clin Epidemiol Renal Dis & Hypertens, Calabria, Italy.
[Karumanchi, S. Ananth] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA.
RP Thadhani, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bullfinch 127,55 Fruit St, Boston, MA 02114 USA.
EM rthadhani@partners.org
RI Tonelli, Marcello/B-3028-2009;
OI Zoccali, Carmine/0000-0002-6616-1996
FU NIH [DK076868]; National Institutes of Health [DK71674, DK076116,
HL093954]
FX D.F. is supported by DK076868 (NIH). R.T. is supported by DK71674,
DK076116, and HL093954, all by the National Institutes of Health.
NR 28
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U1 0
U2 2
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD NOV
PY 2009
VL 24
IS 11
BP 1847
EP 1855
DI 10.1359/JBMR.090516
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 518XU
UT WOS:000271730200010
PM 19419323
ER
PT J
AU Aono, Y
Yamazaki, Y
Yasutake, J
Kawata, T
Hasegawa, H
Urakawa, I
Fujita, T
Wada, M
Yamashita, T
Fukumoto, S
Shimada, T
AF Aono, Yukiko
Yamazaki, Yuji
Yasutake, Junichi
Kawata, Takehisa
Hasegawa, Hisashi
Urakawa, Itaru
Fujita, Toshiro
Wada, Michihito
Yamashita, Takeyoshi
Fukumoto, Seiji
Shimada, Takashi
TI Therapeutic Effects of Anti-FGF23 Antibodies in Hypophosphatemic
Rickets/Osteomalacia
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE fibroblast growth factor 23; X-linked hypophosphatemia; phosphatonin;
neutralizing antibody; novel therapy
ID X-LINKED HYPOPHOSPHATEMIA; VITAMIN-D METABOLISM; HYP-MICE; IN-VIVO;
PHOSPHATE HOMEOSTASIS; PROTEOLYTIC CLEAVAGE; PARATHYROID-HORMONE;
PHYSIOLOGICAL-ROLE; PEX GENE; FGF23
AB X-linked hypophosphatemia (XLH), characterized by renal phosphate wasting, is the most common cause of vitamin D-resistant rickets. It has been postulated that some phosphaturic factor plays a causative role in XLH and its murine homolog, the Hyp mouse. Fibroblast growth factor 23 (FGF23) is a physiological phosphaturic factor; its circulatory level is known to be high in most patients with XLH and Hyp mice, suggesting its pathophysiological role in this disease. To test this hypothesis, we treated Hyp mice with anti-FGF23 antibodies to inhibit endogenous FGF23 action. A single injection of the antibodies corrected the hypophosphatemia and inappropriately normal serum 1,25-dihydroxyvitamin D. These effects were accompanied by increased expressions of type IIa sodium-phosphate cotransporter and 25-hydroxyvitamin-D-1 alpha-hydroxylase and a suppressed expression of 24-hydroxylase in the kidney. Repeated injections during the growth period ameliorated the rachitic bone phenotypes typically observed in Hyp mice, such as impaired longitudinal elongation, defective mineralization, and abnormal cartilage development. Thus, these results indicate that excess actions of FGF23 underlie hypophosphatemic rickets in Hyp mice and suggest a novel therapeutic potential of the FGF23 antibodies for XLH. J Bone Miner Res 2009;24:1879-1888. Published online on May 4, 2009; doi: 10.1359/JBMR.090509
C1 [Fukumoto, Seiji] Tokyo Univ Hosp, Dept Med, Div Nephrol & Endocrinol, Bunkyo Ku, Tokyo 1138655, Japan.
[Yamazaki, Yuji; Yasutake, Junichi; Urakawa, Itaru; Yamashita, Takeyoshi; Shimada, Takashi] Tokyo Univ Hosp, Innovat Drug Res Labs, Tokyo 1138655, Japan.
[Aono, Yukiko; Kawata, Takehisa; Hasegawa, Hisashi; Wada, Michihito] Tokyo Univ Hosp, Pharmacol Res Labs, Tokyo 1138655, Japan.
[Shimada, Takashi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA.
RP Fukumoto, S (reprint author), Tokyo Univ Hosp, Dept Med, Div Nephrol & Endocrinol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.
EM fukumoto-tky@umin.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan;
Ministry of Health, Labor and Welfare of Japan
FX The authors thank K. Ono, R. Hino, N. Kobayashi, S. Miyata, S. Wakita,
and M. Abe for excellent technical assistance and Drs. T. Sakai and M.
Paskewitz for fruitful discussion. This work was partly supported by
grants from the Ministry of Education, Culture, Sports, Science and
Technology of Japan and from the Ministry of Health, Labor and Welfare
of Japan.
NR 39
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U1 4
U2 17
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD NOV
PY 2009
VL 24
IS 11
BP 1879
EP 1888
DI 10.1359/JBMR.090509
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 518XU
UT WOS:000271730200013
PM 19419316
ER
PT J
AU Izamis, ML
Uygun, K
Uygun, B
Yarmush, ML
Berthiaume, F
AF Izamis, Maria-Louisa
Uygun, Korkut
Uygun, Basak
Yarmush, Martin L.
Berthiaume, Francois
TI Effects of Burn Injury on Markers of Hypermetabolism in Rats
SO JOURNAL OF BURN CARE & RESEARCH
LA English
DT Article
ID THERMAL-INJURY; MUSCLE CATABOLISM; FLUID RETENTION; RESISTANCE;
CHILDREN; OUTCOMES; AGE; SURVIVAL; TRAUMA; GENDER
AB The basic metrics of hypermetabolism have not been thoroughly characterized in rat burn injury models. We examined three models expected to differ in sensitivity to burn injury to identify that which group(s) exhibited the most clinically relevant metabolic response. Six and 12 weeks old male CD (6 week mCD and 12 week mCD) rats, and 12 weeks old female Fischer (12 week fFI) rats received a 20% total body surface area burn, followed by saline resuscitation. Activity, core body temperature, heart rate (via implanted telemetry devices), body weight, food and water intake, and fecal output were measured daily for 1 week before and after burn. Rats lost weight initially postburn but resumed weight gain by 1 week, except for 12 week mCD rats. Core body temperature increased above normal 2 days postburn and returned to baseline by 1 week. Food intake, normalized to body weight, remained unchanged postburn for 12 week mCD rats, but decreased in 6 week mCD rats and increased in 12 week fFI rats. Heart rate in the 12 week mCD and 12 week fFI rats remained at 10 to 15% above baseline, whereas, in 6 week mCD, heart rates returned to baseline after 4 days. Activity levels were unchanged for 12 week fFI and 6 week mCD rats postburn, but decreased for 12 week mCD rats. Postburn hypermetabolism was most significant and sustained in 12 week mCD rats, of least consequence and brief in 6 week mCD rats, and intermediate in 12 week tFI rats. The disparate responses indicate that the choice of animal model should be carefully considered in hypermetabolism studies. (J Burn Care Res 2009;30:993-1001)
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med Surg Serv, Boston, MA USA.
Shriners Hosp Children, Boston, MA USA.
RP Berthiaume, F (reprint author), Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA.
RI Uygun, Basak/I-1792-2012
OI Uygun, Basak/0000-0002-2600-7900
FU Shriners Hospitals for Children [8640, 8450, 8460, 8490, 8496, 8503]
FX Supported by the Shriners Hospitals for Children grants 8640, 8450,
8460, 8490, for this work, and Shriners Hospitals for Children
Fellowships 8496 (to K. U.) and 8503 (to B. U.).
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U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1559-047X
J9 J BURN CARE RES
JI J. Burn Care Res.
PD NOV-DEC
PY 2009
VL 30
IS 6
BP 993
EP 1001
DI 10.1097/BCR.0b013e3181bfb7b4
PG 9
WC Emergency Medicine; Dermatology; Surgery
SC Emergency Medicine; Dermatology; Surgery
GA 518BS
UT WOS:000271665700009
PM 19898103
ER
PT J
AU Haime, M
AF Haime, Miguel
TI Right Atrial Myxoma
SO JOURNAL OF CARDIAC SURGERY
LA English
DT Editorial Material
AB (J Card Surg 009;24:691-692).
C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, W Roxbury, MA 02132 USA.
RP Haime, M (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, 1400 VFW Pkwy, W Roxbury, MA 02132 USA.
EM miguel.haime@med.va.gov
NR 0
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U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0886-0440
J9 J CARDIAC SURG
JI J. Card. Surg.
PD NOV
PY 2009
VL 24
IS 6
BP 691
EP 692
DI 10.1111/j.1540-8191.2009.00903.x
PG 2
WC Cardiac & Cardiovascular Systems; Surgery
SC Cardiovascular System & Cardiology; Surgery
GA 516EB
UT WOS:000271523400020
PM 19793251
ER
PT J
AU Ramlawi, B
Otu, H
Russo, MJ
Novick, RJ
Bianchi, C
Sellke, FW
AF Ramlawi, Basel
Otu, Hasan
Russo, Mark J.
Novick, Richard J.
Bianchi, Cesario
Sellke, Frank W.
TI Aprotinin Attenuates Genomic Expression Variability Following Cardiac
Surgery
SO JOURNAL OF CARDIAC SURGERY
LA English
DT Article
ID BYPASS GRAFT-SURGERY; SERINE-PROTEASE INHIBITORS; CARDIOPULMONARY
BYPASS; OLIGONUCLEOTIDE; OUTCOMES; MICROARRAYS; ACTIVATION; DISEASE;
INJURY; SAFETY
AB P>Background: Aprotinin was the subject of recent controversy regarding adverse clinical outcomes following cardiac surgery. We compared the role of Aprotinin and epsilon-aminocaproic acid on clinical outcomes and the attenuation of the postcardiopulmonary bypass (CPB) response at the genomic expression and cytokine (protein) level. Methods: Thirty-nine low-risk patients undergoing coronary revascularization (CABG) and/or valve procedures using cardiopulmonary CPB were enrolled into a prospective cohort study. Aprotinin or epsilon-aminocaproic acid was administered to patients. Gene expression was assessed from whole blood mRNA samples collected preoperatively (PRE) and 6 hours (6H) postoperatively. Validation of gene expression was performed with SYBR Green real-time polymerase chain reaction. Cytokine values were quantified from serum preoperatively and postoperatively at 6 H and 4 days and analyzed in a blinded fashion. Results: No difference was detected in baseline characteristics. Inflammatory markers measured did not reveal significant difference between patients receiving Aprotinin (APR) and those receiving epsilon-aminocaproic acid (Amicar). Intraoperative parameters and postoperative outcomes were not significantly different. Compared with PRE samples, 6H samples had 264 upregulated and 548 downregulated genes uniquely in the APR group compared to 4826 upregulated and 1114 downregulated genes uniquely in the Amicar group (p < 0.001). Compared to patients in the Amicar group, APR patients had significantly different gene expression pathways involving NF-kappa beta regulation, programmed cell death and cell-cell adhesion. None of the patients developed postoperative stroke, myocardial infarction, or systemic infections. Conclusions: Aprotinin leads to significantly less genomic expression variability following CPB compared to Amicar and has a differential effect on specific genomic pathways.
(J Card Surg 2009;24:772-780).
C1 [Bianchi, Cesario; Sellke, Frank W.] Harvard Univ, Div Cardiothorac Surg, Sch Med, BIDMC, Boston, MA 02215 USA.
[Ramlawi, Basel; Russo, Mark J.] Columbia Univ, Columbia Presbyterian Med Ctr, Div Cardiothorac Surg, New York, NY 10032 USA.
[Otu, Hasan] Harvard Univ, Sch Med, Genom Ctr, BIDMC, Boston, MA 02215 USA.
[Novick, Richard J.] Univ Western Ontario, Div Cardiac Surg, London, ON N6A 3K7, Canada.
RP Sellke, FW (reprint author), Harvard Univ, Div Cardiothorac Surg, Sch Med, BIDMC, LMOB 2A,110 Francis St, Boston, MA 02215 USA.
EM fsellke@caregroup.harvard.edu
RI bianchi, cesario/H-6238-2012;
OI Otu, Hasan/0000-0002-9253-8152
FU Irving Bard Memorial Fellowship; NIH [HL04095-06, HL-46716];
CIHR/Canadian Stroke Network Postdoctoral Research Fellowship
FX Financial Support: Research supported by the Irving Bard Memorial
Fellowship. Dr. Basel Ramlawi is supported by grant HL04095-06 from the
NIH as well as a CIHR/Canadian Stroke Network Postdoctoral Research
Fellowship. Dr. Frank Sellke is supported by grant HL-46716 from the
NIH.
NR 37
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U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0886-0440
J9 J CARDIAC SURG
JI J. Card. Surg.
PD NOV
PY 2009
VL 24
IS 6
BP 772
EP 780
DI 10.1111/j.1540-8191.2009.00924.x
PG 9
WC Cardiac & Cardiovascular Systems; Surgery
SC Cardiovascular System & Cardiology; Surgery
GA 516EB
UT WOS:000271523400042
PM 19754679
ER
PT J
AU Todani, A
Melki, SA
AF Todani, Amit
Melki, Samir A.
TI Late-onset epithelial ingrowth after laser in situ keratomileusis
SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY
LA English
DT Article
ID PREVENTION
AB We report a case of late-onset epithelial ingrowth that occurred between 17 months and 20 months after an uneventful laser in situ keratomileusis (LASIK) enhancement. The patient denied a history of trauma or symptoms consistent with epithelial disruption. Post-LASIK treatment had included lifting the flap and scraping the epithelial cells followed by placement of corneal flap sutures for several weeks and a bandage contact lens for 3 days. Gradual regression of epithelial cells was noted. The last recorded uncorrected distance visual acuity 24 months after scraping was 20/25. Epithelial ingrowth can occur many months after LASIK even in the absence of predisposing factors such as trauma or recurrent erosion syndrome. J Cataract Refract Surg 2009; 35:2022-2023 (C) 2009 ASCRS and ESCRS
C1 [Melki, Samir A.] Harvard Univ, Cornea & Refract Surg Serv, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
Boston Eye Grp, Brookline, MA USA.
RP Melki, SA (reprint author), Harvard Univ, Cornea & Refract Surg Serv, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
EM samir_melki@meei.harvard.edu
NR 7
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Z9 3
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0886-3350
J9 J CATARACT REFR SURG
JI J. Cataract. Refract. Surg.
PD NOV
PY 2009
VL 35
IS 11
BP 2022
EP 2023
DI 10.1016/j.jcrs.2009.05.044
PG 2
WC Ophthalmology; Surgery
SC Ophthalmology; Surgery
GA 518WF
UT WOS:000271725600028
PM 19878839
ER
PT J
AU Fangusaro, J
Chi, S
AF Fangusaro, Jason
Chi, Susan
TI Introduction to a Special Issue on Pediatric Neuro-Oncology
SO JOURNAL OF CHILD NEUROLOGY
LA English
DT Editorial Material
ID LONG-TERM SURVIVORS; BRAIN-TUMORS; EPIDEMIOLOGY; CHILDHOOD; CHILDREN;
ADOLESCENCE
C1 [Fangusaro, Jason] Childrens Mem Hosp, Dept Hematol Oncol Stem Cell Transplantat, Chicago, IL 60614 USA.
[Chi, Susan] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Fangusaro, J (reprint author), Childrens Mem Hosp, Dept Hematol Oncol Stem Cell Transplantat, Chicago, IL 60614 USA.
NR 18
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U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0883-0738
J9 J CHILD NEUROL
JI J. Child Neurol.
PD NOV
PY 2009
VL 24
IS 11
BP 1341
EP 1342
DI 10.1177/0883073809338959
PG 2
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 510RP
UT WOS:000271109100002
PM 19841423
ER
PT J
AU Hoffman, KE
Yock, TI
AF Hoffman, Karen E.
Yock, Torunn I.
TI Radiation Therapy for Pediatric Central Nervous System Tumors
SO JOURNAL OF CHILD NEUROLOGY
LA English
DT Article
DE primary central nervous system neoplasms; radiotherapy; proton radiation
ID LOW-GRADE GLIOMAS; CHILDHOOD MEDULLOBLASTOMA; PHOTON RADIOTHERAPY;
PROTON RADIOTHERAPY; CLINICAL-OUTCOMES; BRAIN-TUMORS; SURVIVORS; CANCER;
CHEMOTHERAPY; EPENDYMOMA
AB Radiation therapy is an important component of treatment of many pediatric central nervous system tumors. The radiation treatment target is determined by tumor histology, extent of disease, anticipated pattern of spread, and expected pattern of failure. Children cured of their tumors live to experience the long-term sequelae of radiation treatment, including developmental, neurocognitive, neuroendocrine, and hearing late effects The development of more conformal radiation techniques has decreased inadvertent radiation dose to normal tissues and should decrease long-term treatment sequelae that are the result of normal tissue radiation Intensity-modulated radiation therapy improves treatment conformity and decreases high dose to nearby normal tissues. however, it delivers a larger volume of low- and intermediate-dose radiation. Proton radiation eliminates exit dose to normal tissues, thereby eliminating approximately 50% of unnecessary radiation to normal tissues. The long-term clinical benefits of proton radiation in the pediatric population are just beginning to be reported in the literature.
C1 [Yock, Torunn I.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Hoffman, Karen E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA.
RP Yock, TI (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 341, Boston, MA 02114 USA.
EM tyock@partners.org
NR 31
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U1 0
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0883-0738
J9 J CHILD NEUROL
JI J. Child Neurol.
PD NOV
PY 2009
VL 24
IS 11
BP 1387
EP 1396
DI 10.1177/0883073809342275
PG 10
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 510RP
UT WOS:000271109100006
PM 19841427
ER
PT J
AU Ullrich, NJ
AF Ullrich, Nicole J.
TI Neurologic Sequelae of Brain Tumors in Children
SO JOURNAL OF CHILD NEUROLOGY
LA English
DT Article
DE brain tumors; late effects; neurologic sequelae; chemotherapy; headache;
hydrocephalus
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CENTRAL-NERVOUS-SYSTEM; QUALITY-OF-LIFE;
RADIATION-THERAPY; PUNCTURE HEADACHE; CHILDHOOD-CANCER; SURVIVORS;
SEIZURES; MEDULLOBLASTOMA; CHEMOTHERAPY
AB Neurologic signs and symptoms are often the initial presenting features of a primary brain tumor and may also emerge during the course of therapy of as late effects of the tumor and its treatment. Variables that influence the development of such neurologic complications include the type, size, and location of the tumor, the patient's age at diagnosis, and the treatment modalities used. Heightened surveillance and improved neuroimaging modalities have been instrumental in detecting and addressing such complications, which are often not appreciated until many years after completion of therapy. As Current brain tumor therapies arc continually refined and newer targeted therapies are developed, it will be important for future cooperative group studies to include systematic assessments to determine the incidence of neurologic complications and to provide a framework for the development of novel strategies for prevention and intervention.
C1 [Ullrich, Nicole J.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA.
[Ullrich, Nicole J.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
RP Ullrich, NJ (reprint author), Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA.
EM nicole.ullrich@childrens.harvard.edu
NR 50
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U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0883-0738
J9 J CHILD NEUROL
JI J. Child Neurol.
PD NOV
PY 2009
VL 24
IS 11
BP 1446
EP 1454
DI 10.1177/0883073809342491
PG 9
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 510RP
UT WOS:000271109100012
PM 19841432
ER
PT J
AU Turner, CD
Rey-Casserly, C
Liptak, CC
Chordas, C
AF Turner, Christopher D.
Rey-Casserly, Celiane
Liptak, Cori C.
Chordas, Christine
TI Late Effects of Therapy for Pediatric Brain Tumor Survivors
SO JOURNAL OF CHILD NEUROLOGY
LA English
DT Review
DE late effects, brain tumors; survivorship, neurological deficits;
neurocognitive deficits; psychosocial, quality of life, outcomes;
transitions
ID CHILDHOOD-CANCER SURVIVOR; LONG-TERM SURVIVORS; CENTRAL-NERVOUS-SYSTEM;
QUALITY-OF-LIFE; CEREBELLAR MUTISM SYNDROME; ADULT SURVIVORS; COGNITIVE
FUNCTION; CRANIOSPINAL IRRADIATION; CRANIAL IRRADIATION; CHILDRENS
ONCOLOGY
AB Approximately 2 of every 3 of all pediatric patients with brain tumors will be long-term survivors. However, there is a steep cost for pediatric brain tumor survivors, and the group as a whole faces significantly more late effects than many other survivors of pediatric cancers. Most of these effects can be attributed to direct neurologic damage to the developing brain caused by the tumor and its removal, the long-term toxicity of chemotherapy, or the effects of irradiation on the central nervous system. The late effects experienced by childhood brain tumor survivors involve multiple domains. This article will review the significant late effects that occur within the medical, neurocognitive, psychosocial, and economic domains of the survivorship experience. We conclude by discussing how the late effects in different domains often coexist and can create a complex set of obstacles that pose significant challenges for a survivor of a pediatric brain tumor on a daily basis.
C1 [Turner, Christopher D.; Chordas, Christine] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Rey-Casserly, Celiane] Childrens Hosp, Neuropsychol Program, Dept Psychiat, Boston, MA 02115 USA.
[Liptak, Cori C.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA.
RP Turner, CD (reprint author), Dana Farber Childrens Hosp Canc Care, Pediat Neurooncol Outcomes Program, 44 Binney St,SW 331, Boston, MA 02115 USA.
NR 117
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PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0883-0738
J9 J CHILD NEUROL
JI J. Child Neurol.
PD NOV
PY 2009
VL 24
IS 11
BP 1455
EP 1463
DI 10.1177/0883073809341709
PG 9
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 510RP
UT WOS:000271109100013
PM 19841433
ER
PT J
AU Bergwitz, C
Banerjee, S
Abu-Zahra, H
Kaji, H
Miyauchi, A
Sugimoto, T
Juppner, H
AF Bergwitz, Clemens
Banerjee, Santanu
Abu-Zahra, Hilal
Kaji, Hiroshi
Miyauchi, Akimitsu
Sugimoto, Toshitsugu
Jueppner, Harald
TI Defective O-Glycosylation due to a Novel Homozygous S129P Mutation Is
Associated with Lack of Fibroblast Growth Factor 23 Secretion and
Tumoral Calcinosis
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID MISSENSE MUTATION; FGF23; FIBROBLAST-GROWTH-FACTOR-23;
HYPERPHOSPHATEMIA; DISORDER; PROTEIN; GALNT3
AB Background: Homozygous mutations in fibroblast growth factor (FGF23) have recently been described as the genetic cause of one form of hyperphosphatemic tumoral calcinosis (HFTC). However, it remained unclear to date how these mutations lead to loss of biologically active FGF23 in the circulation.
Methods: We here report a novel homozygous mutation, c. 385T > C in FGF23 exon 2, which changes codon 129 from serine to proline (S129P) in a previously described individual affected by HFTC. The S129P mutation as well as two known FGF23 mutations, S71G and S129F, were introduced into an expression vector encoding wild-type (wt) human (h) FGF23 to yield [P129]hFGF23, [F129]hFGF23, and [G71] hFGF23; whole lysates, glycoprotein fractions, and conditioned media from HEK293 and COS-7 cells expressing these constructs were subjected to Western blot analysis using affinity-purified goat anti-hFGF23(51-69) and anti-hFGF23(206-222) antibodies.
Results: We detected 25-and 32-kDa protein species in total lysates of HEK293 cells expressing wt-hFGF23. The 32-kDa band, representing O-glycosylated hFGF23, was not detectable in the glycoprotein fraction of lysates from HEK293 cells expressing [P129] hFGF23, and in comparison with wt-FGF23 only small amounts of [P129] hFGF23 were secreted into the medium. Similar results were obtained for cells expressing [G71] hFGF23 and [F129] hFGF23.
Conclusion: Our data for the first time directly show that FGF23 mutations associated with HFTC impair O-glycosylation in vitro resulting in poor secretion of the mutant hormone thereby explaining the characteristic hyperphosphatemic phenotype of homozygous carriers in vivo. (J Clin Endocrinol Metab 94: 4267-4274, 2009)
C1 [Bergwitz, Clemens; Banerjee, Santanu; Abu-Zahra, Hilal; Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA.
[Kaji, Hiroshi] Kobe Univ, Grad Sch Med, Dept Internal Med, Div Endocrinol Diabet & Metab, Kobe, Hyogo 6500017, Japan.
[Sugimoto, Toshitsugu] Shimane Univ, Fac Med, Matsue, Shimane 6938501, Japan.
RP Bergwitz, C (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 1038, Boston, MA 02114 USA.
EM cbergwitz@partners.org
FU National Institutes of Health [PO1 DK11794, 1K08 DK078361]; National
Kidney Foundation; American Association for Clinical Investigation
FX This work was supported by the National Institutes of Health Grants PO1
DK11794, Project IV (to H. J.), and 1K08 DK078361; Young Investigator
Awards by the National Kidney Foundation and the American Association
for Clinical Investigation (to C. B.).
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PI CHEVY CHASE
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 NOV
PY 2009
VL 94
IS 11
BP 4267
EP 4274
DI 10.1210/jc.2009-0961
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 515LD
UT WOS:000271470800019
PM 19837926
ER
PT J
AU Raivio, T
Sidis, Y
Plummer, L
Chen, HB
Ma, JH
Mukherjee, A
Jacobson-Dickman, E
Quinton, R
Van Vliet, G
Lavoie, H
Hughes, VA
Dwyer, A
Hayes, FJ
Xu, SY
Sparks, S
Kaiser, UB
Mohammadi, M
Pitteloud, N
AF Raivio, Taneli
Sidis, Yisrael
Plummer, Lacey
Chen, Huaibin
Ma, Jinghong
Mukherjee, Abir
Jacobson-Dickman, Elka
Quinton, Richard
Van Vliet, Guy
Lavoie, Helene
Hughes, Virginia A.
Dwyer, Andrew
Hayes, Frances J.
Xu, Shuyun
Sparks, Susan
Kaiser, Ursula B.
Mohammadi, Moosa
Pitteloud, Nelly
TI Impaired Fibroblast Growth Factor Receptor 1 Signaling as a Cause of
Normosmic Idiopathic Hypogonadotropic Hypogonadism
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID GONADOTROPIN-RELEASING-HORMONE; KALLMANN-SYNDROME; LUTEINIZING-HORMONE;
PEPTIDE RECEPTOR; MUTATIONS; GENE; FGFR1; DEFICIENCY;
FIBROBLAST-GROWTH-FACTOR-RECEPTOR-1; SPECTRUM
AB Context: FGFR1 mutations have been identified in about 10% of patients with Kallmann syndrome. Recently cases of idiopathic hypogonadotropic hypogonadism (IHH) with a normal sense of smell (nIHH) have been reported.
Aims: The objective of the study was to define the frequency of FGFR1 mutations in a large cohort of nIHH, delineate the spectrum of reproductive phenotypes, assess functionality of the FGFR1 mutant alleles in vitro, and investigate genotype-phenotype relationships.
Design: FGFR1 sequencing of 134 well-characterized nIHH patients (112 men and 22 women) and 270 healthy controls was performed. The impact of the identified mutations on FGFR1 function was assessed using structural prediction and in vitro studies.
Results: Nine nIHH subjects (five males and four females; 7%) harbor a heterozygous mutation in FGFR1 and exhibit a wide spectrum of pubertal development, ranging from absent puberty to reversal of IHH in both sexes. All mutations impair receptor function. The Y99C, Y228D, and I239T mutants impair the tertiary folding, resulting in incomplete glycosylation and reduced cell surface expression. The R250Q mutant reduces receptor affinity for FGF. The K618N, A671P, and Q680X mutants impair tyrosine kinase activity. However, the degree of functional impairment of the mutant receptors did not always correlate with the reproductive phenotype, and variable expressivity of the disease was noted within family members carrying the same FGFR1 mutation. These discrepancies were partially explained by additional mutations in known IHH loci.
Conclusions: Loss-of-function mutations in FGFR1 underlie 7% of nIHH with different degrees of impairment in vitro. These mutations act in concert with other gene defects in several cases, consistent with oligogenicity. (J Clin Endocrinol Metab 94: 4380-4390, 2009)
C1 [Raivio, Taneli; Sidis, Yisrael; Plummer, Lacey; Mukherjee, Abir; Jacobson-Dickman, Elka; Hughes, Virginia A.; Dwyer, Andrew; Hayes, Frances J.; Pitteloud, Nelly] Massachusetts Gen Hosp, Harvard Ctr Reprod Endocrine Sci, Boston, MA 02114 USA.
[Raivio, Taneli; Sidis, Yisrael; Plummer, Lacey; Mukherjee, Abir; Jacobson-Dickman, Elka; Hughes, Virginia A.; Dwyer, Andrew; Hayes, Frances J.; Pitteloud, Nelly] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA.
[Xu, Shuyun; Kaiser, Ursula B.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02114 USA.
[Chen, Huaibin; Ma, Jinghong; Mohammadi, Moosa] NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA.
[Quinton, Richard] Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
[Van Vliet, Guy] Hop St Justine, Montreal, PQ H3T 1C5, Canada.
[Lavoie, Helene] Ctr Hosp Univ Montreal, Montreal, PQ H2W 1T8, Canada.
[Lavoie, Helene] Procrea Clin, Montreal, PQ H2W 1T8, Canada.
[Sparks, Susan] Childrens Natl Med Ctr, Dept Genet & Metab, Washington, DC 20010 USA.
[Raivio, Taneli] Univ Helsinki, Inst Biomed Physiol, FIN-00014 Helsinki, Finland.
RP Pitteloud, N (reprint author), Massachusetts Gen Hosp, Harvard Ctr Reprod Endocrine Sci, Bartlett Hall Extens 5, Boston, MA 02114 USA.
EM pitteloud.nelly@mgh.harvard.edu
RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014;
OI Dwyer, Andrew/0000-0002-7023-6794; Mohammadi, Moosa/0000-0003-2434-9437
FU National Institutes of Health [R01 HD015788-21, R01 HD19938,
U54HD028138-16, R01 DE13686-09]; Foundation for Pediatric Research,
Finland; Academy of Finland
FX This work was supported by National Institutes of Health Grants R01
HD015788-21, R01 HD19938, U54HD028138-16, and R01 DE13686-09; Foundation
for Pediatric Research, Finland; and the Academy of Finland.
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SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD NOV
PY 2009
VL 94
IS 11
BP 4380
EP 4390
DI 10.1210/jc.2009-0179
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 515LD
UT WOS:000271470800033
PM 19820032
ER
PT J
AU Ix, JH
Wassel, CL
Chertow, GM
Koster, A
Johnson, KC
Tylavsky, FA
Cauley, JA
Cummings, SR
Harris, TB
Shlipak, MG
AF Ix, Joachim H.
Wassel, Christina L.
Chertow, Glenn M.
Koster, Annemarie
Johnson, Karen C.
Tylavsky, Frances A.
Cauley, Jane A.
Cummings, Steven R.
Harris, Tamara B.
Shlipak, Michael G.
CA Hlth Aging Body Composition Study
TI Fetuin-A and Change in Body Composition in Older Persons
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID INCIDENT DIABETES-MELLITUS; TYROSINE KINASE INHIBITOR; INSULIN-RECEPTOR;
MYOCARDIAL-INFARCTION; RESISTANCE; PLASMA; ADULTS; ADIPOCYTOKINES;
GLYCOPROTEIN; ASSOCIATION
AB Context: Fetuin-A inhibits the insulin receptor in vitro. Higher serum fetuin-A concentrations are associated with type 2 diabetes longitudinally and greater adiposity in cross-sectional analyses. Whether higher fetuin-A concentrations are associated with accumulation of adiposity over time is unknown.
Objective: To determine the association of fetuin-A levels with changes in body composition over 5 yr.
Study Design: Observational cohort study nested in the Health Aging and Body Composition Study.
Predictor: Serum fetuin-A levels.
Outcomes: Visceral adipose tissue (VAT), abdominal sc adipose tissue, and thigh muscle area by computed tomography, and waist circumference and body mass index were measured at baseline and again after 5 yr. Percent change and extreme change (>1.5 SDs) in each measure were calculated.
Results: Over 5 yr, subjects lost body mass in each measure, including 6% decline in VAT. Yet each SD (0.42 g/liter) higher fetuin-A concentration was associated with a 5.5% increase in VAT over 5 yr (95% confidence interval 1.9-9.2%; P = 0.003) in models adjusted for age, sex, race, clinical site, diabetes, physical activity, triglycerides, kidney function, and the baseline VAT score. Similarly, higher fetuin-A concentrations were associated with extreme VAT gain (relative risk 1.70, 95% confidence interval 1.12-2.60, P = 0.01). Fetuin-A concentrations were not statistically significant associated with change in any other measures of body composition (P > 0.20).
Conclusions: Higher fetuin-A concentrations are associated with the accumulation of VAT in well-functioning, community-living older persons. The mechanisms linking fetuin-A, VAT, and insulin resistance remain to be determined. (J Clin Endocrinol Metab 94: 4492-4498, 2009)
C1 [Ix, Joachim H.] Univ Calif San Diego, Div Nephrol, Dept Med, San Diego, CA 92161 USA.
[Ix, Joachim H.; Wassel, Christina L.] Univ Calif San Diego, Div Prevent Med, Dept Family & Prevent Med, San Diego, CA 92161 USA.
[Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA 92161 USA.
[Chertow, Glenn M.] Stanford Univ, Dept Med, Div Nephrol, Stanford, CA 94305 USA.
[Koster, Annemarie; Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Johnson, Karen C.; Tylavsky, Frances A.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN 38163 USA.
[Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Cummings, Steven R.] Calif Pacific Med Ctr, Dept Med, San Francisco, CA 94120 USA.
[Cummings, Steven R.] San Francisco Coordinating Ctr, San Francisco, CA 94107 USA.
[Cummings, Steven R.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Shlipak, Michael G.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA.
RP Ix, JH (reprint author), Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, 3350 La Jolla Village Dr,Mail Code 111-H, San Diego, CA 92161 USA.
EM joeix@ucsd.edu
RI Koster, Annemarie/E-7438-2010; Cauley, Jane/N-4836-2015
OI Cauley, Jane/0000-0003-0752-4408
FU American Diabetes Association (ADA); Association of Subspecialty
Professors (ASP); Atlantic Philanthropies; John A. Hartford Foundation;
American Heart Association; National Institutes of Health, National
Institute on Aging (NIA); [N01-AG-6-2101]; [N01-AG6-2103];
[N01-AG-6-2106]
FX This study was supported by an American Diabetes Association (ADA)
-Association of Subspecialty Professors (ASP) Young Investigator
Innovation Award in Geriatric Endocrinology sponsored by the Atlantic
Philanthropies, ADA, the John A. Hartford Foundation, and ASP, an
American Heart Association Fellow to Faculty Transition Award (J. H.
I.). The Health ABC study was supported by contracts N01-AG-6-2101,
N01-AG6-2103, and N01-AG-6-2106 and by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging (NIA).
The funding sources played no role in the design and conduct of the
study; collection, management, analysis, or interpretation of the data,
nor in the preparation of the manuscript. The NIA reviewed and approved
this manuscript prior to submission.
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SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD NOV
PY 2009
VL 94
IS 11
BP 4492
EP 4498
DI 10.1210/jc.2009-0916
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 515LD
UT WOS:000271470800048
PM 19820014
ER
PT J
AU Cefalu, AB
Noto, D
Arpi, ML
Yin, F
Spina, R
Hilden, H
Barbagallo, CM
Carroccio, A
Tarugi, P
Squatrito, S
Vigneri, R
Taskinen, MR
Peterfy, M
Averna, MR
AF Cefalu, Angelo B.
Noto, Davide
Arpi, Maria Luisa
Yin, Fen
Spina, Rossella
Hilden, Hannele
Barbagallo, Carlo M.
Carroccio, Antonio
Tarugi, Patrizia
Squatrito, Sebastiano
Vigneri, Riccardo
Taskinen, Marja-Riitta
Peterfy, Miklos
Averna, Maurizio R.
TI Novel LMF1 Nonsense Mutation in a Patient with Severe
Hypertriglyceridemia
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID ANGIOPOIETIN-LIKE PROTEIN-4; COMBINED LIPASE DEFICIENCY;
LIPOPROTEIN-LIPASE; ENDOPLASMIC-RETICULUM; MICE; CLD; DYSLIPIDEMIA;
MATURATION
AB Context: Lipase maturation factor 1 (LMF1) gene is a novel candidate gene in severe hypertriglyceridemia. Lmf1 is involved in the maturation of lipoprotein lipase (LPL) and hepatic lipase in endoplasmic reticulum. To date only one patient with severe hypertriglyceridemia and related disorders was found to be homozygous for a nonsense mutation in LMF1 gene (Y439X).
Objective: The objective of the study was to investigate LMF1 gene in hypertriglyceridemic patients in whom mutations in LPL, APOC2, and APOA5 genes had been excluded.
Results: The resequencing of LMF1 gene led to the discovery of a novel homozygous nonsense mutation in one patient with severe hypertriglyceridemia and recurrent episodes of pancreatitis. The mutation causes a G > A substitution in exon 9 (c. 1395G > A), leading to a premature stop codon (W464X). LPL activity and mass were reduced by 76 and 50%, respectively, compared with normolipidemic controls. The proband over the years has shown a good response to treatment. The proband's son, heterozygous for the W464X, shows normal plasma triglyceride levels.
Conclusions: We identified the second novel pathogenic mutation in LMF1 gene in a patient with severe hypertriglyceridemia. LPL deficiency in our patient was milder than in the carrier of the Y439X previously described. (J Clin Endocrinol Metab 94: 4584-4590, 2009)
C1 [Averna, Maurizio R.] Univ Palermo, Policlin Paolo Giaccone, Dept Clin Med & Emerging Dis, I-90127 Palermo, Italy.
[Arpi, Maria Luisa; Squatrito, Sebastiano; Vigneri, Riccardo] Univ Catania, Dept Internal Med, Endocrinol Unit, I-95125 Catania, Italy.
[Yin, Fen; Peterfy, Miklos] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA.
[Yin, Fen; Peterfy, Miklos] Vet Affairs Greater Los Angeles Healthcare Syst, Lipid Res Lab, Los Angeles, CA 90073 USA.
[Yin, Fen; Peterfy, Miklos] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Hilden, Hannele; Taskinen, Marja-Riitta] Helsinki Univ Hosp, Dept Med, FI-00029 Helsinki, Finland.
[Tarugi, Patrizia] Univ Modena & Reggio Emilia, Dept Biomed Sci, I-41100 Modena, Italy.
RP Averna, MR (reprint author), Univ Palermo, Policlin Paolo Giaccone, Dept Clin Med & Emerging Dis, Via Vespro 141, I-90127 Palermo, Italy.
EM avernam@unipa.it
RI Tarugi, Patrizia/D-2179-2015; Carroccio, Antonio/K-4484-2016;
OI Tarugi, Patrizia/0000-0001-6864-7853; Carroccio,
Antonio/0000-0001-8913-7916; Noto, Davide/0000-0002-5346-2829;
Barbagallo, Carlo M./0000-0002-4114-038X; Cefalu', Angelo
Baldassare/0000-0003-1259-8284; Averna, Maurizio/0000-0003-3558-9209
FU University of Palermo; Cedars-Sinai Medical Center; National Institutes
of Health [HL28481]
FX This work was supported by contract grants from the University of
Palermo (60% to M. R. A. and C. M. B.), the Cedars-Sinai Medical Center,
and Grant HL28481 from the National Institutes of Health (to M. P.).
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PU ENDOCRINE SOC
PI CHEVY CHASE
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 NOV
PY 2009
VL 94
IS 11
BP 4584
EP 4590
DI 10.1210/jc.2009-0594
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 515LD
UT WOS:000271470800059
PM 19820022
ER
PT J
AU Kostis, WJ
Kostis, JB
AF Kostis, William J.
Kostis, John B.
TI Age-Neutral Guidelines for the Primary Prevention of Cardiovascular
Disease
SO JOURNAL OF CLINICAL HYPERTENSION
LA English
DT Editorial Material
ID HIGH BLOOD CHOLESTEROL; ADULTS; RISK; HYPERTENSION; PREVALENCE;
AWARENESS; TRENDS; COSTS; WOMEN
AB Use of common guidelines for primary prevention of cardiovascular events based on 10-year risk results in undertreatment of younger individuals, especially women, since age and sex are major determinants of global risk. Women in their late 40s have a 10-year risk lower than the 10% threshold used for cholesterol-lowering treatment even in the presence of marked elevations of blood pressure or cholesterol. Removal of age from risk algorithms and use of lifetime global risk to treat individuals according to the degree of their modifiable risk factors rather than demographics has been proposed. Initiation of therapy at younger ages, aiming at "primordial'' prevention of atherosclerotic disease rather than focusing on cardiovascular events, will result in saving more quality-adjusted life-years. Generic medications can be obtained at an affordable cost, and concerns about long-term safety and efficacy can be tested in a clinical trial of younger individuals at low 10-year risk but high lifetime risk. J Clin Hypertens (Greenwich). 2009;11:644-645. (C) 2009 Wiley Periodicals, Inc.
C1 [Kostis, William J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Kostis, John B.] UMDNJ, Dept Med, Robert Wood Johnson Med Sch, New Brunswick, NJ USA.
RP Kostis, WJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA.
EM wkostis@partners.org
NR 19
TC 3
Z9 3
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1524-6175
J9 J CLIN HYPERTENS
JI J. Clin. Hypertens.
PD NOV
PY 2009
VL 11
IS 11
BP 644
EP 645
DI 10.1111/j.1751-7176.2009.00162.x
PG 2
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 509ZM
UT WOS:000271057800006
PM 19878373
ER
PT J
AU Chen, L
Periquet, M
Wang, X
Negro, A
McLean, PJ
Hyman, BT
Feany, MB
AF Chen, Li
Periquet, Magali
Wang, Xu
Negro, Alessandro
McLean, Pamela J.
Hyman, Bradley T.
Feany, Mel B.
TI Tyrosine and serine phosphorylation of alpha-synuclein have opposing
effects on neurotoxicity and soluble oligomer formation
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID FAMILIAL PARKINSONS-DISEASE; DROSOPHILA MODEL; LEWY BODIES; TRANSGENIC
MICE; CELL-DEATH; RAT MODEL; NEURODEGENERATION; MUTATION; AGGREGATION;
DIAGNOSIS
AB Mutations in the neuronal protein alpha-synuclein cause familial Parkinson disease. Phosphorylation of alpha-synuclein at serine 129 is prominent in Parkinson disease and influences alpha-synuclein neurotoxicity. Here we report that alpha-synuclein is also phosphorylated at tyrosine 125 in transgenic Drosophila expressing wildtype human alpha-synuclein and that this tyrosine phosphorylation protects from alpha-synuclein neurotoxicity in a Drosophila model of Parkinson disease. Western blot analysis of fly brain homogenates showed that levels of soluble oligomeric species of alpha-synuclein were increased by phosphorylation at serine 129 and decreased by tyrosine 125 phosphorylation. Tyrosine 125 phosphorylation diminished during the normal aging process in both humans and flies. Notably, cortical tissue from patients with the Parkinson disease-related synucleinopathy dementia with Lewy bodies showed less phosphorylation at tyrosine 125. Our findings suggest that alpha-synuclein neurotoxicity in Parkinson disease and related synucleinopathies may result from an imbalance between the detrimental, oligomer-promoting effect of serine 129 phosphorylation and a neuroprotective action of tyrosine 125 phosphorylation that inhibits toxic oligomer formation.
C1 [Chen, Li; Periquet, Magali; Feany, Mel B.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Wang, Xu] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Wang, Xu] Harvard Univ, Sch Med, Boston, MA USA.
[Negro, Alessandro] Univ Padua, Dept Biochem, Padua, Italy.
[McLean, Pamela J.; Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA.
RP Feany, MB (reprint author), Brigham & Womens Hosp, Dept Pathol, 77 Louis Pasteur Ave,Room 630, Boston, MA 02115 USA.
EM mel_feany@hms.harvard.edu
FU NIH [R01-NS41536, P50-NS38372]; Parkinson's Disease Foundation
FX We thank D. Rennie (Cutaneous Biology Research Center, Massachusetts
General Hospital) for fly embryo injection. We also acknowledge the
Massachusetts General Hospital ADRC Brain Bank. We appreciate the
assistance of Katherine Sharpe and Paola Merlo with real-time PCR
measurements. This work was supported by NIH grants R01-NS41536 (to M.B.
Feany) and P50-NS38372 (to B.T Hyman) and by the Parkinson's Disease
Foundation (to L. Chen).
NR 55
TC 86
Z9 88
U1 2
U2 11
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 NOV
PY 2009
VL 119
IS 11
BP 3257
EP 3265
DI 10.1172/JCI39088
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 517CC
UT WOS:000271589400010
PM 19855133
ER
PT J
AU Wang, LJ
Harrington, L
Trebicka, E
Shi, HN
Kagan, JC
Hong, CC
Lin, HY
Babitt, JL
Cherayil, BJ
AF Wang, Lijian
Harrington, Lynne
Trebicka, Estela
Shi, Hai Ning
Kagan, Jonathan C.
Hong, Charles C.
Lin, Herbert Y.
Babitt, Jodie L.
Cherayil, Bobby J.
TI Selective modulation of TLR4-activated inflammatory responses by altered
iron homeostasis in mice
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID TOLL-LIKE RECEPTOR; HEREDITARY HEMOCHROMATOSIS; SALMONELLA INFECTION;
HEPCIDIN EXPRESSION; VIBRIO-VULNIFICUS; SIGNALING PATHWAY; C282Y
MUTATION; PROTEIN; HOST; HFE
AB Mice deficient in the hemochromatosis gene, Hfe, have attenuated inflammatory responses to Salmonella infection associated with decreased macrophage TNF-alpha and IL-6 biosynthesis after exposure to LPS. In this study, we show that the abnormal cytokine production is related to impaired TLR4 signaling. Despite their abnormal response to LPS, Hfe KO macrophages produced amounts of TNF-alpha similar to those in WT cells after TLR2 stimulation. Consistent with this finding, LPS-induced activation of Mal/MyD88-dependent events was normal in the mutant macrophages. However, LPS-induced IFN-beta expression, a TRAM/TRIF-dependent response activated by TLR4, was reduced by Hfe deficiency. This reduction could be replicated in WT macrophages with the use of iron chelators. In contrast, TLR3-activated expression of IFN-beta, a TRIF-dependent response, was normal in Hfe KO macrophages and was unaffected by iron chelation. Our data suggest that low intracellular iron selectively impairs signaling via the TLR4/TRAM/TRIF pathway proximal to TRIF and results in reduced LPS-induced cytokine expression. Furthermore, by mimicking the altered iron metabolism associated with Hfe deficiency, we found that 3 different inhibitors of hepcidin attenuated Salmonella-induced and noninfectious enterocolitis. Thus, manipulation of iron homeostasis could represent a new therapeutic approach to controlling inflammation.
C1 [Wang, Lijian; Harrington, Lynne; Trebicka, Estela; Shi, Hai Ning; Cherayil, Bobby J.] Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA.
[Wang, Lijian] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Shi, Hai Ning; Cherayil, Bobby J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Kagan, Jonathan C.] Childrens Hosp, Dept Gastroenterol, Boston, MA 02115 USA.
[Hong, Charles C.] Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville, TN USA.
[Lin, Herbert Y.; Babitt, Jodie L.] Massachusetts Gen Hosp, Program Membrane Biol, Div Nephrol, Boston, MA 02114 USA.
[Lin, Herbert Y.; Babitt, Jodie L.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, Bldg 114,16th St, Charlestown, MA 02129 USA.
EM cherayil@helix.mgh.harvard.edu
RI Hong, Charles/C-9989-2010
FU Broad Medical Research Program [TBD-0253]; Wyeth Nutrition; Center for
Research in Fibrodysplasia Ossificans Progressiva and Related Disorders;
National Institute of Diabetes and Digestive and Kidney Diseases, NIH
[R01-071837]
FX This work was supported by funds from the Broad Medical Research Program
(grant no. TBD-0253) to Bobby J. Cherayil and from Wyeth Nutrition to L.
Wang. C.C. Hong received support from the Center for Research in
Fibrodysplasia Ossificans Progressiva and Related Disorders. H.Y. Lin
was supported in part by grant R01-071837 from the National Institute of
Diabetes and Digestive and Kidney Diseases, NIH. We are grateful to
Nancy Andrews for providing the Hfe KO mice and to Prem Ponka for the
gift of SIH. We thank Sarah A. Faasse for technical assistance with iron
assays.
NR 44
TC 76
Z9 78
U1 0
U2 9
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 NOV
PY 2009
VL 119
IS 11
BP 3322
EP 3328
DI 10.1172/JCI39939
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 517CC
UT WOS:000271589400016
PM 19809161
ER
PT J
AU Mareninova, OA
Hermann, K
French, SW
O'Konski, MS
Pandol, SJ
Webster, P
Erickson, AH
Katunuma, N
Gorelick, FS
Gukovsky, I
Gukovskaya, AS
AF Mareninova, Olga A.
Hermann, Kip
French, Samuel W.
O'Konski, Mark S.
Pandol, Stephen J.
Webster, Paul
Erickson, Ann H.
Katunuma, Nobuhiko
Gorelick, Fred S.
Gukovsky, Ilya
Gukovskaya, Anna S.
TI Impaired autophagic flux mediates acinar cell vacuole formation and
trypsinogen activation in rodent models of acute pancreatitis
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID CERULEIN-INDUCED PANCREATITIS; CATHEPSIN-B; HEREDITARY PANCREATITIS;
LYSOSOMAL-ENZYMES; EARLY EVENTS; MONITORING AUTOPHAGY; ZYMOGEN
ACTIVATION; RAT HEPATOCYTES; IN-VITRO; DISEASE
AB The pathogenic mechanisms underlying acute pancreatitis are not clear. Two key pathologic acinar cell responses of this disease are vacuole accumulation and trypsinogen activation. We show here that both result from defective autophagy, by comparing the autophagic responses in rodent models of acute pancreatitis to physiologic autophagy triggered by fasting. Pancreatitis-induced vacuoles in acinar cells were greater in number and much larger than those induced with fasting. Degradation of long-lived proteins, a measure of autophagic efficiency, was markedly inhibited in in vitro pancreatitis, while it was stimulated by acinar cell starvation. Further, processing of the lysosomal proteases cathepsin L (CatL) and CatB into their fully active, mature forms was reduced in pancreatitis, as were their activities in the lysosome-enriched subcellular fraction. These findings indicate that autophagy is retarded in pancreatitis due to deficient lysosomal degradation caused by impaired cathepsin processing. Trypsinogen activation occurred in pancreatitis but not with fasting and was prevented by inhibiting autophagy. A marker of trypsinogen activation partially localized to autophagic vacuoles, and pharmacologic inhibition of CatL increased the amount of active trypsin in acinar cells. The results suggest that retarded autophagy is associated with an imbalance between CatL, which degrades trypsinogen and trypsin, and CatB, which converts trypsinogen into trypsin, resulting in intra-acinar accumulation of active trypsin in pancreatitis. Thus, deficient lysosomal degradation may be a dominant mechanism for increased intra-acinar trypsin in pancreatitis.
C1 [Mareninova, Olga A.; Hermann, Kip; Pandol, Stephen J.; Gukovsky, Ilya; Gukovskaya, Anna S.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Mareninova, Olga A.; Hermann, Kip; Pandol, Stephen J.; Gukovsky, Ilya; Gukovskaya, Anna S.] Univ Calif Los Angeles, Los Angeles, CA USA.
[French, Samuel W.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA.
[O'Konski, Mark S.] Digest Hlth Phys, Ft Myers, FL USA.
[Webster, Paul] House Ear Res Inst, Los Angeles, CA USA.
[Erickson, Ann H.] Univ N Carolina, Chapel Hill, NC USA.
[Katunuma, Nobuhiko] Tokushima Bunri Univ, Tokushima, Japan.
[Gorelick, Fred S.] Vet Affairs Med Ctr, West Haven, CT USA.
[Gorelick, Fred S.] Yale Univ, West Haven, CT USA.
RP Gukovskaya, AS (reprint author), UCLA Vet Affairs Greater Los Angeles Healthcare S, W Los Angeles Vet Affairs Healthcare Ctr, 11301 Wilshire Blvd,Blg 258,Rm 340, Los Angeles, CA 90073 USA.
EM igukovsk@ucla.edu; agukovsk@ucla.edu
FU Department of Veterans Affairs; NIH [DK59936, P60 AA11999]; American
Gastroenterology Association Foundation Designated Research Scholar
Award in Pancreaeitis
FX This study was supported by the Department of Veterans Affairs, the NIH
grants DK59936 (to A.S. Gukovskaya) and P60 AA11999 (to A.S. Gukovskaya
and SJ. Pandol), and, in part, by the American Gastroenterology
Association Foundation Designated Research Scholar Award in Pancreaeitis
(to O.A. Mareninova). The authors thank Noboru Mizushima (Tokyo Medical
and Dental University, Tokyo, Japan) and RIKEN BioResourse Center
(Koyadai, Japan) for providing the GFP-LC3 transgenic mice and D.S.
Longnecker (Dartmouth Medical School, USA) for providing H&E images of
pancreatic tissue from patients with acute pancreatitis. The authors
also thank the UCLA Microscopic Techniques Core (Marianne Cilluffo) for
expert help with immunolabeling, Moses A. Lee for help with Western blot
densicometry, and Tina Feng for help with quantification of vacuoles.
NR 69
TC 91
Z9 97
U1 1
U2 8
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 NOV
PY 2009
VL 119
IS 11
BP 3340
EP 3355
DI 10.1172/JCI38674
PG 16
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 517CC
UT WOS:000271589400018
PM 19805911
ER
PT J
AU Fox, JG
Shen, Z
Muthupalani, S
Rogers, AR
Kirchain, SM
Dewhirst, FE
AF Fox, J. G.
Shen, Z.
Muthupalani, S.
Rogers, A. R.
Kirchain, S. M.
Dewhirst, F. E.
TI Chronic Hepatitis, Hepatic Dysplasia, Fibrosis, and Biliary Hyperplasia
in Hamsters Naturally Infected with a Novel Helicobacter Classified in
the H. bilis Cluster
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; SYRIAN GOLDEN-HAMSTERS; RIBOSOMAL-RNA GENE;
HUMAN-LIVER FLUKE; OPISTHORCHIS-VIVERRINI; N-NITROSODIMETHYLAMINE;
SPONTANEOUS TUMORS; COMMON DISEASES; SP-NOV; BACTERIAL-INFECTION
AB We recently described helicobacter-associated progressive, proliferative, and dysplastic typhlocolitis in aging (18- to 24-month-old) Syrian hamsters. Other pathogens associated with typhlocolitis in hamsters, Clostridium difficile, Lawsonia intracellularis, and Giardia spp., were not indentified. The presence of Helicobacter genus-specific DNA was noted by PCR in cecal and paraffin-embedded liver samples from aged hamsters by the use of Helicobacter-specific PCR primers. By 16S rRNA analysis, the Helicobacter sp. isolated from the liver tissue was identical to the cecal isolates from hamsters. The six hamster 16S rRNA sequences form a genotypic cluster most closely related to Helicobacter sp. Flexispira taxon 8, part of the Helicobacter bilis/H. cinaedi group. Livers from aged helicobacter-infected hamsters showed various stages of predominantly portocentric and, to a lesser extent, perivenular fibrosis. Within nodules, there was cellular atypia consistent with nodular dysplasia. The livers also exhibited a range of chronic active portal/interface and lobular inflammation, with significant portal hepatitis being present. The inflammation was composed of a mixture of lymphocytes, neutrophils, and macrophages, indicative of its chronic-active nature in these aged hamsters infected with Helicobacter spp. The isolation of novel Helicobacter spp., their identification by PCR from the diseased livers of aged hamsters, and their taxonomic classification as belonging to the Helicobacter bilis cluster strengthen the argument that H. bilis and closely related Helicobacter spp. play an etiological role in hepatobiliary disease in both animals and humans.
C1 [Fox, J. G.; Shen, Z.; Muthupalani, S.; Rogers, A. R.; Kirchain, S. M.] MIT, Div Comparat Med, Cambridge, MA 02139 USA.
[Dewhirst, F. E.] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA.
RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave,Bldg 16-825, Cambridge, MA 02139 USA.
EM jgfox@mit.edu
FU NIH [R01CA67529, P30ES102109, RR07036, DE016937]
FX This work was supported by NIH grants R01CA67529 (to J. G. F.),
P30ES102109 (to J. G. F.), RR07036 (to J. G. F.), and DE016937 (to F. E.
D.).
NR 52
TC 19
Z9 19
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD NOV
PY 2009
VL 47
IS 11
BP 3673
EP 3681
DI 10.1128/JCM.00879-09
PG 9
WC Microbiology
SC Microbiology
GA 514CZ
UT WOS:000271373000043
PM 19759229
ER
PT J
AU Castellon, SA
Ganz, PA
AF Castellon, Steven A.
Ganz, Patricia A.
TI Exploring the Impact of the Hormonal Milieu on Cognitive Functioning
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID STAR P-2 TRIAL; BREAST-CANCER; TAMOXIFEN; CHEMOTHERAPY; PERFORMANCE;
RALOXIFENE; THERAPY; BRAIN; NSABP
C1 [Castellon, Steven A.] Univ Calif Los Angeles, David Geffen Sch Med, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90095 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med, Los Angeles, CA 90024 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Publ Hlth, Los Angeles, CA 90024 USA.
RP Castellon, SA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90095 USA.
NR 13
TC 0
Z9 0
U1 0
U2 0
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 NOV 1
PY 2009
VL 27
IS 31
BP 5119
EP 5121
DI 10.1200/JCO.2009.24.3329
PG 5
WC Oncology
SC Oncology
GA 512TS
UT WOS:000271274300003
PM 19770364
ER
PT J
AU Liebig, C
Ayala, G
Wilks, J
Verstovsek, G
Liu, H
Agarwal, N
Berger, DH
Albo, D
AF Liebig, Catherine
Ayala, Gustavo
Wilks, Jonathan
Verstovsek, Gordana
Liu, Hao
Agarwal, Neeti
Berger, David H.
Albo, Daniel
TI Perineural Invasion Is an Independent Predictor of Outcome in Colorectal
Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID PROSTATE-CANCER; NEURAL INVASION; HIGH-RISK; PANCREATIC-CANCER;
COLON-CANCER; PROGNOSTIC-SIGNIFICANCE; RECTAL-CANCER; NEEDLE-BIOPSY;
CARCINOMA; STAGE
AB Purpose Perineural invasion (PNI) is associated with decreased survival in several malignancies, but its significance in colorectal cancer (CRC) remains to be clearly defined. We evaluated PNI as a potential prognostic indicator in CRC, focusing on its significance in node-negative patients.
Patients and Methods We identified 269 consecutive patients who had CRC resected at our institution. Tumors were rereviewed for PNI by a pathologist blinded to the patients' outcomes. Overall and disease-free survivals were determined using the Kaplan-Meier method, with differences determined by multivariate analysis using the Cox multiple hazards model. Results were compared using the log-rank test.
Results
PNI was identified in less than 0.5% of the initial pathology reports. On rereview, 22% of tumors in our series were found to be PNI positive. The 5-year disease-free survival rate was four-fold greater for patients with PNI-negative tumors versus those with PNI-positive tumors (65% v 16%, respectively; P < .0001). The 5-year overall survival rate was 72% for PNI-negative tumors versus 25% for PNI-positive tumors. On multivariate analysis, PNI was an independent prognostic factor for both cancer-specific overall and disease-free survival. In a subset analysis comparing patients with node-negative disease with patients with stage III disease, the 5-year disease-free survival rate was 56% for stage III patients versus 29% for patients with node-negative, PNI-positive tumors (P = .0002). Similar results were seen for overall survival.
Conclusion
PNI is grossly underreported in CRC and could serve as an independent prognostic factor of outcomes in these patients. PNI should be considered when stratifying CRC patients for adjuvant treatment.
C1 [Albo, Daniel] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
Baylor Coll Med, Micheal E DeBakey Dept Surg, Dept Pathol, Houston, TX 77030 USA.
Baylor Coll Med, Div Biostat, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
RP Albo, D (reprint author), Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd,OCL 112-A, Houston, TX 77030 USA.
EM dalbo@bcm.edu
NR 45
TC 110
Z9 124
U1 0
U2 5
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 NOV 1
PY 2009
VL 27
IS 31
BP 5131
EP 5137
DI 10.1200/JCO.2009.22.4949
PG 7
WC Oncology
SC Oncology
GA 512TS
UT WOS:000271274300006
PM 19738119
ER
PT J
AU Lewis, NL
Lewis, LD
Eder, JP
Reddy, NJ
Guo, F
Pierce, KJ
Olszanski, AJ
Cohen, RB
AF Lewis, Nancy L.
Lewis, Lionel D.
Eder, Joseph P.
Reddy, Nandi J.
Guo, Feng
Pierce, Kristen J.
Olszanski, Anthony J.
Cohen, Roger B.
TI Phase I Study of the Safety, Tolerability, and Pharmacokinetics of Oral
CP-868,596, a Highly Specific Platelet-Derived Growth Factor Receptor
Tyrosine Kinase Inhibitor in Patients With Advanced Cancers
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID PDGF RECEPTORS; TARGETS; TUMORS
AB Purpose
This phase I, first-in-human study evaluated the safety, tolerability, pharmacokinetics, and maximum-tolerated dose (MTD) of an oral platelet-derived growth factor receptor inhibitor, CP-868,596.
Patients and Methods
Patients with advanced solid tumors were eligible. Dose escalations were performed in three groups with two formulations: uncoated on an empty stomach (UES), uncoated with food (UFED), and film-coated (FC) without food. Initial dose escalation in the UES group was followed by parallel escalations in the UFED and FC groups.
Results
Fifty-nine patients enrolled. CP-868,596 was escalated from 100 mg to 340 mg daily in the UES group, from 60 mg to 100 mg twice daily in the UFED group, and from 100 mg once daily to 140 mg twice daily in the FC group. MTDs were 200 mg daily in the UES group and 100 mg twice daily in the FC group; MTD was not reached at 100 mg twice daily in the UFED group. Dose-limiting toxicities included hematuria, increased gamma-glutamyltransferase or ALT, insomnia, and nausea/vomiting. Most treatment-related AEs were of grades 1 to 2 severity; nausea, vomiting, and diarrhea were reported most frequently. Administration with food generally improved tolerability. CP-868,596 was absorbed slowly; systemic exposure parameters appeared to increase greater than proportionally with dose. Mean serum concentrations exceeded the preclinically predicted minimal efficacious concentration (ie, 16 ng/mL) at all dosages. Food and film coating apparently increased interpatient variability of the maximum observed plasma concentration and the area under the concentration-time curve. No objective responses were reported, and eight patients achieved stable disease (mean duration, 5.7 months).
Conclusion
CP-868,596 potentially demonstrated greater than dose-proportional pharmacokinetics. The recommended dosage of 100 mg twice daily with food was well tolerated. Additional development as a single agent in selected populations or in combination with chemotherapy in broader populations is warranted.
C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
Dartmouth Med Sch, Lebanon, NH USA.
Norris Cotton Canc Ctr, Lebanon, NH USA.
Dana Farber Canc Ctr, Boston, MA USA.
Pfizer Oncol, New London, CT USA.
RP Lewis, NL (reprint author), Cooper Canc Inst, 900 Centennial Blvd,Ste A, Voorhees, NJ 08043 USA.
EM lewis-nancy@cooperhealth.edu
FU Pfizer Oncology; National Cancer Institute [CA06927]
FX Supported by Pfizer Oncology and by Grant No. CA06927 from the National
Cancer Institute.
NR 15
TC 39
Z9 40
U1 0
U2 5
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 NOV 1
PY 2009
VL 27
IS 31
BP 5262
EP 5269
DI 10.1200/JCO.2009.21.8487
PG 8
WC Oncology
SC Oncology
GA 512TS
UT WOS:000271274300025
PM 19738123
ER
PT J
AU Martin, JE
Wagner, AJ
Murphy, GF
Pinkus, GS
Wang, LC
AF Martin, Julie E.
Wagner, Andrew J.
Murphy, George F.
Pinkus, Geraldine S.
Wang, Linda C.
TI Granuloma Annulare Heralding Angioimmunoblastic T-Cell Lymphoma in a
Patient With a History of Epstein-Barr Virus-Associated B-Cell Lymphoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID HODGKINS-DISEASE; INITIAL MANIFESTATION; CUTANEOUS INVOLVEMENT;
LABORATORY FINDINGS; MALIGNANT-LYMPHOMA; MYCOSIS-FUNGOIDES; LEUKEMIA;
IMMUNODEFICIENCY; LYMPHADENOPATHY; INFECTION
C1 [Martin, Julie E.; Wang, Linda C.] Harvard Univ, Brigham & Womens Hosp, Dept Dermatol, Sch Med, Boston, MA 02115 USA.
[Murphy, George F.; Pinkus, Geraldine S.] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA.
[Wagner, Andrew J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Martin, JE (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Dermatol, Sch Med, Boston, MA 02115 USA.
NR 38
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U2 0
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 NOV 1
PY 2009
VL 27
IS 31
BP E168
EP E171
DI 10.1200/JCO.2009.23.0409
PG 4
WC Oncology
SC Oncology
GA 512TS
UT WOS:000271274300030
PM 19770367
ER
PT J
AU Surman, CBH
Adamson, JJ
Petty, C
Biederman, J
Kenealy, DC
Levine, M
Mick, E
Faraone, SV
AF Surman, Craig B. H.
Adamson, Joel J.
Petty, Carter
Biederman, Joseph
Kenealy, Deborah C.
Levine, Madeleine
Mick, Eric
Faraone, Stephen V.
TI Association Between Attention-Deficit/Hyperactivity Disorder and Sleep
Impairment in Adulthood: Evidence From a Large Controlled Study
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID DEFICIT HYPERACTIVITY DISORDER; SUBTHRESHOLD DIAGNOSES; LATE-ONSET; ADHD
ADULTS; CHILDREN; SYMPTOMS; COMORBIDITY; ALERTNESS; QUALITY
AB Objective: To examine whether sleep impairment is associated with attention-deficit/hyperactivity disorder (ADHD) in adults.
Method: In a study conducted from 1998 to 2003, we identified sleep characteristics in a community sample of 182 cases of DSM-IV ADHD or ADHD not otherwise specified and 117 non-ADHD controls aged 18 to 55 years. Attention-deficit/hyperactivity disorder status, current and lifetime psychiatric comorbidity, and pharmacologic treatment of ADHD were identified with the Structured Clinical Interview for DSM-IV and with modules from the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version. Sleep problems were characterized by self-report. We separately accounted for the contribution of age at ADHD onset, ADHD pharmacotherapy, lifetime bipolar disorder, and the following lifetime and current comorbidities: depression, generalized anxiety, substance abuse, and multiple anxiety disorders.
Results: Adults with ADHD went to bed later than control subjects and had a wider range of bedtimes (mean +/- SD = 18 +/- 92 min vs 54 +/- 69 min before midnight; P < .001), were more likely to take over an hour to fall asleep (OR = 5.22, P = .001), and were more likely (P < .003) to experience difficulty going to bed, going to sleep, sleeping restfully, or waking in the morning. Adults with ADHD experienced daytime sleepiness more often (OR = 2.23, P = .003) and reported more sleep problems (mean +/- SD = 6.7 +/- 2.5 vs 4.3 +/- 2.2; P < .001) than controls. All sleep impairments were significantly associated with ADHD independent of contributions to sleep disruption from ADHD pharmacotherapy, comorbidities likely to contribute to sleep disturbance, and age at ADHD onset.
Conclusion: Sleep disturbances that are not attributable to comorbid mental health conditions or ADHD pharmacotherapy are associated with ADHD in adulthood. Clinicians and researchers should consider the potential contribution of sleep disruption to the clinical presentation of adults with ADHD. J Clin Psychiatry 2009,70(11):1523-1529 (C) Copyright 2009 Physicians Postgraduate Press, Inc.
C1 [Surman, Craig B. H.; Adamson, Joel J.; Petty, Carter; Biederman, Joseph; Kenealy, Deborah C.; Levine, Madeleine; Mick, Eric] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA.
[Faraone, Stephen V.] NYU, Upstate Med Univ, Dept Psychiat, Syracuse, NY USA.
[Faraone, Stephen V.] NYU, Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA.
RP Surman, CBH (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Suite 2000,185 Alewife Brook Pkwy, Cambridge, MA 02138 USA.
EM csurman@partners.org
OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982
FU Abbott; Alza; Cephalon; Eli Lilly; Hilda and Preston Davis Foundation;
McNeil; Merck; New River; National Institutes of Health (NIH)
[R01MH57934]; AstraZeneca; Bristol-Myers Squibb; Organon; Otsuka; Shire;
National Institute of Child Health and Human Development; Celltech;
Glaxo; Gliatech; Janssen; NARSAD; National Institute on Drug Abuse;
NeuroSearch; Pfizer; Pharmacia; The Prechter Foundation; The Stanley
Foundation; UCB Pharma; Wyeth; Ortho-McNeil-Janssen SA; Shire
Pharmaceuticals
FX Funding/support. This study was supported in part by a grant to Dr
Faraone from NIH (R01MH57934) and by a grant to Dr Mick from Shire
Pharmaceuticals.
NR 36
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U2 4
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 240008, MEMPHIS, TN 38124 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD NOV
PY 2009
VL 70
IS 11
BP 1523
EP 1529
DI 10.4088/JCP.08m04514
PG 7
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 525HQ
UT WOS:000272206200006
PM 19646365
ER
PT J
AU Wilens, TE
Biederman, J
Faraone, SV
Martelon, M
Westerberg, D
Spencer, TJ
AF Wilens, Timothy E.
Biederman, Joseph
Faraone, Stephen V.
Martelon, MaryKate
Westerberg, Diana
Spencer, Thomas J.
TI Presenting ADHD Symptoms, Subtypes, and Comorbid Disorders in Clinically
Referred Adults With ADHD
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY
DISORDER; AGE-DEPENDENT DECLINE; UTAH RATING-SCALE; PSYCHIATRIC
COMORBIDITY; FOLLOW-UP; SURVEY REPLICATION; CONDUCT DISORDER; CHILDREN;
SAMPLE
AB Objective: Despite the increasing presentation of attention-deficit/hyperactivity disorder (ADHD) in adults, many practitioners remain reluctant to assess individuals for ADHD, in part related to the relative lack of data on the presenting symptoms of ADHD in adulthood. Comorbidity among adults with ADHD is also of great interest due to the high rates of psychiatric comorbidity, which can lead to a more persistent ADHD among adults.
Method: We assessed 107 adults with ADHD of both sexes (51% female; mean +/- SD of 37 +/- 10.4 years) using structured diagnostic interviews. Using DSM-IV symptoms, we determined DSM-IV subtypes. The study was conducted from 1998 to 2003.
Results: Inattentive symptoms were most frequently endorsed (> 90%) in adults with ADHD. Using current symptoms, 62% of adults had the combined subtype, 31% the inattentive only subtype, and 7% the hyperactive/impulsive only subtype. Adults with the combined subtype had relatively more psychiatric comorbidity compared to those with the predominately inattentive subtype. Women were similar to men in the presentation of ADHD.
Conclusion: Adults with ADHD have prominent inattentive symptoms of ADHD, necessitating careful questioning of these symptoms when evaluating these individuals. J Clin Psychiatry 2009,70(11):1557-1562 (C) Copyright 2009 Physicians Postgraduate Press, Inc.
C1 [Wilens, Timothy E.] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Pediat Psychopharmacol Clin, Boston, MA 02114 USA.
[Wilens, Timothy E.; Biederman, Joseph; Martelon, MaryKate; Westerberg, Diana; Spencer, Thomas J.] Massachusetts Gen Hosp, ADHD Program, Boston, MA 02114 USA.
[Wilens, Timothy E.; Biederman, Joseph; Martelon, MaryKate; Westerberg, Diana; Spencer, Thomas J.] Harvard Univ, Sch Med, Boston, MA USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Albany, NY USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Albany, NY USA.
RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Pediat Psychopharmacol Clin, YAW 6A,55 Fruit St, Boston, MA 02114 USA.
EM twilens@partners.org
OI Faraone, Stephen/0000-0002-9217-3982
FU Abbott; McNeil; Eli Lilly; National Institutes of Health [RO1 DA12945,
K24 DA016264]; Merck; Shire; Alza; AstraZeneca; Bristol-Myers Squibb;
Janssen; Organon; Otsuka; National Institute of Mental Health (NIMH);
National Institute of Child Health and Human Development; Celltech;
Cephalon; Esai; Forest; GlaxoSmithKline; Gliatech; NARSAD; NIDA; New
River; Novartis; Noven; Neurosearch; Pfizer; Pharmacia; The Prechter
Foundation; The Stanley Foundation; UCB Pharma
FX Dr Wilens receives grant support from Abbott, McNeil, Eli Lilly,
National Institutes of Health (National Institute on Drug Abuse; NIH
(NIDA]), Merck, and Shire; is a speaker for the speakers' bureaus of Eli
Lilly, McNeil, Novartis, and Shire; is a consultant for Abbott,
AstraZeneca, McNeil, Eli Lilly, NIH (NIDA), Novartis, Merck, and Shire;
and has a published book with Guilford Press, Straight Talk About
Psychiatric Medications for Kids. Dr Biederman is currently receiving
research support from Alza, AstraZeneca, Bristol-Myers Squibb, Eli
Lilly, Janssen, McNeil, Merck, Organon, Otsuka, Shire, the National
Institute of Mental Health (NIMH), and the National Institute of Child
Health and Human Development; is currently a consultant/advisory board
member for Janssen, McNeil, Novartis, and Shire; is currently a speaker
for the speakers' bureaus of Janssen, McNeil, Novartis, Shire, UCB
Pharma, Inc, Fundacion Areces, Medice Pharmaceuticals, and the Spanish
Child Psychiatry Association; and in previous years has received
research support, consultation fees, or speaker's fees from Abbott,
AstraZeneca, Celltech, Cephalon, Eli Lilly, Esai, Forest,
GlaxoSmithKline, Gliatech, NARSAD, NIDA, New River, Novartis, Noven,
Neurosearch, Pfizer, Pharmacia, The Prechter Foundation, Shire, The
Stanley Foundation, UCB Pharma, and Wyeth. Dr Faraone has received
consulting fees, been on the advisory boards for, or been a speaker for
Eli Lilly, Shire, McNeil, Janssen, Novartis, and Pfizer and has received
research support from Eli Lilly, Pfizer, Shire, and the NIH. Dr Spencer
receives research support from Shire, Cephalon, Eli Lilly,
GlaxoSmithKline, Janssen, McNeil, Novartis, Pfizer, and NIMH; has been a
speaker for the speakers' bureaus of Shire, Eli Lilly, GlaxoSmithKline,
Janssen, McNeil, and Novartis; and is on the advisory board for Shire,
Cephalon, Eli Lilly, GlaxoSmithKline, Janssen, McNeil, Novartis, and
Pfizer. Mss Martelon and Westerberg have no personal affiliations or
financial relationships with any commercial interest to disclose
relative to the article.; Funding/support: This study was supported by
National Institutes of Health grants RO1 DA12945 (Dr Wilens) and K24
DA016264 (Dr Wilens).
NR 40
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PI MEMPHIS
PA P O BOX 240008, MEMPHIS, TN 38124 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD NOV
PY 2009
VL 70
IS 11
BP 1557
EP 1562
DI 10.4088/JCP.08m04785pur
PG 6
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 525HQ
UT WOS:000272206200012
PM 20031097
ER
PT J
AU Simon, NM
Otto, MW
Worthington, JJ
Hoge, EA
Thompson, EH
LeBeau, RT
Moshier, SJ
Zalta, AK
Pollack, MH
AF Simon, Naomi M.
Otto, Michael W.
Worthington, John J.
Hoge, Elizabeth A.
Thompson, Elizabeth H.
LeBeau, Richard T.
Moshier, Samantha J.
Zalta, Alyson K.
Pollack, Mark H.
TI Next-Step Strategies for Panic Disorder Refractory to Initial
Pharmacotherapy: A 3-Phase Randomized Clinical Trial
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID COGNITIVE-BEHAVIOR THERAPY; COMORBIDITY SURVEY REPLICATION; SEVERITY
SCALE; DOUBLE-BLIND; AGORAPHOBIA; MEDICATION; EFFICACY; PLACEBO;
PSYCHOTHERAPY; IMPROVEMENT
AB Background: More data are needed to guide next-step interventions for panic disorder refractory to initial intervention.
Method: This 24-week randomized clinical trial (RCT) enrolled 46 patients with DSM-IV-defined panic disorder from November 2000 to April 2005 and consisted of 3 phases. Patients who failed to meet remission criteria were eligible for randomization in the next treatment phase. Phase I was a 6-week lead-in with open-label sertraline flexibly dosed to 100 mg (or escitalopram equivalent) to prospectively define treatment refractoriness (lack of remission). Phase 2 was a 6-week double-blind RCT of (1) increased-dose selective serotonin re-uptake inhibitor (SSRI) versus (2) continued SSRI plus placebo. Phase 3 was a 12-week RCT of added cognitive-behavioral therapy (CBT) compared to 11 medication optimization" with SSRI plus clonazepam. Primary endpoints were remission and change in Panic Disorder Severity Scale (PDSS) score in the intent-to-treat sample in each phase.
Results: In phase 1, 20.5% (8/39) of the patients achieved remission, and only baseline severity predicted endpoint PDSS score (beta [SE] = 1.04 [0.15], t = 6.76, P < .001). In phase 2, increasing the SSRI dose did not result in greater improvement or remission rates (placebo 15% [n = 2] vs increased dose 9% [n = 1]: Fisher exact test P = NS). In phase 3, remission was minimal (medication optimization = 11% [n = 1]; CBT = 10% [n = 1]), with a lack of group difference in PDSS score reduction (t(17) = 0.51, P > .60) consistent with a small effect size (d = 0.24).
Conclusions: Although power was limited and larger studies are needed, we failed to find evidence for greater benefit of increased SSRI dose versus continuation of current dose for panic disorder symptomatic after 6 weeks at moderate dose. Further, augmentation with CBT or medication optimization with clonazepam augmentation in nonremitted panic after 12 weeks of an SSRI did not differ, suggesting that both are reasonable next-step options. However, low overall remission rates in this comorbid refractory population suggest that better predictors of response to specific treatments over time and additional interventions are needed.
C1 [Simon, Naomi M.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA.
[Simon, Naomi M.; Worthington, John J.; Hoge, Elizabeth A.; Thompson, Elizabeth H.; LeBeau, Richard T.; Moshier, Samantha J.; Zalta, Alyson K.; Pollack, Mark H.] Harvard Univ, Sch Med, Boston, MA USA.
[Otto, Michael W.] Boston Univ, Boston, MA 02215 USA.
RP Simon, NM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Simches Res Bldg,2nd Floor,185 Cambridge St, Boston, MA 02114 USA.
EM nsimon@partners.org
RI Hoge, Elizabeth/H-5879-2012;
OI Hoge, Elizabeth/0000-0002-5513-2292; Zalta, Alyson/0000-0002-5159-8431
FU Abbott; McNeil; Eli Lilly; National Institutes of Health; Merck; Shire;
AstraZeneca; Alza; Bristol-Myers Squibb; Janssen; Organon; Otsuka;
National Institute of Mental Health (NIMH) [K23 MH 01831]; National
Institute of Child Health and Human Development; Celltech; Cephalon;
Esai; Forest; GlaxoSmithKline; Gliatech; NARSAD; NIDA; New River;
Novartis; Noven; Neurosearch; Pfizer; Pharmacia; The Prechter
Foundation; The Stanley Foundation; UCB Pharma
FX Funding/support. This study was supported by a Career Development Award
from the National Institute of Mental Health (K23 MH 01831) to Dr Simon.
NR 43
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U2 5
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PI MEMPHIS
PA P O BOX 240008, MEMPHIS, TN 38124 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD NOV
PY 2009
VL 70
IS 11
BP 1563
EP 1570
DI 10.4088/JCP.08m04485blu
PG 8
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 525HQ
UT WOS:000272206200013
PM 19814948
ER
PT J
AU Wingo, AP
Wingo, TS
Harvey, PD
Baldessarini, RJ
AF Wingo, Aliza P.
Wingo, Thomas S.
Harvey, Philip D.
Baldessarini, Ross J.
TI Effects of Lithium on Cognitive Performance: A Meta-Analysis
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article; Proceedings Paper
CT 47th Annual Meeting of the American-College-of-Neuropsychopharmacology
CY DEC 07-11, 2008
CL Scottsdale, AZ
SP Amer Coll Neuropsychopharmacol
ID EUTHYMIC BIPOLAR PATIENTS; N-ACETYL-ASPARTATE; ALZHEIMERS-DISEASE;
NEUROCOGNITIVE IMPAIRMENT; HEALTHY-ADULTS; DOUBLE-BLIND; II DISORDER;
MEMORY; CARBONATE; MOOD
AB Background: Cognitive impairment is under-recognized among patients with bipolar disorder and may represent not only effects of the illness but also adverse effects of its treatments. Among these, lithium is the best-studied mood stabilizer. As its cognitive effects are mixed and not well-known, we assessed reported effects of lithium on cognitive performance.
Data sources: MEDLINE, PsycINFO, and EMBASE databases (1950 to December 2008) were queried with the keywords lithium, cognit*, neurocognit*, neuropsych*, psycholog*, attention, concentration, processing speed, memory, executive, and learning. Database searches were supplemented with bibliographic cross-referencing by hand. The literature search was conducted independently by 2 authors (A.P.W. and T.S.W) during August and September 2008, and questions about appropriate inclusion or exclusion were resolved between them by consensus.
Study selection: Of 586 reports initially identified as being of potential interest, 12, involving 539 subjects, met our inclusion criteria: (1) cognitive performance compared between subjects taking lithium and comparable subjects not taking lithium; comparability was assured by: (2) patients with the same affective disorder diagnoses in euthymic or remitted status or healthy volunteers; (3) groups of similar age and sex; (4) similar intelligence, education, or occupation; (5) similar distribution of other concurrent psychotropic drugs; and (6) cognitive abilities (outcomes) assessed with performance-based measures.
Data extraction: Standardized mean-difference effect size (ES), corrected for small-sample bias (Hedges g), was computed for cognitive tasks in each study. ES estimates were transformed so that positive values indicate poorer performance by lithium-treated subjects. Infrequently, when means and standard deviations were not provided, ES was estimated from reported values of t, F, or z tests. For analysis, similar neurocognitive tests were grouped a priori based on the cognitive domains they aimed to assess.
Data synthesis. We identified 12 studies involving 276 lithium-treated and 263 similar or the same subjects, lithium-free. Lithium was taken for a mean duration of 3.9 years by affective disorder patients and 2.5 weeks by healthy volunteers, yielding a mean daily trough serum concentration of 0.80 mEq/L. Overall, lithium treatment was associated with small but significant impairment in immediate verbal learning and memory (ES = 0.24; 95% Cl, 0.05-0.43) and creativity (ES = 0.33; 95% Cl, 0.02-0.64), whereas delayed verbal memory, visual memory, attention, executive function, processing speed, and psychomotor performance were not significantly affected. Selectively, among the 326 affective-disorder patients, in addition to these overall impairments, long-term lithium treatment also was associated with even greater impairment in psychomotor performance (ES = 0.62; 95% Cl, 0.27-0.97), with no evidence of cognitive improvements.
Conclusions: Lithium treatment appears to have only few and minor negative effects on cognition. J Clin Psychiatry 2009,70(11):1588-1597 (C) Copyright 2009 Physicians Postgraduate Press, Inc.
C1 [Wingo, Aliza P.; Harvey, Philip D.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA.
[Wingo, Aliza P.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA.
[Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Baldessarini, Ross J.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA.
[Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Psychopharmacol Program, Belmont, MA USA.
[Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Int Consortium Bipolar Disorder Res, Belmont, MA USA.
RP Wingo, AP (reprint author), Emory Univ, Dept Psychiat & Behav Sci, 101 Woodruff Circle NE Suite 4000, Atlanta, GA 30322 USA.
EM aliza.wingo@emory.edu
NR 75
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U2 30
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 240008, MEMPHIS, TN 38124 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD NOV
PY 2009
VL 70
IS 11
BP 1588
EP 1597
DI 10.4088/JCP.08r04972
PG 10
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 525HQ
UT WOS:000272206200017
PM 19689922
ER
PT J
AU Gross, AF
Wiechers, IR
Stern, TA
AF Gross, Anne F.
Wiechers, Ilse R.
Stern, Theodore A.
TI Peer Review by Early Career Psychiatrists: An Opportunity for
Development
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Editorial Material
C1 [Gross, Anne F.; Wiechers, Ilse R.; Stern, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
RP Stern, TA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Warren 605,55 Fruit St, Boston, MA 02114 USA.
EM tstern@partners.org
NR 0
TC 5
Z9 5
U1 0
U2 0
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 240008, MEMPHIS, TN 38124 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD NOV
PY 2009
VL 70
IS 11
BP 1600
EP 1601
DI 10.4088/JCP.09com05635whi
PG 2
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 525HQ
UT WOS:000272206200021
PM 20031102
ER
PT J
AU Holt, DJ
Lynn, SK
Kuperberg, GR
AF Holt, Daphne J.
Lynn, Spencer K.
Kuperberg, Gina R.
TI Neurophysiological Correlates of Comprehending Emotional Meaning in
Context
SO JOURNAL OF COGNITIVE NEUROSCIENCE
LA English
DT Article
ID EVENT-RELATED POTENTIALS; LANGUAGE COMPREHENSION; BRAIN POTENTIALS; ERP
ANALYSIS; EVALUATIVE CATEGORIZATIONS; NEURAL MECHANISMS; LIFE EVENTS;
WORDS; ATTENTION; STIMULI
AB Although the neurocognitive mechanisms of nonaffective language comprehension have been studied extensively, relatively less is known about how the emotional meaning of language is processed. In this study, electrophysiological responses to affectively positive, negative, and neutral words, presented within nonconstraining, neutral contexts, were evaluated under conditions of explicit evaluation of emotional content ( Experiment 1) and passive reading ( Experiment 2). In both experiments, a widely distributed Late Positivity was found to be larger to negative than to positive words ( a "negativity bias''). In addition, in Experiment 2, a small, posterior N400 effect to negative and positive ( relative to neutral) words was detected, with no differences found between N400 magnitudes to negative and positive words. Taken together, these results suggest that comprehending the emotional meaning of words following a neutral context requires an initial semantic analysis that is relatively more engaged for emotional than for nonemotional words, whereas a later, more extended, attention-modulated process distinguishes the specific emotional valence ( positive vs. negative) of words. Thus, emotional processing networks within the brain appear to exert a continuous influence, evident at several stages, on the construction of the emotional meaning of language.
C1 [Holt, Daphne J.; Kuperberg, Gina R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Lynn, Spencer K.] McLean Hosp, Belmont, MA 02178 USA.
[Kuperberg, Gina R.] Tufts Univ, Medford, MA 02155 USA.
RP Holt, DJ (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, 149 13th St, Charlestown, MA 02129 USA.
EM dholt@partners.org
FU NIMH [R01 MH071635, K23-MH076054]; NARSAD; Sidney R. Baer, Jr.
Foundation; Institute for Mental Illness and Neuroscience Discovery (
MIND); Clinical Research Training Program; GlaxoSmithKline Severe Mental
Illness Award; Jerome Lyle Rappaport Charitable Foundation; Office of
Juvenile Justice and Delinquency Prevention; USDOJ; Harvard Medical
School Center for Mental Health and Media
FX We thank Abigail Swain, Tatiana Sitnikova, Molly Butterworth, Catherine
Garth, and George Nitzburg for their invaluable technical assistance and
Jos Van Berkum and two anonymous reviewers for their helpful comments on
the manuscript. This research was funded by grants from NIMH [ R01
MH071635 ( G. R. K.), K23-MH076054 ( D. J. H.)], NARSAD ( D. J. H., G.
R. K.), the Sidney R. Baer, Jr. Foundation ( D. J. H., G. R. K.), and
the Institute for Mental Illness and Neuroscience Discovery ( MIND). D.
J. H. was also supported by the Clinical Research Training Program, the
GlaxoSmithKline Severe Mental Illness Award, and the Jerome Lyle
Rappaport Charitable Foundation. S. K. L. was supported by a grant from
the Office of Juvenile Justice and Delinquency Prevention, USDOJ, to the
Harvard Medical School Center for Mental Health and Media.
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PU M I T PRESS
PI CAMBRIDGE
PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA
SN 0898-929X
J9 J COGNITIVE NEUROSCI
JI J. Cogn. Neurosci.
PD NOV
PY 2009
VL 21
IS 11
BP 2245
EP 2262
DI 10.1162/jocn.2008.21151
PG 18
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 505ZL
UT WOS:000270741300016
PM 18855550
ER
PT J
AU Marvizon, JCG
Chen, WL
Murphy, N
AF Marvizon, Juan Carlos G.
Chen, Wenling
Murphy, Niall
TI Enkephalins, Dynorphins, and beta-Endorphin in the Rat Dorsal Horn: An
Immunofluorescence Colocalization Study
SO JOURNAL OF COMPARATIVE NEUROLOGY
LA English
DT Article
DE calcitonin gene-related peptide; dorsal root ganglia; mu-opioid
receptor; prodynorphin; spinal cord; substance P
ID MU-OPIOID RECEPTOR; CENTRAL-NERVOUS-SYSTEM; GENE-RELATED PEPTIDE;
ACTIVITY MODIFYING PROTEIN-1; SPINAL-CORD; SUBSTANCE-P; ROOT-GANGLIA;
IMMUNOHISTOCHEMICAL LOCALIZATION; IMMUNOREACTIVE DYNORPHIN;
METHIONINE-ENKEPHALIN
AB To characterize neuronal pathways that release opioid peptides in the rat dorsal horn, multiple-label immunohistochemistry, confocal microscopy, and computerized colocalization measures were used to characterize opioid-containing terminals and cells. An antibody that selectively recognized beta-endorphin labeled fibers and neurons in the ventral horn as well as fibers in the lateral funiculus and lamina X, but practically no fibers in the dorsal horn. An anti-enkephalin antibody, which recognized Leu-, Met-, and Phe-Arg-Met-enkephalin, labeled the dorsolateral funiculus and numerous puncta in laminae I-III and V of the dorsal horn. An antibody against Phe-Arg-Met-enkephalin, which did not recognize Leu- and Met-enkephalin, labeled the same puncta. Antibodies against dynorphin and prodynorphin labeled puncta and fibers in laminae I, II, and V, as well as some fibers in the rest of the dorsal horn. Dynorphin and prodynorphin immunoreactivities colocalized in some puncta and fibers, but the prodynorphin antibody additionally labeled cell bodies. There was no colocalization of dynorphin (or prodynorphin) with enkephalin (or Phe-Arg-Met-enkephalin). Enkephalin immunoreactivity did not colocalize with the C-fiber markers calcitonin gene-related peptide (CGRP), substance P, and isolectin B4. In contrast, there was some colocalization of dynorphin and prodynorphin with CGRP and substance P, but not with isolectin B4. Both enkephalin and dynorphin partly colocalized with vesicular glutamate transporter 2, a marker of glutamatergic terminals. The prodynorphin-positive neurons in the dorsal horn were distinct from neurons expressing mu-opioid receptors, neurokinin 1 receptors, and protein kinase C-gamma. These results show that enkephalins and dynorphins are present in different populations of dorsal horn neurons. In addition, dynorphin is present in some C-fibers. J. Comp. Neurol. 517:51-68, 2009. Published 2009 Wiley-Liss, Inc.
C1 [Marvizon, Juan Carlos G.] VA Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
[Marvizon, Juan Carlos G.; Chen, Wenling] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Ctr Neurobiol Stress,Div Digest Dis, Los Angeles, CA 90095 USA.
[Murphy, Niall] RIKEN, Brain Sci Inst, Mol Neuropathol Grp, Wako, Saitama 3510198, Japan.
RP Marvizon, JCG (reprint author), VA Greater Angeles Healthcare Syst, Bldg 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM marvizon@ucla.edu
FU National Institutes of Health [R01-DA-012609]; Department of Veterans
Affairs [B47661]
FX Grant sponsor: the National Institutes of Health; Grant number:
R01-DA-012609 to (J.C.M.); Grant sponsor: the Department of Veterans
Affairs; Grant number: B47661 (to J.C.M.).
NR 74
TC 31
Z9 31
U1 0
U2 7
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0021-9967
J9 J COMP NEUROL
JI J. Comp. Neurol.
PD NOV 1
PY 2009
VL 517
IS 1
BP 51
EP 68
DI 10.1002/cne.22130
PG 18
WC Neurosciences; Zoology
SC Neurosciences & Neurology; Zoology
GA 494VV
UT WOS:000269848300004
PM 19711397
ER
PT J
AU Chen, JL
Luviano, DM
Chen, JC
Yu, F
Sarraf, D
AF Chen, Jessica L.
Luviano, Damien M.
Chen, John C.
Yu, Fei
Sarraf, David
TI Comparison of diabetic retinopathy phenotype between Latinos and Blacks
SO JOURNAL OF DIABETES AND ITS COMPLICATIONS
LA English
DT Article
CT Annual Meeting of the
Association-for-Research-in-Vision-and-Ophthalmology
CY MAY 06-10, 2007
CL Ft Lauderdale, FL
SP Assoc Res Vis & Ophthalmol
DE Diabetic retinopathy phenotype; Latino; Black
ID VEGF GENE; MACULAR DEGENERATION; UNITED-STATES; PREVALENCE; ASSOCIATION;
POLYMORPHISM; POPULATION; WHITES; ADULTS; RISK
AB Objective: The objective of this study was to delineate the difference in the phenotype of diabetic retinopathy (DR) in Latinos versus Blacks using characteristics shown on fundus photography (FP) and fluorescein angiography (FA). Research Design and Methods: This was a retrospective chart review of 203 adult Black and Latino diabetic patients from the King-Drew Medical Center eye clinic from January 1998 to March 2005. Systemic risk factors such as HbA(1c) and kidney function data were collected. FP and FA were analyzed and graded according to Early Treatment of Diabetic Retinopathy Study criteria. Statistical analysis was performed to determine whether a given lesion type was more characteristic of a particular racial group. Results: Gender, age, median microalbumin-to-creatinine ratio (ACR), and aver-age HbA(1c) values were not significantly different between the groups. The presence of clinically significant macular edema (CSME), focal or diffuse, was very high in both groups (44% in Latinos and 46% in Blacks), and the overall DR grades were similar. However, upon individual lesion analysis, the Latinos were noted to have more prevalent intraretinal hemorrhages involving a greater area of the retina (P=.046). Conclusions: Although Latinos and Blacks of comparable age and glycemic control are equally at risk for CSME and proliferative retinopathy, Latinos may be at greater risk for a specific phenotype of DR characterized by extravasation of intraretinal hemorrhages, which is associated with poor prognosis. Further prospective studies may uncover racial differences that may have implications for prognosis and therapy. Published by Elsevier Inc.
C1 [Yu, Fei; Sarraf, David] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA.
[Chen, Jessica L.] Drew UCLA Med Educ Program, Los Angeles, CA USA.
[Luviano, Damien M.; Sarraf, David] Charles R Drew Univ Med & Sci, Dept Ophthalmol, Los Angeles, CA 90059 USA.
[Chen, John C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Sarraf, David] Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA USA.
RP Sarraf, D (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, Oph Box 957006,1-165 JSEI, Los Angeles, CA 90095 USA.
EM dsarraf@ucla.edu
NR 23
TC 4
Z9 4
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1056-8727
J9 J DIABETES COMPLICAT
JI J. Diabetes Complications
PD NOV-DEC
PY 2009
VL 23
IS 6
BP 371
EP 375
DI 10.1016/j.jdiacomp.2008.05.001
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 519TM
UT WOS:000271791300001
PM 18599323
ER
PT J
AU Singh, B
AF Singh, Bramah
TI Atrial fibrillation: from ion channels to bedside treatment options
SO JOURNAL OF ELECTROCARDIOLOGY
LA English
DT Review
DE Atrial fibrillation; Ion channels; Antiarrhythmic
ID PEPTIDE ROTIGAPTIDE ZP123; GAP-JUNCTION MODIFIER; ANTIARRHYTHMIC
COMPOUND AZD7009; STERILE PERICARDITIS MODEL; REDUCES INFARCT SIZE;
TORSADES-DE-POINTES; OPEN-CHEST DOGS; CLASS IC DRUGS; SINUS RHYTHM;
IN-VITRO
AB Atrial fibrillation is now the most common arrhythmia in clinical practice. Recent understanding of the abnormalities in ion flow that underlie atrial fibrillation has led to the search for new treatment options with improved efficacy and tolerability. The purpose of this article is to review the role of ion channels in the development of atrial fibrillation and discuss the nature of their inhibition by investigational antiarrhythmic agents. Novel treatments include the benzofuran derivative dronedarone, atrial-selective compounds (eg, vernakalant), multichannel blocking agents (eg, tedisamil), and gap junction modifiers (eg, rotigaptide). Targeted antiarrhythmic therapies have the potential to provide safer and more effective management options for patients with atrial fibrillation. (C) 2009 Published by Elsevier Inc.
C1 Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA.
RP Singh, B (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Hlth Care Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM bsingh@ucla.edu
FU Sanofi-Aventis US; Bridgewater, New Jersey, USA
FX Funding for editorial support was provided by Sanofi-Aventis US,
Bridgewater, New Jersey, USA.
NR 102
TC 6
Z9 7
U1 0
U2 12
PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
PI PHILADELPHIA
PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA
SN 0022-0736
J9 J ELECTROCARDIOL
JI J. Electrocardiol.
PD NOV-DEC
PY 2009
VL 42
IS 6
BP 660
EP 670
DI 10.1016/j.jelectrocard.2009.04.002
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 515SZ
UT WOS:000271494500032
PM 19520377
ER
PT J
AU Wilcox, SR
Arbelaez, C
Nadel, ES
Brown, DFM
AF Wilcox, Susan R.
Arbelaez, Christian
Nadel, Eric S.
Brown, David F. M.
TI FOREIGN BODY ASPIRATION AFTER HIGH-VELOCITY TRAUMA
SO JOURNAL OF EMERGENCY MEDICINE
LA English
DT Article
C1 [Wilcox, Susan R.; Nadel, Eric S.; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Wilcox, Susan R.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care, Boston, MA 02114 USA.
[Wilcox, Susan R.; Arbelaez, Christian; Nadel, Eric S.; Brown, David F. M.] Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA.
[Arbelaez, Christian; Nadel, Eric S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA.
RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Founders 114,Fruit St, Boston, MA 02114 USA.
NR 14
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0736-4679
J9 J EMERG MED
JI J. Emerg. Med.
PD NOV
PY 2009
VL 37
IS 4
BP 411
EP 414
PG 4
WC Emergency Medicine
SC Emergency Medicine
GA 530BJ
UT WOS:000272563600013
PM 19836919
ER
PT J
AU Xu, Y
Young, MJ
Battaglino, RA
Morse, LR
Fontana, CR
Pagonis, TC
Kent, R
Soukos, NS
AF Xu, Yan
Young, Mark J.
Battaglino, Ricardo A.
Morse, Leslie R.
Fontana, Carla Raquel
Pagonis, Tom C.
Kent, Ralph
Soukos, Nikolaos S.
TI Endodontic Antimicrobial Photodynamic Therapy: Safety Assessment in
Mammalian Cell Cultures
SO JOURNAL OF ENDODONTICS
LA English
DT Article
DE Endodontic disinfection; mammalian cells; methylene blue; photodynamic
therapy; safety
ID LIGHT-ACTIVATED DISINFECTION; KERATINOCYTES IN-VITRO; METHYLENE-BLUE;
SODIUM-HYPOCHLORITE; TOLUIDINE-BLUE; ENTEROCOCCUS-FAECALIS; ROOT CANALS;
DNA-DAMAGE; APOPTOSIS; VIVO
AB Objectives: The purpose of this study was to assess the in vitro synergistic effect of methylene blue (MB) and red light on human gingival fibroblasts and osteoblasts with parameters similar to those that may be applied in a clinical setting for endodontic disinfection. Materials and Methods: Both cell types were sensitized with 50 mu g/mL MB followed by exposure to red light at 665 nm for 5 minutes with an irradiance of 10, 20, and 40 mW/cm(2). After photodynamic therapy (PDT), cell viability and mitochondrial activity were evaluated by the neutral red and MTT assay, respectively. The assessment of PDT-induced apoptosis was investigated by western blot analysis using cleaved poly(ADPribose) polymerase-specific antibodies. Results: Light at 20 and 40 mW/cm(2) with MB had modest effects at 24 hours on osteoblasts in both assays, whereas sodium hypochlorite completely eliminated cells. Western blot analysis revealed no signs of apoptosis in either cell type. Conclusion: The data suggest that there is a safe therapeutic window whereby PDT can inactivate endodontic pathogens without affecting host cell viability. (J Endod 2009;35:1567-1572)
C1 [Xu, Yan; Fontana, Carla Raquel; Soukos, Nikolaos S.] Forsyth Inst, Appl Mol Photomed Lab, Boston, MA 02115 USA.
[Young, Mark J.; Pagonis, Tom C.] Harvard Univ, Sch Dent Med, Dept Adv Grad Endodont, Div Endodont, Boston, MA 02115 USA.
[Battaglino, Ricardo A.] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA.
[Kent, Ralph] Forsyth Inst, Dept Biostat, Boston, MA 02115 USA.
[Morse, Leslie R.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA.
RP Soukos, NS (reprint author), Forsyth Inst, Appl Mol Photomed Lab, 140 Fenway, Boston, MA 02115 USA.
EM nsoukos@forsyth.org
RI Fontana, Carla/C-2033-2012; battaglino, ricardo/D-2892-2015; Morse,
Leslie/C-9442-2015
OI Fontana, Carla/0000-0002-9135-3690; Morse, Leslie/0000-0002-7426-6341
FU NIDCR [R01-DE-16922]
FX Supported by NIDCR grant R01-DE-16922.
NR 40
TC 38
Z9 39
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0099-2399
J9 J ENDODONT
JI J. Endod.
PD NOV
PY 2009
VL 35
IS 11
BP 1567
EP 1572
DI 10.1016/j.joen.2009.08.002
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 518YB
UT WOS:000271730900017
PM 19840649
ER
PT J
AU Sugimoto, M
Furuta, T
Yamaoka, Y
AF Sugimoto, Mitsushige
Furuta, Takahisa
Yamaoka, Yoshio
TI Influence of inflammatory cytokine polymorphisms on eradication rates of
Helicobacter pylori
SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Review
DE eradication therapy; Helicobacter pylori; IL-1 beta; inflammatory
cytokine; polymorphism; TNF-alpha
ID NECROSIS-FACTOR-ALPHA; INTERLEUKIN-1-BETA GENETIC-POLYMORPHISM;
RANDOMIZED CONTROLLED-TRIAL; GASTRIC-ACID INHIBITION; PROTON PUMP
INHIBITOR; TRIPLE THERAPY; GENOTYPIC DIFFERENCES; INCREASED RISK; CURE
RATES; ENDOSCOPIC RESECTION
AB Pro-inflammatory cytokines and anti-inflammatory cytokines are produced in gastric mucosa from inflammatory cells activated by Helicobacter pylori (H. pylori) infection. Of the inflammatory cytokines, interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha have a potent inhibitive effect on gastric acid production. Polymorphisms in these genes are associated with individual differences in cytokine messenger RNA levels, which result in different gastric mucosal inflammation, different acid inhibition and different gastroduodenal disease risks in response to H. pylori infection. The sustained higher intragastric pH during an eradication therapy is known to be one of the therapeutic determinants of the H. pylori eradication as well as antibiotics resistance and poor compliance. The IL-1B-511 polymorphism is related to eradication rate, and, in combined analysis of previous reports, the eradication rate in patients with the IL-1B-511 C/C genotype (77.4%, 209/270), low IL-1 beta producer genotype, is lower than that of the IL-1B-511 C/T and T/T genotypes (87.2%, 631/724) (Odds ratio for eradication failure: 1.98, 95% confidence interval: 1.38-2.84, P = 0.0002). Moreover, the odds ratio of combined CYP2C19 rapid metabolizer-IL-1B-511 C/C type for eradication failure is 11.15 (5.23-23.78) times that of the CYP2C19 poor metabolizer-IL-1B-511 non-C/C type. However, there is no positive data indicating the role of other inflammatory cytokine polymorphisms (e.g. IL-1RN, TNF-A or IL-10) in eradication therapy. Nevertheless, the studies show that inflammatory cytokine polymorphisms, especially the IL-1B-511 T/T genotype, are the determinants of eradication by affecting gastric acid secretion and mucosal inflammation. Therefore, the tailored eradication therapy, considering inflammatory cytokine polymorphisms, may be effective for the higher eradication rates.
C1 [Sugimoto, Mitsushige] Hamamatsu Univ Sch Med, Clin Res Ctr, Higashi Ku, Hamamatsu, Shizuoka 4313192, Japan.
[Sugimoto, Mitsushige; Yamaoka, Yoshio] Michael E DeBakey Vet Affairs Med Ctr, Dept Med Gastroenterol, Houston, TX USA.
[Sugimoto, Mitsushige; Yamaoka, Yoshio] Baylor Coll Med, Houston, TX 77030 USA.
[Yamaoka, Yoshio] Oita Univ, Dept Environm & Prevent Med, Fac Med, Yufu, Japan.
RP Sugimoto, M (reprint author), Hamamatsu Univ Sch Med, Clin Res Ctr, Higashi Ku, 1-20-1 Handayama, Hamamatsu, Shizuoka 4313192, Japan.
EM mitsuhamamed@yahoo.co.jp
FU National Institute of Health [R01 DK62813]
FX We thank Jared Pinkston for his advice and grammatical editing of this
paper. This study is supported by Grant Number R01 DK62813 (National
Institute of Health). None of the authors had conflicts of interest
related to this study.
NR 74
TC 21
Z9 22
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0815-9319
J9 J GASTROEN HEPATOL
JI J. Gastroenterol. Hepatol.
PD NOV
PY 2009
VL 24
IS 11
BP 1725
EP 1732
DI 10.1111/j.1440-1746.2009.06047.x
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 512KQ
UT WOS:000271248000007
PM 20136959
ER
PT J
AU Bausch, D
Mino-Kenudson, M
Fernandez-del Castillo, C
Warshaw, AL
Kelly, KA
Thayer, SP
AF Bausch, Dirk
Mino-Kenudson, Mari
Fernandez-del Castillo, Carlos
Warshaw, Andrew L.
Kelly, Kimberly A.
Thayer, Sarah P.
TI Plectin-1 is a Biomarker of Malignant Pancreatic Intraductal Papillary
Mucinous Neoplasms
SO JOURNAL OF GASTROINTESTINAL SURGERY
LA English
DT Article
CT 50th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract
CY JUN 01, 2009
CL Chicago, IL
SP Soc Surg Alimentary Tract
DE Plectin-1; Biomarker; Malignant IPMN; Benign IPMN
ID UPDATED EXPERIENCE; FLUID ANALYSIS; IN-SITU; DUCT; RESECTION; TUMORS;
MANAGEMENT; ADENOCARCINOMA; PREDICTORS; CARCINOMAS
AB Pancreatic intraductal papillary mucinous neoplasms (IPMN) are now identified with increasing frequency. The detection of carcinoma in IPMN is difficult and suffers from high false-positive and false-negative rates, often resulting in inappropriate treatment decisions. Improved detection of malignancy using novel biomarkers may therefore improve diagnostic accuracy. One such promising novel biomarker is Plectin-1 (Plec-1).
Using immunohistochemistry, Plec-1 expression was assayed in benign (low and moderate dysplasia, n = 6) as well as malignant IPMN (high-grade dysplasia and invasive carcinoma, n = 31) and lymph node metastases from carcinoma arising in IPMN (n = 12). Furthermore, cyst fluids from benign (n = 3) and malignant IPMN (n = 4) were evaluated for Plec-1 expression.
Twenty-six of 31 malignant IPMN and all 12 lymph node metastases were Plec-1 positive. In contrast, only one of six benign IPMN expressed Plec-1. The specificity of Plec-1 in distinguishing malignant IPMN from benign IPMN was 83% and its sensitivity 84%. Furthermore, all (four out of four) cyst fluids from malignant IPMN, but none of the three benign IPMN, were Plec-1 positive. These data support Plec-1 as an excellent biomarker for the early detection of carcinoma arising in IPMN.
C1 [Bausch, Dirk; Fernandez-del Castillo, Carlos; Warshaw, Andrew L.; Thayer, Sarah P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Thayer, Sarah P.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Kelly, Kimberly A.] Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22908 USA.
RP Thayer, SP (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,WAC 460, Boston, MA 02114 USA.
EM sthayer@partners.org
FU NCI NIH HHS [R01 CA137071, P50 CA127003, R01 CA137071-03]; NIDDK NIH HHS
[K08 DK071329]
NR 32
TC 26
Z9 26
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1091-255X
J9 J GASTROINTEST SURG
JI J. Gastrointest. Surg.
PD NOV
PY 2009
VL 13
IS 11
BP 1948
EP 1953
DI 10.1007/s11605-009-1001-9
PG 6
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA 510QS
UT WOS:000271106200010
PM 19760374
ER
PT J
AU Vollmer, CM
AF Vollmer, Charles M., Jr.
TI Unexpected Identification of Gallbladder Carcinoma During
Cholecystectomy
SO JOURNAL OF GASTROINTESTINAL SURGERY
LA English
DT Article
CT SSAT/AHPBA Joint Symposium on Current Approach to Carcinoma of the
Gallbladder
CY MAY, 2008
CL San Diego, CA
SP Soc Surg Alimentary Tract, AHPBA
DE Gallbladder carcinoma; Incidental gallbladder cancer; Laparoscopic
cholecystectomy; Stop rules
ID STAGING LAPAROSCOPY
C1 Beth Israel Deaconess Med Ctr, Dept Surg, Div Gen Surg, Boston, MA 02215 USA.
RP Vollmer, CM (reprint author), Beth Israel Deaconess Med Ctr, Dept Surg, Div Gen Surg, 330 Brookline Ave,Stoneman 9, Boston, MA 02215 USA.
EM cvollmer@bidmc.harvard.edu
NR 6
TC 2
Z9 3
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1091-255X
J9 J GASTROINTEST SURG
JI J. Gastrointest. Surg.
PD NOV
PY 2009
VL 13
IS 11
BP 2034
EP 2036
DI 10.1007/s11605-009-0808-8
PG 3
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA 510QS
UT WOS:000271106200027
PM 19238496
ER
PT J
AU Saylor, PJ
Keating, NL
Smith, MR
AF Saylor, Philip J.
Keating, Nancy L.
Smith, Matthew R.
TI Prostate Cancer Survivorship: Prevention and Treatment of the Adverse
Effects of Androgen Deprivation Therapy
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE prostate cancer; survivorship; GnRH agonists; osteoporosis;
bisphosphonates; diabetes; obesity; cardiovascular disease
ID RANDOMIZED CONTROLLED-TRIAL; BONE-MINERAL DENSITY;
CORONARY-HEART-DISEASE; HORMONE AGONIST THERAPY; LEAN BODY-MASS;
FRACTURE RISK; POSTMENOPAUSAL WOMEN; CARDIOVASCULAR-DISEASE; SUPPRESSION
THERAPY; ARTERIAL STIFFNESS
AB More than one-third of the estimated 2 million prostate cancer survivors in the United States receive androgen deprivation therapy (ADT). This population of mostly older men is medically vulnerable to a variety of treatment-associated adverse effects.
Androgen-deprivation therapy (ADT) causes loss of libido, vasomotor flushing, anemia, and fatigue. More recently, ADT has been shown to accelerate bone loss, increase fat mass, increase cholesterol and triglycerides, and decrease insulin sensitivity. Consistent with these adverse metabolic effects, ADT has also recently been associated with greater risks for fractures, diabetes and cardiovascular disease.
Primary care clinicians and patients should be aware of the potential benefits and harms of ADT. Screening and intervention to prevent treatment-related morbidity should be incorporated into the routine care of prostate cancer survivors. Evidence-based guidelines to prevent fractures, diabetes, and cardiovascular disease in prostate cancer survivors represent an important unmet need. We recommend the adapted use of established practice guidelines designed for the general population.
C1 [Saylor, Philip J.; Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA.
[Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA.
[Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
RP Saylor, PJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Massachusetts Gen Hosp Lawrence House,POB 2nd Flo, Boston, MA 02114 USA.
EM psaylor@partners.org
FU NIH [5K24CA121990-02]; Prostate Cancer Foundation; Lance Armstrong
Foundation
FX R. Smith is supported by an NIH K24 Midcareer Investigator Award
(5K24CA121990-02) and grants from the Prostate Cancer Foundation and
Lance Armstrong Foundation.
NR 87
TC 24
Z9 24
U1 2
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD NOV
PY 2009
VL 24
BP 389
EP 394
DI 10.1007/s11606-009-0968-y
PG 6
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 507ZB
UT WOS:000270894400003
ER
PT J
AU Park, ER
Bober, SL
Campbell, EG
Recklitis, CJ
Kutner, JS
Diller, L
AF Park, Elyse R.
Bober, Sharon L.
Campbell, Eric G.
Recklitis, Christopher J.
Kutner, Jean S.
Diller, Lisa
TI General Internist Communication about Sexual Function with Cancer
Survivors
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE general internist; survivorship; sexuality communication
ID HEALTH; DYSFUNCTION; BARRIERS; ISSUES; HELP; CARE
AB Sexual dysfunction is an important issue that affects many cancer survivors who are increasingly being cared for by internists.
To examine the attitudes and reported practices of internists regarding survivorship care as it pertains to sexual dysfunction.
Surveys were sent to 406 physicians affiliated with the Department of Internal Medicine at the University of Colorado Denver School of Medicine. Of the 319 eligibles, 227 were returned (71% RR).
Of the 227 responders, 46% were "somewhat/very" likely to initiate a conversation about sexual dysfunction; 62% "never/rarely" addressed sexual dysfunction. Each additional weekly hour spent in patient care was associated with a 2% increase in the likelihood of sexual dysfunction being addressed or discussions about sexual dysfunction being initiated. Reported inadequate preparation/formal training around survivorship issues was associated with sexual dysfunction being addressed less often (odds ratio [OR] = 0.45). Perception of patient anxiety or fears about health was associated with sexual dysfunction being addressed more often (OR = 2.38). Perceived preparedness to evaluate long-term effects was associated with a greater likelihood of physicians initiating discussions about sexual functioning (OR = 2.49).
Cancer survivors receive their long-term care from internists. Our results suggest that sexual dysfunction is often not addressed during their follow-up care. Additional training is needed to prepare physicians to negotiate this difficult issue.
C1 [Park, Elyse R.; Campbell, Eric G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA 02114 USA.
[Bober, Sharon L.; Recklitis, Christopher J.; Diller, Lisa] Harvard Univ, Sch Med, Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA.
[Kutner, Jean S.] Univ Colorado, Sch Med, Denver, CO USA.
RP Park, ER (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM epark@partners.org
FU Swim Across America Foundation; American Cancer Society
FX We are grateful to the Swim Across America Foundation and the American
Cancer Society for supporting this work. We thank Sowmya Rao, PhD, for
her statistical assistance. We would like to acknowledge and thank
Monica Rothwell, Laura Fox, and Jennifer Pandiscio for their assistance
with preparation of these data and the manuscript.
NR 20
TC 22
Z9 22
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD NOV
PY 2009
VL 24
BP 407
EP 411
DI 10.1007/s11606-009-1026-5
PG 5
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 507ZB
UT WOS:000270894400006
ER
PT J
AU McQueen, A
Bartholomew, LK
Greisinger, AJ
Medina, GG
Hawley, ST
Haidet, P
Bettencourt, JL
Shokar, NK
Ling, BS
Vernon, SW
AF McQueen, Amy
Bartholomew, L. Kay
Greisinger, Anthony J.
Medina, Gilda G.
Hawley, Sarah T.
Haidet, Paul
Bettencourt, Judith L.
Shokar, Navkiran K.
Ling, Bruce S.
Vernon, Sally W.
TI Behind Closed Doors: Physician-Patient Discussions About Colorectal
Cancer Screening
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE colorectal cancer screening; physician-patient communication; shared
decision-making; qualitative research; interventions
ID INFORMED DECISION-MAKING; SELF-EXEMPTING BELIEFS; SERVICES TASK-FORCE;
FECAL OCCULT BLOOD; PRIMARY-CARE; RANDOMIZED-TRIAL; UNITED-STATES;
HEALTH; RECOMMENDATION; COLONOSCOPY
AB Despite the availability of multiple effective screening tests for colorectal cancer, screening rates remain suboptimal. The literature documents patient preferences for different test types and recommends a shared decision-making approach for physician-patient colorectal cancer screening (CRCS) discussions, but it is unknown whether such communication about CRCS preferences and options actually occurs in busy primary-care settings.
Describe physician-patient CRCS discussions during a wellness visit.
Cross-sectional; patients audio-recorded with physicians.
A subset of patients (N = 64) participating in a behavioral intervention trial designed to increase CRCS who completed a wellness visit during the trial with a participating physician (N = 8).
Transcripts were analyzed using qualitative methods.
Physicians in this sample consistently recommended CRCS, but focused on colonoscopy. Physicians did not offer a fecal occult blood test alone as a screening choice, which may have created missed opportunities for some patients to get screened. In this single visit, physicians' communication processes generally precluded discussion of patients' test preferences and did not facilitate shared decision-making. Patients' questions indicated their interest in different CRCS test types and appeared to elicit more information from physicians. Some patients remained resistant to CRCS after discussing it with a physician.
If a preference for colonoscopy is widespread among primary-care physicians, the implications for intervention are either to prepare patients for this preference or to train physicians to offer options when recommending screening to patients.
C1 [McQueen, Amy] Washington Univ, Sch Med, Div Hlth Behav Res, St Louis, MO 63108 USA.
[Bartholomew, L. Kay; Medina, Gilda G.; Bettencourt, Judith L.; Vernon, Sally W.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
[Greisinger, Anthony J.] Kelsey Res Fdn, Houston, TX USA.
[Hawley, Sarah T.] Univ Michigan, Sch Med, Ann Arbor, MI USA.
[Haidet, Paul] DeBakey VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA.
[Haidet, Paul] Baylor Coll Med, Houston, TX 77030 USA.
[Shokar, Navkiran K.] Univ Texas Med Branch, Galveston, TX USA.
[Ling, Bruce S.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
RP McQueen, A (reprint author), Washington Univ, Sch Med, Div Hlth Behav Res, 4444 Forest Pk Ave, St Louis, MO 63108 USA.
EM amcqueen@dom.wustl.edu
FU National Cancer Institute [097263]; American Cancer Society Mentored
Research Scholar [CPPB113766]
FX This research was supported by a National Cancer Institute R01 grant
(no. 097263; PI: Sally W. Vernon) and an American Cancer Society
Mentored Research Scholar Grant (CPPB113766; PI: Amy McQueen). We
gratefully acknowledge the support of the physicians and patients in the
Family Medicine and Internal Medicine Departments at Kelsey-Seybold
Clinic. We also thank Nicholas Solomos, MD, for his insightful comments
on the manuscript.
NR 61
TC 57
Z9 57
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD NOV
PY 2009
VL 24
IS 11
BP 1228
EP 1235
DI 10.1007/s11606-009-1108-4
PG 8
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 514VA
UT WOS:000271422600009
PM 19763699
ER
PT J
AU Jupiter, JB
AF Jupiter, Jesse B.
TI Commentary: The Effect of Ulnar Styloid Fractures on Patient-Rated
Outcomes After Volar Locking Plating of Distal Radius Fractures
SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME
LA English
DT Editorial Material
ID SYSTEM
C1 Massachusetts Gen Hosp, Dept Hand Surg, Boston, MA 02114 USA.
RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Dept Hand Surg, Boston, MA 02114 USA.
EM jjupiter1@partners.org
NR 6
TC 15
Z9 17
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 0363-5023
J9 J HAND SURG-AM
JI J. Hand Surg.-Am. Vol.
PD NOV
PY 2009
VL 34A
IS 9
BP 1603
EP 1604
DI 10.1016/j.jhsa.2009.06.022
PG 2
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 517FG
UT WOS:000271598000002
PM 19896005
ER
PT J
AU Guitton, TG
Ring, D
Kloen, P
AF Guitton, Thierry G.
Ring, David
Kloen, Peter
TI Long-Term Evaluation of Surgically Treated Anterior Monteggia Fractures
in Skeletally Mature Patients
SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME
LA English
DT Article
DE Dislocation; elbow; fracture; Monteggia
ID RADIAL HEAD; EQUIVALENT LESIONS; ELBOW; DISLOCATIONS; CHILDREN;
OLECRANON; FOREARM; ULNA; ADULTS
AB Purpose The purpose of this retrospective study was to evaluate the functional and radiological long-term outcome of open reduction and internal fixation of skeletally mature patients with a Bado type 1 Monteggia fracture.
Methods We identified 11 consecutive skeletally mature patients who had surgical treatment of an anterior (Bado type 1) Monteggia fracture. Long-term evaluation at a median of 20 years after injury (range, 7-34 years) was compared with an early evaluation at a median of 13 months after injury (range, 11-32 months). The early and long-term results were evaluated radiographically and according to the system of Broberg and Morrey. The long-term result was also evaluated according to the Mayo Elbow Performance Index, the American Shoulder and Elbow Surgeons, and the Disabilities of the Arm Should and Hand scores.
Results Two patients had subsequent surgery to address a nonunion and 3 elbows had radiographic signs of arthrosis. The mean arc of elbow flexion increased from 110 degrees degrees (range, 35 degrees to 140 degrees) at early follow-up to 120 degrees (range, 40 degrees to 150 degrees) at late follow-up. The mean arc of forearm rotation increased from 145 degrees (range, 90 degrees to 180 degrees) to 149 degrees (range, 90 degrees to 180 degrees). The mean Broberg and Morrey score increased from 89 points (range, 62-100 points) to 94 points (range, 76-100 points). The median DASH score was 7 points (range, 0-34 points) at long-term follow-up. There was no statistical difference between early and late range of motion or Broberg and Morrey score.
Conclusions The results of open reduction and internal fixation of anterior Monteggia fractures in skeletally mature patients are maintained over long-term follow-up. (J Hand Surg 2009;34A:1618-1624. (c) 2009 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.)
C1 [Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Boston, MA 02114 USA.
Univ Amsterdam, Acad Med Ctr, Dept Orthopaed Surg, NL-1105 AZ Amsterdam, Netherlands.
RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
OI Guitton, Thierry/0000-0002-2599-1985
FU Acumed; Tornier; Wright Medical
FX D.R. is a consultant for and has received unrestricted research grants
from Acumed, Tornier, and Wright Medical.
NR 42
TC 8
Z9 8
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 0363-5023
J9 J HAND SURG-AM
JI J. Hand Surg.-Am. Vol.
PD NOV
PY 2009
VL 34A
IS 9
BP 1618
EP 1624
DI 10.1016/j.jhsa.2009.06.026
PG 7
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 517FG
UT WOS:000271598000005
PM 19896007
ER
PT J
AU Lindenhovius, A
Karanicolas, PJ
Bhandari, M
van Dijk, N
Ring, D
AF Lindenhovius, Anneluuk
Karanicolas, Paul Jack
Bhandari, Mohit
van Dijk, Nick
Ring, David
CA Collaboration Outcome Assessment
TI Interobserver Reliability of Coronoid Fracture Classification:
Two-Dimensional Versus Three-Dimensional Computed Tomography
SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME
LA English
DT Article
DE Computed tomography; coronoid; fracture; interobserver; reliability
ID TERRIBLE-TRIAD INJURIES; ANTEROMEDIAL FACET; RADIAL HEAD; ELBOW;
DISLOCATION; RECONSTRUCTIONS; ULNA
AB Purpose This study tests the hypothesis that 3-dimensional computed tomography (CT) reconstructions improve interobserver agreement on classification and treatment of coronoid fractures compared with 2-dimensional CT.
Methods A total of 29 orthopedic surgeons evaluated 10 coronoid fractures on 2 occasions (first with radiographs and 2-dimensional CT and then with radiographs and 3-dimensional CT), separated by a minimum of 2 weeks. Surgeons classified fractures according to the classifications of Regan and Morrey and of O'Driscoll et al., identified specific characteristics, recommended the most appropriate treatment approach, and made treatment recommendations. The kappa multirater measure (kappa) was calculated to estimate agreement between observers.
Results Regardless of the imaging modality used, there was fair to moderate agreement for most of the observations. Three-dimensional CT improved interobserver agreement in Regan and Morrey's classsication (kappa(3-dimensional) = 0.51 vs kappa(2-dimensionol) = 0.40; p < .001) and O'Driscoll et al.'s classifications (kappa(3-dimensional) = 0.48 vs kappa(2-dimensional) = 0.42; p = .009). There were trends toward better reliability for 3-dimensional reconstruction in recognition of coronoid tip fractures (kappa(3-dimensional) = 0.19, kappa(2-dimensional) = 0.03; p = .268), comminution (kappa(3-dimensional) = 0.41 vs kappa(2-dimensional) = 0.29; p = .133), and impacted fragments (kappa(3-dimensional) = 0.39 vs kappa(2-dimensional) = 0.27; p = .094), and in surgeons' opinions on the need for something other than screws or plate for surgical fixation (kappa(3-dimensional) = 0.31 vs kappa(2-dimensional) = 0.15; p = .138). Interobserver agreement on treatment approach was better with 2-dimensional CT (kappa(3-dimensional) = 0.27, kappa(2-dimensional) = 0.32; p = .015).
Conclusions Three-dimensional CT reconstructions improve Interobserver agreement with respect to fracture classification compared with 2-dimensional CT. (J Hand Surg 2009;34A: 1640-1646. (c) 2009 Published by Elsevier Inc. on behalf of the American Society,for Surgery of the Hand.)
C1 [Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA.
Univ Western Ontario, Dept Surg, London, ON N6A 3K7, Canada.
McMaster Univ, Hamilton, ON, Canada.
Univ Amsterdam, Acad Med Ctr, Dept Orthopaed Surg, NL-1012 WX Amsterdam, Netherlands.
RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, 55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
RI Kampen, A./H-8056-2014; Page, Richard/K-6327-2015;
OI Page, Richard/0000-0002-2225-7144; Frihagen, Frede/0000-0002-4811-669X
FU Wright Medical and Skeletal Dynamics
FX D.R. isa consultant for Wright Medical, Acumed, and Tornier. He received
unrestricted research grants from Acumed and Tornier, and he receives
royalties from Wright Medical and Skeletal Dynamics.
NR 26
TC 24
Z9 25
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 0363-5023
J9 J HAND SURG-AM
JI J. Hand Surg.-Am. Vol.
PD NOV
PY 2009
VL 34A
IS 9
BP 1640
EP 1646
DI 10.1016/j.jhsa.2009.07.009
PG 7
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 517FG
UT WOS:000271598000008
PM 19833449
ER
PT J
AU Rivard, AL
Bartel, T
Bianco, RW
O'Donnell, KS
Bonatti, J
Dichtl, W
Cury, RC
Feuchtner, GM
AF Rivard, Andrew L.
Bartel, Thomas
Bianco, Richard W.
O'Donnell, Kasia Simura
Bonatti, Johannes
Dichtl, Wolfgang
Cury, Ricardo C.
Feuchtner, Gudrun M.
TI Evaluation of Aortic Root and Valve Calcifications by Multi-Detector
Computed Tomography
SO JOURNAL OF HEART VALVE DISEASE
LA English
DT Article; Proceedings Paper
CT 3rd Annual Scientific Meeting of the
Society-for-Cardiovascular-Computed-Tomography
CY JUL 17-20, 2008
CL Orlando, FL
SP Soc Cardiovasc Computed Tomog
ID PERCUTANEOUS TRANSCATHETER IMPLANTATION; HIGH-RISK PATIENTS;
HEART-VALVE; COREVALVE PROSTHESIS; POSITION STATEMENT; BALLOON
VALVOTOMY; FOLLOW-UP; STENOSIS; REPLACEMENT; EXPERIENCE
AB Background and aim of the study: In percutaneous aortic valve replacement (AVR), whilst calcifications are used as landmarks in fluoroscopic placement of the stent, they may also complicate stent placement. In response to this problem, the study aim was to examine severe aortic root calcification by using multi-detector computed tomography (MDCT), to better understand the pathology complicating percutaneous valve placement.
Methods: In 33 patients with severe aortic stenosis and scheduled for surgery, the 'inner orifice' and,outer fibrous' annulus diameter and area (with and without calcification) were measured, in addition to the distances of the calcifications and coronary ostia from the annulus, using by ECG-gated 64-slice MDCT. Aortic root calcification was evaluated as minimal (<25% of total circumference), mild (25-50%), moderate (50-75%), and severe (75-100%).
Results: The inner orifice annulus area was 5.9 +/- 1.9 cm 2 (range: 1.4-10.1 cm(2)), while the outer fibrous area was 7.5 +/- 1.8 cm(2) (range: 4.7-11.5 cm(2)). The proximal-to-distal extent of valve calcification from the annulus in the mid-center of leaflets was 0.8 +/- 0.26 cm. In 36% of patients, valvular calcification extended +/-3 mm within the coronary-ostium level. The distance of the coronary ostia from the annulus was variable, with a mean of 1.3 +/- 0.35 cm (range: 0.6-2.4 cm) for the left coronary artery. In 42% of patients, a 'low coro- nary ostium' (<= 1.1 cm), and in 6% a 'critical-low-coronary ostium' (<= 8 mm) was identified. Annulus calcification was present in 100% of cases, but the severity varied widely (severe 50%, moderate 35%, mild 15%). In 36% of cases, the aortic annulus calcification extended caudally into the membranous part of the interventricular septum (and thus into the left ventricular outflow tract), and in 42% of cases (n = 14) into the anterior mitral valve leaflet.
Conclusion: The present results indicated that cardiac MDCT may qualify as a primary pre-procedural imaging modality to select patients for percutaneous AVR, based on the measurement and characterization of the aortic root and valve calcification. In comparison to echocardiography, CT will reduce - if not eliminate - difficulties in visualizing the aortic orifice area in heavily calcified valves. Furthermore, knowledge of the exact location of calcific deposits provides a distinct advantage to the fluroscopist for precise placement of the percutaneous aortic valve. Likewise, knowledge of the coronary arteries orifice in relation to the valve plane is critical to prevent inadvertent coronary artery occlusion, and would clearly be beneficial when planning future valve designs.
C1 [Rivard, Andrew L.] Univ Florida, Dept Radiol, Gainesville, FL 32610 USA.
[Rivard, Andrew L.; Bianco, Richard W.; O'Donnell, Kasia Simura] Univ Minnesota, Dept Surg, Expt Surg Serv, Minneapolis, MN 55455 USA.
[Bartel, Thomas; Bonatti, Johannes; Dichtl, Wolfgang; Feuchtner, Gudrun M.] Innsbruck Med Univ, Dept Radiol & Cardiol 2, Innsbruck, Austria.
[Cury, Ricardo C.; Feuchtner, Gudrun M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Cury, Ricardo C.] Baptist Cardiac & Vasc Inst, Miami, FL USA.
RP Rivard, AL (reprint author), Univ Florida, Dept Radiol, POB 100374, Gainesville, FL 32610 USA.
EM arivard@ufl.edu
NR 33
TC 15
Z9 15
U1 1
U2 3
PU I C R PUBLISHERS
PI NORTHWOOD
PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD HA6 2ET,
ENGLAND
SN 0966-8519
J9 J HEART VALVE DIS
JI J. Heart Valve Dis.
PD NOV
PY 2009
VL 18
IS 6
BP 662
EP 670
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 537SP
UT WOS:000273134600011
PM 20099715
ER
PT J
AU Domart, MC
Degli Esposti, D
Sebagh, M
Olaya, N
Harper, F
Pierron, G
Franc, B
Tanabe, KK
Debuire, B
Azoulay, D
Brenner, C
Lemoine, A
AF Domart, Marie-Charlotte
Degli Esposti, Davide
Sebagh, Mylene
Olaya, Natalia
Harper, Francis
Pierron, Gerard
Franc, Brigitte
Tanabe, Kenneth K.
Debuire, Brigitte
Azoulay, Daniel
Brenner, Catherine
Lemoine, Antoinette
TI Concurrent induction of necrosis, apoptosis, and autophagy in ischemic
preconditioned human livers formerly treated by chemotherapy
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Cell death; Ischemia/reperfusion; Ischemic preconditioning;
Chemotherapy; Bcl-2; Beclin-1; Autophagy; Liver
ID MOUSE-LIVER; PREOPERATIVE CHEMOTHERAPY; REPERFUSION INJURY;
COLORECTAL-CANCER; CELL-DEATH; IN-VIVO; BCL-2; METASTASES; OXALIPLATIN;
MECHANISMS
AB Background/Aims: Liver pathology induced by chemotherapy (steatosis or vascular injury) is known to increase the liver's sensitivity to ischemia/reperfusion (I/R) injury, thereby increasing morbidity and mortality after liver resection. Our aim was to assess whether ischemic preconditioning (IP) reduces I/R injury to livers with chemotherapy-induced pathology.
Methods: We analyzed a series of livers from patients treated with chemotherapy for colorectal cancer who underwent IP (n = 30) or not (n = 31) before hepatectomy. All but one of the livers exhibited chemotherapy-induced steatosis and/or peliosis before the I/R insult.
Results: Necrosis was less frequent (p = 0.038) in livers with IP than in the others. IP had no influence on apoptosis as assessed by terminal transferase uridyl nick-end labeling (TUNEL) assay or caspase-3, -8 and -9 expression. I P induced a twofold increase in B-cell leukemia/lymphoma 2 (Bcl-2; p < 0.05), which was localized to hepatocytes of centrolobular and peliotic areas and colocalized with the autophagy protein beclin-1 in livers with IP, suggesting their coordinated role in autophagy. Increased expression of the phosphorylated Bcl-2 was observed in preconditioned livers and was associated with a decreased immunoprecipitation of beclin-1 and the increased expression of light chain 3 type II (LC3-II). The increased number of autophagic vacuoles seen by electron microscopy confirmed an association of autophagy in chemotherapy-injured livers following I P. However, the differences in protein expression were not reflected in postresection liver-injury tests or measure of patient morbidity.
Conclusions: IP is associated with a reduction in necrosis of hepatocytes already damaged by chemotherapy and an activation of autophagy. Bcl-2 and beclin-1 could be major targets in the regulation of cell death during I/R injury. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
C1 [Domart, Marie-Charlotte; Degli Esposti, Davide; Olaya, Natalia; Debuire, Brigitte; Lemoine, Antoinette] Hop Paul Brousse, AP HP, Serv Biochim & Biol Mol, F-94804 Villejuif, France.
[Domart, Marie-Charlotte; Degli Esposti, Davide; Olaya, Natalia] Univ Paris 11, INSERM, Inst Andre Lwoff IFR89, PRES Universud Paris,U602, Villejuif, France.
[Degli Esposti, Davide; Lemoine, Antoinette] Univ Paris 11, Fac Pharm, Lab Biochim & Biol Cellulaire, F-92290 Chatenay Malabry, France.
[Sebagh, Mylene] Univ Paris 11, AP HP, Hop Paul Brousse, Inst Andre Lwoff,Serv Anat Pathol,Inserm U785, F-94804 Villejuif, France.
[Harper, Francis; Pierron, Gerard] Inst Andre Lwoff, Lab Replicat ADN & Ultrastruct Noyau, UPR 1983, Villejuif, France.
[Franc, Brigitte] Univ Versailles St Quentin, Hop Ambroise Pare, AP HP, Serv Anat Pathol,PRES Universud Paris, Versailles, France.
[Tanabe, Kenneth K.] Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Boston, MA USA.
[Tanabe, Kenneth K.] Harvard Univ, Sch Med, Boston, MA USA.
[Azoulay, Daniel] Univ Paris 11, Hop Paul Brousse, AP HP, Ctr Hepatobiliaire, Villejuif, France.
[Brenner, Catherine] Univ Versailles St Quentin, CNRS, PRES Univsud Paris, UMR 8159, Versailles, France.
RP Lemoine, A (reprint author), Hop Paul Brousse, AP HP, Serv Biochim & Biol Mol, 14 Ave Paul Vaillant Couturier, F-94804 Villejuif, France.
EM antoinette.lemoine@pbr.aphp.fr
RI Ji, Haofeng/G-6206-2012; degli esposti, davide/M-1917-2015
OI degli esposti, davide/0000-0003-1390-4845
FU Ligue Nationale Contre le Cancer (comite de l'Essonne); NRB-Vaincre le
Cancer; Groupement Cooperatif de Transplantation de I'lle de France;
Colciencias (Colombia)
FX Marie-Charlotte Dorriart is a fellow of Ligue Nationale Contre le Cancer
(comite de l'Essonne). Davide Degli Esposti is a fellow of NRB-Vaincre
le Cancer and Groupement Cooperatif de Transplantation de I'lle de
France. Natalia Olaya was supported by a grant from Colciencias
(Colombia).
NR 36
TC 28
Z9 31
U1 0
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD NOV
PY 2009
VL 51
IS 5
BP 881
EP 889
DI 10.1016/j.jhep.2009.06.028
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 519IY
UT WOS:000271760800007
PM 19765849
ER
PT J
AU Thierman, S
Dhaliwal, G
Sooriash, L
Baudendistel, T
AF Thierman, Sara
Dhaliwal, Gurpreet
Sooriash, Lailey
Baudendistel, Thomas
TI Flushing Out the Diagnosis
SO JOURNAL OF HOSPITAL MEDICINE
LA English
DT Editorial Material
ID ANTICONVULSANT-HYPERSENSITIVITY-SYNDROME; SYSTEMIC SYMPTOMS;
PHYSICAL-EXAMINATION; DRESS SYNDROME; DRUG RASH; MANAGEMENT;
EOSINOPHILIA; HISTORY
C1 [Thierman, Sara; Sooriash, Lailey] Calif Pacific Med Ctr, Dept Med, San Francisco, CA 94115 USA.
[Thierman, Sara] SUNY Downstate Med Ctr, Dept Dermatol, Brooklyn, NY 11203 USA.
[Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA.
[Baudendistel, Thomas] Kaiser Permanente, Dept Med, Oakland, CA USA.
RP Thierman, S (reprint author), Calif Pacific Med Ctr, Dept Med, 2333 Buchanan, San Francisco, CA 94115 USA.
NR 14
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1553-5592
J9 J HOSP MED
JI J. Hosp. Med.
PD NOV-DEC
PY 2009
VL 4
IS 9
BP 569
EP 573
DI 10.1002/jhm.603
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 540FD
UT WOS:000273315800008
PM 20013860
ER
PT J
AU Stephen, TL
Tikhonova, A
Riberdy, JM
Laufer, TM
AF Stephen, Tom Li
Tikhonova, Anastasia
Riberdy, Janice M.
Laufer, Terri M.
TI The Activation Threshold of CD4(+) T Cells Is Defined by TCR/Peptide-MHC
Class II Interactions in the Thymic Medulla
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID PROMISCUOUS GENE-EXPRESSION; ANTIGEN PRESENTATION; THYMOCYTE
SENSITIVITY; TYROSINE-PHOSPHATASE; POSITIVE SELECTION; CENTRAL
TOLERANCE; EPITHELIAL-CELLS; PROTEIN-KINASE; IN-VIVO; SELF
AB Immature thymocytes that are positively selected based upon their response to self-peptide-MHC complexes develop into mature T cells that are not overtly reactive to those same complexes. Developmental tuning is the active process through which TCR-associated signaling pathways of single-positive thymocytes are attenuated to respond appropriately to the peptide-MHC molecules that will be encountered in the periphery. In this study, we explore the mechanisms that regulate the tuning of CD4(+) single-positive T cells to MHC class II encountered in the thymic medulla. Experiments with murine BM chimeras demonstrate that tuning can be mediated by MHC class II expressed by either thymic medullary epithelial cells or thymic dendritic cells. Tuning does not require the engagement of CD4 by MHC class II on stromal cells. Rather, it is mediated by interactions between MHC class 11 and the TCR. To understand the molecular changes that distinguish immature hyperactive T cells from tuned mature CD4(+) T cells, we compared their responses to TCR stimulation. The altered response of mature CD4 single-positive thymocytes is characterized by the inhibition of ERK activation by low-affinity self-ligands and increased expression of the inhibitory tyrosine phosphatase SHP-1. Thus, persistent TCR engagement by peptide-MHC class II on thymic medullary stroma inhibits reactivity to self-Ags and prevents autoreactivity in the mature repertoire. The Journal of Immunology, 2009,183: 5554-5562.
C1 [Stephen, Tom Li; Tikhonova, Anastasia; Laufer, Terri M.] Univ Penn, Dept Med, Sch Med, Philadelphia, PA 19104 USA.
[Riberdy, Janice M.] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Laufer, Terri M.] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA 19104 USA.
RP Laufer, TM (reprint author), Univ Penn, Dept Med, Sch Med, 753 Biomed Res Bldg 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA.
EM tlaufer@mail.med.upenn.edu
RI Tikhonova, Anastasia/F-1186-2015
FU National Institutes of Health [R01 AI068819]; Arthritis Foundation
postdoctoral fellowship
FX This work was supported by National Institutes of Health Grant R01
AI068819 (to T.M.L.) and an Arthritis Foundation postdoctoral fellowship
(to T.L.S.).
NR 48
TC 11
Z9 11
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD NOV 1
PY 2009
VL 183
IS 9
BP 5554
EP 5562
DI 10.4049/jimmunol.0901104
PG 9
WC Immunology
SC Immunology
GA 515QU
UT WOS:000271488500017
PM 19843939
ER
PT J
AU Sullivan, RJ
Hoshida, Y
Brunet, JP
Aldridge, J
Tahan, S
Cho, D
Mier, JW
McDermott, DF
Golub, T
Atkins, MB
AF Sullivan, Ryan J.
Hoshida, Yujin
Brunet, Jean-Philippe
Aldridge, Julie
Tahan, Steven
Cho, Daniel
Mier, James W.
McDermott, David F.
Golub, Todd
Atkins, Michael B.
TI Update on the Predictive Nature of a Novel Melanocytic Gene Expression
Signature for Outcome to High-dose Interleukin-2 Treatment in Patients
With Adavnced Melanoma
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 24th Annual Meeting of the
International-Society-for-Biology-Therapy-of-Cancer
CY OCT 29-31, 2009
CL Washington, DC
SP Int Soc Biol Therapy Canc
C1 Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA USA.
[Tahan, Steven] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA.
[Aldridge, Julie] Dana Farber Canc Inst, Boston, MA 02115 USA.
Broad Inst, Cambridge, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 NOV-DEC
PY 2009
VL 32
IS 9
BP 962
EP 962
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 510RX
UT WOS:000271110100072
ER
PT J
AU Arredouani, MS
Tseng-Rogenski, S
Hollenbeck, B
Defeo-Jones, D
Hwang, C
Sanda, MG
AF Arredouani, M. Simo
Tseng-Rogenski, Stephanie
Hollenbeck, Brent
Defeo-Jones, Deborah
Hwang, Clara
Sanda, Martin G.
TI Androgen Ablation Augments Cellular Immune Responses to PSA in a
Humanized PSA/HLA-A2.1 Transgenic Mouse Model
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 24th Annual Meeting of the
International-Society-for-Biology-Therapy-of-Cancer
CY OCT 29-31, 2009
CL Washington, DC
SP Int Soc Biol Therapy Canc
C1 [Arredouani, M. Simo; Sanda, Martin G.] Harvard Univ, Sch Med, BIDMC, Boston, MA USA.
[Tseng-Rogenski, Stephanie; Hollenbeck, Brent; Hwang, Clara] Univ Michigan, Sch Med, Ann Arbor, MI USA.
[Defeo-Jones, Deborah] Merck Labs, Whitehouse Stn, NJ USA.
RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015
NR 0
TC 0
Z9 0
U1 0
U2 0
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 NOV-DEC
PY 2009
VL 32
IS 9
BP 966
EP 966
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 510RX
UT WOS:000271110100083
ER
PT J
AU Haggerty, TJ
Newton, E
Dunn, IS
Rose, LB
Kurnick, JT
AF Haggerty, Timothy J.
Newton, Estelle
Dunn, Ian S.
Rose, Lenota B.
Kurnick, James T.
TI A High-throughput Screening Assay to Identify Agents That Enhance T-cell
Recognition of Human Melanomas
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 24th Annual Meeting of the
International-Society-for-Biology-Therapy-of-Cancer
CY OCT 29-31, 2009
CL Washington, DC
SP Int Soc Biol Therapy Canc
C1 [Haggerty, Timothy J.; Newton, Estelle; Dunn, Ian S.; Rose, Lenota B.; Kurnick, James T.] CvtoCure, Beverly, MA USA.
[Haggerty, Timothy J.; Kurnick, James T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 NOV-DEC
PY 2009
VL 32
IS 9
BP 971
EP 971
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 510RX
UT WOS:000271110100098
ER
PT J
AU Zaupa, C
Rabkin, S
AF Zaupa, Cecile
Rabkin, Samuel
TI Oncolytic Herpes Simplex Virus Activation of FLT3-ligand Generated
Dendritic Cells for Cancer Immunity
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 24th Annual Meeting of the
International-Society-for-Biology-Therapy-of-Cancer
CY OCT 29-31, 2009
CL Washington, DC
SP Int Soc Biol Therapy Canc
C1 [Zaupa, Cecile; Rabkin, Samuel] Massachusetts Gen Hosp, Brain Tumor Res Ctr, Boston, MA 02114 USA.
[Zaupa, Cecile; Rabkin, Samuel] Harvard Univ, Sch Med, Boston, MA USA.
RI rabkin, samuel/C-2443-2012
OI rabkin, samuel/0000-0003-2344-2795
NR 0
TC 0
Z9 0
U1 0
U2 0
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 NOV-DEC
PY 2009
VL 32
IS 9
BP 979
EP 980
PG 2
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 510RX
UT WOS:000271110100123
ER
PT J
AU Zuleger, CL
Bostwick, BL
Macklin, MD
Pei, QL
Newton, MA
Albertini, MR
AF Zuleger, Cindav L.
Bostwick, Biet L.
Macklin, Michael D.
Pei, Qinglin
Newton, Michael A.
Albertini, Mark R.
TI Similar T-cell Receptor-beta Sequences Identified in Melanoma-reactive T
Cells and In Vivo 6-thioguanine-resistant T Cells From Melanoma Patients
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 24th Annual Meeting of the
International-Society-for-Biology-Therapy-of-Cancer
CY OCT 29-31, 2009
CL Washington, DC
SP Int Soc Biol Therapy Canc
C1 [Zuleger, Cindav L.; Macklin, Michael D.; Newton, Michael A.; Albertini, Mark R.] Univ Wisconsin, Carboae Comprehens Canc Ctr, Madison, WI USA.
Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 NOV-DEC
PY 2009
VL 32
IS 9
BP 986
EP 986
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 510RX
UT WOS:000271110100144
ER
PT J
AU Dranoff, G
AF Dranoff, Glenn
TI Enhancing Cancer Vaccines
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 24th Annual Meeting of the
International-Society-for-Biology-Therapy-of-Cancer
CY OCT 29-31, 2009
CL Washington, DC
SP Int Soc Biol Therapy Canc
C1 [Dranoff, Glenn] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 NOV-DEC
PY 2009
VL 32
IS 9
BP 993
EP 993
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 510RX
UT WOS:000271110100165
ER
PT J
AU Zheng, LZ
Rai, P
Evans, C
Spring, B
Hasan, T
AF Zheng, Lei Z.
Rai, Prakash
Evans, Conoi
Spring, Bryan
Hasan, Tayyaba
TI Nanocell Delivery of PHA-665752 and Cetuximab Enables High-Efficacy
Photodynamic Therapy Combination Treatment for Pancreatic Cancer in
Preclinical Mice Model
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 24th Annual Meeting of the
International-Society-for-Biology-Therapy-of-Cancer
CY OCT 29-31, 2009
CL Washington, DC
SP Int Soc Biol Therapy Canc
C1 [Zheng, Lei Z.; Rai, Prakash; Evans, Conoi; Spring, Bryan; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 NOV-DEC
PY 2009
VL 32
IS 9
BP 995
EP 995
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 510RX
UT WOS:000271110100171
ER
PT J
AU Rahmanzadeh, R
Rai, P
Abu-Yousif, A
Rizyi, I
Celli, J
Baron-Luhr, B
Gerdes, J
Hasan, T
AF Rahmanzadeh, Ramtin
Rai, Prakash
Abu-Yousif, Adnan
Rizyi, Imran
Celli, Jon
Baron-Luhr, Bettina
Gerdes, Johannes
Hasan, Tayyaba
TI KI-67 as a Target for Nanotechnology-mediated Light Activatable Cancer
Therapy
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 24th Annual Meeting of the
International-Society-for-Biology-Therapy-of-Cancer
CY OCT 29-31, 2009
CL Washington, DC
SP Int Soc Biol Therapy Canc
C1 [Rai, Prakash; Abu-Yousif, Adnan; Rizyi, Imran; Celli, Jon] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA.
[Baron-Luhr, Bettina; Gerdes, Johannes; Hasan, Tayyaba] Leibniz Res Ctr Borstel, Dept Immunol & Cell Biol, Borstel, Germany.
RI Rahmanzadeh, Ramtin/L-7941-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
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 NOV-DEC
PY 2009
VL 32
IS 9
BP 1008
EP 1008
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 510RX
UT WOS:000271110100212
ER
PT J
AU Dranoff, G
AF Dranoff, Glenn
TI Targets of Protective Tumor Immunity
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 24th Annual Meeting of the
International-Society-for-Biology-Therapy-of-Cancer
CY OCT 29-31, 2009
CL Washington, DC
SP Int Soc Biol Therapy Canc
C1 [Dranoff, Glenn] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
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 NOV-DEC
PY 2009
VL 32
IS 9
BP 1011
EP 1011
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 510RX
UT WOS:000271110100221
ER
PT J
AU Meffert, SM
Marmar, CR
AF Meffert, Susan M.
Marmar, Charles R.
TI Darfur Refugees in Cairo Mental Health and Interpersonal Conflict in the
Aftermath of Genocide
SO JOURNAL OF INTERPERSONAL VIOLENCE
LA English
DT Article
DE refugee; trauma; violence; Sudan; Darfur
ID POSTTRAUMATIC-STRESS-DISORDER; MALE VIETNAM VETERANS; QUALITATIVE
RESEARCH; PTSD SYMPTOMS; TRAUMA; RECONCILIATION; DEPRESSION; ATTITUDES
AB Hundreds of thousands of Darfur people affected by the Sudanese genocide have fled to Cairo, Egypt, in search of assistance. Collaborating with Africa and Middle East Refugee Assistance (AMERA), the authors conducted a mental health care needs assessment among Darfur refugees in Cairo. Information was collected using individual and focus group interviews to identify gaps in mental health care and develop understandings of emotional and relationship problems. The refugee mental health care system has a piecemeal structure with gaps in outpatient services. There is moderate to severe emotional distress among many Darfur refugees, including symptoms of depression and trauma, and interpersonal conflict, both domestic violence and broader community conflict, elevated relative to pregenocide levels. Given the established relationships between symptoms of depression/traumatic stress and interpersonal violence, improving mental health is important for both preventing mental health decompensation and stemming future cycles of intra- and intergroup conflict.
C1 [Meffert, Susan M.; Marmar, Charles R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Marmar, Charles R.] San Francisco Vet Adm Med Ctr, San Francisco, CA USA.
RP Meffert, SM (reprint author), Univ Calif San Francisco, Dept Psychiat, VAMC Bldg 8,Box 116P, San Francisco, CA 94143 USA.
EM smeffert@lppi.ucsf.edu
OI meffert, susan/0000-0002-5882-7102
FU NIMH NIH HHS [R25 MH060482]
NR 26
TC 10
Z9 11
U1 0
U2 7
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0886-2605
J9 J INTERPERS VIOLENCE
JI J. Interpers. Violence
PD NOV
PY 2009
VL 24
IS 11
BP 1835
EP 1848
DI 10.1177/0886260508325491
PG 14
WC Criminology & Penology; Family Studies; Psychology, Applied
SC Criminology & Penology; Family Studies; Psychology
GA 500TI
UT WOS:000270327400004
PM 18945917
ER
PT J
AU Feramisco, JD
Sadreyev, RI
Murray, ML
Grishin, NV
Tsao, H
AF Feramisco, Jamison D.
Sadreyev, Ruslan I.
Murray, Mitzi L.
Grishin, Nick V.
Tsao, Hensin
TI Phenotypic and Genotypic Analyses of Genetic Skin Disease through the
Online Mendelian Inheritance in Man (OMIM) Database
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID ATAXIA TELANGIECTASIA
AB Despite unprecedented gains in genomic technologies and genotype resolution, there remain tremendous challenges in our ability to capture disease "phenomes.'' We propose a previously unreported method for deconvolving human disease into elemental features, thereby creating a third space that interacts with both the disease and genotypic spaces. Using cutaneous and noncutaneous clinical findings available through Johns Hopkins University's Online Mendelian Inheritance in Man (OMIM) database, we set out to deconstruct genetic skin disease (GSD) into its various components, to more fully explore the relationship between these features within the complex phenotypic space and to characterize the genotypic space within which these disorders exist. Using OMIM, we defined the current state of GSD as including 560 distinct disorders associated with 501 unique protein-encoding genes. The most common elemental skin features included cornifying, erosive, and hair/nail phenotypes, and the most common systemic features included those associated with developmental, musculoskeletal, and neurological systems. As a proof of principle, we focused on a single skin feature-cafe-au-lait macules-and partitioned the disease space into hierarchical groupings on the basis of this finding. Finally, functional analyses among GSD loci were mapped back to skin features, providing insights into pigmentary and auditory features. Phenotypic deconvolution provides a framework for analyzing medical disorders and can aid in the organization and elucidation of biological mechanisms related to human disease.
C1 [Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Feramisco, Jamison D.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
[Sadreyev, Ruslan I.; Grishin, Nick V.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
[Sadreyev, Ruslan I.; Grishin, Nick V.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
[Murray, Mitzi L.] Univ Washington, Dept Med Genet, Seattle, WA 98195 USA.
[Tsao, Hensin] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Bartlett 622,48 Blossom St, Boston, MA 02114 USA.
EM htsao@partners.org
FU American Cancer Society; Massachusetts General Hospital (MGH)
Institutional
FX This work was supported in part by the American Cancer Society,
Massachusetts General Hospital (MGH) Institutional start-up funds, and
generous philanthropic donors to the MGH ( all to H. T.).
NR 9
TC 23
Z9 25
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD NOV
PY 2009
VL 129
IS 11
BP 2628
EP 2636
DI 10.1038/jid.2009.108
PG 9
WC Dermatology
SC Dermatology
GA 509AJ
UT WOS:000270982900016
PM 19536140
ER
PT J
AU Yin, F
Doolittle, MH
Peterfy, M
AF Yin, Fen
Doolittle, Mark H.
Peterfy, Miklos
TI A quantitative assay measuring the function of lipase maturation factor
1
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE combined lipase deficiency; hypertriglyceridemia; lipoprotein lipase;
genetic complementation
ID LIPOPROTEIN-LIPASE; ENDOPLASMIC-RETICULUM; DEFICIENCY; MUTATIONS;
LETHAL; MICE; CLD
AB Newly synthesized lipoprotein lipase (LPL) and related members of the lipase gene family require an endoplasmic reticulum maturation factor for attainment of enzyme activity. This factor has been identified as lipase maturation factor 1 (Lmf1), and mutations affecting its function and/or expression result in combined lipase deficiency (cld) and hypertriglyceridemia. To assess the functional impact of Lmf1 sequence variations, both naturally occurring and induced, we report the development of a cell-based assay using LPL activity as a quantitative reporter of Lmf1 function. The assay uses a cell line homozygous for the cld mutation, which renders endogenous Lmf1 nonfunctional. LPL transfected into the mutant cld cell line fails to attain activity; however, cotransfection of LPL with wildtype Lmf1 restores its ability to support normal lipase maturation. In this report, we describe optimized conditions that ensure the detection of a complete range of Lmf1 function ( full, partial, or complete loss of function) using LPL activity as the quantitative reporter. To illustrate the dynamic range of the assay, we tested several novel mutations in mouse Lmf1. Our results demonstrate the ability of the assay to detect and analyze Lmf1 mutations having a wide range of effects on Lmf1 function and protein expression.Yin, F., M. H. Doolittle, and M. Peterfy. A quantitative assay measuring the function of lipase maturation factor 1. J. Lipid Res. 2009. 50: 2265-2269.
C1 [Yin, Fen; Doolittle, Mark H.; Peterfy, Miklos] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Yin, Fen; Doolittle, Mark H.; Peterfy, Miklos] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
[Yin, Fen; Peterfy, Miklos] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
RP Doolittle, MH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
EM markdool@ucla.edu; mpeterfy@ucla.edu
FU Cedars-Sinai Medical Center, the Department of Veterans Affairs;
National Institutes of Health [HL-24841]
FX This work was supported by the Cedars-Sinai Medical Center, the
Department of Veterans Affairs, and Grant HL-24841 from the National
Institutes of Health. Its contents are solely the responsibility of the
authors and do not necessarily represent the official views of the
National Institutes of Health.
NR 10
TC 9
Z9 9
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0022-2275
J9 J LIPID RES
JI J. Lipid Res.
PD NOV
PY 2009
VL 50
IS 11
BP 2265
EP 2269
DI 10.1194/jlr.M900196-JLR200
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 507NJ
UT WOS:000270860900015
PM 19471043
ER
PT J
AU Ikeda, H
Shiojima, I
Ozasa, Y
Yoshida, M
Holzenberger, M
Kahn, CR
Walsh, K
Igarashi, T
Abel, ED
Komuro, I
AF Ikeda, Hiroyuki
Shiojima, Ichiro
Ozasa, Yukako
Yoshida, Masashi
Holzenberger, Martin
Kahn, C. Ronald
Walsh, Kenneth
Igarashi, Takashi
Abel, E. Dale
Komuro, Issei
TI Interaction of myocardial insulin receptor and IGF receptor signaling in
exercise-induced cardiac hypertrophy
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Article
DE Insulin-like growth factor receptor; Insulin receptor; Exercise; Cardiac
hypertrophy; Tyrosine phosphorylation
ID TRANSGENIC MICE; HEART-FAILURE; GROWTH; EXPRESSION; PATHWAY; SIZE;
CARDIOMYOPATHY; ANGIOGENESIS; DELETION; GENE
AB Insulin-like growth factor-1 (IGF-1) signaling has recently been implicated in the development of cardiac hypertrophy after long-term endurance training, via mechanisms that may involve energetic stress. Given the potential overlap of insulin and IGF-1 signaling we sought to determine if both signaling pathways could contribute to exercise-induced cardiac hypertrophy following shorter-term exercise training. Studies were performed in mice with cardiac-specific IGF-1 receptor (IGF1R) knockout (CIGFRKO), mice with cardiac-specific insulin receptor (IR) knockout (CIRKO), CIGFRKO mice that lacked one IR allele in cardiomyocytes (IGFR-/-IR+/-), and CIRKO mice that lacked one IGF1R allele in cardiomyocytes (IGFR+/-IR-/-) Intravenous administration of IGF-1 or 75 hours of swimming over 4 weeks increased IGF1R tyrosine phosphorylation in the heart in control and CIRKO mice but not in CIGFRKO mice. Intriguingly, IR tyrosine phosphorylation in the heart was also increased following IGF-1 administration or exercise training in control and CIGFRKO mice but not in CIRKO mice. The extent of cardiac hypertrophy following exercise training in CIGFRKO and CIRKO mice was comparable to that in control mice. In contrast, exercise-induced cardiac hypertrophy was significantly attenuated in IGFR-/-IR+/- and IGFR+/-IR-/- mice. Thus, IGF-1 and exercise activates both IGF1R and IR in the heart, and IGF1R- and IR-mediated signals may serve redundant roles in the hypertrophic responses of the heart to exercise training. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Ikeda, Hiroyuki; Shiojima, Ichiro; Ozasa, Yukako; Yoshida, Masashi; Komuro, Issei] Chiba Univ, Dept Cardiovasc Sci & Med, Grad Sch Med, Chiba, Japan.
[Ikeda, Hiroyuki; Igarashi, Takashi] Univ Tokyo, Dept Pediat, Grad Sch Med, Tokyo, Japan.
[Shiojima, Ichiro; Komuro, Issei] Osaka Univ, Dept Cardiovasc Med, Grad Sch Med, Suita, Osaka, Japan.
[Holzenberger, Martin] Hop St Antoine, INSERM, UMR893, F-75571 Paris, France.
[Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
[Kahn, C. Ronald] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Walsh, Kenneth] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Abel, E. Dale] Univ Utah, Sch Med, Program Mol Med, Salt Lake City, UT USA.
[Abel, E. Dale] Univ Utah, Sch Med, Div Endocrinol Diabet & Metab, Salt Lake City, UT USA.
RP Komuro, I (reprint author), Chiba Univ, Dept Cardiovasc Sci & Med, Grad Sch Med, Chiba, Japan.
EM komuro-tky@umin.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT);
NIH [RO1HL070070]
FX We thank E. Fujita, R. Kobayashi, and Y Ishiyama for technical
assistance. This work was supported by grants from the Ministry of
Education, Culture, Sports, Science and Technology (MEXT) to I.K. and by
NIH grant RO1HL070070 to E.D.A.
NR 32
TC 21
Z9 22
U1 0
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2828
EI 1095-8584
J9 J MOL CELL CARDIOL
JI J. Mol. Cell. Cardiol.
PD NOV
PY 2009
VL 47
IS 5
BP 664
EP 675
DI 10.1016/j.yjmcc.2009.08.028
PG 12
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA 510RG
UT WOS:000271108000013
PM 19744489
ER
PT J
AU Ogino, S
Irahara, N
Nosho, K
Lindeman, N
Hazra, A
Hunters, D
Fuchs, C
AF Ogino, S.
Irahara, N.
Nosho, K.
Lindeman, N.
Hazra, A.
Hunters, D.
Fuchs, C.
TI Precision of Pyrosequencing Assay to Measure LINE-1 Methylation Level in
Paraffin-Embedded Colorectal Cancer and Normal Colon Specimens and Blood
Cells
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology
CY NOV 19-22, 2009
CL Orlando, FL
SP Assoc Mole Pathol
C1 [Ogino, S.; Lindeman, N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Hazra, A.; Hunters, D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 1525-1578
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2009
VL 11
IS 6
BP 657
EP 657
PG 1
WC Pathology
SC Pathology
GA 518HK
UT WOS:000271681400179
ER
PT J
AU Barletta, JA
Xiao, Y
Joshi, VA
Jackman, DM
Janne, PA
Lee, C
Lindeman, NI
AF Barletta, J. A.
Xiao, Y.
Joshi, V. A.
Jackman, D. M.
Janne, P. A.
Lee, C.
Lindeman, N. I.
TI MET Copy-Number Status in Lung Adenocarcinomas with EGFR Alterations
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology
CY NOV 19-22, 2009
CL Orlando, FL
SP Assoc Mole Pathol
C1 [Barletta, J. A.; Xiao, Y.; Lee, C.; Lindeman, N. I.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Barletta, J. A.; Xiao, Y.; Joshi, V. A.; Jackman, D. M.; Janne, P. A.; Lee, C.; Lindeman, N. I.] Harvard Univ, Sch Med, Boston, MA USA.
[Joshi, V. A.] Partners Ctr Personalized Genet Med, Mol Med Lab, Cambridge, MA USA.
[Jackman, D. M.; Janne, P. A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 1525-1578
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2009
VL 11
IS 6
BP 664
EP 664
PG 1
WC Pathology
SC Pathology
GA 518HK
UT WOS:000271681400209
ER
PT J
AU Dias-Santagata, DC
Akhavanfard, S
David, SS
Vemovsky, K
Kuhlmann, G
Boisvert, SL
Settleman, J
Sequist, LV
Engelman, JA
Louis, DN
Ellisen, LW
Borger, DR
Iafrate, AJ
AF Dias-Santagata, D. C.
Akhavanfard, S.
David, S. S.
Vemovsky, K.
Kuhlmann, G.
Boisvert, S. L.
Settleman, J.
Sequist, L. V.
Engelman, J. A.
Louis, D. N.
Ellisen, L. W.
Borger, D. R.
Iafrate, A. J.
TI Real Time Targeted Mutational Analysis of Human Tumors: a Clinical
Platform to Guide Personalized Cancer Medicine
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology
CY NOV 19-22, 2009
CL Orlando, FL
SP Assoc Mole Pathol
C1 [Akhavanfard, S.; David, S. S.; Vemovsky, K.; Boisvert, S. L.; Settleman, J.; Sequist, L. V.; Engelman, J. A.; Ellisen, L. W.; Borger, D. R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Dias-Santagata, D. C.; Settleman, J.; Engelman, J. A.; Louis, D. N.; Ellisen, L. W.; Borger, D. R.; Iafrate, A. J.] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 1525-1578
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2009
VL 11
IS 6
BP 666
EP 666
PG 1
WC Pathology
SC Pathology
GA 518HK
UT WOS:000271681400217
ER
PT J
AU Wildemore, BM
Cook, J
Fiorentino, M
Wu, L
Bailey, D
Brown, M
Loda, M
AF Wildemore, B. M.
Cook, J.
Fiorentino, M.
Wu, L.
Bailey, D.
Brown, M.
Loda, M.
TI Immunohistochemistry Used for the Better Identification of the Atypical
Cells in Lymphangioleiomyomatosis
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology
CY NOV 19-22, 2009
CL Orlando, FL
SP Assoc Mole Pathol
C1 [Wildemore, B. M.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Loda, M.] Dana Farber Canc Inst, Ctr Oncol Pathol, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 1525-1578
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2009
VL 11
IS 6
BP 669
EP 669
PG 1
WC Pathology
SC Pathology
GA 518HK
UT WOS:000271681400228
ER
PT J
AU Piccirillo, SGM
Binda, E
Fiocco, R
Vescovi, AL
Shah, K
AF Piccirillo, Sara G. M.
Binda, Elena
Fiocco, Roberta
Vescovi, Angelo L.
Shah, Khalid
TI Brain cancer stem cells
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Review
DE Neural stem cells; Cancer stem cells; Glioblastoma multiforme;
Tumorigenicity; Brain tumor; Glioblastoma; Cancer therapy
ID TUMOR-INITIATING CELLS; ACUTE MYELOID-LEUKEMIA; IN-VIVO; HUMAN
GLIOBLASTOMA; MOUSE MODELS; GROWTH; IDENTIFICATION; TEMOZOLOMIDE;
HEDGEHOG; RENEWAL
AB Cancers comprise heterogeneous cells, ranging from highly proliferative immature precursors to more differentiated cell lineages. In the last decade, several groups have demonstrated the existence of cancer stem cells in both nonsolid solid tumors, including some of the brain: glioblastoma multiforme (GBM), medulloblastoma, and ependymoma. These cells, like their normal counterpart in homologous tissues, are multipotent, undifferentiated, self-sustaining, yet transformed cells. In particular, glioblastoma-stem like cells (GBSCs) self-renew under clonal conditions and differentiate into neuron- and glia-like cells, with aberrant, mixed neuronal/astroglial phenotypes. Remarkably, upon subcutaneous and intracerebral transplantation in immunosuppressed mice, GBSCs are able to form secondary tumors that closely resemble the human pathology, a property retained also throughout serial transplantation. The search is up for the identification of the markers and the molecular mechanisms that underpin the tumorigenic potential of these cells. This is critical if we aim at defining new therapeutic approaches for the treatment of malignant brain tumors. Lately, it has been shown that some key regulatory system that plays pivotal roles in neural stem cell physiology can also regulate the tumorigenic ability of cancer stem cells in GBMs. This suggests that the study of cancer stem cells in brain tumors might help to identify new and more specific therapeutic molecular effectors, with the cancer stem cells themselves representing one of the main targets, in fact the Holy Grail, in cancer cell therapy. This review includes a summary review on brain cancer cells and their usefulness as emerging targets in cancer cell therapy.
C1 [Piccirillo, Sara G. M.; Vescovi, Angelo L.] Univ Milano Bicocca, Dept Biosci & Biotechnol, I-20126 Milan, Italy.
[Binda, Elena; Fiocco, Roberta; Vescovi, Angelo L.] StemGen SpA, I-20126 Milan, Italy.
[Shah, Khalid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA.
RP Vescovi, AL (reprint author), Univ Milano Bicocca, Dept Biosci & Biotechnol, Piazza Sci 2,Bldg U3, I-20126 Milan, Italy.
EM vescovi@tin.it; kshah@helix.mgh.harvard.edu
RI Binda, Elena/B-2650-2017;
OI Binda, Elena/0000-0002-8750-2905; Piccirillo, Sara Grazia
Maria/0000-0003-4109-1992; Vescovi, Angelo Luigi/0000-0002-1742-4112
FU Associazione Italiana Ricerca sul Cancro (AIRC)
FX ALV is an awardee of a grant from Associazione Italiana Ricerca sul
Cancro (AIRC).
NR 66
TC 39
Z9 41
U1 0
U2 15
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0946-2716
J9 J MOL MED-JMM
JI J. Mol. Med.
PD NOV
PY 2009
VL 87
IS 11
BP 1087
EP 1095
DI 10.1007/s00109-009-0535-3
PG 9
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA 514RI
UT WOS:000271412300008
PM 19784875
ER
PT J
AU Germano, PM
Lieu, SN
Xue, JJ
Cooke, HJ
Christofi, FL
Lu, YX
Pisegna, JR
AF Germano, Patrizia M.
Lieu, Sandy N.
Xue, Janjing
Cooke, Helen J.
Christofi, Fievos L.
Lu, Yuxin
Pisegna, Joseph R.
TI PACAP Induces Signaling and Stimulation of 5-Hydroxytryptamine Release
and Growth in Neuroendocrine Tumor Cells
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Article
DE BON cell; Carcinoid tumor; PACAP
ID CYCLASE-ACTIVATING POLYPEPTIDE; LUNG-CANCER CELLS; VASOACTIVE INTESTINAL
POLYPEPTIDE; CARCINOID BON CELLS; PROTEIN-KINASE-C; ADENYLATE-CYCLASE;
FUNCTIONAL EXPRESSION; NEUROTENSIN SECRETION; RECEPTOR ANTAGONIST;
CHROMAFFIN CELLS
AB Neuroendocrine tumors, although rare, are currently diagnosed with increasing frequency, owing to improved imaging techniques and a greater clinical awareness of this condition. To date, BON is a very well established and characterized human pancreatic neuroendocrine tumor cell line used to study the signal transduction and genetic regulation of neuroendocrine tumors secretion and growth. The secretory activity of BON cells is known to release peptides, such as chromogranin A, neurotensin, and biogenic amines, as 5-HT, permitting an assessment of their biological activity. The neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP), released from the enteric neurons in the gastrointestinal tract by binding to its high affinity receptor PAC1, has been previously shown to regulate the secretory activity and growth of the neuroendocrine-derived enterochromaffin-like cells in the stomach. This led us to speculate that PACAP might also play an important role in regulating the growth of human neuroendocrine tumors. Accordingly, in the current study, we have shown that BON cells express PAC1 receptors, which are rapidly internalized upon PACAP activation. Furthermore, PAC1 receptor activation, in BON cells, couple to intracellular Ca(2+) as well as cAMP responses and induce the release of intracellular 5-HT, activate mitogen activated protein kinases, and stimulate cellular growth. These data indicate that PACAP functionally can stimulate 5-HT release and promote the growth of the BON neuroendocrine tumor cell line. Therefore, PACAP and its receptors regulate neuroendocrine tumor secretory activity and growth in vivo, and this knowledge will permit the development of novel diagnostic and therapeutic targets for managing neuroendocrine tumors in humans.
C1 [Germano, Patrizia M.; Lieu, Sandy N.; Lu, Yuxin; Pisegna, Joseph R.] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA.
[Xue, Janjing; Cooke, Helen J.; Christofi, Fievos L.] Ohio State Univ, Dept Neurosci, Columbus, OH 43210 USA.
[Xue, Janjing; Cooke, Helen J.; Christofi, Fievos L.] Ohio State Univ, Dept Anesthesiol, Columbus, OH 43210 USA.
RP Germano, PM (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 115,Room 316, Los Angeles, CA 90073 USA.
EM pgermano@ucla.edu
FU Department of Veterans Affairs; National Institutes of Health [DK37240]
FX This work was supported by the Department of Veterans Affairs Merit
Review Grant (JRP) and National Institutes of Health DK37240 (HJC).
NR 51
TC 9
Z9 9
U1 0
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 NOV
PY 2009
VL 39
IS 3
BP 391
EP 401
DI 10.1007/s12031-009-9283-7
PG 11
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 505YZ
UT WOS:000270739700012
PM 19701709
ER
PT J
AU Pallast, S
Arai, K
Wang, XY
Lo, EH
van Leyen, K
AF Pallast, Stefanie
Arai, Ken
Wang, Xiaoying
Lo, Eng H.
van Leyen, Klaus
TI 12/15-Lipoxygenase targets neuronal mitochondria under oxidative stress
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE cytochrome c; glutathione; lipoxygenase; mitochondria; reactive oxygen
species
ID GLUTATHIONE DEPLETION; CELL-DEATH; GLUTAMATE TOXICITY; ORGANELLE
DEGRADATION; CORTICAL-NEURONS; BRAIN; 12-LIPOXYGENASE; CULTURES;
LIPOXYGENASE; INHIBITION
AB 12/15-Lipoxygenase (12/15-LOX) is an important mediator of brain injury following experimental stroke in rodents. It contributes to neuronal death, but the underlying mechanism remains unclear. We demonstrate here that in neuronal HT22 cells subjected to glutamate-induced oxidative stress, 12/15-LOX damages mitochondria, and this represents the committed step that condemns the cell to die. Importantly these events, including breakdown of the mitochondrial membrane potential, the production of reactive oxygen species, and cytochrome c release, can all be replicated by incubation of 12/15-LOX with mitochondria in vitro, without the need to add other cytosolic factors. Proteasome activity is required downstream of mitochondrial damage to complete the cell death cascade, but proteasome inhibition is only partially protective. These findings position 12/15-LOX as the central executioner in an oxidative stress-related neuronal death program.
C1 [Pallast, Stefanie; Arai, Ken; Wang, Xiaoying; Lo, Eng H.; van Leyen, Klaus] Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA 02129 USA.
RP van Leyen, K (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, 149 13th St,R 2401, Charlestown, MA 02129 USA.
EM klaus_vanleyen@hms.harvard.edu
RI van Leyen, Klaus/C-9126-2013
FU NIH [R01NS049430, R01NS53560, P01NS555104]; American Heart Association
FX Support through grants from the NIH (R01NS049430 to K.v.L., R01NS53560
and P01NS555104 to E.H.L.), and a Scientist Development Grant from the
American Heart Association (to K.v.L.), is gratefully acknowledged. The
authors declare no conflict of interest.
NR 34
TC 42
Z9 45
U1 1
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD NOV
PY 2009
VL 111
IS 3
BP 882
EP 889
DI 10.1111/j.1471-4159.2009.06379.x
PG 8
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 505VY
UT WOS:000270728600024
PM 19737346
ER
PT J
AU Dickey, MW
Thompson, CK
AF Dickey, Michael Walsh
Thompson, Cynthia K.
TI Automatic processing of wh- and NP-movement in agrammatic aphasia:
Evidence from eyetracking
SO JOURNAL OF NEUROLINGUISTICS
LA English
DT Article
DE Aphasia; Agrammatism; Eyetracking; Filler-gap dependencies; NP-movement;
Sentence comprehension; wh-movement
ID EMPTY CATEGORIES; EYE-MOVEMENTS; TIME-COURSE; SENTENCE COMPREHENSION;
BROCAS APHASIA; ALTERED SPEECH; DEPENDENCIES; TRACKING; ASSIGNMENT;
PREFERENCE
AB Individuals with agrammatic Broca's aphasia show deficits in comprehension of non-canonical wh-movement and NP-movement sentences. Previous work using eyetracking has found that agrammatic and unimpaired listeners show very similar patterns of automatic processing for wh-movement sentences. The current study attempts to replicate this finding for sentences with wh-movement (in object relatives in the Current study) and to extend it to sentences with NP-movement (passives). For wh-movement sentences, aphasic and control participants' eye-movements differed most dramatically in late regions of the sentence and post-offset, with aphasic participants exhibiting lingering attention to a salient but grammatically impermissible competitor. The eye-movement differences between correct and incorrect trials for wh-movement sentences were similar. with incorrect trials also exhibiting competition from an impermissible interpretation late in the sentence. Furthermore, the two groups exhibited similar eye-movement patterns in response to passive NP-movement sentences, but showed little evidence of gap-filling for passives. The results suggest that aphasic and unimpaired individuals may generate similar representations during comprehension, but that aphasics are highly vulnerable to interference from alternative interpretations (Ferreira, F. (2003). The misinterpretation of non-canonical sentences. Cognitive Psychology, 47(2),164-203). (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Dickey, Michael Walsh] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA.
[Dickey, Michael Walsh] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Thompson, Cynthia K.] Northwestern Univ, Aphasia & Neurolinguist Res Lab, Evanston, IL USA.
[Thompson, Cynthia K.] Northwestern Univ, Dept Commun Sci & Disorders, Evanston, IL USA.
[Thompson, Cynthia K.] Northwestern Univ, Dept Neurol, Evanston, IL USA.
[Thompson, Cynthia K.] Northwestern Univ, Cognit Neurol & Alzheimers Dis Ctr, Evanston, IL USA.
RP Dickey, MW (reprint author), Univ Pittsburgh, Dept Commun Sci & Disorders, 4032 Forbes Tower, Pittsburgh, PA 15260 USA.
EM mdickey@pitt.edu
OI Dickey, Michael Walsh/0000-0002-9068-3313
FU NIDCD NIH HHS [R01 DC001948, R01 DC001948-14]
NR 56
TC 25
Z9 26
U1 2
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0911-6044
J9 J NEUROLINGUIST
JI J. Neurolinguist.
PD NOV
PY 2009
VL 22
IS 6
BP 563
EP 583
DI 10.1016/j.jneuroling.2009.06.004
PG 21
WC Linguistics; Neurosciences; Psychology, Experimental
SC Linguistics; Neurosciences & Neurology; Psychology
GA 500PN
UT WOS:000270315700004
PM 20161014
ER
PT J
AU Healy, B
Valsasina, P
Filippi, M
Bakshi, R
AF Healy, B.
Valsasina, P.
Filippi, M.
Bakshi, R.
TI Sample size requirements for treatment effects using gray matter, white
matter and whole brain volume in relapsing-remitting multiple sclerosis
SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
LA English
DT Article
ID COGNITIVE IMPAIRMENT; ATROPHY; MS; DISABILITY; NEUROPROTECTION; DISEASE;
MRI; T2
AB Objective: To compare the sample size requirements for a neuroprotection trial with change in cerebral gray matter volume (GMV), white matter volume (WMV) or whole brain parenchymal volume (BPV) as outcome measures in patients with relapsing-remitting multiple sclerosis (RRMS).
Methods: Two datasets with longitudinal MRI measures of untreated patients with RRMS (n = 116 and n = 26) and one dataset of treated patients with RRMS (n = 109) were investigated. In each dataset, normalised GMV, normalised WMV and normalised BPV were analysed using a random intercepts and slopes model to estimate the variance components and per cent change. The required sample size to observe a 33%, 50% and 90% reduction in the per cent change was calculated for each dataset using both a constant per cent change for each measurement and the estimated per cent change for each dataset.
Results: The per cent change was greatest in GMV but all variance components were smallest in BPV. Using the estimated per cent change, the sample size required in the untreated cohorts was similar for GMV and BPV, and both were lower than WMV. In the treated cohort, the sample size for GMV was the smallest of all measures. Including additional scans reduced the sample size but increasing the length of the trial and clustering scans led to greater reductions.
Conclusions: Cerebral GMV may be a viable outcome measure for clinical trials investigating neuroprotection in RRMS patients, especially considering that the treatment effect may be larger on GMV compared with BPV. However, GMV was somewhat limited by increased variability versus BPV.
C1 [Healy, B.; Bakshi, R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol,Partners MS Ctr,Lab Neuroimaging Res, Brookline, MA 02445 USA.
[Healy, B.] Massachusetts Gen Hosp, Dept Neurol, Ctr Biostat, Boston, MA 02114 USA.
[Valsasina, P.; Filippi, M.] Univ Osped San Raffaele, Milan, Italy.
[Valsasina, P.; Filippi, M.] Inst Sci, Neuroimaging Res Unit, Milan, Italy.
[Bakshi, R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Brookline, MA 02445 USA.
RP Bakshi, R (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol,Partners MS Ctr,Lab Neuroimaging Res, 1 Brookline Pl,Suite 602, Brookline, MA 02445 USA.
EM rbakshi@bwh.harvard.edu
RI Valsasina, Paola/K-5820-2016
OI Valsasina, Paola/0000-0001-5390-2655
FU Partners MS Center; National Institutes of Health [1R01NS055083-01];
National Multiple Sclerosis Society [RG3705A1, RG3798A2]
FX BH acknowledges support from the Partners MS Center. RB acknowledges
support of research grants from the National Institutes of Health
(1R01NS055083-01) and National Multiple Sclerosis Society (RG3705A1;
RG3798A2). Teva kindly accepted to use the placebo and treated data of
the European/Canadian MRI trial of Copaxone in MS.
NR 28
TC 11
Z9 11
U1 0
U2 2
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-3050
J9 J NEUROL NEUROSUR PS
JI J. Neurol. Neurosurg. Psychiatry
PD NOV
PY 2009
VL 80
IS 11
BP 1218
EP 1223
DI 10.1136/jnnp.2008.154732
PG 6
WC Clinical Neurology; Psychiatry; Surgery
SC Neurosciences & Neurology; Psychiatry; Surgery
GA 512PE
UT WOS:000271261400200
PM 19204021
ER
PT J
AU Prerau, MJ
Smith, AC
Eden, UT
Kubota, Y
Yanike, M
Suzuki, W
Graybiel, AM
Brown, EN
AF Prerau, M. J.
Smith, A. C.
Eden, Uri T.
Kubota, Y.
Yanike, M.
Suzuki, W.
Graybiel, A. M.
Brown, E. N.
TI Characterizing Learning by Simultaneous Analysis of Continuous and
Binary Measures of Performance
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
ID BEHAVIORAL-EXPERIMENTS; PROSTHETIC DEVICES; PREFRONTAL CORTEX;
ACQUISITION; MEMORY; HIPPOCAMPUS; ALGORITHM; NEURONS; LESIONS; DESIGN
AB Prerau MJ, Smith AC, Eden UT, Kubota Y, Yanike M, Suzuki W, Graybiel AM, Brown EN. Characterizing learning by simultaneous analysis of continuous and binary measures of performance. J Neurophysiol 102: 3060-3072, 2009. First published August 19, 2009; doi:10.1152/jn.91251.2008. Continuous observations, such as reaction and run times, and binary observations, such as correct/incorrect responses, are recorded routinely in behavioral learning experiments. Although both types of performance measures are often recorded simultaneously, the two have not been used in combination to evaluate learning. We present a state-space model of learning in which the observation process has simultaneously recorded continuous and binary measures of performance. We use these performance measures simultaneously to estimate the model parameters and the unobserved cognitive state process by maximum likelihood using an approximate expectation maximization (EM) algorithm. We introduce the concept of a reaction-time curve and reformulate our previous definitions of the learning curve, the ideal observer curve, the learning trial and between-trial comparisons of performance in terms of the new model. We illustrate the properties of the new model in an analysis of a simulated learning experiment. In the simulated data analysis, simultaneous use of the two measures of performance provided more credible and accurate estimates of the learning than either measure analyzed separately. We also analyze two actual learning experiments in which the performance of rats and of monkeys was tracked across trials by simultaneously recorded reaction and run times and the correct and incorrect responses. In the analysis of the actual experiments, our algorithm gave a straightforward, efficient way to characterize learning by combining continuous and binary measures of performance. This analysis paradigm has implications for characterizing learning and for the more general problem of combining different data types to characterize the properties of a neural system.
C1 [Brown, E. N.] Massachusetts Gen Hosp, Neurosci Stat Res Lab, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Graybiel, A. M.; Brown, E. N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Kubota, Y.; Graybiel, A. M.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA.
[Yanike, M.; Suzuki, W.] NYU, Ctr Neural Sci, New York, NY 10003 USA.
[Brown, E. N.] Harvard Univ, Sch Med, Div Hlth Sci & Technol, MIT, Cambridge, MA 02138 USA.
[Eden, Uri T.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Prerau, M. J.; Eden, Uri T.] Boston Univ, Program Neurosci, Boston, MA 02215 USA.
RP Brown, EN (reprint author), Massachusetts Gen Hosp, Neurosci Stat Res Lab, Dept Anesthesia & Crit Care, 55 Fruit St,Clin 3, Boston, MA 02114 USA.
EM brown@neurostat.mgh.harvard.edu
FU National Institutes of Health [DA-015644, DPI0D003646, MH-59733,
MH-071847, P50 NS-38372]
FX Support was provided by National Institutes of Health Grants DA-015644
to E. N. Brown and W. Suzuki, DPI0D003646, MH-59733 and MH-071847 to E.
N. Brown, and P50 NS-38372 to A. M. Graybiel.
NR 42
TC 10
Z9 10
U1 0
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD NOV
PY 2009
VL 102
IS 5
BP 3060
EP 3072
DI 10.1152/jn.91251.2008
PG 13
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 515JZ
UT WOS:000271467300044
PM 19692505
ER
PT J
AU Mitha, AP
Reichardt, B
Grasruck, M
Macklin, E
Bartling, S
Leidecker, C
Schmidt, B
Flohr, T
Brady, TJ
Ogilvy, CS
Gupta, R
AF Mitha, Alim P.
Reichardt, Benjamin
Grasruck, Michael
Macklin, Eric
Bartling, Soenke
Leidecker, Christianne
Schmidt, Bernhard
Flohr, Thomas
Brady, Thomas J.
Ogilvy, Christopher S.
Gupta, Rajiv
TI Dynamic imaging of a model of intracranial saccular aneurysms using
ultra-high-resolution flat-panel volumetric computed tomography
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE intracranial aneurysm; aneurysm model; flat-panel volumetric computed
tomography; high spatial resolution; dynamic computed tomography
ID CT-SCANNER; RUPTURE; DESIGN
AB Object. Imaging of intracranial aneurysms using conventional multidetector CT (MDCT) is limited because of nonvisualization of features such as perforating vessels, pulsatile blebs, and neck remnants after clip placement or coil embolization. In this study, a model of intracranial saccular aneurysms in rabbits was used to assess the ultra-high resolution and dynamic scanning capabilities of a prototype flat-panel volumetric CT (fpVCT) scanner in demonstrating these features.
Methods. Ten New Zealand white rabbits underwent imaging before and after clipping or coil embolization of surgically created aneurysms in the proximal right carotid artery. Imaging was performed using a prototype fpVCT scanner, a 64-slice MDCT scanner, and traditional catheter angiography. In addition to the slice data and 3D views, 4D dynamic views, a capability unique to fpVCT, were also created and reviewed. The images were subjectively compared on 1) 4 image quality metrics ( spatial resolution, noise, motion artifacts, and aneurysm surface features); 2) 4 posttreatment features reflecting the metal artifact profile of the various imaging modalities ( visualization of clip or coil placement, perianeurysmal clip/coil anatomy, neck remnant, and white-collar sign); and 3) 2 dynamic features ( blood flow pattern and aneurysm pulsation).
Results. Flat-panel volumetric CT provided better image resolution than MDCT and was comparable to traditional catheter angiography. The surface features of aneurysms were demonstrated with much higher resolution, detail, and clarity by fpVCT compared with MDCT and angiography. Flat-panel volumetric CT was inferior to both MDCT and angiography in terms of image noise and motion artifacts. In fpVCT images, the metallic artifacts from clips and coils were significantly fewer than those in MDCT images. As a result, clinically important information about posttreatment aneurysm neck remnants could be derived from fpVCT images but not from MDCT images. Time-resolved dynamic sequences were judged slightly inferior to conventional angiography but superior to static MDCT images.
Conclusions. The spatial resolution, surface anatomy visualization, metal artifact profile, and 4D dynamic images from fpVCT are superior to those from MDCT. Flat-panel volumetric CT demonstrates aneurysm surface features to better advantage than angiography and is comparable to angiography in metal artifact profile. Even though the temporal resolution of fpVCT is not quite as good as that of angiography, fpVCT images yield clinically important anatomical information about aneurysm surface features and posttreatment neck remnants not attainable with either angiography or MDCT images. (DOI: 10.3171/2009.2.JNS08828)
C1 [Reichardt, Benjamin; Brady, Thomas J.; Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Mitha, Alim P.; Ogilvy, Christopher S.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Macklin, Eric] Massachusetts Gen Hosp, MGH Biostat Ctr, Boston, MA 02114 USA.
[Mitha, Alim P.] Foothills Med Ctr, Div Neurosurg, Calgary, AB, Canada.
[Grasruck, Michael; Leidecker, Christianne; Schmidt, Bernhard; Flohr, Thomas] Siemens Med Solut, Forchheim, Germany.
[Bartling, Soenke] German Canc Res Ctr, D-6900 Heidelberg, Germany.
RP Gupta, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, Room 273A,55 Fruit St, Boston, MA 02114 USA.
EM rgupta1@partners.org
RI Macklin, Eric/E-2955-2013
OI Macklin, Eric/0000-0003-1618-3502
NR 11
TC 5
Z9 5
U1 0
U2 1
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD NOV
PY 2009
VL 111
IS 5
BP 947
EP 957
DI 10.3171/2009.2.JNS08828
PG 11
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 514DW
UT WOS:000271375500015
PM 19374491
ER
PT J
AU Garces-Ambrossi, GL
McGirt, MJ
AF Garces-Ambrossi, Giannina L.
McGirt, Matthew J.
TI Factors predicting the resectability of intramedullary spinal cord
tumors and the progression-free survival following microsurgical
treatment Response
SO JOURNAL OF NEUROSURGERY-SPINE
LA English
DT Editorial Material
C1 [Garces-Ambrossi, Giannina L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02163 USA.
[McGirt, Matthew J.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
RP Garces-Ambrossi, GL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02163 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 1547-5654
J9 J NEUROSURG-SPINE
JI J. Neurosurg.-Spine
PD NOV
PY 2009
VL 11
IS 5
BP 590
EP 590
PG 1
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 512JM
UT WOS:000271244200017
ER
PT J
AU Tejima, E
Guo, SZ
Murata, Y
Arai, K
Lok, J
van Leyen, K
Rosell, A
Wang, XY
Lo, EH
AF Tejima, Emiri
Guo, Shuzhen
Murata, Yoshihiro
Arai, Ken
Lok, Josephine
van Leyen, Klaus
Rosell, Anna
Wang, Xiaoying
Lo, Eng H.
TI Neuroprotective Effects of Overexpressing Tissue Inhibitor of
Metalloproteinase TIMP-1
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE blood-brain barrier; neuroprotection; neurovascular unit; stroke;
traumatic brain injury
ID FOCAL CEREBRAL-ISCHEMIA; BLOOD-BRAIN-BARRIER; GENE KNOCK-OUT; MATRIX
METALLOPROTEINASES; ALZHEIMERS-DISEASE; CELL-DEATH;
PLASMINOGEN-ACTIVATOR; MMP-9/TIMP-1 RATIO; REPERFUSION INJURY;
ENDOTHELIAL-CELLS
AB Accumulating data suggest that matrix metalloproteinases (MMPs) may be important mediators in the pathophysiology of acute brain injury after trauma or stroke. Here, we test the hypothesis that the endogenous tissue inhibitor of metalloproteinase (TIMP-1) is neuroprotective in vitro and in vivo. For in vitro studies, primary cortical neuronal cultures were subjected to hypoxia and reoxygenation. Treatment with recombinant TIMP-1 protein significantly decreased neuronal death. In vivo studies in models of brain trauma and stroke supported these cell culture results. After controlled cortical impact, 24-h MMP-9 levels were significantly reduced in transgenic mice overexpressing TIMP-1 compared to wild-type mice. And at 7 days post-trauma, brain lesion volumes were also significantly decreased by TIMP-1 overexpression as well. In a model of transient 2-h focal cerebral ischemia, MMP-9 levels were lower in TIMP-1 transgenic mice compared with wild-types. Correspondingly, blood-brain barrier leakage was ameliorated by TIMP-1 overexpression, and 24-h infarction volumes were also reduced. Taken together, these cell culture and in vivo data provide initial proof-of-principle that TIMP-1 is neuroprotective against traumatic and ischemic brain injury in mice.
C1 [Tejima, Emiri; Guo, Shuzhen; Murata, Yoshihiro; Arai, Ken; Lok, Josephine; van Leyen, Klaus; Rosell, Anna; Wang, Xiaoying; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA 02129 USA.
[Tejima, Emiri; Guo, Shuzhen; Murata, Yoshihiro; Arai, Ken; Lok, Josephine; van Leyen, Klaus; Rosell, Anna; Wang, Xiaoying; Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA.
[Tejima, Emiri; Guo, Shuzhen; Murata, Yoshihiro; Arai, Ken; Lok, Josephine; van Leyen, Klaus; Wang, Xiaoying; Lo, Eng H.] Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA USA.
[Lok, Josephine] Harvard Univ, Sch Med, Boston, MA USA.
[Lok, Josephine] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
RP Lo, EH (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, MGH E 149-2401, Charlestown, MA 02129 USA.
EM Lo@helix.mgh.harvard.edu
RI van Leyen, Klaus/C-9126-2013
FU NINDS; American Stroke Association
FX This research was supported in part by grants from NINDS and a Bugher
award from the American Stroke Association.
NR 49
TC 52
Z9 55
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD NOV
PY 2009
VL 26
IS 11
BP 1935
EP 1941
DI 10.1089/neu.2009.0959
PG 7
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 523CO
UT WOS:000272049600009
PM 19469687
ER
PT J
AU Abukawa, H
Phelps, M
Jackson, P
Smith, RM
Vacanti, JP
Kaban, LB
Troulis, MJ
AF Abukawa, Harutsugi
Phelps, Maynard
Jackson, Pamela
Smith, R. Malcolm
Vacanti, Joseph P.
Kaban, Leonard B.
Troulis, Maria J.
TI Effect of Ibuprofen on Osteoblast Differentiation of Porcine Bone
Marrow-Derived Progenitor Cells
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MESENCHYMAL STEM-CELLS; MINERAL
DENSITY; OLDER WOMEN; IN-VITRO; SELECTIVITY; RATS; CYCLOOXYGENASE;
CONDYLE; ASPIRIN
AB Purpose: Nonsteroidal anti-inflammatory drugs are commonly prescribed to reduce inflammation and pain. However, little is known about the direct effect of these drugs on the differentiation of bone marrow-derived progenitor cells into osteoblasts. The purpose of this Study was to determine the effect of ibuprofen on osteoblast differentiation and proliferation in a minipig model
Materials and Methods: Bone marrow was aspirated from the minipig ilium,and porcine bone marrow-derived progenitor cells (pBMPCs) were isolated and expanded in standard culture medium The pBMPCs were replated and differentiated into osteoblasts by use of osteogenic supplements (OS). Five groups were studied: negative control-pBMPCs in standard medium only; positive control-pBMPCs, standard culture medium, and OS; and 3 experimental groups-PBMPCs, standard culture medium, OS, and ibuprofen added in doses of 0.1, 10, and 3.0 mmol/L. Cell cultures were evaluated quantitatively by alkaline phosphatase (ALP) stain, von Kossa stain, and deoxyribonucleic acid (DNA) content.
Results: pBMPCs cultured with OS and low-dose ibuprofen (0 1 mmol/l.) showed ALP stain, von Kossa stain, and DNA content similar to pBMPCs cultured in OS (positive control) pBMPCs cultured in higher doses of ibuprofen (1.0 and 3.0 mmol/L) produced significantly less positive staining of ALP and von Kossa and decreased DNA content
Conclusion: The results indicate that high-dose ibuprofen has a deleterious effect on pBMPC differentiation into osteoblasts whereas low-dose ibuprofen does not. The low dose of 0.1 mmol/L is the typical serum level when prescribed for clinical use (C) 2009 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 67-2412-2417, 2009
C1 [Troulis, Maria J.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Minimally Invas Oral & Maxillofacial Surg Program, Boston, MA 02114 USA.
[Troulis, Maria J.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Residency Program, Boston, MA 02114 USA.
[Phelps, Maynard; Kaban, Leonard B.; Troulis, Maria J.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
[Abukawa, Harutsugi] Tokyo Med Univ, Dept Oral & Maxillofacial Surg, Tokyo, Japan.
[Smith, R. Malcolm] Massachusetts Gen Hosp, Orthoped Trauma Serv, Boston, MA 02114 USA.
[Smith, R. Malcolm; Vacanti, Joseph P.] Harvard Univ, Sch Med, Boston, MA USA.
[Vacanti, Joseph P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Vacanti, Joseph P.] Massachusetts Gen Hosp, Tissue Engn & Organ Fabricat Lab, Boston, MA 02114 USA.
RP Troulis, MJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Minimally Invas Oral & Maxillofacial Surg Program, Warren Bldg 1201,55 Fruit St, Boston, MA 02114 USA.
NR 32
TC 12
Z9 13
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 0278-2391
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD NOV
PY 2009
VL 67
IS 11
BP 2412
EP 2417
DI 10.1016/j.joms.2009.05.434
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 512JC
UT WOS:000271243100014
PM 19837310
ER
PT J
AU Williams, WB
Jiang, YD
AF Williams, W. Bradford
Jiang, Yandong
TI Management of a Difficult Airway With Direct Ventilation Through Nasal
Airway Without Facemask
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article
ID GENERAL-ANESTHESIA
C1 [Jiang, Yandong] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Williams, W. Bradford] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
[Jiang, Yandong] Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02115 USA.
RP Jiang, YD (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Jackson 422, Boston, MA 02114 USA.
NR 7
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 0278-2391
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD NOV
PY 2009
VL 67
IS 11
BP 2541
EP 2543
DI 10.1016/j.joms.2009.04.092
PG 3
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 512JC
UT WOS:000271243100037
PM 19837332
ER
PT J
AU Glatt, V
Kwong, FN
Park, K
Parry, N
Griffin, D
Vrahas, M
Evans, CH
Harris, M
AF Glatt, Vaida
Kwong, Francois N.
Park, Kichul
Parry, Nicola
Griffin, Damian
Vrahas, Mark
Evans, Christopher H.
Harris, Mitchel
TI Ability of Recombinant Human Bone Morphogenetic Protein 2 to Enhance
Bone Healing in the Presence of Tobramycin: Evaluation in a Rat
Segmental Defect Model
SO JOURNAL OF ORTHOPAEDIC TRAUMA
LA English
DT Article
DE tobramycin; BMP-2; Segmental defect; rat model
ID OPEN FRACTURES; ANTIBIOTIC-THERAPY; DELIVERY; FEMUR; BEADS; MANAGEMENT;
INFECTION; TOXICITY; RHBMP-2
AB Objective: To determine whether locally applied tobramycin influences the ability of recombinant human bone morphogenetic protein 2 (rhBMP-2) to heal a segmental defect in the rat femur.
Methods: The influence of tobramycin on the osteogenic differentiation of mesenchymal stein cells was first evaluated in vitro. For the subsequent, in vivo experiments, a 5-mm segmental defect was created in the right femur of each of 25 Sprague-Dawley rats and stabilized with an external fixator and four Kirschner wires. Rats were divided in four groups: empty control, tobramycin (11 mg)/absorbable collagen sponge, rhBMP-2 (11 p,g)/absorbable collagen sponge, and rhBMP-2/absorbable collagen sponge with tobramycin. Bone healing was monitored by radiography at 3 and 8 weeks. Animals were euthanized at 8 weeks and the properties of the defect were compared with the intact contralateral femur. Bone formation in the defect region was assessed by dual-energy x-ray absorptiometry, microcomputed tomography, histology, and mechanical testing.
Results: Tobramycin exerted a dose-dependent inhibition of alkaline phosphatase induction and calcium deposition by mesenchymal stein cells cultured under osteogenic conditions. The inhibition was reversed in the presence of 500 ng/mL of rhBMP-2. Segmental defects in the rat femora failed to heal in the absence of rhBMP-2. Tobramycin exerted no inhibitory effects on the ability of rhBMP-2 to heal these defects and increased the bone area of the defects treated with rhBMP-2. Data obtained from all other parameters of healing, including dual-energy x-ray absorptiometry, microcomputed tomography, histology, and mechanical testing, were unaffected by tobramycin.
Conclusions: Although our in vitro results suggested that tobramycin inhibits the osteogenic differentiation of mesenchymal stein cells, this could be overcome by rhBMP-2. Tobramycin did not impair the ability of rhBMP-2 to heal critical-sized femoral defects in rats. Indeed, bone area was increased by nearly 20% in the rhBMP-2 group treated with tobramycin. This study shows that locally applied tobramycin can be used in conjunction with rhBMP-2 to enhance bone formation at fracture sites.
C1 [Glatt, Vaida] Harvard Univ, Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, Sch Med, Boston, MA 02215 USA.
[Glatt, Vaida; Kwong, Francois N.; Griffin, Damian] Univ Warwick, Dept Orthopaed Surg, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England.
[Kwong, Francois N.; Evans, Christopher H.] Harvard Univ, Sch Med, Ctr Mol Orthoped, Brigham & Womens Hosp, Boston, MA 02215 USA.
[Vrahas, Mark; Harris, Mitchel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners Orthoped Trauma Serv, Boston, MA USA.
[Parry, Nicola] Tufts Univ, Cummings Sch Vet Med, Sect Pathol, North Grafton, MA USA.
RP Evans, CH (reprint author), Harvard Univ, Sch Med, Ctr Mol Orthoped, Brigham & Womens Hosp, BIDMC RN 115,300 Brookline Ave, Boston, MA 02215 USA.
EM cevans@bidmc.harvard.edu
FU Medtronic
FX This work was financially supported by Medtronic.
NR 27
TC 12
Z9 13
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0890-5339
J9 J ORTHOP TRAUMA
JI J. Orthop. Trauma
PD NOV-DEC
PY 2009
VL 23
IS 10
BP 693
EP 701
PG 9
WC Orthopedics; Sport Sciences
SC Orthopedics; Sport Sciences
GA 513HO
UT WOS:000271313500002
PM 19858977
ER
PT J
AU Heath, JA
Clarke, NE
McCarthy, M
Donath, SM
Anderson, VA
Wolfe, J
AF Heath, John A.
Clarke, Naomi E.
McCarthy, Maria
Donath, Susan M.
Anderson, Vicki A.
Wolfe, Joanne
TI Quality of care at the end of life in children with cancer
SO JOURNAL OF PAEDIATRICS AND CHILD HEALTH
LA English
DT Article
DE childhood cancer; palliative care; quality of life
ID PEDIATRIC PALLIATIVE CARE; FAMILY PERSPECTIVES; PARENTS; INTEGRATION;
PROGNOSIS; IMPACT
AB Aim:
Current Australian guidelines for the provision of paediatric palliative care highlight the importance of services being focused on the needs of the child and family. We aimed to establish parents' level of satisfaction with the quality of care currently being provided to children dying of cancer.
Methods:
We interviewed 96 parents of children who died of cancer in Melbourne, Australia between 1996 and 2004 to ascertain how they rated the care provided to their child during the end-of-life period.
Results:
A majority of parents were satisfied with the care provided by their primary oncologist, local doctors, palliative care services and home-care nurses. Most parents felt that discussions about key medical and treatment decisions were appropriate and clearly understood. Parents were generally satisfied with the leadership roles undertaken in decision-making in the end-of-life period; however, parents who were not satisfied indicated that they would like additional involvement of their primary oncologist.
Conclusions:
Current approaches to end-of-life care in children with cancer appear to be satisfactory. The main focus should continue to be on open and honest communication.
C1 [Heath, John A.; Clarke, Naomi E.; McCarthy, Maria] Univ Melbourne, Royal Childrens Hosp, Childrens Canc Ctr, Melbourne, Vic, Australia.
[Heath, John A.; Clarke, Naomi E.; Donath, Susan M.; Anderson, Vicki A.] Univ Melbourne, Murdoch Childrens Res Inst, Melbourne, Vic, Australia.
[Heath, John A.; Clarke, Naomi E.; Donath, Susan M.; Anderson, Vicki A.] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia.
[Wolfe, Joanne] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Wolfe, Joanne] Harvard Univ, Dept Pediat, Cambridge, MA 02138 USA.
RP Heath, JA (reprint author), Royal Childrens Hosp, Flemington Rd, Parkville, Vic 3052, Australia.
EM john.heath@rch.org.au
NR 23
TC 17
Z9 17
U1 0
U2 7
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1034-4810
J9 J PAEDIATR CHILD H
JI J. Paediatr. Child Health
PD NOV
PY 2009
VL 45
IS 11
BP 656
EP 659
DI 10.1111/j.1440-1754.2009.01590.x
PG 4
WC Pediatrics
SC Pediatrics
GA 513HY
UT WOS:000271314500008
PM 19903251
ER
PT J
AU Tilden, LB
Williams, BR
Tucker, RO
MacLennan, PA
Ritchie, CS
AF Tilden, Lauren B.
Williams, Beverly R.
Tucker, Rodney O.
MacLennan, Paul A.
Ritchie, Christine S.
TI Surgeons' Attitudes and Practices in the Utilization of Palliative and
Supportive Care Services for Patients with a Sudden Advanced Illness
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Article
ID OUTCOMES; UNIT
AB Background: There is growing interest in the interface between palliative care and other medical specialties, yet little is known about decision-making processes characterizing such collaborations. At the University of Alabama at Birmingham (UAB), the trauma-burn surgery and neurosurgery services frequently request consults from the palliative care team for patients with a sudden advanced illness from catastrophic injuries or physiologic insult.
Objective: We explored surgeons' attitudes and decision-making practices regarding utilization of palliative and supportive care for patients with a sudden advanced illness from traumatic injury or physiologic insult at UAB Hospital, an American College of Surgeons certified level 1 trauma center.
Design and Analysis: We conducted face-to-face, open-ended interviews with nine attending trauma-burn surgeons and neurosurgeons at UAB, utilizing a grounded theory approach to discover salient themes in surgeons' accounts of the palliative care consultative process. Surgeons' descriptions of exemplary cases provided the context for elucidating the larger dynamic involved in assessing patients' situations and identifying the need for palliative and supportive care services.
Results: We organized the data using decision-making diagrams, identifying multiple pathways within the larger consultative framework. Although case-based responses exhibited variations in surgeons diagnostic or prognostic criteria, patient's location in the illness/injury trajectory, and surgeon's goals/desired outcomes; a general decision-making pathway emerged.
Conclusions: Through collaboration with the palliative care service at UAB, trauma-burn surgeons and neurosurgeons are better equipped to manage the multidimensional nature of suffering and provide a holistic approach to care for patients and families dealing with a sudden advanced illness.
C1 [Williams, Beverly R.; Ritchie, Christine S.] Birmingham VA Med Ctr, Birmingham Atlanta VA Geriatr Res Educ & Clin Ctr, Birmingham, AL 35233 USA.
[Tilden, Lauren B.; Williams, Beverly R.; Tucker, Rodney O.; Ritchie, Christine S.] Univ Alabama, Dept Gerontol Geriatr Palliat Care, Birmingham, AL USA.
[Tilden, Lauren B.; Williams, Beverly R.; Tucker, Rodney O.; Ritchie, Christine S.] Univ Alabama, Ctr Palliat Care, Birmingham, AL USA.
[MacLennan, Paul A.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA.
RP Williams, BR (reprint author), Birmingham VA Med Ctr, Birmingham Atlanta VA Geriatr Res Educ & Clin Ctr, 700 19th St S, Birmingham, AL 35233 USA.
EM beverly.williams3@va.gov
NR 13
TC 10
Z9 10
U1 3
U2 4
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
J9 J PALLIAT MED
JI J. Palliat. Med.
PD NOV
PY 2009
VL 12
IS 11
BP 1037
EP 1042
DI 10.1089/jpm.2009.0120
PG 6
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 521IS
UT WOS:000271914900011
PM 19663713
ER
PT J
AU Ayyanar, K
Blackman, SC
Chordas, C
Frazier, L
Kieran, MW
AF Ayyanar, Kanyalakshmi
Blackman, Samuel C.
Chordas, Christine
Frazier, Lindsay
Kieran, Mark W.
TI Metachronous Mediastinal Seminoma Occurring After Intracranial Germinoma
in an Adolescent
SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
LA English
DT Article
DE germinoma; metachronous; germ cell tumor; brain tumor
ID GERM-CELL TUMORS; OF-THE-LITERATURE; KLINEFELTERS-SYNDROME; TESTICULAR
SEMINOMA; SYNCHRONOUS LESIONS; SUPRASELLAR REGIONS; RADIATION-THERAPY;
PINEAL GERMINOMA; METASTASIS; ORIGIN
AB We report a case of a mediastinal seminoma occurring 19 months after the resolution of a pineal germinoma. A 15-yearold boy with headaches and Visual changes was diagnosed with a pineal germinoma by biopsy and mildly elevated beta-human chorionic gonadatropin (beta-HCG) in serum and cerebral spinal fluid. Radiation therapy leads to the resolution of his pineal germinoma and normalization of the beta-HCG. A mediastinal seminoma (germinoma) was diagnosed nearly 2),cars later because of rising serum beta-HCG. There was no evidence of recurrent central nervous system disease. The patient underwent systemic chemotherapy with the complete resolution of the mediastinal seminoma.
C1 [Ayyanar, Kanyalakshmi] Univ Louisville, Kosair Childrens Hosp, Div Pediat Hematol Oncol, Louisville, KY 40202 USA.
[Blackman, Samuel C.; Chordas, Christine; Frazier, Lindsay; Kieran, Mark W.] Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA.
[Blackman, Samuel C.; Chordas, Christine; Frazier, Lindsay; Kieran, Mark W.] Childrens Hosp, Boston, MA 02115 USA.
RP Ayyanar, K (reprint author), Univ Louisville, Kosair Childrens Hosp, Div Pediat Hematol Oncol, 571 S Floyd St,Suite 445, Louisville, KY 40202 USA.
EM k0ayya01@louisville.edu
OI Kieran, Mark/0000-0003-2184-7692
NR 26
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1077-4114
J9 J PEDIAT HEMATOL ONC
JI J. Pediatr. Hematol. Oncol.
PD NOV
PY 2009
VL 31
IS 11
BP 861
EP 864
PG 4
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 519JZ
UT WOS:000271763900015
PM 19779380
ER
PT J
AU Wang, LY
Martin, B
Brenneman, R
Luttrell, LM
Maudsley, S
AF Wang, Liyun
Martin, Bronwen
Brenneman, Randall
Luttrell, Louis M.
Maudsley, Stuart
TI Allosteric Modulators of G Protein-Coupled Receptors: Future
Therapeutics for Complex Physiological Disorders
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Review
ID BETA(2) ADRENERGIC-RECEPTOR; MUSCARINIC ACETYLCHOLINE-RECEPTORS;
AGONIST-DIRECTED TRAFFICKING; DELTA-OPIOID RECEPTORS;
SIGNAL-TRANSDUCTION; BETA(2)-ADRENERGIC RECEPTOR; DRUG DISCOVERY;
IN-VIVO; FUNCTIONAL SELECTIVITY; MOLECULAR-MECHANISM
AB G protein-coupled receptors (GPCRs) are one of the most important classes of proteins in the genome, not only because of their tremendous molecular diversity but because they are the targets of nearly 50% of current pharmacotherapeutics. The majority of these drugs affect GPCR activity by binding to a similar molecular site as the endogenous cognate ligand for the receptor. These "orthosterically" targeted drugs currently dominate the existing pharmacopeia. Over the past two decades, novel opportunities for drug discovery have risen from a greater understanding of the complexity of GPCR signaling. A striking example of this is the appreciation that many GPCRs possess functional allosteric binding sites. Allosteric modulator ligands bind receptor domains topographically distinct from the orthosteric site, altering the biological activity of the orthosteric ligand by changing its binding affinity, functional efficacy, or both. This additional receptor signaling complexity can be embraced and exploited for the next generation of GPCR-targeted therapies. Despite the challenges associated with detecting and quantifying the myriad of possible allosteric effects on GPCR activity, allosteric ligands offer the prospect of engendering a facile stimulus-bias in orthosteric ligand signaling, paving the way for not only receptor-selective but also signaling pathway-selective therapies. Allosteric modulators possess specific advantages when considering the treatment of multifactorial syndromes, such as metabolic diseases or age-related cognitive impairment, because they may not greatly affect neurotransmitter or hormone release patterns, thus maintaining the integrity of complex signaling networks that underlie perception, memory patterns, or neuroendocrinological axes while introducing therapeutically beneficial signal bias.
C1 [Maudsley, Stuart] NIA, Biomed Res Ctr, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA.
[Martin, Bronwen] NIA, Metab Unit, NIH, Baltimore, MD 21224 USA.
[Brenneman, Randall] Univ Miami, Miller Sch Med, Canc Biol Program, Miami, FL 33136 USA.
[Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
[Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Div Endocrinol, Charleston, SC 29425 USA.
RP Maudsley, S (reprint author), NIA, Biomed Res Ctr, Receptor Pharmacol Unit, NIH, Room 5C228,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM maudsleyst@mail.nih.gov
FU National Institutes of Health National Institute on Aging; National
Institutes of Health National Institute of Diabetes and Digestive and
Kidney Diseases [R01-DK055524]; Research Service of the Ralph H. Johnson
Veterans Affairs Medical Center
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health National Institute on Aging; the
National Institutes of Health National Institute of Diabetes and
Digestive and Kidney Diseases [Grant R01-DK055524] (L. M. L.); and the
Research Service of the Ralph H. Johnson Veterans Affairs Medical Center
(L. M. L.).
NR 109
TC 56
Z9 56
U1 0
U2 5
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 NOV
PY 2009
VL 331
IS 2
BP 340
EP 348
DI 10.1124/jpet.109.156380
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 509HR
UT WOS:000271006200001
PM 19667132
ER
PT J
AU Zhou, JY
Petritis, BO
Petritis, K
Norbeck, AD
Weitz, KK
Moore, RJ
Camp, DG
Kulkarni, RN
Smith, RD
Qian, WJ
AF Zhou, Jian-Ying
Petritis, Brianne O.
Petritis, Konstantinos
Norbeck, Angela D.
Weitz, Karl K.
Moore, Ronald J.
Camp, David G., II
Kulkarni, Rohit N.
Smith, Richard D.
Qian, Wei-Jun
TI Mouse-Specific Tandem IgY7-SuperMix Immunoaffinity Separations for
Improved LC-MS/MS Coverage of the Plasma Proteome
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE Immunoaffinity separation; LC-MS/MS; Proteomics; Mouse plasma; SuperMix
ID MASS-SPECTROMETRY; BREAST-CANCER; PROTEINS; MODEL; CHROMATOGRAPHY;
IDENTIFICATIONS; BIOMARKERS; DISCOVERY; DEPLETION; STRATEGY
AB We report on a mouse specific SuperMix immunoaffinity separation system for separating low-abundance proteins from high and moderate abundance proteins in mouse plasma. When applied in tandem with a mouse IgY7 column that removes the seven most abundant proteins in plasma, the SuperMix column captures more than 100 additional moderate abundance proteins, thus allowing significant enrichment of low-abundance proteins in the flow-through fraction. A side-by-side comparison of results obtained from 2D-LC-MS/MS analyses of flow-through samples from IgY7 and SuperMix columns revealed a nearly 2-fold improvement in the overall proteome coverage. Detection of low-abundance proteins was also enhanced, as evidenced by a more than 2-fold increase in the coverage of cytokines, growth factors, and other low-abundance proteins. Moreover, the tandem separations are automated, reproducible, and allow effective identification of protein abundance differences from LC-MS/MS analyses. Considering the overall reproducibility and increased sensitivity using the IgY7-SuperMix separation system, we anticipate broad applications of this strategy for biomarker discovery using mouse models.
C1 [Zhou, Jian-Ying; Petritis, Brianne O.; Petritis, Konstantinos; Norbeck, Angela D.; Weitz, Karl K.; Moore, Ronald J.; Camp, David G., II; Smith, Richard D.; Qian, Wei-Jun] Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA.
[Zhou, Jian-Ying; Petritis, Brianne O.; Petritis, Konstantinos; Norbeck, Angela D.; Weitz, Karl K.; Moore, Ronald J.; Camp, David G., II; Smith, Richard D.; Qian, Wei-Jun] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA.
[Kulkarni, Rohit N.] Harvard Univ, Sch Med, Div Cell & Mol Biol, Joslin Diabet Ctr,Dept Med, Boston, MA 02215 USA.
RP Qian, WJ (reprint author), Pacific NW Natl Lab, Environm Mol Sci Lab, POB 999,MSIN K8-98, Richland, WA 99352 USA.
RI Petritis, Konstantinos/F-2156-2010; Zhou, Jian-Ying/B-1336-2011; Qian,
Weijun/C-6167-2011; Zhou, Jian-Ying/D-1308-2012; Smith,
Richard/J-3664-2012
OI Smith, Richard/0000-0002-2381-2349
FU National Institutes of Health [R01 DK074795, RR018522]
FX Portions of this research were supported by National Institutes of
Health grants R01 DK074795 and RR018522. Experimental work was performed
in the Environmental Molecular Sciences Laboratory, a U.S. Department of
Energy (DOE) Office of Biological and Environmental Research national
scientific user facility on the Pacific Northwest National Laboratory
(PNNL) campus PNNL is multiprogram national laboratory operated by
Battelle for the DOE under Contract No DE-AC05-76RLO 1830
NR 29
TC 12
Z9 12
U1 2
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1535-3893
J9 J PROTEOME RES
JI J. Proteome Res.
PD NOV
PY 2009
VL 8
IS 11
BP 5387
EP 5395
DI 10.1021/pr900564f
PG 9
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 586XV
UT WOS:000276949600048
PM 19722698
ER
PT J
AU Boynton, L
Bentley, J
Strachan, E
Barbato, A
Raskind, M
AF Boynton, Lorin
Bentley, Jacob
Strachan, Eric
Barbato, Anna
Raskind, Murray
TI Preliminary Findings Concerning the Use of Prazosin for the Treatment of
Posttraumatic Nightmares in a Refugee Population
SO JOURNAL OF PSYCHIATRIC PRACTICE
LA English
DT Article
DE posttraumatic stress disorder; prazosin; nightmares; refugees; global
concern
ID STRESS-DISORDER; SLEEP DISTURBANCE; TRAUMA NIGHTMARES; COMBAT VETERANS;
PTSD; SYMPTOMS
AB Prazosin, a centrally active alpha-1 adrenergic receptor antagonist, has reduced nightmares and sleep disturbances in placebo-controlled studies involving patients with combat and civilian related posttraumatic stress disorder (PTSD). In this retrospective chart review, we analyzed data from 23 refugees diagnosed with chronic PTSD who were treated with prazosin. The recurrent distressing dreams item of the Clinician Administered PTSD Scale (CAPS) was used to quantify nightmare severity. A Clinical Global Impressions-Change (CGI-C) score assessed change in overall PTSD severity exclusive of nightmares. Using a paired-samples t-test, we found that CAPS scores decreased significantly (p < 0.0005) from baseline after 8 weeks of treatment with a stable dose of prazosin. Overall PTSD severity was "markedly improved" in 6 patients, "moderately improved" in 11 patients, and "minimally improved" in 6 patients. These data provide preliminary support for the use of prazosin in targeting reduction of trauma-related nightmares and promoting improvement of global clinical status within an international sample of severely traumatized refugee patients. (Journal of Psychiatric Practice 2009;15:454-459)
C1 [Boynton, Lorin] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA.
[Bentley, Jacob] Seattle Pacific Univ, Seattle, WA USA.
[Barbato, Anna] Univ Hawaii, Hilo, HI 96720 USA.
[Raskind, Murray] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
RP Boynton, L (reprint author), Univ Washington, Harborview Med Ctr, 325 9Th Ave,Box 359896, Seattle, WA 98104 USA.
EM loring@u.washington.edu
NR 17
TC 15
Z9 15
U1 2
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1527-4160
J9 J PSYCHIATR PRACT
JI J. Psychiatr. Pract.
PD NOV
PY 2009
VL 15
IS 6
BP 454
EP 459
PG 6
WC Psychiatry
SC Psychiatry
GA 525GZ
UT WOS:000272204400005
PM 19934720
ER
PT J
AU Riedl, A
Maass, J
Fliege, H
Stengel, A
Schmidtmann, M
Klapp, BF
Monnikes, H
AF Riedl, Andrea
Maass, Julia
Fliege, Herbert
Stengel, Andreas
Schmidtmann, Marco
Klapp, Burghard F.
Moennikes, Hubert
TI Subjective theories of illness and clinical and psychological outcomes
in patients with irritable bowel syndrome
SO JOURNAL OF PSYCHOSOMATIC RESEARCH
LA English
DT Article
DE IBS; Quality of life; Subjective theories of illness
ID QUALITY-OF-LIFE; SYNDROME IBS; SYMPTOMS; IMPACT; REPRESENTATION;
ATTRIBUTIONS; PERSONALITY; PERCEPTION; DISORDERS; DISEASES
AB Objectives: Patients' ideas about the nature, cause, and treatment of their illnesses are pail of the complex process of coping with illness. To date, limited research on subjective theories of illness in patients with irritable bowel syndrome (IBS) has been performed. The aim of the study was to investigate patients' subjective theories of illness and how these are related to clinical and psychological outcome criteria, in particular IBS symptom severity and quality of life. Methods: Eighty-eight patients with IBS, as defined by Rome III criteria, were administered a battery of questionnaires to collect the following data: sociodemographic variables, subjective theories of illness (Subjektive Krankheitstheorien, Cause Questionnaire), anxiety (Hospital Anxiety and Depression Scale), depression (Beck Depression Inventory), quality of life (SF-12), and IBS symptoms (Questionnaire for Gastrointestinal Symptoms). Results: Almost all patients reported theories of illness reflecting their subjective causal assumptions. The most frequently mentioned causal factors were physical illness, intrapsychic factors, and stress. Patients with mainly somatic attributions had higher IBS symptoms scores (P<.05) and reduced physical quality of life. Intrapsychic attributions were associated with reduced mental quality of life and enhanced physical quality of life (P<.01). All correlations were independent of gender, age, and irritable bowel subgroups. Conclusions: Subjective theories of illness can have significant implications for IBS symptom severity, as well as for physical and mental quality of life. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Riedl, Andrea; Fliege, Herbert; Schmidtmann, Marco] Charite, Dept Med, Div Psychosomat Med & Psychotherapy, D-10117 Berlin, Germany.
[Riedl, Andrea; Maass, Julia; Schmidtmann, Marco; Klapp, Burghard F.] Charite, Dept Med, Div Hepatol Gastroenterol & Endocrinol, D-10117 Berlin, Germany.
[Stengel, Andreas] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA.
[Stengel, Andreas] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, Digest Dis Div,Dept Med,VA Greater Los Angeles He, Los Angeles, CA 90095 USA.
[Moennikes, Hubert] Martin Luther Hosp, Dept Med, Berlin, Germany.
[Moennikes, Hubert] Martin Luther Hosp, Inst Neurogastroenterol, Berlin, Germany.
RP Riedl, A (reprint author), Charite, Dept Med, Div Psychosomat Med & Psychotherapy, Luisenstr 13A, D-10117 Berlin, Germany.
EM andrea.riedl@charite.de
NR 37
TC 14
Z9 14
U1 3
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3999
J9 J PSYCHOSOM RES
JI J. Psychosomat. Res.
PD NOV
PY 2009
VL 67
IS 5
BP 449
EP 455
DI 10.1016/j.jpsychores.2009.02.001
PG 7
WC Psychiatry
SC Psychiatry
GA 513TZ
UT WOS:000271348000011
PM 19837208
ER
PT J
AU Mori, S
Lu, HM
Wolfgang, JA
Choi, NC
Chen, GTY
AF Mori, Shinichiro
Lu, Hsiao-Ming
Wolfgang, John A.
Choi, Noah C.
Chen, George T. Y.
TI Effects of Interfractional Anatomical Changes on Water-Equivalent
Pathlength in Charged-Particle Radiotherapy of Lung Cancer
SO JOURNAL OF RADIATION RESEARCH
LA English
DT Article
DE Charged-particle; Four-dimensional; Lung cancer; Lung density;
Radiotherapy planning; Beam range variation; Tumor shrinkage
ID 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; BEAM RADIOTHERAPY; TUMOR-TRACKING;
ORGAN MOTION; IRRADIATION; REGRESSION
AB Intrafractional motion and interfractional changes affect the accuracy of the delivered dose in radio- therapy, particularly in charged-particle radiotherapy. Most recent studies are focused oil intrafractional motion (respiratory motion). Here, we report a quantitative Simulation analysis of the effects of interfractional changes oil water-equivalent pathlength (WEL) in charged-particle lung therapy. Serial four-, dimensional (4D) CT scans were performed under free breathing conditions; the time span between the first and second 4DCT scans was five weeks. We quantified WEL changes between the first and second CT scans due to interfractional changes (turner shrinkage and tissue density changes) and compared the particle-beam-stopping point between the serial 4DCT scans with use of the same initial bolus. Both tumor-shrinkage and lung-density changes were observed in a single patient over the course of therapy. The lung density decreased by approximately 0.1 g/cm(3) between the first and second-CT scans, resulting in a 1.5 cm WEL changes. Tumor shrinkage resulted in approximately 3 cm WEL changes. If the same initial bolus and plan were used through the treatment Course. an unexpected significant beam overshoot would occur by interfractional changes due to tumor shrinkage and king density variation.
C1 [Mori, Shinichiro; Lu, Hsiao-Ming; Wolfgang, John A.; Choi, Noah C.; Chen, George T. Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Cambridge, MA 02138 USA.
RP Mori, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Cambridge, MA 02138 USA.
EM shinshin@nirs.go.jp
OI Mori, Shinichiro/0000-0002-0412-4399
NR 19
TC 6
Z9 6
U1 0
U2 2
PU JAPAN RADIATION RESEARCH SOC
PI CHIBA
PA C/O NAT INST RADIOLOGICAL SCI 9-1 ANAGAWA-4-CHOME INAGE-KU, CHIBA, 263,
JAPAN
SN 0449-3060
J9 J RADIAT RES
JI J. Radiat. Res.
PD NOV
PY 2009
VL 50
IS 6
BP 513
EP 519
DI 10.1269/jrr.09032
PG 7
WC Biology; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Radiology, Nuclear Medicine
& Medical Imaging
GA 537RO
UT WOS:000273131700004
PM 19959880
ER
PT J
AU Omurtag, KR
Styer, AK
Session, D
Toth, TL
AF Omurtag, Kenan R.
Styer, Aaron K.
Session, Donna
Toth, Thomas L.
TI Economic Implications of Insurance Coverage for in Vitro Fertilization
in the United States A Review
SO JOURNAL OF REPRODUCTIVE MEDICINE
LA English
DT Article; Proceedings Paper
CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine
CY OCT 13-17, 2007
CL Washington, DC
SP Amer Soc Reprod Med
DE fertilization, in vitro; health policy; infertility; insurance health;
mandated benefits
ID ASSISTED-REPRODUCTIVE-TECHNOLOGY; SINGLE-BLASTOCYST TRANSFER; MULTIPLE
BIRTHS; OVARIAN STIMULATION; COST-EFFECTIVENESS; INFERTILITY; TRENDS;
CARE; PREGNANCY; MEDICINE
AB OBJECTIVE: To analyze cost-effectiveness studies in regard to the costs of in vitro fertilization (IVF) and discuss specific economic trends that may affect the future utilization of IVF in the United States.
STUDY DESIGN: Health economics. A Pub Med literature review and the Centers for Disease Control's (CDC) Fertility Clinic Success Rate registry served to access cost analyses and trends, respectively.
RESULTS: The average cost of an IVF cycle in the U.S. is $9,226. Among policies that provide IVF set-vices, the increase in premium pet, month ranges front $0.67 to $14.
CONCLUSION: When IVF is provided as a health benefit, the cost increases can be variable. As utilization increases, contemporary cost analyses and outcomes research will aid providers, third-party payers and policymakers in better understanding the economic impact of IVF. (J Reprod Med 2009;54:661-668)
C1 [Omurtag, Kenan R.] Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA 30303 USA.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Obstet & Gynecol Serv, Boston, MA USA.
RP Omurtag, KR (reprint author), Emory Univ, Sch Med, Dept Gynecol & Obstet, Glenn Bldg,4th Floor,69 Jesse Hill Dr, Atlanta, GA 30303 USA.
EM komurta@emory.edu
NR 42
TC 6
Z9 6
U1 1
U2 7
PU J REPROD MED INC
PI ST LOUIS
PA 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA
SN 0024-7758
J9 J REPROD MED
JI J. Reprod. Med.
PD NOV-DEC
PY 2009
VL 54
IS 11-12
BP 661
EP 668
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 540CR
UT WOS:000273308900001
PM 20120898
ER
PT J
AU Campbell, R
Cooper, GS
Gilkeson, GS
AF Campbell, Robert, Jr.
Cooper, Glinda S.
Gilkeson, Gary S.
TI The Impact of Systemic Lupus Erythematosus on Employment
SO JOURNAL OF RHEUMATOLOGY
LA English
DT Article
DE JOB LOSS; LOST WAGES; SYSTEMIC LUPUS ERYTHEMATOSUS; CAROLINA LUPUS
STUDY; ARTHRITIS; PLEURITIS
ID RHEUMATOID-ARTHRITIS PATIENTS; SOUTHEASTERN UNITED-STATES; WORK
DISABILITY; REVISED CRITERIA; RISK-FACTORS; CLASSIFICATION; POPULATION;
COSTS; RACE
AB Objective. Our primary objective was to examine work status (e.g., job loss, changes in amount worked) and predictors of job loss in patients with systemic lupus erythematosus (SLE).
Methods. Recently diagnosed SLE patients were enrolled in the Carolina Lupus Study between 1997 and 1999: ail age-, sex-, and state-matched control group selected through driver's license registries for the 60-county study area was also enrolled. In 2001, a followup study of both groups was conducted (median 4 yrs since diagnosis). Work history data were obtained in ail in-person interview at enrollment and a telephone interview at followup.
Results. Fifty-one patients (26%) and 26 controls (9%) (p < 0.0001) who were working the year before diagnosis (or for controls, it corresponding reference year) were no longer working at followup; 92% of patients compared with 40% of controls who were no longer working indicated that they had stopped working because of their health (p < 0.0001). College graduates were less likely to quit their jobs due to health compared to non-college graduates (adjusted OR = 0.27, 95% CI 0.09, 0.84). SLE patients with arthritis were 3 times more likely to have left their jobs due to health reasons compared to those who didn't have arthritis (adjusted OR = 3.3. 95% CI 1.2, 8.8); ail association was also seen with pleuritis (adjusted OR 2.3, 95% CI 1.1, 4.6).
Conclusion. The burden expressed as work cessation due to health, especially among lesser educated patients and those with arthritis or pleuritis, is significant even early in the disease process. (First Release Oct 1 2009; J Rheumatol 2009;36:2470-5, doi: 10.3899/jrheum.080586)
C1 [Campbell, Robert, Jr.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA.
NIEHS, NIH, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Cooper, Glinda S.] US EPA, Washington, DC 20460 USA.
[Gilkeson, Gary S.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA.
RP Campbell, R (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, 96 Jonathan Lucas St,Suite 912, Charleston, SC 29425 USA.
EM campber@musc.edu
FU Intramural NIH HHS; NIAMS NIH HHS [2R01-AR045476, 1T32-AR050958,
P60-AR049459]
NR 28
TC 12
Z9 12
U1 0
U2 0
PU J RHEUMATOL PUBL CO
PI TORONTO
PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA
SN 0315-162X
J9 J RHEUMATOL
JI J. Rheumatol.
PD NOV
PY 2009
VL 36
IS 11
BP 2470
EP 2475
DI 10.3899/jrheum.080586
PG 6
WC Rheumatology
SC Rheumatology
GA 517DP
UT WOS:000271593700016
PM 19273454
ER
PT J
AU La Fountaine, MF
Radulovic, M
Cardozo, CP
Spungen, AM
DeMeersman, RE
Bauman, WA
AF La Fountaine, Michael F.
Radulovic, Miroslav
Cardozo, Christopher P.
Spungen, Ann M.
DeMeersman, Ronald E.
Bauman, William A.
TI Effects of Acute Nitric Oxide Synthase Inhibition on Lower Leg Vascular
Function in Chronic Tetraplegia
SO JOURNAL OF SPINAL CORD MEDICINE
LA English
DT Article
DE Spinal cord injuries; L-NAME; Nitric oxide synthase; Tetraplegia;
Vascular resistance; Vasoregulation
ID SPINAL-CORD-INJURY; BLOOD-PRESSURE; L-NAME; PLASMA-CATECHOLAMINES;
SKELETAL-MUSCLE; NERVOUS-SYSTEM; RESPONSES; HUMANS; TONE;
PLETHYSMOGRAPHY
AB Background/Objective: To improve our understanding of the lower-leg vascular responses of nitric oxide synthase inhibition in persons with tetraplegia.
Participants: Six people with chronic tetraplegia and 6 age-matched controls.
Methods: Lower-leg relative vascular resistance and venous volume variation were obtained by venous occlusion plethysmography and blood pressure by auscultation at baseline. Postintravenous infusion of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine-methyl-ester (1 mg.kg(-1)) or placebo on separate days.
Results: At baseline in the group with tetraplegia compared with controls, mean arterial pressure and relative vascular resistance of the leg were significantly lower. After nitric oxide synthase inhibition, mean arterial pressure and lower leg vascular resistance were significantly elevated in both groups. There were no group or intervention differences in venous volume variation.
Conclusion: These preliminary results suggest that nitric oxide synthase inhibition with I mg.kg-1 N(G)-nitro-L-arginine-methyl-ester normalizes seated blood pressure and lower leg vascular resistance to control group baseline levels.
C1 [La Fountaine, Michael F.; Radulovic, Miroslav; Cardozo, Christopher P.; Spungen, Ann M.; Bauman, William A.] James J Peters VA Med Ctr, VA Ctr Excellence Med Consequences Spinal Cord In, Bronx, NY 10468 USA.
[DeMeersman, Ronald E.] Columbia Univ, Teachers Coll, Dept Biobehav Sci, New York, NY 10027 USA.
RP La Fountaine, MF (reprint author), James J Peters VA Med Ctr, VA Ctr Excellence Med Consequences Spinal Cord In, SCI Room 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA.
EM michael.lafountaineg@gmail.com
FU Veterans Affairs Rehabilitation Research and Development Service
[B4335V, 3755, B4162C]; James J. Peters VA Medical Center; VIDDA
Foundation
FX This research was supported by the Veterans Affairs Rehabilitation
Research and Development Service (#B4335V, ARCD #3755 and #B4162C),
James J. Peters VA Medical Center, and VIDDA Foundation.
NR 44
TC 2
Z9 2
U1 0
U2 0
PU AMER PARAPLEGIA SOC
PI JACKSON HWIGHTS
PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA
SN 1079-0268
J9 J SPINAL CORD MED
JI J. Spinal Cord. Med.
PD NOV
PY 2009
VL 32
IS 5
BP 538
EP 544
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 534JX
UT WOS:000272893500004
PM 20025149
ER
PT J
AU Liu, M
Gu, M
Wu, YC
Zhu, PC
Zhang, W
Yin, CJ
Zhang, WJ
AF Liu, Min
Gu, Min
Wu, Yichao
Zhu, Pengcheng
Zhang, Wei
Yin, Changjun
Zhang, Wei (J)
TI Therapeutic Effect of Y-27632 on Chronic Allograft Nephropathy in Rats
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Article
DE kidney transplantation; chronic allograft nephropathy; Rho-kinase;
Y-27632, fibrosis
AB Background. Chronic allograft nephropathy (CAN) is a major cause of late allograft loss. Recent evidences suggest that Rho and its downstream effector ROCK may be greatly involved in the progression of renal fibrosis. Inhibition of Rho/ROCK pathway might interact with the inflammatory process in the renal interstitium, and antagonize the process of epithelial-to-mesenchymal transition (EMT). We hypothesized that Y-27632 could inhibit the chronic inflammatory process and prevent the progression of CAN.
Materials and Methods. Fisher (F344) kidneys were orthotopically transplanted into Lewis rat recipients. Lewis to Lewis rat kidney transplantation was served as the syngeneic control (Syn group). Allograft recipients were randomized and treated with either cyclosporine A alone (Allo group), or in combination with Y-27632 (30 mg/kg body weight/d intragastric, Y-27632 group). Renal function and urine protein excretion levels of the rats were analyzed. Animals were sacrificed 12 wk post-transplantation for histological and immunohistochemical studies, as well as analysis of the expression levels of chemokines, transforming growth factor (TGF-beta) 1 and alpha smooth muscle actin (alpha-SMA).
Results. Renal function deteriorated progressively in the Allo group, and there was typical CAN morphology in the kidneys. However, Y-27632-treatment significantly prevented the deterioration of graft function, lessened the level of urine protein excretion, and preserved the renal structure. Attenuation of ED1 positive mononuclear cell infiltration and amelioration of tubulointerstitial fibrosis were achieved by Y-27632 intervention. This was associated with down-regulation of the expression of tubular monocyte chemoattractant protein-1, RANTES (regulated upon expression normal T cell expressed and secreted), and phosphorylated NF-kappa B (which was a marker for activation). Profibrotic protein (TGF-beta 1) and alpha-SMA, a marker of EMT, were significantly down-regulated by Y-27632 treatment as well.
Conclusions. The Rho/ROCK pathway plays an important role in the progression of CAN, and specific inhibition of Rho activity by Y-27632 showed favorable effects on blocking renal interstitial inflammation and fibrosis, thus efficiently retarding the development of CAN, which might provide us with a novel strategy to improve long-term renal graft survival. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Liu, Min; Gu, Min; Zhang, Wei; Yin, Changjun; Zhang, Wei (J)] Nanjing Med Univ, Affiliated Hosp 1, Div Urol & Kidney Transplantat, Nanjing 210029, Jiangsu, Peoples R China.
[Wu, Yichao; Zhu, Pengcheng] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA.
RP Zhang, WJ (reprint author), Nanjing Med Univ, Affiliated Hosp 1, Div Urol & Kidney Transplantat, Nanjing 210029, Jiangsu, Peoples R China.
EM Kidneyliu@163.com
OI Liu, Min/0000-0002-8117-4808
NR 33
TC 11
Z9 13
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0022-4804
J9 J SURG RES
JI J. Surg. Res.
PD NOV
PY 2009
VL 157
IS 1
BP E117
EP E127
DI 10.1016/j.jss.2008.10.018
PG 11
WC Surgery
SC Surgery
GA V17NW
UT WOS:000207944900015
PM 19589538
ER
PT J
AU Favero, M
AF Favero, Marcus
TI Child and Adolescent Neurology for Psychiatrists
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Book Review
C1 [Favero, Marcus] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Favero, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM mfavero@partners.org
NR 1
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD NOV
PY 2009
VL 48
IS 11
BP 1130
EP 1132
DI 10.1097/01.CHI.0000359012.71922.50
PG 3
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 510DL
UT WOS:000271068100022
ER
PT J
AU Clark, D
AF Clark, Deborah
TI Handbook of Depression in Adolescents
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Book Review
C1 [Clark, Deborah] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Clark, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM DAClark@partners.org
NR 1
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD NOV
PY 2009
VL 48
IS 11
BP 1132
EP 1133
DI 10.1097/01.CHI.0000359013.66084.16
PG 2
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 510DL
UT WOS:000271068100023
ER
PT J
AU Merkow, RP
Bilimoria, KY
Cohen, ME
Richards, K
Ko, CY
Hall, BL
AF Merkow, Ryan P.
Bilimoria, Karl Y.
Cohen, Mark E.
Richards, Karen
Ko, Clifford Y.
Hall, Bruce L.
TI Variability in Reoperation Rates at 182 Hospitals: A Potential Target
for Quality Improvement
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Article
ID OPERATING-ROOM; UNPLANNED RETURN; SURGICAL CARE; SURGERY; OUTCOMES;
RISK; INDICATOR; PROGRAM; FUTURE; NSQIP
AB BACKGROUND: Reoperation rate has gained increasing attention as a potential indicator of surgical quality. Objectives of this study were to examine the feasibility of assessing reoperation rates at 182 hospitals to identify institutions with Outlying performance, to examine potentially modifiable factors that are associated with reoperations, and to determine if a more parsimonious logistic regression model effectively predicts reoperations.
STUDY DESIGN: Patients were identified who underwent colorectal procedures at 182 hospitals participating in the American College of Surgeon's National Surgical Quality Improvement Program in 2006-2007. Risk-adjusted regression models for reoperation were developed to identify hospitals that had ratios of observed-to-expected events that were substantial outliers.
RESULTS: Of 23,098 patients identified, 1,320 (5.7%) required reoperations. Reoperation occurred significantly more often than expected in 16 hospitals and less often than expected in 7 hospitals (P 0.05). Factors that were associated with all increased risk of reoperation were advanced American Society of Anesthesiologists class, male gender, contaminated wounds, surgical extent, Surgical indication, smoking, poor functional status, disseminated cancer, COPD, steroid dependence, anemia, body mass index (calculated as kg/m(2)) >35 or <= 18.5, and hypertension. Compared with the full logistic regression model, there was a high degree of correlation with the more parsimonious logistic model containing only the first six variables (r = 0.996).
CONCLUSIONS: There is considerable variability in reoperation rates at American College of Surgeon's National Surgical Quality Improvement Program hospitals. American College of Surgeon's National Surgical Quality Improvement Program data call be used to provide individual hospitals with risk-adjusted self-assessment data on reoperations to potentially identify quality-improvement opportunities. (J Am Coll Surg 2009;209:557-564. (C) 2009 by the American College of Surgeons)
C1 [Bilimoria, Karl Y.; Cohen, Mark E.; Richards, Karen; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA.
[Merkow, Ryan P.] Univ Colorado, Denver Sch Med, Dept Surg, Aurora, CO USA.
[Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA.
[Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA.
[Ko, Clifford Y.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Hall, Bruce L.] Washington Univ, Sch Med, Dept Surg, John Cochran St Louis Vet Affairs Med Ctr,Ctr Hlt, St Louis, MO 63110 USA.
[Hall, Bruce L.] Washington Univ, John M Olin Sch Business, St Louis, MO 63130 USA.
RP Bilimoria, KY (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Fl, Chicago, IL 60611 USA.
EM kbilimoria@facs.org
NR 26
TC 28
Z9 29
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD NOV
PY 2009
VL 209
IS 5
BP 557
EP 564
DI 10.1016/j.jamcollsurg.2009.07.003
PG 8
WC Surgery
SC Surgery
GA 520VB
UT WOS:000271876400002
PM 19854394
ER
PT J
AU Itani, KMF
Fitzgibbons, R
Awad, SS
Duh, QY
Ferzli, GS
AF Itani, Kamal M. F.
Fitzgibbons, Robert, Jr.
Awad, Samir S.
Duh, Quan-Yang
Ferzli, George S.
TI Management of Recurrent Inguinal Hernias
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Review
ID LAPAROSCOPIC TRANSABDOMINAL PREPERITONEAL; PROSPECTIVE RANDOMIZED-TRIAL;
MESH PLUG MIGRATION; GROIN HERNIA; FEMORAL HERNIA; CLINICAL-TRIAL;
REPAIR; HERNIORRHAPHY; REOPERATION; EXPERIENCE
AB The ultimate measure of success of inguinal hernia repair is the rate of recurrence. Although other procedure-related complications are important and have been shown to affect health-related quality-of-life parameters,(1) recurrence is more challenging for the patients and the surgeon. From the patients' perspective, the initial physical and mental investment in the operation has failed. A new investment has to be made, with fewer guarantees for success, more risks for more serious complications, and more time off from work. For the surgeon, repair of a recurrent inguinal hernia is technically more demanding because scar tissue causes the inguinal canal to be obscured and distorted. In addition, the tissue tends to be weaker than at the time of primary repair, resulting in a substantially higher risk for complications or development: of another recurrence. Although much has been published about primary repair of inguinal hernias, less is known about the best approach to address a recurrent hernia. In this review, we address the "pros and cons" of popular surgical approaches and watchful waiting for recurrent inguinal hernias and indications for each. In the absence of best evidence in this field, the authors present an opinion based on their experience and a review of the available literature primarily extracted from large trials and large cohorts for inguinal hernia repair in general.
C1 [Itani, Kamal M. F.] Boston Vet Affairs Hlth Care Syst, Dept Surg, Boston, MA USA.
[Itani, Kamal M. F.] Boston Univ, Boston, MA 02215 USA.
[Fitzgibbons, Robert, Jr.] Creighton Univ, Dept Surg, Omaha, NE 68178 USA.
[Awad, Samir S.] Michael E DeBakey Vet Affairs Med Ctr, Dept Surg, Houston, TX USA.
[Awad, Samir S.] Baylor Coll Med, Houston, TX 77030 USA.
[Duh, Quan-Yang] San Francisco VA Med Ctr, Dept Surg, San Francisco, CA USA.
[Duh, Quan-Yang] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Ferzli, George S.] SUNY Hlth Sci Ctr, Dept Surg, Brooklyn, NY 11203 USA.
[Ferzli, George S.] Lutheran Med Ctr, Brooklyn, NY USA.
RP Itani, KMF (reprint author), Boston Vet Affairs Hlth Care Syst 112A, 1400 VFW Pkwy, W Roxbury, MA 02132 USA.
EM kitani@va.gov
OI Ferzli, George/0000-0003-0095-6216
FU Lifecell Corporation
FX Dr Irani received research support from Lifecell Corporation. Dr
Fitzgibbons is a consultant and receives research support from Lifecell
Corporation and royalties from Cook Surgical for the Fitzgibbons-Jenkins
Multi Purpose Common Bile Duct Catheter. Dr Duh is on the clinical
advisory board of Covidien. Dr Awad is a speaker and ad hoc consultant
and has received research support from Lifecell Corporation. Dr Ferzli
has nothing to disclose.
NR 49
TC 12
Z9 18
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD NOV
PY 2009
VL 209
IS 5
BP 653
EP 658
DI 10.1016/j.jamcollsurg.2009.07.015
PG 6
WC Surgery
SC Surgery
GA 520VB
UT WOS:000271876400016
PM 19854408
ER
PT J
AU Wang, LY
Larson, EB
Sonnen, JA
Shofer, JB
McCormick, W
Bowen, JD
Montine, TJ
Li, G
AF Wang, Lucy Y.
Larson, Eric B.
Sonnen, Joshua A.
Shofer, Jane B.
McCormick, Wayne
Bowen, James D.
Montine, Thomas J.
Li, Ge
TI Blood Pressure and Brain Injury in Older Adults: Findings from a
Community-Based Autopsy Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE dementia; blood pressure; hypertension; neuropathology; autopsy
ID ALZHEIMERS-DISEASE; RISK-FACTORS; NEUROFIBRILLARY TANGLES;
CARDIOVASCULAR HEALTH; ATHEROSCLEROSIS RISK; CEREBRAL INFARCTION;
PROSPECTIVE COHORT; DEMENTIA; POPULATION; PATHOLOGY
AB OBJECTIVES
To examine correlations between blood pressure (BP) and dementia-related pathological brain changes in a community-based autopsy sample.
DESIGN
Prospective cohort study.
SETTING
A large health maintenance organization in Seattle, Washington.
PARTICIPANTS
A cohort of 250 participants aged 65 and older and cognitively normal at time of enrollment in the Adult Changes in Thought (ACT) Study and who underwent autopsy.
MEASUREMENTS
BP and history of antihypertensive treatment were taken at enrollment. A linear regression model was used to examine the relationship between BP (systolic (SBP) and diastolic (DBP)) at enrollment and pathological changes in the cerebrum (cystic macroscopic infarcts, microinfarcts, neuritic plaques, neurofibrillary tangles, and cortical Lewy bodies).
RESULTS
The presence of more than 2 microinfarcts, but not any other pathological change, was independently associated with SBP in younger participants (65-80, n=137) but not in older participants (> 80, n=91). The relative risk (RR) for more than two microinfarcts with each 10-mmHg increase in SBP was 1.15 (95% confidence interval (CI)=1.00-1.33) in the younger participants, adjusted for age at entry, sex, and time to death. This RR was particularly strong in younger participants not taking antihypertensive medications (RR=1.48, 95% CI=1.21, 1.81); significant associations were not observed in participants treated for hypertension. Findings for DBP were negative.
CONCLUSION
The association between high SBP and cerebrovascular damage in untreated older adults (65-80) suggests that adequate hypertension treatment may reduce dementia risk by minimizing microvascular injury to cerebrum.
C1 [Wang, Lucy Y.; Li, Ge] Vet Affairs Puget Sound Healthcare Syst, Mental Illness Res & Educ Clin Ctr, Seattle, WA USA.
[Wang, Lucy Y.; Shofer, Jane B.; Li, Ge] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Larson, Eric B.; McCormick, Wayne] Univ Washington, Dept Med, Seattle, WA USA.
[Sonnen, Joshua A.; Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Bowen, James D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Larson, Eric B.] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA.
RP Wang, LY (reprint author), 1660 S Columbian Way,S-116-6E, Seattle, WA 98108 USA.
EM wanglucy@u.washington.edu
RI Sonnen, 37382016/H-3738-2016
OI Sonnen, 37382016/0000-0001-9267-8705
FU National Institute on Aging [AG020020, AG006781, AG023801, AG005136];
Nancy and Buster Alvord Endowment; Department of Veterans Affairs Mental
Illness Research, Education, and Clinical Center Special Fellowship in
Advanced Psychiatry
FX We thank all of the faculty and staff who worked on this study and made
this article possible. Specifically, we gratefully acknowledge Mary Lou
Thompson, PhD, for providing statistical consultation. Conflict of
Interest: The editor in chief has reviewed the conflict of interest
checklist provided by the authors and has determined that the authors
have no financial or any other kind of personal conflicts with this
paper. This material is the result of work supported by resources from
the Veterans Affairs Puget Sound Health Care System, Seattle,
Washington. This work was supported by Grants AG020020, AG006781,
AG023801, and AG005136 from the National Institute on Aging, the Nancy
and Buster Alvord Endowment, and the Department of Veterans Affairs
Mental Illness Research, Education, and Clinical Center Special
Fellowship in Advanced Psychiatry. Author Contributions: Study concept
and design: LY Wang, JA Sonnen, TJ Montine, G Li, EB Larson, acquisition
of study participants and data: JD Bowen, W McCormick, EB Larson, JA
Sonnen, TJ Montine, analysis and interpretation of data: JB Shofer,
preparation of manuscript: LY Wang, JA Sonnen, TJ Montine, G Li, and
critical review of the manuscript: LY Wang, EB Larson, JA Sonnen, JB
Shofer, W McCormick, JD Bowen, TJ Montine, G Li. Sponsor's Role: The
funding sources had no role in the design, methodology, data analysis,
or preparation of this manuscript.
NR 46
TC 27
Z9 29
U1 1
U2 5
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD NOV
PY 2009
VL 57
IS 11
BP 1975
EP 1981
DI 10.1111/j.1532-5415.2009.02493.x
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 512KU
UT WOS:000271248500001
PM 19793158
ER
PT J
AU Hernandez, RK
Farwell, W
Cantor, MD
Lawler, EV
AF Hernandez, Rohini K.
Farwell, Wildon
Cantor, Michael D.
Lawler, Elizabeth V.
TI Cholinesterase Inhibitors and Incidence of Bradycardia in Patients with
Dementia in the Veterans Affairs New England Healthcare System
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE cholinesterase inhibitors; bradycardia; dementia; Alzheimer's disease
ID ALZHEIMERS-DISEASE; HEART-RATE; DONEPEZIL; SAFETY; SYNCOPE;
TOLERABILITY; HYPERTENSION
AB OBJECTIVES
To quantify the association between cholinesterase inhibitors (ChE-Is) and a new diagnosis of bradycardia and to evaluate the clinical significance of bradycardia.
DESIGN
Cox proportional hazards with time-dependent exposures were used to evaluate the association and examine the dose effect for donepezil and bradycardia.
SETTING
New England Veterans Affairs Healthcare System.
PARTICIPANTS
Patients with dementia who received care between January 1999 and June 2007 (N=11,328).
MEASUREMENTS
Bradycardia was defined using three methods using a combination of International Classification of Diseases, Ninth Revision, codes and recorded heart rates of less than 60 beats per minute.
RESULTS
A greater risk for bradycardia was found in patients taking any ChE-Is than in the no-treatment group (adjusted hazard ratio (HR)=1.4, 95% confidence interval (CI)=1.1-1.6). A dose-response effect was observed for donepezil, with the highest-dose group at greatest risk (HR=2.1, 95% CI=1.5-2.9). Results were consistent regardless of bradycardia definition. Patients with bradycardia were more likely to fall, experience syncope, or need a pacemaker implantation than those without.
CONCLUSION
Using a large cohort, a modestly greater risk of bradycardia was found in patients with dementia taking ChE-Is than in those not taking these drugs. In patients taking donepezil, the risk of bradycardia may increase with increasing doses. Because of the potential clinical consequences, monitoring for bradycardia may be warranted in patients with dementia treated with ChE-Is.
C1 [Hernandez, Rohini K.; Farwell, Wildon; Lawler, Elizabeth V.] VA Boston Healthcare Syst, MAVERIC, Cooperat Studies Program, Boston, MA 02130 USA.
[Hernandez, Rohini K.; Lawler, Elizabeth V.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Farwell, Wildon; Lawler, Elizabeth V.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Aging, Boston, MA 02115 USA.
[Cantor, Michael D.] Tufts Univ, Sch Med, Tufts Med Ctr, Dept Med, Boston, MA 02111 USA.
RP Lawler, EV (reprint author), VA Boston Healthcare Syst, MAVERIC, Cooperat Studies Program, 150 S Huntington Ave,151 MAV, Boston, MA 02130 USA.
EM Elizabeth.Lawler@va.gov
FU VA Healthcare System Boston; VA Cooperative Studies Program
FX This study was conducted using the facilities and resources of the VA
Healthcare System Boston and the VA Cooperative Studies Program.
Conflict of Interest: The editor in chief has reviewed the conflict of
interest checklist provided by the authors and has determined that the
authors have no financial or any other kind of personal conflicts with
this paper. Author Contributions: All authors made substantial
contributions to conception and design, acquisition of data, analysis
and interpretation of data, and preparation of the manuscript. Sponsor's
Role: Not applicable.
NR 21
TC 42
Z9 44
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD NOV
PY 2009
VL 57
IS 11
BP 1997
EP 2003
DI 10.1111/j.1532-5415.2009.02488.x
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 512KU
UT WOS:000271248500004
PM 19793162
ER
PT J
AU Min, L
Yoon, W
Mariano, J
Wenger, NS
Elliott, MN
Kamberg, C
Saliba, D
AF Min, Lillian
Yoon, William
Mariano, Jeff
Wenger, Neil S.
Elliott, Marc N.
Kamberg, Caren
Saliba, Debra
TI The Vulnerable Elders-13 Survey Predicts 5-Year Functional Decline and
Mortality Outcomes in Older Ambulatory Care Patients
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE vulnerable elder; functional decline; survival
ID QUALITY INDICATORS; ELDERLY-PATIENTS; PEOPLE; DISABILITY; COMMUNITY;
CANCER; INTERVENTION; DEMENTIA; DEATH; LIFE
AB OBJECTIVES
To test the predictive properties of the Vulnerable Elders-13 Survey (VES-13) a short tool that predicts functional decline and mortality over a 1- to 2-year follow-up interval over a 5-year interval.
DESIGN
Longitudinal evaluation with mean follow-up of 4.5 years.
SETTING
Two managed-care organizations.
PARTICIPANTS
Six hundred forty-nine community-dwelling older adults (>= 75) enrolled in the Assessing Care of Vulnerable Elders observational study who screened positive for symptoms of falls or fear of falling, bothersome urinary incontinence, or memory problems.
MEASUREMENTS
VES-13 score (range 1-10, higher score indicates worse prognosis), functional decline (decline in count of 5 activities of daily living or nursing home entry), and deaths.
RESULTS
Higher VES-13 scores were associated with greater predicted probability of death and decline in older patients over a mean observation period of 4.5 years. For each additional VES-13 point, the odds of the combined outcome of functional decline or death was 1.37 (95% confidence interval (CI)=1.25-1.50), and the area under the receiver operating curve was 0.75 (95% CI=0.71-0.80). In the Cox proportional hazards model predicting time to death, the hazard ratio was 1.23 (95% CI=1.19-1.27) per additional VES-13 point.
CONCLUSION
This study extends the utility of the VES-13 to clinical decisions that require longer-term prognostic estimates of functional status and survival.
C1 [Min, Lillian; Mariano, Jeff; Saliba, Debra] Univ Calif Los Angeles, Div Geriatr, Los Angeles, CA USA.
[Wenger, Neil S.] Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA.
[Yoon, William] Virginia Commonwealth Univ, Sch Med, Richmond, VA 23284 USA.
[Wenger, Neil S.; Elliott, Marc N.; Kamberg, Caren; Saliba, Debra] RAND Corp, Santa Monica, CA USA.
[Saliba, Debra] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Care Ctr, Los Angeles, CA USA.
[Saliba, Debra] Univ Calif Los Angeles, Jewish Homes Borun Ctr Gerontol Res, Los Angeles, CA USA.
RP Min, L (reprint author), 10945 Le Conte Ave,Suite 2339,Box 951687, Los Angeles, CA 90095 USA.
EM lmin@mednet.ucla.edu
FU Agency for Healthcare Research and Quality [R21 HS017621-01]; National
Institute on Aging (NIA)-UCLA [K12 AG001004]; Donald W. Reynolds
Foundation; University of California at Los Angeles (UCLA) Older
Americans Independence Center (Pepper Center)
FX Conflict of Interest: The editor in chief has reviewed the conflict of
interest checklist provided by the authors and has determined that the
authors have no financial or any other kind of personal conflicts with
this paper. Dr. Min is supported by grants from the Agency for
Healthcare Research and Quality (R21 HS017621-01) and National Institute
on Aging (NIA)-UCLA (K12 AG001004). Mr. Yoon was a NIA/American
Federation for Aging Research and Lillian R. Gleitsman Medical Student
Training in Aging Research Program Scholar in 2008. Dr. Mariano was
supported by a Faculty Development to Advance Geriatric Education award
from the Donald W. Reynolds Foundation. This project also received
support from the University of California at Los Angeles (UCLA) Older
Americans Independence Center (Pepper Center). This paper was presented
as an abstract at the 2009 American Geriatrics Society Scientific
Meeting. Author Contributions: Lillian Min, Neil S. Wenger, and Debra
Saliba: concept and design, acquisition of subjects and data, analysis
and interpretation of data, and preparation of manuscript. William Yoon:
acquisition of subjects and data, analysis and interpretation of data,
and preparation of manuscript. Jeff Mariano: concept and design,
acquisition of subjects and data, and preparation of manuscript. Marc
Elliot: concept and design, analysis and interpretation of data, and
preparation of manuscript. Caren Kamberg: concept and design,
acquisition of subjects and data. Sponsor's Role: Pfizer Inc. supported
the recruitment of the original ACOVE-2 cohort but had no role in
obtaining outcomes data, data analysis, or preparation of this
manuscript. The UCLA Older Americans Independence Center (Pepper Center)
provided support for statistical analysis.
NR 22
TC 51
Z9 53
U1 1
U2 7
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD NOV
PY 2009
VL 57
IS 11
BP 2070
EP 2076
DI 10.1111/j.1532-5415.2009.02497.x
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 512KU
UT WOS:000271248500013
PM 19793154
ER
PT J
AU Kirk, JB
Goetz, MB
AF Kirk, Jason B.
Goetz, Matthew Bidwell
TI Human Immunodeficiency Virus in an Aging Population, a Complication of
Success
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE human immunodeficiency virus; acquired immunodeficiency syndrome;
antiretroviral therapy; immune activation
ID HIV-INFECTED PATIENTS; ACTIVE ANTIRETROVIRAL THERAPY;
REVERSE-TRANSCRIPTASE INHIBITORS; MULTICENTER AIDS COHORT; HEALTH-CARE
SETTINGS; D-A-D; MYOCARDIAL-INFARCTION; MEDICINE ASSOCIATION; LIFE
EXPECTANCY; PATIENTS OLDER
AB The proportion of human immunodeficiency virus (HIV)-infected patients aged 50 and older has greatly increased since the beginning of the epidemic, particularly since 1996, when combination antiretroviral therapy became available. By 2015, 50% of HIV-infected individuals in the United States are likely to be aged 50 and older. The rate of progression of untreated HIV disease, response to therapy, and complicating effects of comorbidities differ in older and younger patients. Older untreated patients with HIV demonstrate faster rates of CD4+ cell loss and more rapid progression to acquired immunodeficiency syndrome (AIDS) and death than younger individuals. Synergistic deleterious effects of chronic immune activation on the course of HIV infection with the immune senescence of aging may promote this accelerated course. Despite the increasing prevalence in older patients and cost-effectiveness analyses that favor HIV testing, older patients are less likely to be routinely evaluated for HIV infection. Consequently, when diagnosed, older patients have more-advanced disease than do younger patients and, upon presentation with AIDS-defining conditions, are less likely to receive timely appropriate therapy. The treatment of older HIV-infected patients is complicated by preexisting comorbid conditions, including cardiovascular, hepatic, and metabolic complications, which in turn may be exacerbated by the effects of HIV infection per se, modest immunodeficiency (i.e., at CD4+ counts > 350 cells/mu L), and the metabolic and other adverse effects of combination antiretroviral therapy. Nevertheless, older patients derive substantial benefit from combination antiretroviral therapy despite having less of an immunological response than expected given their adherence to therapy and excellent virological responses.
C1 VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, Dept Med, Los Angeles, CA 90073 USA.
Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
RP Goetz, MB (reprint author), VA Greater Los Angeles Healthcare Syst, Infect Dis Sect 111 F, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM matthew.goetz@va.gov
OI Goetz, Matthew/0000-0003-4542-992X
NR 69
TC 85
Z9 86
U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD NOV
PY 2009
VL 57
IS 11
BP 2129
EP 2138
DI 10.1111/j.1532-5415.2009.02494.x
PG 10
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 512KU
UT WOS:000271248500022
PM 19793157
ER
PT J
AU Braddy, KK
Imam, SN
Palla, KR
Lee, TA
AF Braddy, Kathryn K.
Imam, Syed N.
Palla, Kavita R.
Lee, Todd A.
TI Vitamin D Deficiency/Insufficiency Practice Patterns in a Veterans
Health Administration Long-Term Care Population: A Retrospective
Analysis
SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION
LA English
DT Article
DE Vitamin D; long-term care; vitamin D insufficiency; vitamin D deficiency
ID D DEFICIENCY; SECONDARY HYPERPARATHYROIDISM; D INADEQUACY; PREVALENCE;
METAANALYSIS; FRACTURES
AB Objectives: To evaluate the prevalence of vitamin D deficiency/insufficiency in long-term care patients at a Veterans Health Administration (VHA) hospital and to assess treatment and follow-up of low vitamin D levels.
Design: Observational cohort study.
Setting: VA hospital extended care center (ECC).
Participants: 2218 ECC patients between January 2001 and December 2006 were screened.
Measurement: Serum 25-hydroxyvitamin D (25[OH]D) level, vitamin D therapy regimen, time to follow-up, documented adverse event to vitamin D therapy.
Results: Of 2218 patients admitted to the ECC during the study period, 229 (10%) had a vitamin D level measured. Among these 229 patients, 49% were vitamin D sufficient (25[OH]D >= 30 ng/mL), 14% were insufficient (25[OH]D = 21-29 ng/mL), and 37% were deficient (25[OH]D <= 20 ng/mL). Sixty-nine percent of patients with low vitamin D levels received some form of vitamin D therapy, whereas 43% received treatment as well as follow-up evaluation of vitamin D status within 3 months. Only 13% received a formulation of vitamin D appropriate for the severity of their deficiency/insufficiency with concurrent calcium supplementation and had a repeat vitamin D level within 3 months.
Conclusion: Vitamin D levels were measured infrequently in long-term care patients. Among those monitored, the rate of vitamin D deficiency/insufficiency is high. Few patients with low vitamin D status received proper treatment and follow-up. These data support the need to educate physicians regarding the high prevalence of vitamin D insufficiency/deficiency among long-term care patients to ensure that patients with low vitamin D levels are identified and treated appropriately. (J Am Med Dir Assoc 2009; 10: 653-657)
C1 [Braddy, Kathryn K.] VA Maryland Hlth Care Syst, Baltimore, MD 21201 USA.
[Braddy, Kathryn K.; Imam, Syed N.; Palla, Kavita R.; Lee, Todd A.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA.
RP Braddy, KK (reprint author), VA Maryland Hlth Care Syst, 10 N Greene St,119, Baltimore, MD 21201 USA.
EM kathryn.kuhn@va.gov
NR 13
TC 44
Z9 44
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-8610
J9 J AM MED DIR ASSOC
JI J. Am. Med. Dir. Assoc.
PD NOV
PY 2009
VL 10
IS 9
BP 653
EP 657
DI 10.1016/j.jamda.2009.08.010
PG 5
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 524NQ
UT WOS:000272150400012
PM 19883889
ER
PT J
AU Hua, LQ
Walker, JD
Adams, MS
Marshall, JE
Picard, MH
Passeri, JJ
AF Hua, Lanqi
Walker, Jennifer D.
Adams, Mark S.
Marshall, Jane E.
Picard, Michael H.
Passeri, Jonathan J.
TI Unusual Position of a Prosthetic Mitral Valve
SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
LA English
DT Article
DE Calcified mitral annulus; Mitral regurgitation; Prosthetic mitral valve
ID EXTENSIVE CALCIFICATION; ANNULUS; ANULUS
AB Extensive calcification of the mitral annulus in patients who require mitral valvereplacement presents a significant challenge to the surgeon. Several techniques, includingdebridement of the calcium, reconstruction of the annulus, and insertion of the prosthesis in a locationother than the annulus, have been used in such patients. We report the echocardiographictechniques used to evaluate the case of a woman with an unusually positioned prosthetic mitralvalve. (J Am Soc Echocardiogr 2009;22:1309.e7-1309.e9.)
C1 [Hua, Lanqi] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA.
RP Hua, LQ (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St 260, Boston, MA 02114 USA.
EM lhua1@partners.org
OI Picard, Michael/0000-0002-9264-3243
NR 8
TC 0
Z9 0
U1 0
U2 18
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0894-7317
J9 J AM SOC ECHOCARDIOG
JI J. Am. Soc. Echocardiogr.
PD NOV
PY 2009
VL 22
IS 11
AR 1309.e7
DI 10.1016/j.echo.2009.05.025
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 513TL
UT WOS:000271346300019
PM 19647402
ER
PT J
AU Smith, RG
Rubin, SA
Ellestad, MH
AF Smith, Ryan G.
Rubin, Stanley A.
Ellestad, Myrvin H.
TI Exercise hypertension: an adverse prognosis?
SO JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION
LA English
DT Review
DE Exercise hypertension; prognosis; hypertension; cardiovascular events
ID BLOOD-PRESSURE RESPONSE; CORONARY-ARTERY-DISEASE; MIDDLE-AGED MEN;
LEFT-VENTRICULAR MASS; MYOCARDIAL-INFARCTION; CARDIOVASCULAR MORTALITY;
RISK; INCREASE
AB We sought to clarify the prognostic importance of an "exaggerated" or "hypertensive" systolic blood pressure response to exercise during an exercise test. Studies evaluating the prognosis for cardiovascular events and cardiovascular mortality in those with hypertension during exercise testing were systematically reviewed. Fourteen studies were identified. Six studies were of healthy volunteers or hypertensives. Eight studies were in subjects with known or suspected heart disease. Without established heart disease, exercise hypertension predicted cardiovascular events and cardiovascular death. However, two of the six studies included a multivariate analysis; both demonstrated no independent association. Studies in subjects with known or suspected heart disease demonstrated that exercise hypertension predicted fewer cardiac events and lesser mortality or, after multivariate adjustment, no associated risk. In a healthy population, a higher exercise blood pressure may indicate hypertension or prehypertension, instead of normal vascular function, and an associated long-term adverse prognosis. In a population with a high burden of heart disease, the highest risk subjects with the most extensive cardiac disease may not be capable of generating pressure or workload to allow the manifestation of exercise systolic hypertension. By comparison, therefore, those with exercise hypertension have a better prognosis. J Am Soc Hypertens 2009;3(6):366-373. (C) 2009 American Society of Hypertension. All rights reserved.
C1 [Smith, Ryan G.; Rubin, Stanley A.] Univ Calif Los Angeles, Sch Med Los Angeles, Los Angeles, CA 90024 USA.
[Smith, Ryan G.; Rubin, Stanley A.] Greater Los Angeles, Vet Adm, Los Angeles, CA USA.
[Ellestad, Myrvin H.] UCI Sch Med, Irvine, CA USA.
[Ellestad, Myrvin H.] Long Beach Mem Hosp Med Ctr, Long Beach, CA USA.
RP Smith, RG (reprint author), VA Greater Los Angeles Healthcare Syst, Div Cardiol 111E, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM smithryang@ucla.edu
NR 28
TC 14
Z9 15
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1933-1711
J9 J AM SOC HYPERTENS
JI J. Am. Soc. Hypertens.
PD NOV-DEC
PY 2009
VL 3
IS 6
BP 366
EP 373
DI 10.1016/j.jash.2009.10.003
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 589ZV
UT WOS:000277193700003
PM 20409979
ER
PT J
AU Palevsky, PM
Weisbord, SD
AF Palevsky, Paul M.
Weisbord, Steven D.
TI Critical Care Nephrology: It's Not Just Acute Kidney Injury
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Editorial Material
ID STAGE RENAL-DISEASE; CLINICAL-FEATURES; UNIT; DIALYSIS; FAILURE
C1 [Palevsky, Paul M.; Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA.
[Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA.
[Palevsky, Paul M.; Weisbord, Steven D.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA.
RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Room 7E123 111F-U,Univ Dr, Pittsburgh, PA 15240 USA.
EM palevsky@pitt.edu
OI Palevsky, Paul/0000-0002-7334-5400
NR 11
TC 0
Z9 0
U1 0
U2 1
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 NOV
PY 2009
VL 20
IS 11
BP 2281
EP 2282
DI 10.1681/ASN.2009080875
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 526BD
UT WOS:000272261600003
PM 19797471
ER
PT J
AU Thadhani, R
AF Thadhani, Ravi
TI Is Calcitriol Life-Protective for Patients with Chronic Kidney Disease?
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID VITAMIN-D DEFICIENCY; STAGE RENAL-DISEASE; MAINTENANCE
HEMODIALYSIS-PATIENTS; CORONARY-HEART-DISEASE; D-RECEPTOR ACTIVATORS;
VASCULAR CALCIFICATION; SECONDARY HYPERPARATHYROIDISM; INTRAVENOUS
CALCITRIOL; DIALYSIS PATIENTS; KNOCKOUT MICE
C1 Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Med,Renal Unit, Boston, MA 02114 USA.
RP Thadhani, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Med,Renal Unit, Bulfinch 127,55 Fruit St, Boston, MA 02114 USA.
EM thadhani.ravi@mgh.harvard.edu
FU National Institutes of Health [DK 071674, HL 093954, DK 084974]
FX R.T. is supported by Grants DK 071674, HL 093954, and DK 084974 from the
National Institutes of Health.
NR 81
TC 6
Z9 6
U1 0
U2 2
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2009
VL 20
IS 11
BP 2285
EP 2290
DI 10.1681/ASN.2009050494
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 526BD
UT WOS:000272261600005
PM 19679671
ER
PT J
AU Wang, WC
Chen, HJ
Tseng, YH
Lai, YC
AF Wang, Wen-Chung
Chen, Hui-Ju
Tseng, Yu-Hua
Lai, Yen-Chein
TI Identification of Somatic Mutations in the von Hippel-Lindau (VHL) Gene
in a Patient With Renal Cell Carcinoma
SO JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION
LA English
DT Article
DE mutation; renal cell carcinoma; Taiwan; von Hippel-Lindau gene
ID TUMOR-SUPPRESSOR GENE; GERMLINE MUTATIONS; DISEASE; DELETIONS; RFLP
AB One of the known causal molecular events in renal cell carcinoma is somatic mutation in the von Hippel-Lindau (VHL) gene. Our study describes a 51-year-old Taiwanese man who had bilateral renal cell carcinoma. The patient underwent radical nephrectomy without postoperative chemotherapy or radiotherapy, and is still alive after renal transplantation without tumor recurrence after > 5 years. To clarify his predisposition for bilateral tumors, we performed molecular genetic analysis of the VHL gene in this study. Polymerase chain reaction-single-strand conformation polymorphism and direct sequencing were performed on DNA of blood samples and paraffin-embedded tumor specimens from this patient. DNA from peripheral blood lymphocytes tested negative for germline mutations. However, there were two heterozygous alleles in the promoter and 3' untranslated regions of this gene. Nonetheless, the DNA from his tumors showed loss of heterozygosity (LOH) in these two loci. In addition to the LOH, we identified some different somatic mutations in his tumor tissues: C287T and G460A in the right-sided tumor, and G244A and C390A in the left-sided tumor. The possible roles of these genetic polymorphisms and point mutations in his renal tumorigenesis are discussed. This report provides new insights into renal cell carcinoma that result from VHL gene alterations in Taiwan. [J Formos Med Assoc 2009; 108(11):886-893]
C1 [Chen, Hui-Ju; Lai, Yen-Chein] Chung Shan Med Univ, Sch Med Lab & Biotechnol, Taichung 402, Taiwan.
[Wang, Wen-Chung] Jen Ai Hosp, Dept Obstet & Gynecol, Taichung, Taiwan.
[Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res,Dept Med, Boston, MA 02115 USA.
RP Lai, YC (reprint author), Chung Shan Med Univ, Sch Med Lab & Biotechnol, 110,Sect 1,Chien Kuo N Rd, Taichung 402, Taiwan.
EM yenchein@csmu.edu.tw
NR 25
TC 3
Z9 3
U1 0
U2 1
PU ELSEVIER SINGAPORE PTE LTD
PI SINGAPORE
PA 3 KILLINEY ROAD 08-01, WINSLAND HOUSE 1, SINGAPORE, 239519, SINGAPORE
SN 0929-6646
J9 J FORMOS MED ASSOC
JI J. Formos. Med. Assoc.
PD NOV
PY 2009
VL 108
IS 11
BP 886
EP 893
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 535HK
UT WOS:000272957800010
PM 19933033
ER
PT J
AU Vasterling, JJ
Verfaellie, M
AF Vasterling, Jennifer J.
Verfaellie, Mieke
TI Posttraumatic stress disorder: A neurocognitive perspective INTRODUCTION
SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
LA English
DT Editorial Material
ID PREFRONTAL CORTEX; MEMORY; PTSD; VETERANS; VULNERABILITY; AMYGDALA;
VOLUME; SELF
C1 [Vasterling, Jennifer J.] Psychol Serv, Boston, MA 02130 USA.
[Vasterling, Jennifer J.] VA Boston Healthcare Syst, VA Natl Ctr PTSD, Boston, MA USA.
[Vasterling, Jennifer J.; Verfaellie, Mieke] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
[Verfaellie, Mieke] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA USA.
[Verfaellie, Mieke] VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA.
RP Vasterling, JJ (reprint author), Psychol Serv, 150 S Huntington Ave, Boston, MA 02130 USA.
EM jennifer.vasterling@va.gov; verf@bu.edu
NR 30
TC 19
Z9 19
U1 0
U2 4
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1355-6177
J9 J INT NEUROPSYCH SOC
JI J. Int. Neuropsychol. Soc.
PD NOV
PY 2009
VL 15
IS 6
BP 826
EP 829
DI 10.1017/S1355617709990683
PG 4
WC Clinical Neurology; Neurosciences; Psychiatry; Psychology
SC Neurosciences & Neurology; Psychiatry; Psychology
GA 523ZV
UT WOS:000272114500002
PM 19891816
ER
PT J
AU Woodward, SH
Kaloupek, DG
Grande, LJ
Stegman, WK
Kutter, CJ
Leskin, L
Prestel, R
Schaer, M
Reiss, AL
Eliez, S
AF Woodward, Steven H.
Kaloupek, Danny G.
Grande, Laura J.
Stegman, Wendy K.
Kutter, Catherine J.
Leskin, Loraine
Prestel, Rebecca
Schaer, Marie
Reiss, Allan L.
Eliez, Stephan
TI Hippocampal volume and declarative memory function in combat-related
PTSD
SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
LA English
DT Article
DE PTSD; Memory; Cognition; Hippocampus; Neocortex; Magnetic resonance
imaging
ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; SURFACE-BASED
ANALYSIS; HUMAN CEREBRAL-CORTEX; CORTICAL SURFACE; ALZHEIMERS-DISEASE;
COORDINATE SYSTEM; VERBAL MEMORY; AREA CA3; MRI
AB The proposition that declarative memory deficits are systematically related to smaller hippocampal Volume was tested in a relatively large sample (n = 95) of U.S. military veterans with and without combat-related posttraumatic stress disorder. This correlative analysis was extended by including multiple measures of verbal and visual declarative memory and multiple memory-relevant regional brain volumes that had been shown to exhibit main effects of PTSD in prior work. Small-to-moderate effects were observed on verbal declarative memory in line with a recent meta-analysis; nevertheless, little or no evidence of systematic linear covariation between memory measures and brain Volumes was observed. (JINS, 2009, 15, 830-839.)
C1 [Woodward, Steven H.] VA Palo Alto Hlth Care Syst, Disseminat & Training Div, Natl Ctr PTSD, Palo Alto, CA 94304 USA.
[Kaloupek, Danny G.; Prestel, Rebecca] VA New England Hlth Care Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA.
[Kaloupek, Danny G.] Boston Univ, Sch Med, Div Psychiat, Boston, MA 02118 USA.
[Grande, Laura J.] VA New England Hlth Care Syst, Psychol Serv, Boston, MA USA.
[Stegman, Wendy K.] Earth Syst, Melbourne, Vic, Australia.
[Kutter, Catherine J.] White River Junct Vet Affairs Med Ctr, Psychol Serv, White River Jct, VT USA.
[Leskin, Loraine] VA Greater Los Angeles Hlth Care System, Psychol Serv, Los Angeles, CA USA.
[Schaer, Marie; Eliez, Stephan] Univ Geneva, Dept Psychiat, Geneva, Switzerland.
[Schaer, Marie] Swiss Fed Inst Technol, Signal Proc Lab, CH-1015 Lausanne, Switzerland.
[Reiss, Allan L.] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA.
RP Woodward, SH (reprint author), VA Palo Alto Hlth Care Syst, Disseminat & Training Div, Natl Ctr PTSD, Mail Code 334 PTSD,3801 Miranda Ave, Palo Alto, CA 94304 USA.
EM steve.woodward@va.gov
OI Kaloupek, Danny/0000-0002-0795-593X
FU National Institute on Alcohol Abuse and Alcoholism [K23AA13149]; Swiss
National Fund for Research Career Development [32-63135-00,
PP00B-102864/1]
FX Major funding for this work was provided under a VA/DoD assistance
agreement to Drs. Woodward and Kaloupek from the U.S. Army Medical
Research and Materiel Command (DoD) administered through the Institute
for Medical Research (VA). Special thanks are due to Stephen Grate and
Lori Moll who facilitated the necessary arrangements at those
institutions. Support was also provided by a National Institute on
Alcohol Abuse and Alcoholism award (K23AA13149) and a VA Career
Development Award to Dr. Streeter. Support for Dr. Eliez was provided by
the Swiss National Fund for Research Career Development Award
(32-63135-00 and PP00B-102864/1). The authors wish to thank the Research
Services of the VA Palo Alto and VA Boston Healthcare Systems for their
support. Important institutional and technical support was also provided
by the following individuals: at the VA Palo Alto HCS, John E. Drace,
Patricia Spezia, Carla Ambriz, and Gary E. Gold; at the VA Boston HCS,
Chris C. Streeter, Kelly Teresi, Frederick Kanter, Steven Blank, Susan
Proctor, and Erica Stone; at Stanford University, Thomas J. Brosnan,
Anil Patwardhan, and Eric Schmitt; at McLean Hospital, Perry Renshaw,
Blaise Frederick, Rosemond Villafuerte, Ann Smith, and Eileen Connolly;
and at the Defense Manpower Database Command, Michael A. Dove. The
authors are also grateful for the guidance provided by Kelvin O. Lim,
Stephen E. Lindley, Craig Rosen, and H. Stefan Bracha. The
neuropsychological assessment results and relations to neuroimaging have
not been published either electronically or in print. No authors have
conflicts of interest in relation to the findings published in this
article.
NR 69
TC 19
Z9 19
U1 3
U2 8
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1355-6177
J9 J INT NEUROPSYCH SOC
JI J. Int. Neuropsychol. Soc.
PD NOV
PY 2009
VL 15
IS 6
BP 830
EP 839
DI 10.1017/S1355617709990476
PG 10
WC Clinical Neurology; Neurosciences; Psychiatry; Psychology
SC Neurosciences & Neurology; Psychiatry; Psychology
GA 523ZV
UT WOS:000272114500003
PM 19703322
ER
PT J
AU Marx, BP
Doron-Lamarca, S
Proctor, SP
Vasterling, JJ
AF Marx, Brian P.
Doron-Lamarca, Susan
Proctor, Susan P.
Vasterling, Jennifer J.
TI The influence of pre-deployment neurocognitive functioning on
post-deployment PTSD symptom outcomes among Iraq-deployed Army soldiers
SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
LA English
DT Article
DE Visual memory; Verbal memory; Attention; Neurocognitive functioning;
PTSD; Combat
ID POSTTRAUMATIC-STRESS-DISORDER; GULF-WAR VETERANS; PREFRONTAL CORTEX;
COGNITIVE-ABILITY; VIETNAM VETERANS; RISK-FACTORS; AUTOBIOGRAPHICAL
MEMORY; PSYCHOMETRIC PROPERTIES; HIPPOCAMPAL VOLUME; TWINS DISCORDANT
AB This study evaluated associations between pre-deployment neurocognitive performance and post-deployment posttraumatic stress disorder (PTSD) symptoms in a sample of deployed active duty Army soldiers. As part of a larger longitudinal study, each participant completed baseline measures of memory, executive attention, and response inhibition, and baseline and post-deployment self-report measures of PTSD symptom severity. Data were subjected to multiple regression analyses that examined associations between baseline neurocognitive performances and longitudinal PTSD symptom outcome. Results revealed that pre-trauma immediate recall Of Visual information was associated with post-deployment PTSD symptom severity, even after controlling for pre-deployment PTSD symptom levels, combat intensity, age, gender, and test-retest interval. There was also an interaction between pre-deployment PTSD symptom severity and pre-deployment immediate visual recall and Verbal learning, indicating that neurocognitive performances were more strongly (and negatively) associated with residualized post-deployment PTSD symptoms at higher levels of pre-deployment PTSD symptoms. These findings highlight the potential role of pre-trauma neurocognitive functioning in moderating the effects of trauma exposure on PTSD symptoms. (JINS, 2009 15, 840-852.)
C1 [Marx, Brian P.; Doron-Lamarca, Susan; Vasterling, Jennifer J.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA.
[Marx, Brian P.; Doron-Lamarca, Susan; Proctor, Susan P.; Vasterling, Jennifer J.] VA Boston Healthcare Syst, Dept Psychol, Boston, MA 02130 USA.
[Marx, Brian P.; Doron-Lamarca, Susan; Vasterling, Jennifer J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
[Proctor, Susan P.] USA, Environm Med Res Inst, Mil Performance Div, Natick, MA 01760 USA.
[Proctor, Susan P.] Boston Univ, Sch Med, Dept Environm Hlth, Boston, MA 02118 USA.
RP Marx, BP (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, 150 S Huntington Ave, Boston, MA 02130 USA.
EM brain.marx@va.gov
FU U.S. Army Medical Research and Materiel Command [17-03-0020, A-11815];
VA Clinical Sciences Research and Development; South Central Mental
Illness Research, Education, and Clinical Center; U.S. Army Research
Institute for Environmental Medicine; U.S. Army Medical Research
Acquisition Activity [DAMD 17-03-0020]
FX This work was Supported by the U.S. Army Medical Research and Materiel
Command (DAMD 17-03-0020; HSRRB Log No. A-11815) and VA Clinical
Sciences Research and Development awards. The work also was Supported in
part by resources provided by the South Central Mental Illness Research,
Education, and Clinical Center and U.S. Army Research Institute for
Environmental Medicine. Some of the work was completed at the Southeast
Louisiana Veterans Healthcare System and Tulane University. The U.S.
Army Medical Research Acquisition Activity (Fort Detrick, MD) is the
awarding and administering acquisition office for DAMD 17-03-0020
NR 88
TC 31
Z9 31
U1 3
U2 13
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1355-6177
J9 J INT NEUROPSYCH SOC
JI J. Int. Neuropsychol. Soc.
PD NOV
PY 2009
VL 15
IS 6
BP 840
EP 852
DI 10.1017/S1355617709990488
PG 13
WC Clinical Neurology; Neurosciences; Psychiatry; Psychology
SC Neurosciences & Neurology; Psychiatry; Psychology
GA 523ZV
UT WOS:000272114500004
PM 19891817
ER
PT J
AU Samuelson, KW
Neylan, TC
Lenoci, M
Metzler, TJ
Cardenas, V
Weiner, MW
Marmar, CR
AF Samuelson, Kristin W.
Neylan, Thomas C.
Lenoci, Maryanne
Metzler, Thomas J.
Cardenas, Valerie
Weiner, Michael W.
Marmar, Charles R.
TI Longitudinal effects of PTSD on memory functioning
SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
LA English
DT Article
DE Veterans; Neuropsychology; Verbal learning; Delayed memory; Immediate
recall; Aging
ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE;
SHORT-TERM-MEMORY; HOLOCAUST SURVIVORS; DECLARATIVE MEMORY; COMBAT
VETERANS; PERFORMANCE; ATTENTION; WOMEN; DEFICITS
AB Numerous Studies have demonstrated explicit and working memory deficits related to posttraumatic stress disorder (PTSD), but few have addressed longitudinal changes in memory functioning. There is some evidence to Suggest in interactive effect of PTSD and aging on verbal memory decline in Holocaust Survivors (Yehuda et al., 2006). However. the longitudinal trajectory of neuropsychologgical functioning has not been investigated in Vietnam veterans, a younger but substantial population of aging trauma Survivors. We administered tests 017 Visual and verbal memory, and working memory to derive different dependent measures in veterans between the ages of 41 and 63, the majority of whom served in the Vietnam War. Twenty-five veterans with PTSD and 22 veterans without PTSD were assessed over two time points (mean age at follow-up = 54.0; mean inter-test interval = 34 months). The PTSD+group, consisting of veterans with chronic, primarily combat-related PTSD, did not show a significant change in PTSD symptoms over time. Compared to veterans without PTSD. veterans with PTSD showed it greater decline in delayed facial recognition only, and this decline was extremely Subtle. (JINS, 2009, 15, 853-861.)
C1 [Samuelson, Kristin W.] Alliant Int Univ, Calif Sch Profess Psychol, San Francisco, CA 94133 USA.
[Samuelson, Kristin W.; Neylan, Thomas C.; Lenoci, Maryanne; Metzler, Thomas J.; Cardenas, Valerie; Weiner, Michael W.; Marmar, Charles R.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA.
[Neylan, Thomas C.; Metzler, Thomas J.; Weiner, Michael W.; Marmar, Charles R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Cardenas, Valerie; Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA.
RP Samuelson, KW (reprint author), Alliant Int Univ, Calif Sch Profess Psychol, 1 Beach St,Suite 100, San Francisco, CA 94133 USA.
EM ksamuelson@alliant.edu
FU Sierra Pacific (VISN 21) Mental Illness Research, Education, and
Clinical Center (MIRECC); Department of Defense
FX This study was supported by the Sierra Pacific (VISN 21) Mental Illness
Research, Education, and Clinical Center (MIRECC) and the Department of
Defense. The authors do not have any conflicts of interest that might be
interpreted as influencing the research.
NR 48
TC 13
Z9 14
U1 1
U2 11
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1355-6177
J9 J INT NEUROPSYCH SOC
JI J. Int. Neuropsychol. Soc.
PD NOV
PY 2009
VL 15
IS 6
BP 853
EP 861
DI 10.1017/S1355617709990282
PG 9
WC Clinical Neurology; Neurosciences; Psychiatry; Psychology
SC Neurosciences & Neurology; Psychiatry; Psychology
GA 523ZV
UT WOS:000272114500005
PM 19703319
ER
PT J
AU Benge, JF
Perrier, ND
Massman, PJ
Meyers, CA
Kayl, AE
Wefel, JS
AF Benge, Jared F.
Perrier, Nancy D.
Massman, Paul J.
Meyers, Christina A.
Kayl, Anne E.
Wefel, Jeffrey S.
TI Cognitive and affective sequelae of primary hyperparathyroidism and
early response to parathyroidectomy
SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
LA English
DT Article
DE Hyperparathyroidism; Parathyroidectomy; Cognition; Depression;
Neuropsychology; Surgery
ID ASYMPTOMATIC PRIMARY HYPERPARATHYROIDISM; TEST-RETEST RELIABILITY;
NORMATIVE DATA; HYPER-PARATHYROIDISM; HORMONE; BRAIN; DYSFUNCTION;
EDUCATION; BEHAVIOR; DEFICITS
AB Cognitive and affective complaints are common in patients with primary hyperparathyroidism (PHPT), but few studies have used psychometric testing to document these symptoms and their response to parathyroidectomy. The current Study sought to clarify the nature of cognitive and affective impairments in PHPT and changes postparathyroidectomy. One hundred eleven patients with PHPT underwent neuropsychological evaluation prior to parathyroidectomy with 68 returning for an early postsurgical evaluation. Changes in cognition were assessed using practice effect corrected reliable change indices. Biochemical and anesthesia variables were compared between groups who improved and declined. In a subset of patients, assessment revealed a significant pattern of cognitive slowing, reductions in psychomotor speed, memory impairment, and depression prior to parathyroidectomy. Postsurgical evaluations revealed a trend for improvements on timed tests and depression but a decline in memory. Older patients responded less well to surgical intervention, as did patients who experienced more dramatic changes in biochemical status following surgery. Cognitive changes early postparathyroidectomy are characterized by improved information processing speed and decline in verbal memory, with younger patients more likely to recover during this acute phase. The need for longer-term follow-up studies and increasing utilization of neuropsychological assessments in this population are discussed. (JINS, 2009, 15, 1002-1011.)
C1 [Wefel, Jeffrey S.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Unit 431, Sect Neuropsychol, Houston, TX 77230 USA.
[Benge, Jared F.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA.
[Benge, Jared F.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
[Perrier, Nancy D.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77230 USA.
[Massman, Paul J.] Univ Houston, Dept Psychol, Houston, TX USA.
RP Wefel, JS (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Unit 431, Sect Neuropsychol, POB 301402, Houston, TX 77230 USA.
EM jwefel@mdanderson.org
FU American Geriatric Society, Jahnigan
FX No pharmaceutical or corporate funding was used in the preparation of
this manuscript or collection of data. Support was in part funded by the
American Geriatric Society, Jahnigan Scholars grant. Portions of this
work were presented previously as a poster at the 36th Annual Meeting of
the International Neuropsychological Society, Waikoloa, HI.
NR 51
TC 16
Z9 17
U1 1
U2 3
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1355-6177
J9 J INT NEUROPSYCH SOC
JI J. Int. Neuropsychol. Soc.
PD NOV
PY 2009
VL 15
IS 6
BP 1002
EP 1011
DI 10.1017/S1355617709990695
PG 10
WC Clinical Neurology; Neurosciences; Psychiatry; Psychology
SC Neurosciences & Neurology; Psychiatry; Psychology
GA 523ZV
UT WOS:000272114500022
PM 19807940
ER
PT J
AU Burstein, HJ
AF Burstein, Harold J.
TI Screening Contretemps: The Real Issue in the Mammogram Guideline Debate
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Editorial Material
C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA USA.
[Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU JONES AND BARTLETT PUBLISHERS
PI SUDBURY
PA 40 TALL PINE DR, SUDBURY, MA 01776 USA
SN 1540-1405
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD NOV
PY 2009
VL 7
IS 10
BP 1039
EP 1040
PG 2
WC Oncology
SC Oncology
GA 527SH
UT WOS:000272386300002
PM 19930972
ER
PT J
AU Bevers, TB
Anderson, BO
Bonaccio, E
Buys, S
Daly, MB
Dempsey, PJ
Farrar, WB
Fleming, I
Garber, JE
Harris, RE
Heerdt, AS
Helvie, M
Huff, JG
Khakpour, N
Khan, SA
Krontiras, H
Lyman, G
Rafferty, E
Shaw, S
Smith, ML
Tsangaris, TN
Williams, C
Yaneeklov, T
AF Bevers, Therese B.
Anderson, Benjamin O.
Bonaccio, Ermelinda
Buys, Sandra
Daly, Mary B.
Dempsey, Peter J.
Farrar, William B.
Fleming, Irving
Garber, Judy E.
Harris, Randall E.
Heerdt, Alexandra S.
Helvie, Mark
Huff, John G.
Khakpour, Nazanin
Khan, Seema A.
Krontiras, Helen
Lyman, Gary
Rafferty, Elizabeth
Shaw, Sara
Smith, Mary Lou
Tsangaris, Theodore N.
Williams, Cheryl
Yaneeklov, Thomas
TI Breast Cancer Screening and Diagnosis
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Review
DE NCCN Clinical Practice Guidelines; breast carcinoma; carcinoma in situ;
screening; diagnosis; mammography; risk assessment; biopsy; hyperplasia
ID CORE-NEEDLE-BIOPSY; FIELD DIGITAL MAMMOGRAPHY; CARCINOMA IN-SITU;
ATYPICAL LOBULAR HYPERPLASIA; CHILDHOOD HODGKINS-DISEASE; BRCA2 MUTATION
CARRIERS; HIGH FAMILIAL RISK; NIPPLE DISCHARGE; FILM MAMMOGRAPHY;
FOLLOW-UP
C1 [Bevers, Therese B.; Dempsey, Peter J.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA.
[Anderson, Benjamin O.] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA.
[Bonaccio, Ermelinda] Roswell Pk Canc Inst, Buffalo, NY USA.
[Buys, Sandra] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
[Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA USA.
[Farrar, William B.; Harris, Randall E.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA.
[Fleming, Irving] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA.
[Garber, Judy E.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA.
[Heerdt, Alexandra S.] Mem Sloan Kettering Canc Ctr, New York, NY USA.
[Helvie, Mark] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Huff, John G.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Khakpour, Nazanin] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Khan, Seema A.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA.
[Krontiras, Helen] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL USA.
[Lyman, Gary] Duke Comprehens Canc Ctr, Durham, NC 27705 USA.
[Rafferty, Elizabeth] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Shaw, Sara] City Hope Comprehens Canc Ctr, Duarte, CA 91010 USA.
[Williams, Cheryl] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA.
[Yaneeklov, Thomas] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
RP Bevers, TB (reprint author), Univ Texas MD Anderson Canc Ctr, Houston, TX USA.
NR 108
TC 137
Z9 143
U1 0
U2 11
PU JONES AND BARTLETT PUBLISHERS
PI SUDBURY
PA 40 TALL PINE DR, SUDBURY, MA 01776 USA
SN 1540-1405
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD NOV
PY 2009
VL 7
IS 10
BP 1060
EP 1096
PG 37
WC Oncology
SC Oncology
GA 527SH
UT WOS:000272386300005
PM 19930975
ER
PT J
AU Ng, AK
Travis, LB
AF Ng, Andrea K.
Travis, Lois B.
TI Radiation Therapy and Breast Cancer Risk
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Article
DE Breast cancer; second malignant neoplasm; radiation therapy
ID ATOMIC-BOMB SURVIVORS; ACUTE POSTPARTUM MASTITIS; CASE-CONTROL
INTERVIEW; 2ND PRIMARY BREAST; CONTRALATERAL BREAST; HODGKINS-DISEASE;
FOLLOW-UP; CHILDHOOD-CANCER; YOUNG-WOMEN; ADJUVANT RADIOTHERAPY
AB Exposure to ionizing radiation has clearly been established as one of the risk factors for the development of breast cancer. Much data on the relationship between radiation exposures and subsequent breast cancer are derived from atomic bomb survivors and women who received medical exposures either for diagnostic or therapeutic purposes. Although these populations differ in background breast cancer risks and the dose, quality, and timing of radiation, consistent findings include an increased risk with younger age at exposure, long latency to breast cancer development, and increasing risk with increasing radiation dose. Although therapeutic radiation is rarely used to treat benign conditions, it remains an important and effective treatment modality for a wide range of cancers. Increased knowledge of radiation-related breast cancer and modifying influences plays an important role in guiding the initial treatment approach for young women and optimizing long-term follow-up care. (JNCCN 2009;7:1121-1128)
C1 [Ng, Andrea K.] Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Ng, Andrea K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Travis, Lois B.] Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA.
[Travis, Lois B.] Univ Rochester, Med Ctr, Rubin Ctr Canc Survivorship, Rochester, NY 14642 USA.
RP Ng, AK (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St,ASB1-L2, Boston, MA 02115 USA.
EM ang@lroc.harvard.edu
NR 65
TC 7
Z9 7
U1 0
U2 0
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
EI 1540-1413
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD NOV
PY 2009
VL 7
IS 10
BP 1121
EP 1128
PG 8
WC Oncology
SC Oncology
GA 527SH
UT WOS:000272386300008
PM 19930978
ER
PT J
AU Mitsiades, CS
Anderson, KC
AF Mitsiades, Constantine S.
Anderson, Kenneth C.
TI Epigenetic Modulation in Hematologic Malignancies: Challenges and
Progress
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Review
DE Epigenetics; hematologic malignancy
ID HISTONE DEACETYLASE INHIBITOR; ACUTE MYELOID-LEUKEMIA; T-CELL LYMPHOMA;
SUBEROYLANILIDE HYDROXAMIC ACID; HUMAN HEPATOCELLULAR-CARCINOMA; CHRONIC
MYELOGENOUS LEUKEMIA; TUMOR-SUPPRESSOR GENE; HYPERMETHYLATION-ASSOCIATED
INACTIVATION; RISK MYELODYSPLASTIC SYNDROMES; ACUTE
LYMPHOBLASTIC-LEUKEMIA
AB Genetic alterations, including gene mutations, and chromosomal amplifications, deletions, inversions, and translocations, are hallmarks of the molecular biology of cancer. These events lead to oncogene activation, formation of chimeric oncoproteins, and/or inactivation of tumor suppressor genes. Such genetic changes contribute to the neoplastic transformation of cells, as well as the eventual acquisition by malignant cells of a more aggressive biologic and clinical behavior. However, in recent years, it has become apparent that these genetic events are not the sole determinants of the biologic behavior of tumor cells. Indeed, it is becoming increasingly apparent that tumor cells with a given genotype exhibit a differential phenotype depending on the microenvironment in which they reside. Furthermore, extensive data have shown that derivative daughter cells of neoplastic, as well as normal cells, inherit changes in the patterns of gene expression that are not associated with changes in the primary DNA sequence but are instead related to changes in chromatin structure and its accessibility for transcriptional activity. These heritable gene expression changes that are not associated with changes in the primary nucleotide sequence are referred to as epigenetic changes. This review provides an overview of the regulation of the "epigenome" in neoplastic cells, with particular emphasis on DNA methylation and histone acetylation as therapeutic targets for hematologic malignancies. (JNCCN 2009;7[Suppl 8]:S1-S12)
C1 [Mitsiades, Constantine S.] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA.
[Mitsiades, Constantine S.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
[Anderson, Kenneth C.] Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA.
RP Mitsiades, CS (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA.
NR 140
TC 4
Z9 4
U1 0
U2 1
PU JONES AND BARTLETT PUBLISHERS
PI SUDBURY
PA 40 TALL PINE DR, SUDBURY, MA 01776 USA
SN 1540-1405
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD NOV
PY 2009
VL 7
BP S1
EP S12
PG 12
WC Oncology
SC Oncology
GA 518TU
UT WOS:000271717400001
PM 19930971
ER
PT J
AU Raemer, DB
AF Raemer, Daniel B.
TI Simulation in cardiothoracic surgery: A paradigm shift in education?
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Editorial Material
C1 [Raemer, Daniel B.] Ctr Med Simulat, Cambridge, MA 02139 USA.
[Raemer, Daniel B.] Soc Simulat Healthcare, Cambridge, MA USA.
[Raemer, Daniel B.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA.
[Raemer, Daniel B.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
RP Raemer, DB (reprint author), Ctr Med Simulat, 65 Landsdowne St, Cambridge, MA 02139 USA.
EM draemer@partners.org
NR 9
TC 3
Z9 3
U1 0
U2 0
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 NOV
PY 2009
VL 138
IS 5
BP 1065
EP 1066
DI 10.1016/j.jtcvs.2009.07.056
PG 2
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 507RG
UT WOS:000270871700004
PM 19837214
ER
PT J
AU Dwyer, HA
Matthews, PB
Azadani, A
Ge, L
Guy, TS
Tseng, EE
AF Dwyer, Harry A.
Matthews, Peter B.
Azadani, Ali
Ge, Liang
Guy, T. Sloane
Tseng, Elaine E.
TI Migration forces of transcatheter aortic valves in patients with
noncalcific aortic insufficiency
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID PERCUTANEOUS HEART-VALVE; HIGH-RISK PATIENTS; BLOOD-FLOW; IMPLANTATION;
PROSTHESIS; STENOSIS; MODEL; EXPERIENCE; FEASIBILITY; REPLACEMENT
AB Objective: Transcatheter aortic valves have been successfully implanted into the calcified leaflets of patients with severe aortic stenosis. However, their stability in patients with noncalcified aortic insufficiency is unknown. Similar to thoracic and abdominal aortic stent grafts, transcatheter aortic valves are subjected to antegrade ejection forces during systole. However, retrograde migration forces into the left ventricle are also generated by the diastolic pressure gradient across the closed valve. It has been suggested that leaflet calcification anchors the prosthesis, and measurements of migration forces should be considered before clinical trials in noncalcified aortic insufficiency. The objective of this study was to use computational fluid dynamics simulations to quantify forces that could potentially dislodge the prosthesis.
Methods: A computational fluid dynamics model was developed to simulate systolic flow through a geometric mesh of the aortic root and transcatheter aortic valves. Hemodynamic measurements were made at discrete moments during ejection. Unsteady control volume analysis was used for calculations of force on the mesh.
Results: Results of the simulation indicate that a total force of 0.602 N acts on the transcatheter aortic valves during systole, 99% of which is in the direction of axial flow. The largest contributor to force was the dynamic pressure gradient through the transcatheter aortic valves. This antegrade force is approximately 10 times smaller than the retrograde force (6.01 N) on the closed valve during diastole.
Conclusion: Our model simulated systolic flow through a transcatheter aortic valve and demonstrated migration into the left ventricle to be of greater concern than antegrade ejection.
C1 [Tseng, Elaine E.] UCSF Med Ctr, Div Cardiothorac Surg, Dept Surg, San Francisco, CA 94143 USA.
[Dwyer, Harry A.] Univ Calif Davis, Dept Mech & Aeronaut Engn, Davis, CA 95616 USA.
[Matthews, Peter B.; Azadani, Ali; Ge, Liang; Guy, T. Sloane; Tseng, Elaine E.] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Tseng, EE (reprint author), UCSF Med Ctr, Div Cardiothorac Surg, Dept Surg, 500 Parnassus Ave,Suite W405,Box 0118, San Francisco, CA 94143 USA.
EM elaine.tseng@ucsfmedctr.org
FU American Heart Association Beginning [0565148Y]; Northern California
Institute for Research and Education
FX This work was supported by the American Heart Association Beginning
Grant-in-Aid 0565148Y (Burlingame, Calif) and the Northern California
Institute for Research and Education (San Francisco, Calif). The authors
have no financial conflicts of interest to disclose.
NR 25
TC 22
Z9 22
U1 1
U2 4
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 NOV
PY 2009
VL 138
IS 5
BP 1227
EP 1233
DI 10.1016/j.jtcvs.2009.02.057
PG 7
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 507RG
UT WOS:000270871700026
PM 19748632
ER
PT J
AU Abbott, GF
Rosado-de-Christenson, ML
Rossi, SE
Suster, S
AF Abbott, Gerald F.
Rosado-de-Christenson, Melissa L.
Rossi, Santiago E.
Suster, Saul
TI Imaging of Small Airways Disease
SO JOURNAL OF THORACIC IMAGING
LA English
DT Article
DE small airways disease; bronchioles; bronchiolitis; constrictive
bronchiolitis
ID HIGH-RESOLUTION CT; THIN-SECTION CT; BRONCHIOLITIS OBLITERANS SYNDROME;
LUNG-TRANSPLANT RECIPIENTS; CHRONIC OCCULT ASPIRATION; HYPERSENSITIVITY
PNEUMONITIS; COMPUTED-TOMOGRAPHY; DISORDERS; DIAGNOSIS; SPECTRUM
AB Small airways disease includes a spectrum of inflammatory and fibrotic pulmonary diseases centered on the small conducting airways. High-resolution computed tomography plays a key role in the detection and classification of small airways disease and, when combined with relevant clinical and pathologic findings, leads to a more accurate diagnosis. The imaging manifestations of small airways disease on high-resolution Computed tomography may be direct or indirect signs of small airway involvement and include centrilobular nodules and branching nodular (tree-in-bud) opacities, or the demonstration of mosaic attenuation that is typically exaggerated on expiratory computed tomography. This article reviews the normal anatomy and histology of bronchioles and the clinical, pathologic, and imaging features of small airways diseases.
C1 [Abbott, Gerald F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Rosado-de-Christenson, Melissa L.] Uniformed Serv Univ Hlth Sci, Dept Radiol & Nucl Med, Bethesda, MD 20814 USA.
[Rosado-de-Christenson, Melissa L.] St Lukes Hosp Kansas City, Dept Radiol, Kansas City, MO USA.
[Rosado-de-Christenson, Melissa L.] Univ Missouri, Dept Radiol, Kansas City, MO 64110 USA.
[Rossi, Santiago E.] Ctr Diagnost Dr Enrique Rossi, Dept Radiol, Buenos Aires, DF, Argentina.
[Suster, Saul] Med Coll Wisconsin, Dept Pathol & Lab Med, Milwaukee, WI 53226 USA.
RP Abbott, GF (reprint author), Massachusetts Gen Hosp, Dept Radiol, Thorac Radiol FND 202,55 Fruit St, Boston, MA 02114 USA.
EM GABBOTT@PARTNERS.ORG
NR 50
TC 10
Z9 10
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0883-5993
J9 J THORAC IMAG
JI J. Thorac. Imaging
PD NOV
PY 2009
VL 24
IS 4
BP 285
EP 298
PG 14
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 528XW
UT WOS:000272481300006
PM 19935225
ER
PT J
AU Sequist, LV
Fidias, PM
Temel, JS
Kolevska, T
Rabin, MS
Boccia, RV
Burris, HA
Belt, RJ
Huberman, MS
Melnyk, O
Mills, GM
Englund, CW
Caldwell, DC
Keck, JG
Meng, L
Jones, M
Brown, GL
Edelman, MJ
Lynch, TJ
AF Sequist, Lecia V.
Fidias, Panos M.
Temel, Jennifer S.
Kolevska, Tatjana
Rabin, Michael S.
Boccia, Ralph V.
Burris, Howard A.
Belt, Robert J.
Huberman, Mark S.
Melnyk, Ostap
Mills, Glenn M.
Englund, Craig W.
Caldwell, David C.
Keck, James G.
Meng, Lisa
Jones, Marsha
Brown, Gail L.
Edelman, Martin J.
Lynch, Thomas J.
TI Phase 1-2a Multicenter Dose-Ranging Study of Canfosfamide in Combination
with Carboplatin and Paclitaxel as First-Line Therapy for Patients with
Advanced Non-small Cell Lung Cancer
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article
DE Canfosfamide; Carboplatin; Paclitaxel; NSCLC; Phase 2
ID GLUTATHIONE-S-TRANSFERASE; CHEMOTHERAPY-NAIVE PATIENTS; III TRIAL; PLUS
CARBOPLATIN; DRUG-RESISTANCE; ONCOLOGY-GROUP; GEMCITABINE; CISPLATIN;
CISPLATIN/VINORELBINE; MALIGNANCIES
AB Introduction: We aimed to evaluate the safety and efficacy of canfosfamide in combination with carboplatin and paclitaxel as first-line therapy in patients with locally advanced or metastatic non-small cell lung cancer.
Methods: This was a phase 1-2a, multicenter, dose-ranging trial that enrolled patients with stage IIIB or IV non-small cell lung cancer with measurable disease. Patients received canfosfamide in doses ranging from 400 to 1000 mg/m(2) intravenously (IV) with carboplatin at area under the curve 6 IV and paclitaxel at 200 mg/m(2) IV day I every 3 weeks. The primary end point was objective response rate, and the secondary endpoints were safety and progression-free survival.
Results: One hundred twenty-nine patients were treated with canfosfamide at dose levels of 400 (n = 3), 500 (n = 51), 750 (n = 54), and 1000 mg/m(2) (n = 21). Objective tumor responses by RECIST were observed in 40 patients [34% (95% confidence interval [CI], 26-44)], the median progression-free survival was 4.3 months (95% Cl, 3.7-5.2) and the median survival 9.9 months (95% Cl, 7.7-11.9). The percent of patients alive at I year was 43.1%. The overall safety profile of the combination was acceptable and consistent with the profiles of the individual agents. In an exploratory analysis, patients receiving the optional maintenance canfosfamide therapy had a prolonged median Survival of 16.8 months compared with those eligible for but not receiving maintenance therapy at 8.8 months (hazard ratio = 0.38, p < 0.001).
Conclusions: The combination of canfosfamide with carboplatin and paclitaxel chemotherapy is well tolerated and active. Maintenance canfosfamide may further improve outcomes. This regimen is worthy of additional study.
C1 [Sequist, Lecia V.; Fidias, Panos M.; Temel, Jennifer S.; Lynch, Thomas J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Kolevska, Tatjana] Kaiser Permanente Med Ctr, Vallejo, CA USA.
[Rabin, Michael S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Boccia, Ralph V.] Ctr Canc & Blood Disorders, Bethesda, MD USA.
[Burris, Howard A.] Sarah Cannon Canc Ctr, Nashville, TN USA.
[Belt, Robert J.] Kansas City Canc Ctr, Kansas City, MO USA.
[Huberman, Mark S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Melnyk, Ostap] Bay Area Canc Res Grp LLC, Concord, CA USA.
[Englund, Craig W.] Florida Well Care, Inverness, FL USA.
[Caldwell, David C.] Danville Hematol & Oncol Inc, Danville, VA USA.
[Keck, James G.; Meng, Lisa; Jones, Marsha; Brown, Gail L.] Telik Inc, Palo Alto, CA USA.
[Edelman, Martin J.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA.
EM lvsequist@partners.org
FU Telik, Inc.; Palo Alto, CA.
FX Supported by Telik, Inc., Palo Alto, CA.
NR 39
TC 10
Z9 12
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD NOV
PY 2009
VL 4
IS 11
BP 1389
EP 1396
PG 8
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 514KT
UT WOS:000271394000016
PM 19701107
ER
PT J
AU Sequist, LV
AF Sequist, Lecia V.
TI Protein Degradation/Chaperone System and Histone Deacetylase Pathway
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Editorial Material
ID GROWTH-FACTOR RECEPTORS; CANCER; CHAPERONE; THERAPY
C1 Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA.
RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Med, 55 Fruit St,POB 212, Boston, MA 02114 USA.
EM LVSequist@partners.org
NR 9
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD NOV
PY 2009
VL 4
IS 11
BP S1077
EP S1078
PG 2
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 514KU
UT WOS:000271394100011
PM 19861924
ER
PT J
AU Moreira, DM
Presti, JC
Aronson, WJ
Terris, MK
Kane, CJ
Amling, CL
Freedland, SJ
AF Moreira, Daniel M.
Presti, Joseph C., Jr.
Aronson, William J.
Terris, Martha K.
Kane, Christopher J.
Amling, Christopher L.
Freedland, Stephen J.
TI Natural History of Persistently Elevated Prostate Specific Antigen After
Radical Prostatectomy: Results From the SEARCH Database
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostate; prostatic neoplasms; mortality; prostate-specific antigen;
prostatectomy
ID BIOCHEMICAL RECURRENCE; DOUBLING TIME; FREE SURVIVAL; CANCER; PSA; RISK;
PROGRESSION; MORTALITY; PREDICTS; RELAPSE
AB Purpose: We examined natural history, predictors of biochemical recurrence and all cause mortality in patients with persistently elevated prostate specific antigen after radical prostatectomy in the Shared Equal Access Regional Cancer Hospital cohort.
Materials and Methods: We reviewed data on 1,156 men treated with radical prostatectomy after 1997. Prostate specific antigen persistence was defined as failure to achieve prostate specific antigen less than 0.03 ng/ml within 6 months postoperatively. Disease-free and overall survival was compared between men with and without persistence using the log rank test. Predictors of biochemical recurrence and all cause death were analyzed using the Cox model.
Results: A total of 291 men (25%) had persistence, which was associated with increased biochemical recurrence and all cause death (p <0.001 and 0.041, respectively). In patients with persistence 1 and 5-year biochemical recurrence-free survival was 68% and 36%, significantly lower than 95% and 72%, respectively, in men without persistence. Ten-year overall survival in patients with vs without persistence was 63% vs 80%. In men with persistence independent predictors of prostate specific antigen recurrence were higher prostate specific antigen nadir (HR 2.19, p <0.001), positive surgical margins (HR 1.75, p = 0.022) and high pathological Gleason score (8-10 vs 2-6 HR 2.40, p = 0.026). Independent predictors of overall mortality were a higher prostate specific antigen nadir (HR 1.46, p = 0.013) and seminal vesicle invasion (HR 3.15, p = 0.047).
Conclusions: Prostate specific antigen persistence is associated with increased biochemical recurrence and overall mortality. In men with persistence the prostate specific antigen nadir is an independent predictor of recurrence and mortality. Thus, prostate specific antigen persistence and nadir are important tools for early postoperative risk stratification.
C1 [Freedland, Stephen J.] Duke Univ, Sch Med, Div Urol, Dept Pathol, Durham, NC 27710 USA.
[Moreira, Daniel M.; Freedland, Stephen J.] Duke Univ, Sch Med, Div Urol Surg, Dept Surg, Durham, NC 27710 USA.
[Moreira, Daniel M.; Freedland, Stephen J.] Duke Univ, Sch Med, Duke Prostate Ctr, Durham, NC 27710 USA.
[Moreira, Daniel M.; Freedland, Stephen J.] Vet Affairs Med Ctr Durham, Urol Sect, Durham, NC USA.
[Presti, Joseph C., Jr.; Aronson, William J.] Stanford Univ, Med Ctr, Dept Urol, Palo Alto, CA 94304 USA.
[Presti, Joseph C., Jr.] Vet Affairs Med Ctr, Urol Sect, Dept Surg, Palo Alto, CA 94304 USA.
[Aronson, William J.] Univ Calif Los Angeles, Med Ctr, Dept Surg, Urol Sect,W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90024 USA.
[Aronson, William J.] Univ Calif Los Angeles, Med Ctr, Dept Urol, Los Angeles, CA 90024 USA.
[Kane, Christopher J.] Univ Calif San Diego, Med Ctr, Dept Surg, Div Urol, San Diego, CA 92103 USA.
[Terris, Martha K.] Vet Affairs Med Ctr, Urol Sect, Div Surg, Augusta, GA USA.
[Terris, Martha K.] Med Coll Georgia, Dept Surg, Div Urol Surg, Augusta, GA 30912 USA.
[Amling, Christopher L.] Univ Alabama, Dept Surg, Div Urol, Birmingham, AL 35294 USA.
RP Freedland, SJ (reprint author), Duke Univ, Sch Med, Div Urol, Dept Pathol, Box 2626 DUMC, Durham, NC 27710 USA.
EM steve.freedland@duke.edu
OI Terris, Martha/0000-0002-3843-7270
FU Department of Veterans Affairs; National Institute of Health
[R01CA100938]; National Institutes of Health Specialized Programs of
Research Excellence [P50 CA92131-01A1]; Georgia Cancer Coalition (MKT);
Department of Defense; Prostate Cancer Research Program (SJF); American
Urological Association Foundation; Astellas Rising Star in Urology Award
(SJF)
FX Supported by Department of Veterans Affairs, National Institute of
Health R01CA100938 WIN, National Institutes of Health Specialized
Programs of Research Excellence Grant P50 CA92131-01A1 (WJA), Georgia
Cancer Coalition (MKT), Department of Defense, Prostate Cancer Research
Program (SJF) and American Urological Association Foundation/Astellas
Rising Star in Urology Award (SJF).
NR 18
TC 17
Z9 17
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD NOV
PY 2009
VL 182
IS 5
BP 2250
EP 2255
DI 10.1016/j.juro.2009.07.022
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 506EO
UT WOS:000270756900049
PM 19758614
ER
PT J
AU Bhoopalam, N
Campbell, SC
Moritz, T
Broderick, WR
Iyer, P
Arcenas, AG
Van Veldhuizen, PJ
Friedman, N
Reda, D
Warren, S
Garewal, H
AF Bhoopalam, Nirmala
Campbell, Steven C.
Moritz, Thomas
Broderick, William R.
Iyer, Padmini
Arcenas, Anthony G.
Van Veldhuizen, Peter J.
Friedman, Nicholas
Reda, Domenic
Warren, Stuart
Garewal, Harinder
TI Intravenous Zoledronic Acid to Prevent Osteoporosis in a Veteran
Population With Multiple Risk Factors for Bone Loss on Androgen
Deprivation Therapy
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostate; prostatic neoplasms; androgen antagonists; zoledronic acid;
osteoporosis
ID RANDOMIZED CONTROLLED-TRIAL; PROSTATE-CANCER; MINERAL DENSITY; CLINICAL
FRACTURES; MEN; HEALTH
AB Purpose: Androgen deprivation therapy for prostate cancer is associated with osteoporosis and increased fracture risk. Previous studies of zoledronic acid demonstrated bone loss prevention in patients initiating androgen deprivation therapy. There are limited data on patients on prolonged androgen deprivation therapy or in Veterans Affairs patients with multiple risk factors for osteoporosis.
Methods: We randomized 93 patients with MO prostate cancer in this placebo controlled trial in the Veterans Affairs health care system. Preplanned strata included 50 patients on androgen deprivation therapy for less than 1 year (stratum 1) and 43 on androgen deprivation therapy for greater than 1 year (stratum 2). In each stratum patients were randomized to 4 mg zoledronic acid intravenously every 3 months for 4 treatments or intravenous placebo. The primary end point was the percent change in bone mineral density at the lumbar spine at 12 months.
Results: Age, race, body mass index and osteoporosis risk factors were similar for the 2 treatments. Most patients were former smokers, had moderate alcohol intake, were not on calcium/vitamin D supplements and were relatively sedentary at baseline. In stratum 1 spine bone mineral density increased 5.95% in the zoledronic acid arm and decreased 3.23% in the placebo arm (p = 0.0044). In stratum 2 spine bone mineral density increased 6.08% in the zoledronic acid arm and only increased 1.57% in the placebo arm (p = 0.0005). Treatment was well tolerated with minimal impact on renal function.
Conclusions: Zoledronic acid improved bone mineral density in patients with MO prostate cancer on androgen deprivation therapy for 1 year or less, or greater than 1 year. This finding indicates that bisphosphonate therapy remains effective when initiated later in the course of androgen deprivation therapy and is efficacious in Veterans Affairs patients with multiple risk factors for osteoporosis.
C1 [Bhoopalam, Nirmala; Campbell, Steven C.; Moritz, Thomas; Broderick, William R.; Friedman, Nicholas; Reda, Domenic] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA.
[Iyer, Padmini] Vet Affairs Long Beach Healthcare Syst, Washington, DC USA.
[Arcenas, Anthony G.] Vet Affairs Med Ctr, Washington, DC 20422 USA.
[Van Veldhuizen, Peter J.] Kansas City Vet Affairs, Kansas City, MO USA.
[Warren, Stuart] Cooperat Studies Clin Res Pharm Coordinating Ctr, Albuquerque, NM USA.
[Garewal, Harinder] So Arizona Vet Affairs Healthcare Syst, Tucson, AZ USA.
RP Bhoopalam, N (reprint author), Loyola Univ Chicago, Edward Hines Vet Affairs Hosp, Stritch Sch Med, Bldg 200,Room 910,5000 S 5th Ave, Hines, IL 60141 USA.
EM nirmala.bhoopalam@va.gov
FU Novartis Pharmaceutical Corp., East Hanover, New Jersey
FX Supported by a grant from Novartis Pharmaceutical Corp., East Hanover,
New Jersey.
NR 24
TC 29
Z9 29
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD NOV
PY 2009
VL 182
IS 5
BP 2257
EP 2264
DI 10.1016/j.juro.2009.07.046
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 506EO
UT WOS:000270756900052
PM 19758618
ER
PT J
AU Hirata, H
Kawamoto, K
Kikuno, N
Kawakami, T
Kawakami, K
Saini, S
Yamamura, S
Dahiya, R
AF Hirata, Hiroshi
Kawamoto, Ken
Kikuno, Nobuyuki
Kawakami, Toshifumi
Kawakami, Kazumori
Saini, Sharanjot
Yamamura, Soichiro
Dahiya, Rajvir
TI Restoring Erectile Function by Antioxidant Therapy in Diabetic Rats
SO JOURNAL OF UROLOGY
LA English
DT Article
DE penis; diabetes mellitus; gene expression; tempol; insulin
ID OXIDATIVE STRESS; DYSFUNCTION; APOPTOSIS; IMPACT; PENIS; EXPRESSION;
PROTEIN; MUSCLE; INJURY
AB Purpose: Diabetes mediates an increase in reactive oxygen species that can lead to impaired endothelial function, decreased smooth muscle in the diabetic corpus cavernosum and increased apoptosis. We hypothesized that antioxidant therapy may restore erectile function by inhibiting apoptosis in diabetic rat crura.
Materials and Methods: A total of 40 male Sprague-Dawley rats were randomized to 5 groups of 8 each, including healthy controls, rats with diabetes, and rats with diabetes with the antioxidant tempol. (4-hydroxytetramethyl-piperidine-1-oxyl) (Sigma-Aldrich (R)), with insulin, and with tempol and insulin. Intracavernous pressure was measured for functional analysis. Smooth muscle and collagen fiber levels in the rat penile corpus cavernosum were assessed by hematoxylin and eosin, and Masson's trichrome staining. Endothelial cells were assessed by CD31 staining. Reactive oxygen species related genes were analyzed by cDNA microarray. We confirmed mRNA and protein expression profiles for these genes in diabetic and treated rats using real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. TUNEL assay was done to analyze apoptosis status.
Results: Intracavernous pressure in diabetic rats was significantly decreased vs controls. After treatment with tempol or insulin alone intracavernous pressure was significantly increased compared to that in untreated diabetic rats. In the diabetic group mean smooth muscle area significantly decreased but was restored after combined tempol and insulin. Endothelial cell area in diabetic rats significantly decreased and was not restored by any treatments. However, apoptosis was restored to normal by combined insulin and tempol. Of 84 reactive oxidative stress and antioxidant genes 32 were identified specific to diabetic rats compared to healthy controls. UCP3 expression was significantly increased in diabetic rats and normal levels were restored by all treatments.
Conclusions: To our knowledge this is the first report that tempol and insulin can restore erectile function in diabetic rats by inhibiting apoptosis.
C1 San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA.
Univ Calif San Francisco, San Francisco, CA 94121 USA.
RP Dahiya, R (reprint author), Vet Affairs Med Ctr, Urol Res Ctr, 112F,4150 Clement St, San Francisco, CA 94121 USA.
EM rdahiya@urology.ucsf.edu
FU NIDDK NIH HHS [R01DK075524]
NR 21
TC 15
Z9 19
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD NOV
PY 2009
VL 182
IS 5
BP 2518
EP 2525
DI 10.1016/j.juro.2009.07.009
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 506EO
UT WOS:000270756900142
PM 19765757
ER
PT J
AU Groeneveld, PW
Yang, L
Greenhut, A
Yang, FF
AF Groeneveld, Peter W.
Yang, Lin
Greenhut, Alexis
Yang, Feifei
TI Comparative effectiveness of carotid arterial stenting versus
endarterectomy
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article
ID HIGH-RISK PATIENTS; RANDOMIZED-TRIAL; CLINICAL-TRIAL; STENOSIS
AB Background Carotid arterial stent (CAS) systems are an alterative to carotid endarterectomy for the treatment of moderate to severe carotid stenosis, but the effectiveness of CAS compared to endarterectomy in preventing stroke and death is uncertain. This study's objective was to compare the clinical outcomes among Medicare beneficiaries undergoing carotid revascularization before and after CAS became widely available. Objectives. This observational, retrospective cohort study compared 46,784 patients undergoing carotid revascularization from August 2005-March 2006 (the coverage era) to propensity-score-matched patients undergoing carotid revascularization between October 2002-September 2004 (the pre-coverage era), before widespread Medicare coverage of CAS.
Methods. Mortality was compared at 90 and 270 days after revascularization, as were the combined outcomes of periprocedural acute myocardial infarction and any stroke or death within 90 and 270 days after revascularization, between the two eras. Comparisons were also made between localities with high (23% of carotid procedures being CAS) and lower (9% of carotid procedures being CAS) adoption rates of carotid stents during the coverage era.
Results: There were no significant differences in 90-day mortality (2.2% vs; 2.2%; P = .79), 90-day combined outcomes (4.5% vs 4.3%; P = .13), or 270-day mortality (4.8% vs 4.6%; P = .17) between the coverage and pre-coverage eras, but there were more 270-day combined outcomes in the coverage era (7.7% vs 7.3%; P = .03). In localities with higher adoption of carotid stents, there was higher 90-day mortality (adjusted odds ratio [OR] 1.15; P = .16), 90-day combined outcomes (OR = 1.17; P = .03), 270-day mortality (OR = 1.13; P = .07), and 270-day combined outcomes (OR = 1.10; P = .09) in the coverage era. There were no differences in event rates between eras in areas with lower carotid stent adoption.
Conclusion: The adoption of carotid stents for treatment of carotid stenosis was associated with increased rates of adverse clinical outcomes after carotid revascularization. (J Vasc Surg 2009;50:1040-8.)
C1 [Groeneveld, Peter W.] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA.
[Groeneveld, Peter W.; Yang, Lin; Greenhut, Alexis; Yang, Feifei] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA.
[Groeneveld, Peter W.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
RP Groeneveld, PW (reprint author), 1229 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM peter.groeneveld@va.gov
FU NHLBI NIH HHS [1-R01-HL086919, R01 HL086919-02, R01 HL086919]
NR 22
TC 10
Z9 10
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD NOV
PY 2009
VL 50
IS 5
BP 1040
EP 1048
DI 10.1016/j.jvs.2009.05.054
PG 9
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 514JL
UT WOS:000271390300011
PM 19628358
ER
PT J
AU Hovav, AH
Santosuosso, M
Bivas-Benita, M
Plair, A
Cheng, A
Elnekave, M
Righi, E
Chen, T
Kashiwagi, S
Panas, MW
Xiang, SH
Furmanov, K
Letvin, NL
Poznansky, MC
AF Hovav, Avi-Hai
Santosuosso, Michael
Bivas-Benita, Maytal
Plair, Andre
Cheng, Alex
Elnekave, Mazal
Righi, Elda
Chen, Tao
Kashiwagi, Satoshi
Panas, Michael W.
Xiang, Shi-Hua
Furmanov, Karina
Letvin, Norman L.
Poznansky, Mark C.
TI X4 Human Immunodeficiency Virus Type 1 gp120 Down-Modulates Expression
and Immunogenicity of Codelivered Antigens
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CD8(+) T-CELLS; IMMUNE-RESPONSES; ENVELOPE PROTEIN; HIV-1 ENVELOPE; DNA
VACCINATION; IN-VIVO; GAG-POL; GLYCOPROTEIN; PROGRESSION; ANTIBODIES
AB In order to increase the immune breadth of human immunodeficiency virus (HIV) vaccines, strategies such as immunization with several HIV antigens or centralized immunogens have been examined. HIV-1 gp120 protein is a major immunogen of HIV and has been routinely considered for inclusion in both present and future AIDS vaccines. However, recent studies proposed that gp120 interferes with the generation of immune response to codelivered antigens. Here, we investigate whether coimmunization with plasmid-encoded gp120 alters the immune response to other coadministered plasmid encoded antigens such as luciferase or ovalbumin in a mouse model. We found that the presence of gp120 leads to a significant reduction in the expression level of the codelivered antigen in vivo. Antigen presentation by antigen-presenting cells was also reduced and resulted in the induction of weak antigen-specific cellular and humoral immune responses. Importantly, gp120-mediated immune interference was observed after administration of the plasmids at the same or at distinct locations. To characterize the region in gp120 mediating these effects, we used plasmid constructs encoding gp120 that lacks the V1V2 loops (Delta V1V2) or the V3 loop (Delta V3). After immunization, the Delta V1V2, but not the Delta V3 construct, was able to reduce antigen expression, antigen presentation, and subsequently the immunogenicity of the codelivered antigen. The V3 loop dependence of this phenomenon seems to be limited to V3 loops known to interact with the CXCR4 molecule but not with CCR5. Our study presents a novel mechanism by which HIV-1 gp120 interferes with the immune response against coadministered antigen in a polyvalent vaccine preparation.
C1 [Hovav, Avi-Hai] Hebrew Univ Jerusalem, Hadassah Fac Dent Med, Inst Dent Sci, Hadassah Sch Dent Med, IL-91120 Jerusalem, Israel.
[Santosuosso, Michael; Plair, Andre; Cheng, Alex; Righi, Elda; Chen, Tao; Kashiwagi, Satoshi; Poznansky, Mark C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr,Dept Infect Dis, Charlestown, MA 02129 USA.
[Bivas-Benita, Maytal; Panas, Michael W.; Letvin, Norman L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA.
[Xiang, Shi-Hua] Dana Farber Canc Inst, Canc Immunol & AIDS, Boston, MA 02115 USA.
RP Hovav, AH (reprint author), Hebrew Univ Jerusalem, Hadassah Fac Dent Med, Inst Dent Sci, Hadassah Sch Dent Med, POB 122722, IL-91120 Jerusalem, Israel.
EM avihaih@ekmd.huji.ac.il
FU Israeli Ministry of Health [300000-4790]; National Institutes of Health
[RO1 AI49757]; National Institute of Allergy and Infection Diseases
Center for HIV/AIDS Vaccine Immunology [AI067854]; Canadian Institutes
of Heath Research
FX This study received financial support from the Israeli Ministry of
Health (300000-4790 [A.-H. H.]). M. C. P. was supported by National
Institutes of Health grant RO1 AI49757, N. L. L. was supported by the
National Institute of Allergy and Infection Diseases Center for HIV/AIDS
Vaccine Immunology (AI067854), and M. S. was funded by the Canadian
Institutes of Heath Research.
NR 29
TC 10
Z9 10
U1 1
U2 1
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 NOV
PY 2009
VL 83
IS 21
BP 10941
EP 10950
DI 10.1128/JVI.00394-09
PG 10
WC Virology
SC Virology
GA 504FW
UT WOS:000270602300009
PM 19692474
ER
PT J
AU Li, Y
Kar, AK
Sodroski, J
AF Li, Yuan
Kar, Alak Kanti
Sodroski, Joseph
TI Target Cell Type-Dependent Modulation of Human Immunodeficiency Virus
Type 1 Capsid Disassembly by Cyclophilin A
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MURINE LEUKEMIA-VIRUS; TRIM5-ALPHA RESTRICTION FACTOR;
CYCLOSPORINE-A-RESISTANT; OLD-WORLD MONKEY; GAG PROTEIN; REVERSE
TRANSCRIPTION; RETROVIRUS INFECTION; VIRAL REPLICATION; HIV-1
INFECTIVITY; TERMINAL DOMAIN
AB The binding of cyclophilin A (CypA) to the human immunodeficiency virus type 1 (HIV-1) capsid protein (CA protein) is required soon after virus entry into natural target cells. In Jurkat T lymphocytes, disrupting CypA-CA interaction either by cyclosporine (Cs) treatment or by alteration (e. g., P90A) of the CA inhibits HIV-1 infection. In HeLa cells, however, treatment with Cs or Cs analogues minimally inhibits the early phase of HIV-1 infection but selects for a Cs-dependent virus with a change (A92E) in CA. To understand these phenomena, we examined the effects of the P90A and A92E changes in the HIV-1 CA protein on the stability of capsid complexes assembled in vitro and on capsid disassembly in the cytosol of virus-exposed target cells. The A92E change impaired CA-CA interactions in vitro and decreased the amount of particulate capsids in the cytosol of HeLa target cells. Reducing the binding of CypA to the A92E mutant capsid, either by Cs treatment or by an additional P90A change in the CA protein, increased the amount of particulate capsids and viral infectivity in HeLa cells. In contrast, reduction of the binding of CypA to HIV-1 capsids in Jurkat T lymphocytes resulted in a decrease in the amount of particulate capsids and infectivity. Thus, depending on the capsid and the target cell, CypA-CA binding either stabilized or destabilized the capsid, indicating that CypA modulates HIV-1 capsid disassembly. In both cell types examined, decreased stability of the capsid was associated with a decrease in the efficiency of HIV-1 infection.
C1 [Li, Yuan; Kar, Alak Kanti; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Div AIDS, Boston, MA 02115 USA.
[Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Div AIDS, 44 Binney St,CLS 1010, Boston, MA 02115 USA.
EM joseph_sodroski@dfci.harvard.edu
RI Li, Yuan/B-4098-2013
FU National Institutes of Health [AI063987, AI076094]; Center for AIDS
Research Award [AI06354]; International AIDS Vaccine Initiative
FX This study was supported by the National Institutes of Health (AI063987
and AI076094), Center for AIDS Research Award AI06354, the International
AIDS Vaccine Initiative, and the late William F. McCarty-Cooper.
NR 61
TC 62
Z9 62
U1 2
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 NOV
PY 2009
VL 83
IS 21
BP 10951
EP 10962
DI 10.1128/JVI.00682-09
PG 12
WC Virology
SC Virology
GA 504FW
UT WOS:000270602300010
PM 19656870
ER
PT J
AU Cohen, MH
Fabri, M
Cai, XT
Shi, QH
Hoover, DR
Binagwaho, A
Culhane, MA
Mukanyonga, H
Karegeya, DK
Anastos, K
AF Cohen, Mardge H.
Fabri, Mary
Cai, Xiaotao
Shi, Qiuhu
Hoover, Donald R.
Binagwaho, Agnes
Culhane, Melissa A.
Mukanyonga, Henriette
Karegeya, Davis Ksahaka
Anastos, Kathryn
TI Prevalence and Predictors of Posttraumatic Stress Disorder and
Depression in HIV-Infected and At-Risk Rwandan Women
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID INTIMATE-PARTNER VIOLENCE; MENTAL-HEALTH; SOUTH-AFRICA; POSTWAR
AFGHANISTAN; DOMESTIC VIOLENCE; SYMPTOMS; HIV/AIDS; MORTALITY; ABUSE;
PROGRESSION
AB Objective: During the 1994 Rwandan genocide, rape was used as a weapon of war to transmit HIV. This study measures trauma experiences of Rwandan women and identifies predictors associated with posttraumatic stress disorder (PTSD) and depressive symptoms.
Methods: The Rwandan Women's Interassociation Study and Assessment (RWISA) is a prospective observational cohort study designed to assess effectiveness and toxicity of antiretroviral therapy in HIV-infected Rwandan women. In 2005, a Rwandan-adapted Harvard Trauma Questionnaire (HTQ) and the Center for Epidemiologic Studies Depression Scale (CES-D) were used to assess genocide trauma events and prevalence of PTSD (HTQ mean > 2) and depressive symptoms (CES-D >= 16) for 850 women (658 HIV-positive and 192 HIV-negative).
Results: PTSD was common in HIV-positive (58%) and HIV-negative women (66%) (p - 0.05). Women with HIV had a higher prevalence of depressive symptoms than HIV-negative women (81% vs. 65%, p<0.0001). Independent predictors for increased PTSD were experiencing more genocide-related trauma events and having more depressive symptoms. Independent predictors for increased depressive symptoms were making <$18 a month, HIV infection (and, among HIV-positive women, having lower CD4 cell counts), a history of genocidal rape, and having more PTSD symptoms.
Conclusions: The prevalence of PTSD and depressive symptoms is high in women in the RWISA cohort. Four of five HIV-infected women had depressive symptoms, with highest rates among women with CD4 cell counts <200. In addition to treatment with antiretroviral therapy, economic empowerment and identification and treatment of depression and PTSD may reduce morbidity and mortality among women in postconflict countries.
C1 [Cohen, Mardge H.] John Stroger Hosp, Dept Med, Chicago, IL USA.
[Cohen, Mardge H.] Rush Univ, Dept Med, Chicago, IL 60612 USA.
[Fabri, Mary] Heartland Alliance Marjorie Kovler Ctr, Chicago, IL USA.
[Cai, Xiaotao] Data Solut LLC, Bronx, NY USA.
[Shi, Qiuhu] New York Med Coll, Sch Publ Hlth, Valhalla, NY 10595 USA.
[Hoover, Donald R.] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, New Brunswick, NJ 08903 USA.
[Hoover, Donald R.] Rutgers State Univ, Dept Stat & Biostat, New Brunswick, NJ 08903 USA.
[Culhane, Melissa A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Mukanyonga, Henriette] Rwanda Womens Interassoc Study & Assessment, Kigali, Rwanda.
[Karegeya, Davis Ksahaka] Forum Activistes Torture Rwanda, Kigali, Rwanda.
[Anastos, Kathryn] Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA.
[Anastos, Kathryn] Montefiore Med Ctr, Dept Epidemiol, Bronx, NY 10467 USA.
[Anastos, Kathryn] Montefiore Med Ctr, Dept Populat Hlth, Bronx, NY 10467 USA.
[Anastos, Kathryn] Albert Einstein Coll Med, Bronx, NY 10467 USA.
RP Cohen, MH (reprint author), 2020 W Harrison, Chicago, IL 60612 USA.
EM mardge.cohen@gmail.com
FU NIAID NIH HHS [AI-51519, U01-AI-35004]; NIDDK NIH HHS [DK54615]; PHS HHS
[U01-A1- 34993]
NR 45
TC 19
Z9 19
U1 1
U2 10
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 NOV
PY 2009
VL 18
IS 11
BP 1783
EP 1791
DI 10.1089/jwh.2009.1367
PG 9
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 525XH
UT WOS:000272250500008
PM 19951212
ER
PT J
AU Galofre, JC
Davies, TF
AF Galofre, Juan C.
Davies, Terry F.
TI Autoimmune Thyroid Disease in Pregnancy: A Review
SO JOURNAL OF WOMENS HEALTH
LA English
DT Review
ID SUBCLINICAL HYPOTHYROIDISM; ENDOCRINE-SOCIETY; LEVOTHYROXINE
REQUIREMENTS; CLINICAL ENDOCRINOLOGISTS; AMERICAN ASSOCIATION; FETAL
MICROCHIMERISM; JOINT STATEMENT; DYSFUNCTION; MANAGEMENT; WOMEN
AB The maternal physiological changes that occur in normal pregnancy induce complex endocrine and immune responses. During a normal pregnancy, thyroid gland volume may enlarge, and thyroid hormone production increases. Hence, the interpretation of thyroid function during gestation needs to be adjusted according to pregnancy-specific ranges. The elevated prevalence of gestation-related thyroid disorders (10%-15%) and the important repercussions for both mother and fetus reported in multiple studies throughout the world denote, in our opinion, the necessity for routine thyroid function screening both before and during pregnancy. Once thyroid dysfunction is suspected or confirmed, management of the thyroid disorder necessitates regular monitoring in order to ensure a successful outcome. The aim of treating hyperthyroidism in pregnancy with antithyroid drugs is to maintain serum thyroxine (T-4) in the upper normal range of the assay used with the lowest possible dose of drug, whereas in hypothyroidism, the goal is to return serum thyroid-stimulating hormone (TSH) to the range between 0.5 and 2.5mU/L.
C1 [Galofre, Juan C.; Davies, Terry F.] Mt Sinai Hosp, Mt Sinai Sch Med, Thyroid Res Unit, New York, NY 10029 USA.
[Galofre, Juan C.; Davies, Terry F.] James J Peters VA Med Ctr, New York, NY 10029 USA.
[Galofre, Juan C.] Univ Navarra, Dept Endocrinol & Nutr, Clin Univ, E-31080 Pamplona, Spain.
RP Davies, TF (reprint author), Mt Sinai Med Ctr, Box 1055,1 Gustave L Levy Pl, New York, NY 10029 USA.
EM terry.davies@mssm.edu
NR 74
TC 14
Z9 14
U1 0
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
EI 1931-843X
J9 J WOMENS HEALTH
JI J. Womens Health
PD NOV
PY 2009
VL 18
IS 11
BP 1847
EP 1856
DI 10.1089/jwh.2008.1234
PG 10
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 525XH
UT WOS:000272250500017
PM 19951221
ER
PT J
AU VanSwearingen, JM
Perera, S
Brach, JS
Cham, R
Rosano, C
Studenski, SA
AF VanSwearingen, Jessie M.
Perera, Subashan
Brach, Jennifer S.
Cham, Rakie
Rosano, Caterina
Studenski, Stephanie A.
TI A Randomized Trial of Two Forms of Therapeutic Activity to Improve
Walking: Effect on the Energy Cost of Walking
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Exercise; Gait; Energy cost
ID DWELLING OLDER-ADULTS; HEMIPARETIC STROKE PATIENTS; LOWER-EXTREMITY
FUNCTION; STEP WIDTH VARIABILITY; PHYSICAL PERFORMANCE; GAIT
VARIABILITY; AEROBIC EXERCISE; FALL RISK; METABOLIC COST; HEART-RATE
AB Background. Therapeutic activities to improve mobility often include walking practice and exercises to improve deficits in endurance, strength. and balance. Because walking may also be energy inefficient in people with decreased mobility, another approach is to reduce energy cost by improving timing and coordination (TC) of movement.
Methods. This pilot randomized trial of older adults with slow and variable gait offered two types of therapeutic activity over 12 weeks. One addressed Walking, Endurance, Balance, and Strength (WEBS) and the other focused on TC. Outcomes were energy cost of walking and measures of mobility.
Results. Of 50 participants (mean age. 77.2 +/- 5.5 years, 65% women). 47 completed the study. Baseline gait speed was 0.85 +/- 0.13 m/s and energy cost of walking was 0.30 +/- 0.10 mL/kg/m, nearly twice normal. Both interventions increased gait speed (TC by 0.21 m/s and WEBS by 0.14 m/s, p < .001). TC reduced the energy cost of walking 0.10 +/- 0.03 mL/kg/m more than WEBS (p < .001) and reduced the modified Gait Abnormalities Rating Scale 1.5 +/- 0.6 more points than WEBS (p < .05). TC had a 9.8 +/- 3.5 points greater gain than WEBS in self-reported confidence in walking (p < .01).
Conclusions. In older adults with slow and variable gait, activity focused on TC reduced the energy cost of walking and improved confidence in walking more than WEBS while generating at least equivalent gains in mobility. To optimize mobility, future larger studies should assess various combinations of TC and WEBS over longer periods of time.
C1 [VanSwearingen, Jessie M.; Brach, Jennifer S.] Univ Pittsburgh, Dept Phys Therapy, Sch Hlth & Rehabil Sci, Pittsburgh, PA 15260 USA.
[Perera, Subashan; Studenski, Stephanie A.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr Med, Pittsburgh, PA 15260 USA.
[Cham, Rakie] Univ Pittsburgh, Sch Engn, Dept Bioengn, Pittsburgh, PA 15260 USA.
[Rosano, Caterina] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Studenski, Stephanie A.] VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA.
RP VanSwearingen, JM (reprint author), Univ Pittsburgh, Dept Phys Therapy, Sch Hlth & Rehabil Sci, 6035 Forbes Tower, Pittsburgh, PA 15260 USA.
EM jessievs@pitt.edu
RI Perera, Subashan/D-7603-2014
FU NIA NIH HHS [AG023641, 1 K23 AG026766-01, P30 AG024827, 1 P30 AG024827]
NR 84
TC 36
Z9 36
U1 7
U2 12
PU GERONTOLOGICAL SOC AMER
PI WASHINGTON
PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD NOV
PY 2009
VL 64
IS 11
BP 1190
EP 1198
DI 10.1093/gerona/glp098
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 509UU
UT WOS:000271044900015
PM 19643842
ER
PT J
AU Siedlecki, KL
Tatarina, O
Sanders, L
Albert, M
Blacker, D
Dubois, B
Brandt, J
Stern, Y
AF Siedlecki, Karen L.
Tatarina, Oksana
Sanders, Linda
Albert, Marilyn
Blacker, Deborah
Dubois, Bruno
Brandt, Jason
Stern, Yaakov
TI Comparison of Patient and Caregiver Reports of Patient Activity
Participation and Its Relationship to Mental Health in Patients With
Alzheimer's Disease
SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL
SCIENCES
LA English
DT Article
DE Activities; Alzheimer's disease; Invariance analyses; Structural
equation modeling
ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; EVENTS SCHEDULE-AD;
COGNITIVE IMPAIRMENT; DEMENTIA; MULTICENTER; DEPRESSION; PREDICTORS;
CARE
AB The relationship between engagement in pleasant activities as rated by the patient and as rated by the caregiver from the patient's perspective was examined using structural equation modeling in a sample of patients (N=277) diagnosed with mild to moderate Alzheimer's disease. The two activity participation ratings were only moderately related to one another. Furthermore, depression was the only significant predictor of the patient-rated activity participation, whereas severity of depression, degree of personality change, level of dependence, and cognition were all significant predictors of caregiver-rated activity participation. These findings suggest that caregivers consider a wider range of variables when evaluating the patient's engagement in activities than does the patient. Predictors of patient-rated activity participation did not differ as a function of age or cognition.
C1 [Siedlecki, Karen L.; Tatarina, Oksana; Sanders, Linda; Stern, Yaakov] Columbia Univ, Cognit Neurosci Div, Taub Inst, New York, NY 10032 USA.
[Albert, Marilyn] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
[Blacker, Deborah] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Dubois, Bruno] Hop La Pitie Salpetriere, Dept Neurol, Paris, France.
RP Siedlecki, KL (reprint author), Columbia Univ, Cognit Neurosci Div, Taub Inst, 630 W 168th St, New York, NY 10032 USA.
EM ks2513@columbia.edu
OI Brandt, Jason/0000-0001-7381-6244
FU National Institute of Health [AG07370, RR00645]; NIMH [T32MH020004-09]
FX This study was supported by National Institute of Health federal grants
AG07370 and RR00645. KLS is supported as a trainee by a grant
(T32MH020004-09) from the NIMH.
NR 29
TC 9
Z9 9
U1 0
U2 3
PU GERONTOLOGICAL SOC AMER
PI WASHINGTON
PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA
SN 1079-5014
J9 J GERONTOL B-PSYCHOL
JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci.
PD NOV
PY 2009
VL 64
IS 6
BP 687
EP 695
DI 10.1093/geronb/gbp071
PG 9
WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology,
Multidisciplinary
SC Geriatrics & Gerontology; Psychology
GA 518TY
UT WOS:000271718200001
PM 19805487
ER
PT J
AU Mehrotra, R
Kermah, DA
Salusky, IB
Wolf, MS
Thadhani, RI
Chiu, YW
Martins, D
Adler, SG
Norris, KC
AF Mehrotra, Rajnish
Kermah, Dulcie A.
Salusky, Isidro B.
Wolf, Myles S.
Thadhani, Ravi I.
Chiu, Yi-Wen
Martins, David
Adler, Sharon G.
Norris, Keith C.
TI Chronic kidney disease, hypovitaminosis D, and mortality in the United
States
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE cardiovascular; chronic kidney disease; mortality; non-cardiovascular;
vitamin D
ID SERUM 25-HYDROXYVITAMIN-D STATUS; VITAMIN-D DEFICIENCY;
HEMODIALYSIS-PATIENTS; ASSOCIATION; SURVIVAL; RISK; NEPHROPATHY;
POPULATION; PREVALENCE; EXPRESSION
AB Low serum 25-hydroxy vitamin D (25OHD) predicts a higher cardiovascular risk in the general population. Because patients with chronic kidney disease are more likely to have low serum 25OHD, we determined the relationship between hypovitaminosis D and death in this group. Analysis was done using a cohort composed of 3011 patients from the Third National Health and Nutrition Examination Survey who had chronic kidney disease but were not on dialysis and who had a mean follow-up of 9 years. In analyses adjusted for demographics, cardiovascular risk factors, serum phosphorus, albumin, hemoglobin, stage of chronic kidney disease, albuminuria, and socioeconomic status, individuals with serum 25OHD levels less than 15 ng/ml had an increased risk for all-cause mortality when compared to those with levels over 30 ng/ml. This significantly higher risk for death with low serum 25OHD was evident in 15 of the 23 subgroups. The higher risk for cardiovascular and non-cardiovascular mortality became statistically nonsignificant on multivariable adjustment. The trend for higher mortality in patients with 25OHD levels 15-30 ng/ml was not statistically significant. Our results indicate there is a graded relationship between serum 25OHD and the risk for death among subjects with chronic kidney disease who are not undergoing dialysis. Randomized, controlled trials are needed to conclusively determine whether vitamin D supplementation reduces mortality. Kidney International (2009) 76, 977-983; doi:10.1038/ki.2009.288; published online 5 August 2009
C1 [Mehrotra, Rajnish; Adler, Sharon G.] Los Angeles Biomed Res Inst, Div Nephrol & Hypertens, Dept Med, Torrance, CA 90502 USA.
[Mehrotra, Rajnish; Salusky, Isidro B.; Adler, Sharon G.; Norris, Keith C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Mehrotra, Rajnish; Salusky, Isidro B.; Adler, Sharon G.; Norris, Keith C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA.
[Kermah, Dulcie A.; Martins, David; Norris, Keith C.] Charles Drew Univ, Dept Med, Los Angeles, CA USA.
[Wolf, Myles S.] Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA.
[Thadhani, Ravi I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Boston, MA USA.
[Chiu, Yi-Wen] Kaohsiung Med Univ, Dept Med, Kaohsiung, Taiwan.
RP Mehrotra, R (reprint author), Los Angeles Biomed Res Inst, Div Nephrol & Hypertens, Dept Med, 1124 W Carson St, Torrance, CA 90502 USA.
EM rmehrotra@labiomed.org
RI Chiu, Yi-Wen/D-5041-2009
FU NIH [RR18298, RR019234, RR14616, RR11145, MD00182]; NIDDK [35423, 67563,
HL 093954]; NCRR [RR 00865]; [R01DK076116]; [R01DK081374]
FX Rajnish Mehrotra is supported by a grant from the NIH (RR18298 and
RR019234) and DaVita. Isidro B. Salusky is supported by grants from
NIDDK (35423 and 67563) and NCRR (RR 00865), Myles Wolf by R01DK076116
and R01DK081374, and Ravi Thadhani by a grant from NIDDK (HL 093954).
Dulcie Kermah, David Martins, and Keith Norris are supported by NIH
grants RR14616, RR11145, RR019234, and MD00182.
NR 30
TC 114
Z9 124
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD NOV
PY 2009
VL 76
IS 9
BP 977
EP 983
DI 10.1038/ki.2009.288
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 507LC
UT WOS:000270853800010
PM 19657329
ER
PT J
AU Johansen, KL
Zhang, R
Huang, YJ
Chen, SC
Blagg, CR
Goldfarb-Rumyantzev, AS
Hoy, CD
Lockridge, RS
Miller, BW
Eggers, PW
Kutner, NG
AF Johansen, Kirsten L.
Zhang, Rebecca
Huang, Yijian
Chen, Shu-Cheng
Blagg, Christopher R.
Goldfarb-Rumyantzev, Alexander S.
Hoy, Chistopher D.
Lockridge, Robert S., Jr.
Miller, Brent W.
Eggers, Paul W.
Kutner, Nancy G.
TI Survival and hospitalization among patients using nocturnal and short
daily compared to conventional hemodialysis: a USRDS study
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE daily hemodialysis; hospitalization; survival; USRDS
ID LEFT-VENTRICULAR HYPERTROPHY; QUALITY-OF-LIFE; IN-CENTER HEMODIALYSIS;
VASCULAR ACCESS; HOME HEMODIALYSIS; DAILY DIALYSIS; LONG-TERM; COST;
MORTALITY; TRIAL
AB We estimated the survival and hospitalization among frequent hemodialysis users in comparison to those patients undergoing thrice-weekly conventional hemodialysis. All patients had similar characteristics and medical histories. In this cohort study of frequent hemodialysis users and propensity score-matched controls, the collaborating clinicians identified 94 patients who used nocturnal hermodialysis (NHD) and 43 patients who used short-duration daily hemodialysis (SDHD) for a minimum of 60 days. Ten propensity score-matched control patients for each NHD and SDHD patient were identified from the United States Renal Data System database. Primary outcomes were risk for all-cause mortality and risk for the composite outcome of mortality or major morbid event (acute myocardial infarction or stroke) estimated using Cox proportional hazards models. Risks for all-cause, cardiovascular-related, infection-related, and vascular access-related hospital admissions were also studied. Nocturnal hemodialysis was associated with significant reductions in mortality risk and risk for mortality or major morbid event when compared to conventional hemodialysis. There was a reduced but non-significant risk of death for patients using SDHD compared to controls. All-cause and specific hospitalizations did not differ significantly between NHD and SDHD patients and their matched control cohorts. Our study suggests that NHD may improve patient survival. Kidney International (2009) 76, 984-990; doi:10.1038/ki.2009.291; published online 19 August 2009
C1 [Kutner, Nancy G.] Emory Univ, Dept Rehabil Med, USRDS Rehabil QoL Special Studies Ctr, Atlanta, GA 30322 USA.
[Johansen, Kirsten L.] Univ Calif San Francisco, Nephrol Sect, San Francisco VA Med Ctr, San Francisco, CA 94143 USA.
[Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA.
[Chen, Shu-Cheng] USRDS Coordinating Ctr, Minneapolis, MN USA.
[Blagg, Christopher R.] NW Kidney Ctr, Seattle, WA USA.
[Goldfarb-Rumyantzev, Alexander S.] Harvard Univ, Sch Med, Boston, MA USA.
[Hoy, Chistopher D.] Rubin Dialysis Ctr, Saratoga Springs, NY USA.
[Lockridge, Robert S., Jr.] Lynchburg Nephrol Dialysis, Lynchburg, VA USA.
[Miller, Brent W.] Washington Univ, Sch Med, St Louis, MO USA.
[Eggers, Paul W.] NIDDK, NIH, Bethesda, MD USA.
RP Kutner, NG (reprint author), Emory Univ, Dept Rehabil Med, USRDS Rehabil QoL Special Studies Ctr, 1441 Clifton Rd NE, Atlanta, GA 30322 USA.
EM nkutner@emory.edu
FU National Institutes of Health [N01-DK-1-2471, HHSN267200715004C]
FX This study was supported by the National Institutes of Health contracts
N01-DK-1-2471 and HHSN267200715004C, ADB No. N01-DK-7-5004. The
interpretation and reporting of the data presented here are the
responsibility of the authors and in no way should be seen as an
official policy or interpretation of the United States government. An
abstract was presented in poster form at the annual meeting of the
American Society of Nephrology; 3 November 2007, San Francisco, CA, USA.
NR 37
TC 101
Z9 101
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD NOV
PY 2009
VL 76
IS 9
BP 984
EP 990
DI 10.1038/ki.2009.291
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 507LC
UT WOS:000270853800011
PM 19692997
ER
PT J
AU Shakespeare, T
Lezzoni, LI
Groce, NE
AF Shakespeare, Tom
Lezzoni, Lisa I.
Groce, Nora E.
TI The art of medicine Disability and the training of health professionals
SO LANCET
LA English
DT Editorial Material
C1 [Shakespeare, Tom] WHO, Dept Violence & Injury Prevent & Disabil, CH-1211 Geneva 27, Switzerland.
[Lezzoni, Lisa I.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA.
[Groce, Nora E.] UCL, Leonard Cheshire Ctr Disabil & Inclus Dev, London, England.
RP Shakespeare, T (reprint author), WHO, Dept Violence & Injury Prevent & Disabil, CH-1211 Geneva 27, Switzerland.
EM shakespearet@who.int
NR 8
TC 47
Z9 47
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD NOV-DEC
PY 2009
VL 374
IS 9704
BP 1815
EP 1816
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 527MC
UT WOS:000272370200017
PM 19957403
ER
PT J
AU Burns, JA
Kim, KH
Kobler, JB
deBoer, JF
Lopez-Guerra, G
Zeitels, SM
AF Burns, James A.
Kim, Ki Hean
Kobler, James B.
deBoer, Johannes F.
Lopez-Guerra, Gerardo
Zeitels, Steven M.
TI Real-Time Tracking of Vocal Fold Injections With Optical Coherence
Tomography
SO LARYNGOSCOPE
LA English
DT Article; Proceedings Paper
CT 130th Annual Meeting of the American-Laryngological-Association Combined
Otolaryngology Spring Meeting
CY MAY 28, 2009
CL Phoenix, AZ
SP Amer Laryngol Assoc
DE Optical coherence tomography; larynx; glottis; vocal fold; vocal fold
injection
ID IN-VIVO
AB Objectives/Hypothesis: Optical coherence tomography (OCT) is a promising new imaging modality that can help discern the layered microstructure of vocal folds. In the future, subepithelial injections of implants will improve vocal fold pliability where there is stiffness of phonatory mucosa. Using OCT both to delineate the depth of subepithelial injections real-time and to serially image the implant over time would be valuable, and has not been demonstrated previously.
Study Design: Ex vivo study using excised calf larynges and survival study using canines in vivo.
Methods: An investigation was done employing real-time OCT imaging of subepithelial injection pulses into phonatory mucosa of four calf larynges ex vivo to track the presence of subepithelial implants in phonatory mucosa in a survival study using an in vivo canine model.
Results: OCT readily identified polyethylene glycol (PEG)-based hydrogel in the subepithelial plane in both the ex vivo calf study and the in vivo canine study. Ex vivo calf images correlated with histological specimens obtained immediately postinjection. Images obtained in this study provide confirmation of the hydrogel injection depth in real time, and allow for the implant to be tracked during a canine survival study.
Conclusions: OCT can confirm subepithelial placement of hydrogel implant in the vocal fold with sufficient resolution to provide instantaneous feedback of an injection pulse. Survival studies in an in vivo canine model indicate that OCT can potentially be helpful in monitoring rheologically appropriate implants within the superficial lamina propria.
C1 [Burns, James A.; Kobler, James B.; Lopez-Guerra, Gerardo; Zeitels, Steven M.] Harvard Univ, Sch Med, Ctr Laryngeal Surg & Voice Rehabil, Dept Surg, Boston, MA 02114 USA.
[Kim, Ki Hean] Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[deBoer, Johannes F.] Vrije Univ Amsterdam, Dept Phys, Amsterdam, Netherlands.
RP Burns, JA (reprint author), Harvard Univ, Sch Med, Ctr Laryngeal Surg & Voice Rehabil, Massachusetts Gen Hosp, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA.
EM burns.james@mgh.harvard.edu
RI de Boer, Johannes/B-7590-2012;
OI de Boer, Johannes/0000-0003-1253-4950; Lopez-Guerra,
Gerardo/0000-0003-0305-4680
NR 18
TC 16
Z9 18
U1 0
U2 4
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0023-852X
J9 LARYNGOSCOPE
JI Laryngoscope
PD NOV
PY 2009
VL 119
IS 11
BP 2182
EP 2186
DI 10.1002/lary.20654
PG 5
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA 518LG
UT WOS:000271692900018
PM 19676103
ER
PT J
AU Herrera, VLM
Viereck, JC
Lopez-Guerra, G
Kumai, Y
Kobler, J
Karajanagi, S
Park, H
Hillman, R
Zeitels, SM
AF Herrera, Victoria L. M.
Viereck, Jason C.
Lopez-Guerra, Gerardo
Kumai, Yoshihiko
Kobler, James
Karajanagi, Sandeep
Park, Hyoungshin
Hillman, Robert
Zeitels, Steven M.
TI 11.7 Tesla Magnetic Resonance Microimaging of Laryngeal Tissue
Architecture
SO LARYNGOSCOPE
LA English
DT Article
DE 11.7 T MRI; microimaging; VF implants; vocal fold scar
ID MRI
AB Objectives/Hypothesis: High-resolution imaging of vocal folds that distinguishes vocal fold (VF) layered microstructure and VF implants would provide a key experimental tool for translational research investigating biomaterial-based interventions to treat vocal fold scar. To establish proof of concept, we studied whether 11.7 Tesla (T) magnetic resonance (MR) microimaging provides the needed resolution to resolve vocal fold tissue architecture.
Study Design: We performed ex vivo MR microimaging of fixed ferret and canine larynges to determine whether changes in the layered architecture can be detected in the presence of scar and subsequent to biomaterial injections into the vocal folds. Serial section histological analyses were done to corroborate MR microimaging findings.
Methods: Multiple axial and transverse/coronal 300-mu m slices were obtained using an 11.7 T MR speetrometer/500 MHz for proton with gradient-recalled echo and rapid acquisition with relaxation enhancement imaging sequences.
Results: High-resolution (39 mu m/pixel) MR microimages distinguished VF epithelium, lamina propria, muscle, and cartilage in ferret and canine larynges. In ferret scarred VFs (n = 25), collagen-rich dense scar tissue was distinguishable from contralateral nonscarred VFs and from normal ferret VFs (n = 25), as confirmed on histology. MR microimaging accurately detected injected autologous fat, hyaluronic acid-based and polyethylene glycol (PEG)based implants injected into both ferret and canine VFs. Importantly, MRI accurately showed resorption of PEG implants in ferrets and canines, as confirmed on histology. Additionally, ex vivo MR spectroscopy distinguished fat from PEG-based implants.
Conclusions: Ex vivo 11.7 T MR microimaging provided high-resolution images of ferret and canine laryngeal tissue microstructure, although the superficial lamina propria could not be distinguished. Histology confirmed MR microimaging findings, indicating utility of MR microimaging of modeled scar, implant residence time, and tissue responses, thus providing integrative insight relevant to translational research.
C1 [Herrera, Victoria L. M.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Viereck, Jason C.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Lopez-Guerra, Gerardo; Kumai, Yoshihiko; Kobler, James; Karajanagi, Sandeep; Park, Hyoungshin; Hillman, Robert; Zeitels, Steven M.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Herrera, VLM (reprint author), Boston Univ, Sch Med, Dept Med, 700 Albany St,Room W-609, Boston, MA 02118 USA.
EM vherrera@bu.edu
OI Lopez-Guerra, Gerardo/0000-0003-0305-4680
FU Institute of Laryngeal and Voice Restoration; Eugene B. Casey Foundation
FX This work was supported by the Institute of Laryngeal and Voice
Restoration and the Eugene B. Casey Foundation.
NR 16
TC 9
Z9 10
U1 0
U2 6
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0023-852X
J9 LARYNGOSCOPE
JI Laryngoscope
PD NOV
PY 2009
VL 119
IS 11
BP 2187
EP 2194
DI 10.1002/lary.20643
PG 8
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA 518LG
UT WOS:000271692900019
PM 19824052
ER
PT J
AU Quesnel, AM
Hartnick, CJ
AF Quesnel, Alicia M.
Hartnick, Christopher J.
TI A Contemporary Review of Voice and Airway After Laryngeal Trauma in
Children
SO LARYNGOSCOPE
LA English
DT Article; Proceedings Paper
CT Eastern Section Meeting of the Triological-Society
CY JAN 24-25, 2009
CL Boston, MA
SP Triol Soc
DE Pediatric airway; voice; laryngeal trauma
ID LARYNGOTRACHEAL TRAUMA; MANAGEMENT
AB Objectives/Hypothesis: To discuss three cases of pediatric laryngeal trauma that highlight current techniques in diagnosis and treatment of the voice following laryngeal trauma. To examine the diagnostic utility of "chip tip" video laryngoscopy and to explore the current uses for open, endoscopic, or combined approaches within the context of these cases.
Study Design: Case series with review of contemporary techniques.
Methods: A case series of three children who sustained laryngeal trauma is presented. Ages range from 6 weeks to 17 years. The diagnostic evaluation and treatment strategies are reviewed with a focus on contemporary techniques.
Results: A 15-year-old boy who sustained blunt neck trauma was diagnosed with a vocal fold avulsion on video laryngoscopy with digital image processing and a significant mucosal tear with exposure of the paraglottic space on direct laryngoscopy. Anatomical reapproximation required a combined open and endoscopic repair. A 17-year-old football player developed a glottic hematoma after blunt cervical trauma. This was managed conservatively with serial chip tip video laryngoscopy that provided high fidelity images and facilitated proper and timely diagnosis and treatment. A 6-week-old male suffered vocal fold avulsion from a traumatic intubation. Laryngofissure with reattachment of the vocal fold resolved his aspiration and reconstructed the laryngeal anatomy.
Conclusions: Enhanced imaging via chip tip video laryngoscopy, compared to conventional fiberoptic endoscopy, might provide additional diagnostic information in pediatric patients with laryngeal trauma. Additionally, there could be a role for video strobolaryngoscopy in selected laryngeal trauma patients. Open, endoscopic, and combined approaches could be used to optimize voice and swallowing outcomes in pediatric laryngeal trauma.
C1 [Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Div Pediat Otolaryngol, Dept Otol & Laryngol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Div Pediat Otolaryngol, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA.
EM christopher_hartnick@meei.harvard.edu
NR 13
TC 5
Z9 5
U1 1
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0023-852X
J9 LARYNGOSCOPE
JI Laryngoscope
PD NOV
PY 2009
VL 119
IS 11
BP 2226
EP 2230
DI 10.1002/lary.20492
PG 5
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA 518LG
UT WOS:000271692900025
PM 19434680
ER
PT J
AU Zelickson, BD
Walgrave, SE
Al-Arashi, MYH
Altshuler, GB
Yaroslavsky, IV
Childs, JJ
Cohen, RH
Erofeev, AV
Depina, EF
Smirnov, MZ
Kist, DA
Tabatadze, DR
AF Zelickson, Brian D.
Walgrave, Susan E.
Al-Arashi, Munir Yahya H.
Altshuler, Gregory B.
Yaroslavsky, Ilya V.
Childs, James J.
Cohen, Rich H.
Erofeev, Andrei V.
Depina, Erminaldo F.
Smirnov, Mikhail Z.
Kist, David A.
Tabatadze, David R.
TI Semi-Automated Method of Analysis of Horizontal Histological Sections of
Skin for Objective Evaluation of Fractional Devices
SO LASERS IN SURGERY AND MEDICINE
LA English
DT Article
DE fractional lasers; columns of micro-damage; histological evaluation
ID OPTICAL COHERENCE TOMOGRAPHY; LASER; PHOTOTHERMOLYSIS; TISSUE
AB Background and Objective: The treatment of skin with fractional devices creates columns of micro-ablation or micro-denaturation depending on the device. Since the geometric profiles of thermal damage depend on the treatment parameters or physical properties of the treated tissue, the size of these columns may vary from a few microns to a few millimeters. For objective evaluation of the damage profiles generated by fractional devices, this report describes an innovative and efficient method of processing and evaluating horizontal sections of skin using a novel software program.
Materials and Methods: Ex vivo porcine skin was treated with the Lux1540/10, Lux1540 Zoom and Lux2940 with 500 optics. Horizontal (radial) sections of biopsies were obtained and processed with H&E and NBTC staining. Digital images of the histologic sections were taken in either transmission or reflection illumination and were processed using the SAFHIR program.
Results: NBTC- and H&E-stained horizontal sections of ex vivo skin treated with ablative and non-ablative fractional devices were obtained. Geometric parameters, such as depth, diameter, and width of the coagulated layer (if applicable), and micro-columns of thermal damage, were evaluated using the SAFHIR software. The feasibility of objective comparison of the performance of two different fractional devices was demonstrated.
Conclusion: The proposed methodology provides a comprehensive, objective, and efficient approach for the comparison of various fractional devices. Correlation of device settings with the objective dimensions of post-treatment damage profiles serve as a powerful tool for the prediction and modulation of clinical response. Lasers Surg. Med. 41:634-642, 2009. (C) 2009 Wiley-Liss, Inc.
C1 [Zelickson, Brian D.; Walgrave, Susan E.] Zel Skin & Laser Specialists, Edina, MN 55424 USA.
[Zelickson, Brian D.; Kist, David A.] Univ Minnesota, Dept Dermatol, Minneapolis, MN 55455 USA.
[Al-Arashi, Munir Yahya H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Al-Arashi, Munir Yahya H.; Altshuler, Gregory B.; Yaroslavsky, Ilya V.; Childs, James J.; Cohen, Rich H.; Erofeev, Andrei V.; Depina, Erminaldo F.; Smirnov, Mikhail Z.; Tabatadze, David R.] Palomar Med Technol Inc, Burlington, MA 01803 USA.
RP Zelickson, BD (reprint author), Zel Skin & Laser Specialists, 4100 W 50th St, Edina, MN 55424 USA.
EM zelic002@earthlink.net
NR 15
TC 11
Z9 11
U1 0
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0196-8092
J9 LASER SURG MED
JI Lasers Surg. Med.
PD NOV
PY 2009
VL 41
IS 9
BP 634
EP 642
DI 10.1002/lsm.20843
PG 9
WC Dermatology; Surgery
SC Dermatology; Surgery
GA 515VB
UT WOS:000271499900005
PM 19816914
ER
PT J
AU Lacy, MQ
Jacobus, S
Blood, EA
Kay, NE
Rajkumar, SV
Greipp, PR
AF Lacy, Martha Q.
Jacobus, Susanna
Blood, Emily A.
Kay, Neil E.
Rajkumar, S. Vincent
Greipp, Philip R.
TI Phase II study of interleukin-12 for treatment of plateau phase multiple
myeloma (E1A96): A trial of the Eastern Cooperative Oncology Group
SO LEUKEMIA RESEARCH
LA English
DT Article
DE Multiple myeloma; Interleukin-12; Immunomodulatory therapy
ID MAINTENANCE THERAPY; RANDOMIZED TRIALS; INTERFERON; COMBINATION;
PREDNISONE; RITUXIMAB; LYMPHOMA
AB The Eastern Cooperative Oncology Group (ECOG) conducted a phase II trial of interleukin-12 (IL-12) for plateau phase multiple myeloma. Patients were initially treated with IL-12 250 ng/kg I.V. daily for 5 days every 3 weeks. The trial was modified due to toxicity after the first 16 patients. IL-12 was given 300 ng/kg subcutaneously twice weekly for 24 weeks. Of 48 eligible patients, there were 4 objective responses (8.3%), all CR. The median survival and progression-free survival were 42.8 and 11.4 months. Unacceptable grade 3 or 4 non-hematologic toxicity (31% with IL-12 subcutaneously and 63% with IL-12 intravenously) was observed. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Lacy, Martha Q.] Mayo Clin, Div Hematol, Rochester, MN 55905 USA.
[Jacobus, Susanna; Blood, Emily A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Lacy, MQ (reprint author), Mayo Clin, Div Hematol, 200 1st St SW, Rochester, MN 55905 USA.
EM lacy.martha@mayo.edu
OI Rajkumar, S. Vincent/0000-0002-5862-1833
FU Celgene Corporation; Millennium; Takeda Oncology Company; Genzyme
FX Dr. Lacy: Grant/Research Support: Celgene Corporation, Millennium, The
Takeda Oncology Company, and Genzyme.
NR 14
TC 18
Z9 20
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0145-2126
J9 LEUKEMIA RES
JI Leuk. Res.
PD NOV
PY 2009
VL 33
IS 11
BP 1485
EP 1489
DI 10.1016/j.leukres.2009.01.020
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA 495DM
UT WOS:000269870400012
PM 19243818
ER
PT J
AU Schiodt, FV
Chung, RT
Schilsky, ML
Hay, JE
Christensen, E
Lee, WM
AF Schiodt, Frank V.
Chung, Raymond T.
Schilsky, Michael L.
Hay, J. Eileen
Christensen, Erik
Lee, William M.
CA Acute Liver Failure Study Grp
TI Outcome of Acute Liver Failure in the Elderly
SO LIVER TRANSPLANTATION
LA English
DT Article
ID FULMINANT HEPATIC-FAILURE; SINGLE-CENTER EXPERIENCE; REGENERATING RAT
LIVER; AGE-RELATED-CHANGES; EARLY INDICATORS; UNITED-STATES; BLOOD-FLOW;
DONOR AGE; TRANSPLANTATION; PROGNOSIS
AB Older age is considered a poor prognostic factor in acute liver failure (ALF) and may still be considered a relative contraindication for liver transplantation for ALF. We aimed to evaluate the impact of older age, defined as age >= 60 years, on outcomes in patients with ALF. One thousand one hundred twenty-six consecutive prospective patients from the US Acute Liver Failure Study Group registry were studied. The median age was 38 years (range, 15-81 years). One thousand sixteen patients (90.2%) were younger than 60 years (group 1), and 499 (49.1%) of these had acetaminophen-induced ALF; this rate of acetaminophen-induced ALF was significantly higher than that in patients >= 60 years (group 2; n = 110; 23.6% with acetaminophen-induced ALF, P < 0.001). The overall survival rate was 72.7% in group 1 and 60.0% in group 2 (not significant) for acetaminophen patients and 67.9% in group 1 and 48.2% in group 2 for non-acetaminophen patients (P < 0.001). The spontaneous survival rate (ie, survival without liver transplantation) was 64.9% in group 1 and 60.0% in group 2 (not significant) for acetaminophen patients and 30.8% in group 1 and 24.7% in group 2 for non-acetaminophen patients (P = 0.27). Age was not a significant predictor of spontaneous survival in multiple logistic regression analyses. Group 2 patients were listed for liver transplantation significantly less than group 1 patients. Age was listed as a contraindication for transplantation in 5 patients. In conclusion, in contrast to previous studies, we have demonstrated a relatively good spontaneous survival rate for older patients with ALF when it is corrected for etiology. However, overall survival was better for younger non-acetaminophen patients. Fewer older patients were listed for transplantation. Liver Transpl 15:1481-1487, 2009. (C) 2009 AASLD.
C1 [Schiodt, Frank V.; Christensen, Erik] Bispebjerg Hosp, Dept Internal Med 1, DK-2400 Copenhagen NV, Denmark.
[Schiodt, Frank V.; Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA.
[Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Schilsky, Michael L.] Yale New Haven Transplant Ctr, New Haven, CT USA.
[Hay, J. Eileen] Mayo Clin, Rochester, MN USA.
RP Schiodt, FV (reprint author), Bispebjerg Hosp, Dept Internal Med 1, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark.
EM schiodt@get2net.dk
FU National Institute of Diabetes and Digestive and Kidney Diseases for the
Acute Liver Failure Study Group [DK U-01 58369]; Tips Fund of the
Northwestern Medical Foundation; Jeanne Roberts and Rollin and Mary Ella
King Funds of the Southwestern Medical Foundation
FX This study was funded by a National Institutes of Health grant (DK U-01
58369) provided by the National Institute of Diabetes and Digestive and
Kidney Diseases for the Acute Liver Failure Study Group. Additional
funding was provided by the Tips Fund of the Northwestern Medical
Foundation and the Jeanne Roberts and Rollin and Mary Ella King Funds of
the Southwestern Medical Foundation.
NR 36
TC 11
Z9 11
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1527-6465
J9 LIVER TRANSPLANT
JI Liver Transplant.
PD NOV
PY 2009
VL 15
IS 11
BP 1481
EP 1487
DI 10.1002/lt.21865
PG 7
WC Gastroenterology & Hepatology; Surgery; Transplantation
SC Gastroenterology & Hepatology; Surgery; Transplantation
GA 517HQ
UT WOS:000271604400015
PM 19877205
ER
PT J
AU Cooley, ME
Sarna, L
Kotlerman, J
Lukanich, JM
Jaklitsch, M
Green, SB
Bueno, R
AF Cooley, Mary E.
Sarna, Linda
Kotlerman, Jenny
Lukanich, Jeanne M.
Jaklitsch, Michael
Green, Sarah B.
Bueno, Raphael
TI Smoking cessation is challenging even for patients recovering from lung
cancer surgery with curative intent
SO LUNG CANCER
LA English
DT Article
DE Lung cancer; Thoracic surgery; Smoking cessation; Symptom management;
Tobacco dependence; Nicotine dependence treatment; Smoking; Cancer
treatment
ID QUALITY-OF-LIFE; CONTINUED TOBACCO USE; LONG-TERM SURVIVORS; DEPENDENCE
TREATMENT; NICOTINE DEPENDENCE; CLINICAL-TRIALS; PREVALENCE; PREDICTORS;
ABSTINENCE; SMOKERS
AB Background: Although it is recommended that smokers undergoing surgery for lung cancer quit smoking to reduce post-operative complications, few studies have examined patterns of smoking in the peri-operative period. The goals of this study were to determine: (1) patterns of smoking during post-operative recovery, (2) types of cessation strategies used to quit smoking, and (3) factors related to smoking after lung cancer surgery.
Methods: Data were collected from 94 patients through chart review, tobacco, health status, and symptom questionnaires at 1, 2, and 4 months after surgery. Smoking status was assessed through self-report and urinary cotinine measurement.
Results: Eighty-four patients (89%)were ever-smokers and 35 (37%) reported smoking at diagnosis. Thirty-nine (46%) ever-smokers remained abstinent, 13 (16%) continued smoking at all time-points, and 32 (38%) relapsed. Ten (46%) of those who relapsed were former-smokers and had not smoked for at least 1 year. Sixteen (46%) of those who were smoking at diagnosis received cessation assistance with pharmacotherapy being the most common strategy. Factors associated with smoking during recovery were younger age and quitting smoking <6 months before the diagnosis of lung cancer. Factors that were marginally significant were lower educational level, male gender, lower number of comorbidities, and the presence of pain.
Conclusion: Only half of those who were smoking received assistance to quit prior to surgery. Some patients were unable to quit and relapse rates post-surgery were high even among those who quit more than 1 year prior. Innovative programs incorporating symptom management and relapse prevention may enhance smoking abstinence during post-operative care. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Cooley, Mary E.; Green, Sarah B.] Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA.
[Cooley, Mary E.] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA.
[Sarna, Linda] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA.
[Kotlerman, Jenny] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Lukanich, Jeanne M.; Jaklitsch, Michael; Bueno, Raphael] Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA.
RP Cooley, ME (reprint author), Dana Farber Canc Inst, Phyllis F Cantor Ctr, 44 Binney St,CP 302, Boston, MA 02115 USA.
EM mary_cooley@dfci.harvard.edu; lsarna@sonnet.ucla.edu;
jkotlerman@mednet.ucla.edu; jlukanich@partners.org;
Mjaklitsch@partners.org; rbueno@partners.org
FU National Cancer Institute [1 K07 CA92696-02]; James B. Gillen Thoracic
Oncology Research Fund; Dana-Farber Cancer Institute; Oncology Nursing
Foundation Center for Leadership, Information, and Research [018652]
FX Funding from the National Cancer Institute 1 K07 CA92696-02 and James B.
Gillen Thoracic Oncology Research Fund, Dana-Farber Cancer Institute
(Mary E. Cooley) and Oncology Nursing Foundation Center for Leadership,
Information, and Research (#018652) (PI: Linda Sarna).
NR 53
TC 41
Z9 41
U1 0
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0169-5002
J9 LUNG CANCER
JI Lung Cancer
PD NOV
PY 2009
VL 66
IS 2
BP 218
EP 225
DI 10.1016/j.lungcan.2009.01.021
PG 8
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 527ME
UT WOS:000272370400012
PM 19321223
ER
PT J
AU Liu, S
Gonen, O
Fleysher, R
Fleysher, L
Babb, JS
Soher, BJ
Joo, CG
Ratai, EM
Gonzalez, RG
AF Liu, Songtao
Gonen, Oded
Fleysher, Roman
Fleysher, Lazar
Babb, James S.
Soher, Brian J.
Joo, Chan-Gyu
Ratai, Eva-Maria
Gonzalez, R. Gilberto
TI Metabolite Proton T-2 Mapping in the Healthy Rhesus Macaque Brain at 3 T
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE animal models; brain metabolites; high magnetic field; MR spectroscopic
imaging; rhesus macaque; transverse relaxation time
ID AUTOMATED SPECTRAL-ANALYSIS; RELAXATION-TIMES; MR SPECTROSCOPY;
ACQUISITION STRATEGY; MAGNETIC-FIELDS; TESLA; RESOLUTION; DISEASE;
MODEL; WATER
AB The structure and metabolism of the rhesus macaque brain, an advanced model for neurologic diseases and their treatment response, is often studied noninvasively with MRI and H-1-MR spectroscopy. Due to the shorter transverse relaxation time (T-2) at the higher magnetic fields these studies favor, the echo times used in H-1-MR spectroscopy subject the metabolites to unknown T-2 weighting, decreasing the accuracy of quantification which is key for inter- and intra-animal comparisons. To establish the "baseline" (healthy animal) T-2 values, we mapped them for the three main metabolites' T(2)s at 3 T in four healthy rhesus macaques and tested the hypotheses that their mean values are similar (i) among animals; and (ii) to analogs regions in the human brain. This was done with three-dimensional multivoxel H-1-MR spectroscopy at (0.6 x 0.6 x 0.5 cm)(3) = 180 mu L spatial resolution over a 4.2 x 3.0 x 2.0 = 25 cm(3) (similar to 30%) of the macaque brain in a two-point protocol that optimizes T-2 precision per unit time. The estimated T(2)s in several gray and white matter regions are all within 10% of those reported in the human brain (mean +/- standard error of the mean): N-acetylaspartate = 316 +/- 7, creatine = 177 +/- 3, and choline = 264 +/- 9 ms, with no statistically significant gray versus white matter differences. Magn Reson Med 62:1292-1299, 2009. (C) 2009 Wiley-Liss, Inc.
C1 [Liu, Songtao; Gonen, Oded; Fleysher, Roman; Fleysher, Lazar; Babb, James S.] NYU, Sch Med, Dept Radiol, New York, NY 10016 USA.
[Joo, Chan-Gyu; Ratai, Eva-Maria; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Joo, Chan-Gyu; Ratai, Eva-Maria; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Neuroradiol Div, Charlestown, MA USA.
[Soher, Brian J.] Duke Univ, Med Ctr, Dept Radiol, Ctr Adv MR Dev, Durham, NC 27710 USA.
RP Gonen, O (reprint author), NYU, Sch Med, Dept Radiol, 660 1st Ave,4th Floor, New York, NY 10016 USA.
EM oded.gonen@med.nyu.edu
OI Gonen, Oded/0000-0002-3148-2028
FU National Institutes of Health [EB01015, NS050520, NS050041, NS051129,
NS059331, P51RR000168, A1028691, NS040237]; National Center for Research
Resources [P41RR14075]
FX Grant sponsor: National Institutes of Health; Grant numbers: EB01015,
NS050520, NS050041, NS051129, NS059331, P51RR000168, A1028691 and
NS040237; National Center for Research Resources; Grant number:
P41RR14075.
NR 25
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD NOV
PY 2009
VL 62
IS 5
BP 1292
EP 1299
DI 10.1002/mrm.22117
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 514XX
UT WOS:000271431200023
PM 19780178
ER
PT J
AU Kressin, NR
Nunn, ME
Singh, H
Orner, MB
Pbert, L
Hayes, C
Culler, C
Glicken, SR
Palfrey, S
Geltman, PL
Cadoret, C
Henshaw, MM
AF Kressin, Nancy R.
Nunn, Martha E.
Singh, Harpreet
Orner, Michelle B.
Pbert, Lori
Hayes, Catherine
Culler, Corinna
Glicken, Stephan R.
Palfrey, Sean
Geltman, Paul L.
Cadoret, Cynthia
Henshaw, Michelle M.
TI Pediatric Clinicians Can Help Reduce Rates of Early Childhood Caries
Effects of a Practice Based Intervention
SO MEDICAL CARE
LA English
DT Article
DE early childhood caries; physician-patient relations; physicians,';
practice patterns; intervention studies
ID WORCESTER-AREA TRIAL; ORAL-HEALTH; HYPERLIPIDEMIA WATCH; SMOKING
INTERVENTION; PRESCHOOL-CHILDREN; CARE PROVIDERS; DENTAL-CARIES;
PREVALENCE; RESIDENTS; ETHNICITY
AB Objective: Early childhood caries (ECC) is a serious and preventable disease which pediatric clinicians can help address by counseling to reduce risk.
Research Design: We implemented a multifaceted practice-based intervention in a pediatric outpatient clinic treating children vulnerable to ECC (N = 635), comparing results to those from a similar nearby clinic providing usual care (N = 452).
Intervention: We provided communication skills training using the approach of patient centered counseling, edited the electronic medical record to prompt counseling, and provided parents/caregivers with an educational brochure.
Outcome Measures: We assessed changes in provider knowledge about ECC after the intervention, and examined providers' counseling practices and incidence of ECC over time by site, controlling for baseline ECC, patient sociodemographics and parents'/caregivers' practice of risk factors (diet, oral hygiene, tooth-monitoring), among 1045 children with complete data.
Results: Provider knowledge about ECC increased after the intervention training (percentage correct answers improved from 66% to 79%). Providers at the intervention site used more counseling strategies, which persisted after adjustment for socio-demographic characteristics. Children at the intervention site had a 77% reduction in risk for developing ECC at follow up, after controlling for age and race/ethnicity, sociodemographics and ECC risk factors; P <= 0.004.
Conclusions: The multifaceted intervention was associated with increased provider knowledge and counseling, and significantly attenuated incidence of ECC. If validated by additional studies, similar interventions could have the potential to make a significant public health impact on reducing ECC among young children.
C1 [Kressin, Nancy R.] Boston Univ, Gen Internal Med Sect, Crosstown Ctr, HealthCare Dispar Res Program,Sch Med, Boston, MA 02118 USA.
[Kressin, Nancy R.; Nunn, Martha E.; Singh, Harpreet; Orner, Michelle B.; Hayes, Catherine; Culler, Corinna; Geltman, Paul L.; Cadoret, Cynthia; Henshaw, Michelle M.] NE Ctr Res Evaluate & Eliminate Dent Dispar, Boston, MA USA.
[Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA.
[Kressin, Nancy R.; Orner, Michelle B.] VAMC, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA.
[Nunn, Martha E.; Singh, Harpreet; Culler, Corinna; Cadoret, Cynthia; Henshaw, Michelle M.] Boston Univ, Sch Dent Med, Boston, MA 02118 USA.
[Pbert, Lori] Univ Massachusetts, Sch Med, Dept Med, Div Prevent & Behav Med, Worcester, MA 01605 USA.
[Hayes, Catherine] Tufts Univ, Sch Dent Med, Boston, MA 02111 USA.
[Glicken, Stephan R.] Allegheny Gen Hosp, Dept Pediat, Pittsburgh, PA 15212 USA.
[Palfrey, Sean; Geltman, Paul L.] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA.
RP Kressin, NR (reprint author), Boston Univ, Gen Internal Med Sect, Crosstown Ctr, HealthCare Dispar Res Program,Sch Med, 2nd Floor,801 Massachusetts Ave, Boston, MA 02118 USA.
EM nkressin@bu.edu
OI Culler, Corinna/0000-0003-4680-0436
FU NCRR NIH HHS [U54 RR024381]; NIDCR NIH HHS [U54 DE019275, U54
DE14264-S2, K23 DE00454, U54 DE014264-020002, K24 DE000419, K24 DE00419,
U54 DE014264, K23 DE000454]
NR 34
TC 22
Z9 22
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7079
J9 MED CARE
JI Med. Care
PD NOV
PY 2009
VL 47
IS 11
BP 1121
EP 1128
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 515DM
UT WOS:000271447000003
PM 19786919
ER
PT J
AU Sidky, EY
Pan, XC
Reiser, IS
Nishikawa, RM
Moore, RH
Kopans, DB
AF Sidky, Emil Y.
Pan, Xiaochuan
Reiser, Ingrid S.
Nishikawa, Robert M.
Moore, Richard H.
Kopans, Daniel B.
TI Enhanced imaging of microcalcifications in digital breast tomosynthesis
through improved image-reconstruction algorithms
SO MEDICAL PHYSICS
LA English
DT Article
DE digital breast tomosynthesis; iterative image-reconstruction;
total-variation; nonconvex optimization
ID MINIMIZATION; TOMOGRAPHY
AB Purpose: The authors develop a practical, iterative algorithm for image-reconstruction in under-sampled tomographic systems, such as digital breast tomosynthesis (DBT).
Methods: The algorithm controls image regularity by minimizing the image total p variation (TpV), a function that reduces to the total variation when p=1.0 or the image roughness when p=2.0. Constraints on the image, such as image positivity and estimated projection-data tolerance, are enforced by projection onto convex sets. The fact that the tomographic system is undersampled translates to the mathematical property that many widely varied resultant volumes may correspond to a given data tolerance. Thus the application of image regularity serves two purposes: (1) Reduction in the number of resultant volumes out of those allowed by fixing the data tolerance, finding the minimum image TpV for fixed data tolerance, and (2) traditional regularization, sacrificing data fidelity for higher image regularity. The present algorithm allows for this dual role of image regularity in undersampled tomography.
Results: The proposed image-reconstruction algorithm is applied to three clinical DBT data sets. The DBT cases include one with microcalcifications and two with masses.
Conclusions: Results indicate that there may be a substantial advantage in using the present image-reconstruction algorithm for microcalcification imaging. (C) 2009 American Association of Physicists in Medicine. [DOI: 10.1118/1.3232211]
C1 [Sidky, Emil Y.; Pan, Xiaochuan; Reiser, Ingrid S.; Nishikawa, Robert M.] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA.
[Moore, Richard H.; Kopans, Daniel B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Sidky, EY (reprint author), Univ Chicago, Dept Radiol, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM sidky@uchicago.edu; xpan@uchicago.edu
OI Nishikawa, Robert/0000-0001-7720-9951
FU NIH R01 [CA120540, EB000225]; Illinois Department of Public Health
Ticket for the Cure; NIH SPORE [CA125183-03]; NIH [R33 CA109963, R21
EB8801, S10 RR021039, P30 CA14599]; US ARMY [DAMD1798-8309]; NIH-NCI
[5R33CA107863-01]
FX Two of the authors (E.Y.S. and X.P.) were supported in part by NIH R01
Grant Nos. CA120540 and EB000225 and by an Illinois Department of Public
Health Ticket for the Cure Grant. E.Y.S. was also supported in part by a
Career Development Award from NIH SPORE grant CA125183-03. Other two
authors (I.S.R. and R.M.N.) were supported in part by NIH Grant Nos. R33
CA109963 and R21 EB8801. The original MGH-GE instrument was funded by
the US ARMY via Clinical translational research (CTR) DAMD1798-8309, GE
provided the current clinical prototype system designated DBT Senographe
DS. NIH-NCI funded the use of this instrument to acquire 3000 screening
studies as 5R33CA107863-01. Computations for this work were performed on
a cluster, partially funded by NIH Grant Nos. S10 RR021039 and P30
CA14599. The contents of this article are solely the responsibility of
the authors and do not necessarily represent the official views of the
National Institutes of Health.
NR 17
TC 98
Z9 99
U1 0
U2 13
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD NOV
PY 2009
VL 36
IS 11
BP 4920
EP 4932
DI 10.1118/1.3232211
PG 13
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 512BR
UT WOS:000271217900011
PM 19994501
ER
PT J
AU Moriyama, K
Wiener-Kronish, JP
Sawa, T
AF Moriyama, Kiyoshi
Wiener-Kronish, Jeanine P.
Sawa, Teiji
TI Protective effects of affinity-purified antibody and truncated vaccines
against Pseudomonas aeruginosa V-antigen in neutropenic mice
SO MICROBIOLOGY AND IMMUNOLOGY
LA English
DT Article
DE affinity-purified antibody; component vaccine; Pseudomonas aeruginosa
PcrV
ID YERSINIA-PESTIS; MONOCLONAL-ANTIBODY; PASTEURELLA-PESTIS;
PASSIVE-IMMUNITY; VIRULENCE; PCRV; IMMUNIZATION; PNEUMONIA; INFECTION;
STRAINS
AB Virulent P. aeruginosa strainsexpress PcrV, one of the translocational components of the type III secretion system. PcrV has been reported to be a protective antigen against lethal P. aeruginosa infection. The PcrV region, which contributes to protective immunity against P. aeruginosa infection, was investigated by using genetically engineered, truncated PcrV proteins and affinity-purified anti-PcrV antibodies against the truncated PcrV proteins. The efficacy of active and passive immunization against PcrV was tested in mice with cyclophosphamide-induced immunosuppression by intraabdominal challenge of P. aeruginosa. Active immunization with either full-length PcrV1-294 or PcrV139-294 significantly improved the survival of mice infected with P. aeruginosa, while PcrV139-258, PcrV139-234, PcrV197-294, and PcrV261-294 were not protective. These results suggest that an effective PcrV vaccine needs to contain not only the Mab166 epitope (PcrV144-257) but also the carboxyl terminal tail of PcrV. In the case of passive immunization, administration of affinity-purified anti-PcrV IgG against either PcrV1-294 or PcrV139-258 showed significantly higher efficacy against lethal P. aeruginosa infection than did original anti-PcrV IgG and Mab166. The increased efficacy of affinity-purified anti-PcrV IgG implies that more potent anti-PcrV strategies are possible. The results of this study are crucial to the development of an effective PcrV vaccine for active immunization and to an appropriate blocking anti-PcrV antibody against P. aeruginosa infection in humans.
C1 [Moriyama, Kiyoshi] Kyorin Univ, Sch Med, Dept Anesthesiol, Tokyo 1818611, Japan.
[Sawa, Teiji] Kyoto First Red Cross Hosp, Dept Anesthesiol, Kyoto 6050981, Japan.
[Moriyama, Kiyoshi; Wiener-Kronish, Jeanine P.; Sawa, Teiji] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA.
[Wiener-Kronish, Jeanine P.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Wiener-Kronish, Jeanine P.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
[Wiener-Kronish, Jeanine P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA.
RP Moriyama, K (reprint author), Kyorin Univ, Sch Med, Dept Anesthesiol, 6-20-2 Shinkawa, Tokyo 1818611, Japan.
EM mokiyokeio@gmail.com
FU American Lung Association [RG004N]; National Institutes of Health
[HL067600, HL59239, AI44101]
FX This work was supported in part by American Lung Association RG004N (to
T. S.), National Institutes of Health HL067600 (to T. S), and HL59239,
AI44101 (to J.P.W.-K.).
NR 30
TC 12
Z9 14
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0385-5600
J9 MICROBIOL IMMUNOL
JI Microbiol. Immunol.
PD NOV
PY 2009
VL 53
IS 11
BP 587
EP 594
DI 10.1111/j.1348-0421.2009.00165.x
PG 8
WC Immunology; Microbiology
SC Immunology; Microbiology
GA 510BO
UT WOS:000271063200001
PM 19903258
ER
PT J
AU Gariti, KO
Sadeghi, L
Joisa, SD
Holmes, WC
AF Gariti, Katherine O.
Sadeghi, Leila
Joisa, Sowmya D.
Holmes, William C.
TI Veterans' Distress Related to Participation in a Study About Detainee
Abuse
SO MILITARY MEDICINE
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMA-FOCUSED RESEARCH; RISK-FACTORS;
LOCUS; BENEFITS
AB Unintended consequences of participating in research studies are not well characterized, particularly in veterans who are frequent study participants. Our objective, then, was to assess the rate of and variables associated with distress resulting from veterans' participation in a study on a sensitive subject. Veterans Administration (VA) hospital outpatients were administered questionnaires with three increasingly severe scenarios of a U.S. soldier abusing a detainee. Distress-upset requiring clinical intervention-was assessed, as were sociodemographic characteristics, post-traumatic stress disorder (PTSD), depression, and locus of control (LOC). Three hundred fifty-one veterans participated. Forty-three (12%) became distressed. Modeling indicated distress was associated with minority status (odds ratio [OR] = 5.72, 95% confidence interval [CI] = 1.59, 20.58), PTSD (OR = 2.66, 95% CI = 1.12, 6.29), and external LOC (OR = 6.27, 95% CI = 2.82, 13.90). Distress related to study participation was high in this veteran sample. Higher rates in some subgroups suggested that some individuals may not be able to accurately anticipate risk for harm in sensitive studies.
C1 [Gariti, Katherine O.] Philadelphia Vet Affairs Med Ctr, Mental Hlth Clin, Philadelphia, PA 19104 USA.
[Sadeghi, Leila] NYU Langone Med Ctr, Dept Pediat, New York, NY 10016 USA.
[Joisa, Sowmya D.] Good Samaritan Hosp, Lebanon, PA 17042 USA.
[Holmes, William C.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA.
RP Gariti, KO (reprint author), Philadelphia Vet Affairs Med Ctr, Mental Hlth Clin, Univ & Woodland Ave, Philadelphia, PA 19104 USA.
NR 17
TC 1
Z9 1
U1 1
U2 1
PU ASSOC MILITARY SURG US
PI BETHESDA
PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA
SN 0026-4075
EI 1930-613X
J9 MIL MED
JI Milit. Med.
PD NOV
PY 2009
VL 174
IS 11
BP 1149
EP 1154
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 601LL
UT WOS:000278060900005
PM 19960821
ER
PT J
AU Zhu, Y
Li, Q
Chen, ZY
Kun, Y
Liu, LJ
Liu, X
Yuan, HJ
Zhai, SQ
Han, DY
Dai, P
AF Zhu, Yuhua
Li, Qi
Chen, Zhengyi
Kun, Yao
Liu, Lijia
Liu, Xin
Yuan, Huijun
Zhai, Suoqiang
Han, Dongyi
Dai, Pu
TI Mitochondrial haplotype and phenotype of 13 Chinese families may suggest
multi-original evolution of mitochondrial C1494T mutation
SO MITOCHONDRION
LA English
DT Article
DE Hearing loss; Aminoglycosides; Mitochondrial DNA; Haplotype; 12S rRNA
mutation; Penetrance
ID 12S RIBOSOMAL-RNA; NONSYNDROMIC HEARING-LOSS; COMPLETE
NUCLEOTIDE-SEQUENCE; A1555G MUTATION; AMINOGLYCOSIDE OTOTOXICITY;
MOLECULAR ANALYSIS; T7511C MUTATION; GJB2 MUTATION; DEAFNESS; GENE
AB Mutations in mitochondrial DNA (mtDNA) are associated with sensorineural hearing loss. In this study, we traced the origin of the 12S rRNA C1494T mutation through analysis of the clinical, genetic, and molecular characteristics of 13 Han Chinese pedigrees with aminoglycoside-induced and non-syndromic bilateral hearing loss that were selected by C1494T screening in 3133 subjects with non-syndromic hearing impairment from 27 regions of China (13/3133). Clinical evaluation revealed the variable phenotypes of hearing impairment including severity, age-of-onset, and audiometric configuration in these subjects. Through the whole mitochondrial genome DNA sequence analysis, we identified two evolutionarily conservative variants in protein-coding genes: tRNA(Ala) T 5628C and tRNA(Tyr) A5836G mutations. However, the pedigrees with these mutations did not have a higher or lower penetrance of deafness than in other pedigrees. These results suggested that both T 5628C and A5836G mutations might not significantly modify the manifestation of the C1494T mutation. Sequencing analysis of the whole mitochondrial genome of the probands showed that 13 pedigrees from seven different provinces were classified into 10 haplogroups by the distinct sets of mtDNA polymorphisms, including haplogroups A, B, D, D4, D4b2, F1, M, M7c, N9a1, and H2b. This result suggested that the C1494T mutation occurred sporadically with multi-origins through the evolution of the mtDNA in China, and these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the C1494T mutation in these Chinese families with different penetrance of hearing loss. In addition, the lack of a significant mutation in the GJB2 gene ruled out the possible involvement of GJB2 in the phenotypic expression of the C1494T mutation in those affected subjects. Therefore, the aminoglycosides is solo well-established factor to contribute to the deafness manifestation of the C1494T mutation, and prevention by avoiding the administration of aminoglycosides in individuals carrying C1494T mutation is the most effective way to protect their vulnerability to deafness. (C) 2009 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
C1 [Zhu, Yuhua; Li, Qi; Liu, Xin; Yuan, Huijun; Zhai, Suoqiang; Han, Dongyi; Dai, Pu] Chinese Peoples Liberat Army Gen Hosp, Dept Otolaryngol, Beijing, Peoples R China.
[Li, Qi] Nanjing Childrens Hosp, Dept Otolaryngol, Nanjing, Jiangsu, Peoples R China.
[Chen, Zhengyi] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Chen, Zhengyi] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Kun, Yao] Fuyang Peoples Hosp, Dept Otolaryngol, Fuyang, Anhui, Peoples R China.
[Liu, Lijia] Mudanjiang First Hosp, Dept Otolaryngol, Mudanjiang, Heilongjiang, Peoples R China.
RP Zhai, SQ (reprint author), Chinese Peoples Liberat Army Gen Hosp, Dept Otolaryngol, 28 Fuxing Road, Beijing, Peoples R China.
EM zhaisq@plagh.com.cn; hdy301@263.net; daipu301@vip.sina.com
FU Chinese National Nature Science Foundation Research [30728030,
30872862]; Chinese Capital Medical Development Scientific Funding
[2005-1032]; [2007BAI18B12]; [2006BAI02B06]
FX This work was supported by the Chinese National Nature Science
Foundation Research Grant 30728030, 30872862 to Pu Dai and Zhengyi Chen,
and Chinese Capital Medical Development Scientific Funding 2005-1032 and
11th 5 Year Supporting Funding 2007BAI18B12, 2006BAI02B06 to Dongyi Han
and Suoqiang Zhai.
NR 34
TC 18
Z9 27
U1 0
U2 8
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1567-7249
J9 MITOCHONDRION
JI Mitochondrion
PD NOV
PY 2009
VL 9
IS 6
BP 418
EP 428
DI 10.1016/j.mito.2009.07.006
PG 11
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 523RW
UT WOS:000272093200006
PM 19682603
ER
PT J
AU Nath, SD
He, X
Voruganti, VS
Blangero, J
MacCluer, JW
Comuzzie, AG
Arar, NH
Abboud, HE
Thameem, F
AF Nath, Subrata D.
He, Xin
Voruganti, V. Saroja
Blangero, John
MacCluer, Jean W.
Comuzzie, Anthony G.
Arar, Nedal H.
Abboud, Hanna E.
Thameem, Farook
TI The 27-bp repeat polymorphism in intron 4 (27 bp-VNTR) of endothelial
nitric oxide synthase (eNOS) gene is associated with albumin to
creatinine ratio in Mexican Americans
SO MOLECULAR AND CELLULAR BIOCHEMISTRY
LA English
DT Article
DE eNOS; Genetic polymorphisms; Association analyses; ACR; Triglycerides;
Mexican Americans
ID GLOMERULAR-FILTRATION-RATE; WIDE LINKAGE SCANS; TRANSMISSION
DISEQUILIBRIUM; DIABETIC-NEPHROPATHY; RISK-FACTORS; DISEASE; KIDNEY;
ECNOS; GENOTYPE; REGION
AB The T-786C, Glu298Asp, and 27 bp variable number of tandem repeats (27 bp-VNTR-a/b) polymorphsims of the endothelial nitric oxide synthase (eNOS) gene are thought to alter nitric oxide production and contribute to the development of vascular and renal disease risk. The objective of this study is to investigate whether these three polymorphisms examined previously by others are associated with cardiovascular and renal disease risk in Mexican Americans. Study participants (N = 848; 21 families) were genotyped for T-786C, Glu298Asp, and 27 bp-VNTR-a/b polymorphisms by PCR followed by restriction digestion. Association analyses were performed by a measured genotype approach implemented in the program SOLAR. Of the phenotypes (type 2 diabetes, hypertension, body mass index, waist circumference, total cholesterol, high density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressure, albumin to creatinine ratio (ACR), and estimated glomerular filtration rate) examined for association, the 27 bp-VNTR-a/b variant exhibited statistically significant association with ACR (P = 0.047) after accounting for the trait specific covariate effects. In addition, the promoter variant (T-786C) showed a significant association with triglycerides (P = 0.034) after accounting for covariate influences. In conclusion, the present study adds evidence to the role of eNOS candidate gene polymorphisms in modulating the risk factors related to cardiovascular-renal disease in Mexican Americans although the magnitude of the genetic effect is small.
C1 [Nath, Subrata D.; He, Xin; Arar, Nedal H.; Abboud, Hanna E.; Thameem, Farook] Univ Texas Hlth Sci Ctr San Antonio, Div Nephrol, Dept Med, San Antonio, TX 78229 USA.
[Arar, Nedal H.; Abboud, Hanna E.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
[Voruganti, V. Saroja; Blangero, John; MacCluer, Jean W.; Comuzzie, Anthony G.] SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78227 USA.
RP Thameem, F (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Nephrol, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM thameem@uthscsa.edu
FU American Heart Association; Carl W. Gottschalk Research Scholars of the
American Society of Nephrology; George O'Brien Kidney Research Center
[P50 DK061597]; Satellite Healthcare; San Antonio Area Foundation; NIH
[P01 HL45522]; National Center for Research Resources [UL1 RR025767, KL2
RR025766]; [R01 MH59490]
FX We thank the members of SAFHS for their participation and cooperation.
This study was supported by the Grant-in-Aid from the American Heart
Association (FT), Carl W. Gottschalk Research Scholars of the American
Society of Nephrology (FT), George O'Brien Kidney Research Center (P50
DK061597; HEA, FT), Norman S. Coplan grant from the Satellite Healthcare
(FT), San Antonio Area Foundation (FT), VA-MERIT Review (HEA, NHA). The
SAFHS is supported by NIH grant P01 HL45522. The development of SOLAR
was supported by R01 MH59490. This work was supported by the National
Center for Research Resources contracts UL1 RR025767 and KL2 RR025766
for the Institute for Integration of Medicine and Science.
NR 29
TC 9
Z9 10
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0300-8177
J9 MOL CELL BIOCHEM
JI Mol. Cell. Biochem.
PD NOV
PY 2009
VL 331
IS 1-2
BP 201
EP 205
DI 10.1007/s11010-009-0159-5
PG 5
WC Cell Biology
SC Cell Biology
GA 513FN
UT WOS:000271308000023
PM 19468830
ER
PT J
AU Minamishima, YA
Moslehi, J
Padera, RF
Bronson, RT
Liao, R
Kaelin, WG
AF Minamishima, Yoji Andrew
Moslehi, Javid
Padera, Robert F.
Bronson, Roderick T.
Liao, Ronglih
Kaelin, William G., Jr.
TI A Feedback Loop Involving the Phd3 Prolyl Hydroxylase Tunes the
Mammalian Hypoxic Response In Vivo
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID PAS DOMAIN PROTEIN; INDUCIBLE-FACTOR; VASCULAR TUMORS; TRANSCRIPTIONAL
ACTIVITY; MITOCHONDRIAL AUTOPHAGY; MYOCARDIAL-INFARCTION; MOUSE MODEL;
HIF; INACTIVATION; HEART
AB Hypoxia-inducible factor (HIF), consisting of a labile alpha subunit and a stable beta subunit, is a master regulator of hypoxia-responsive mRNAs. HIF alpha undergoes oxygen-dependent prolyl hydroxylation, which marks it for polyubiquitination by a complex containing the von Hippel-Lindau protein (pVHL). Among the three Phd family members, Phd2 appears to be the primary HIF prolyl hydroxylase. Phd3 is induced by HIF and, based on findings from in vitro studies, may participate in a HIF-regulatory feedback loop. Here, we report that Phd3 loss exacerbates the HIF activation, hepatic steatosis, dilated cardiomyopathy, and premature mortality observed in mice lacking Phd2 alone and produces a closer phenocopy of the changes seen in mice lacking pVHL than the loss of Phd2 alone. Importantly, the degree to which Phd3 can compensate for Phd2 loss and the degree to which the combined loss of Phd2 and Phd3 resembles pVHL loss appear to differ for different HIF-responsive genes and in different tissues. These findings highlight that the responses of different HIF target genes to changes in prolyl hydroxylase activity differ, quantitatively and qualitatively, in vivo and have implications for the development of paralog-specific prolyl hydroxylase inhibitors as therapeutic agents.
C1 [Minamishima, Yoji Andrew; Moslehi, Javid; Kaelin, William G., Jr.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Moslehi, Javid; Liao, Ronglih] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Cardiovasc Med, Boston, MA 02115 USA.
[Padera, Robert F.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM william_kaelin@dfci.harvard.edu
RI Minamishima, Yoji/E-5380-2010
OI Minamishima, Yoji/0000-0001-7995-9318
FU NIH [T32]; Fibrogen, Inc.
FX J. M. was supported by an NIH Clinical Research Training Program (T32)
for cardiovascular medicine. W. G. K. was supported by NIH, is a Howard
Hughes Medical Institute (HHMI) Investigator, and is a Doris Duke
Distinguished Clinical Scientist. W. G. K. has a financial interest in
Fibrogen, Inc., which is developing prolyl hydroxylase inhibitors as
drugs.
NR 55
TC 77
Z9 80
U1 0
U2 5
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 NOV 1
PY 2009
VL 29
IS 21
BP 5729
EP 5741
DI 10.1128/MCB.00331-09
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 505SV
UT WOS:000270716800009
PM 19720742
ER
PT J
AU Rhodes, J
Amsterdam, A
Sanda, T
Moreau, LA
McKenna, K
Heinrichs, S
Ganem, NJ
Ho, KW
Neuberg, DS
Johnston, A
Ahn, Y
Kutok, JL
Hromas, R
Wray, J
Lee, C
Murphy, C
Radtke, I
Downing, JR
Fleming, MD
MacConaill, LE
Amatruda, JF
Gutierrez, A
Galinsky, I
Stone, RM
Ross, EA
Pellman, DS
Kanki, JP
Look, AT
AF Rhodes, Jennifer
Amsterdam, Adam
Sanda, Takaomi
Moreau, Lisa A.
McKenna, Keith
Heinrichs, Stefan
Ganem, Neil J.
Ho, Karen W.
Neuberg, Donna S.
Johnston, Adam
Ahn, Yebin
Kutok, Jeffery L.
Hromas, Robert
Wray, Justin
Lee, Charles
Murphy, Carly
Radtke, Ina
Downing, James R.
Fleming, Mark D.
MacConaill, Laura E.
Amatruda, James F.
Gutierrez, Alejandro
Galinsky, Ilene
Stone, Richard M.
Ross, Eric A.
Pellman, David S.
Kanki, John P.
Look, A. Thomas
TI Emi1 Maintains Genomic Integrity during Zebrafish Embryogenesis and
Cooperates with p53 in Tumor Suppression
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID ANAPHASE-PROMOTING COMPLEX/CYCLOSOME; ACUTE LYMPHOBLASTIC-LEUKEMIA;
ACUTE MYELOID-LEUKEMIA; TOPOISOMERASE-II; INSERTIONAL MUTAGENESIS;
MAMMALIAN-CELLS; DNA-DAMAGE; INHIBITION; PROGRESSION; CHECKPOINT
AB A growing body of evidence indicates that early mitotic inhibitor 1 (Emi1) is essential for genomic stability, but how this function relates to embryonic development and cancer pathogenesis remains unclear. We have identified a zebrafish mutant line in which deficient emi1 gene expression results in multilineage hematopoietic defects and widespread developmental defects that are p53 independent. Cell cycle analyses of Emi1-depleted zebrafish or human cells showed chromosomal rereplication, and metaphase preparations from mutant zebrafish embryos revealed rereplicated, unsegregated chromosomes and polyploidy. Furthermore, EMI1-depleted mammalian cells relied on topoisomerase II alpha-dependent mitotic decatenation to progress through metaphase. Interestingly, the loss of a single emi1 allele in the absence of p53 enhanced the susceptibility of adult fish to neural sheath tumorigenesis. Our results cast Emi1 as a critical regulator of genomic fidelity during embryogenesis and suggest that the factor may act as a tumor suppressor.
C1 [Rhodes, Jennifer; Ross, Eric A.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Amsterdam, Adam] MIT, Cambridge, MA 02139 USA.
[Sanda, Takaomi; Moreau, Lisa A.; McKenna, Keith; Heinrichs, Stefan; Ganem, Neil J.; Ho, Karen W.; Neuberg, Donna S.; Johnston, Adam; Ahn, Yebin; MacConaill, Laura E.; Gutierrez, Alejandro; Galinsky, Ilene; Stone, Richard M.; Pellman, David S.; Kanki, John P.; Look, A. Thomas] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kutok, Jeffery L.; Lee, Charles; Murphy, Carly] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Hromas, Robert; Wray, Justin] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA.
[Radtke, Ina; Downing, James R.] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Fleming, Mark D.] Childrens Hosp, Boston, MA 02115 USA.
[Amatruda, James F.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
RP Rhodes, J (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave, Philadelphia, PA 19111 USA.
EM Jennifer.Rhodes@fccc.edu
OI Gutierrez, Alejandro/0000-0002-0249-9007
FU NIH [R01 CA93152, K01 DK69672, P01 CA66996-11A1, R01 CA111560, R01
RR12589]
FX This work was supported by NIH grants R01 CA93152 (A. T. L.), K01
DK69672 (J. R.), P01 CA66996-11A1 (R. M. S. and J. D. Griffin), R01
CA111560 (C. L.), and R01 RR12589 (A. A. and Nancy Hopkins).
NR 42
TC 24
Z9 24
U1 0
U2 7
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 NOV 1
PY 2009
VL 29
IS 21
BP 5911
EP 5922
DI 10.1128/MCB.00558-09
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 505SV
UT WOS:000270716800023
PM 19704007
ER
PT J
AU Saydam, O
Shen, YP
Wurdinger, T
Senol, O
Boke, E
James, MF
Tannous, BA
Stemmer-Rachamimov, AO
Yi, M
Stephens, RM
Fraefel, C
Gusella, JF
Krichevsky, AM
Breakefield, XO
AF Saydam, Okay
Shen, Yiping
Wuerdinger, Thomas
Senol, Ozlem
Boke, Elvan
James, Marianne F.
Tannous, Bakhos A.
Stemmer-Rachamimov, Anat O.
Yi, Ming
Stephens, Robert M.
Fraefel, Cornel
Gusella, James F.
Krichevsky, Anna M.
Breakefield, Xandra O.
TI Downregulated MicroRNA-200a in Meningiomas Promotes Tumor Growth by
Reducing E-Cadherin and Activating the Wnt/beta-Catenin Signaling
Pathway
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID MIR-200 FAMILY; MESENCHYMAL TRANSITION; COLORECTAL-CANCER; REPRESSORS
ZEB1; GENETIC MODEL; BETA-CATENIN; IN-VIVO; CELLS; EXPRESSION; NF2
AB Meningiomas, one of the most common human brain tumors, are derived from arachnoidal cells associated with brain meninges, are usually benign, and are frequently associated with neurofibromatosis type 2. Here, we define a typical human meningioma microRNA (miRNA) profile and characterize the effects of one downregulated miRNA, miR-200a, on tumor growth. Elevated levels of miR-200a inhibited meningioma cell growth in culture and in a tumor model in vivo. Upregulation of miR-200a decreased the expression of transcription factors ZEB1 and SIP1, with consequent increased expression of E-cadherin, an adhesion protein associated with cell differentiation. Downregulation of miR-200a in meningiomas and arachnoidal cells resulted in increased expression of beta-catenin and cyclin D1 involved in cell proliferation. miR-200a was found to directly target beta-catenin mRNA, thereby inhibiting its translation and blocking Wnt/beta-catenin signaling, which is frequently involved in cancer. A direct correlation was found between the downregulation of miR-200a and the upregulation of beta-catenin in human meningioma samples. Thus, miR-200a appears to act as a multifunctional tumor suppressor miRNA in meningiomas through effects on the E-cadherin and Wnt/beta-catenin signaling pathways. This reveals a previously unrecognized signaling cascade involved in meningioma tumor development and highlights a novel molecular interaction between miR-200a and Wnt signaling, thereby providing insights into novel therapies for meningiomas.
C1 [Saydam, Okay; Wuerdinger, Thomas; Senol, Ozlem; Boke, Elvan; Tannous, Bakhos A.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA.
[Saydam, Okay; Wuerdinger, Thomas; Senol, Ozlem; Boke, Elvan; Tannous, Bakhos A.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA.
[Saydam, Okay; Wuerdinger, Thomas; Senol, Ozlem; Boke, Elvan; Tannous, Bakhos A.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02129 USA.
[Shen, Yiping; James, Marianne F.; Gusella, James F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res,Mol Neurogenet Unit, Boston, MA 02114 USA.
[Wuerdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Dept Neurosurg, Neurooncol Res Grp, Amsterdam, Netherlands.
[Stemmer-Rachamimov, Anat O.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA.
[Stemmer-Rachamimov, Anat O.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02129 USA.
[Yi, Ming; Stephens, Robert M.] NCI, Adv Biomed Comp Ctr, Frederick, MD 21702 USA.
[Fraefel, Cornel] Univ Zurich, Inst Virol, CH-8057 Zurich, Switzerland.
[Krichevsky, Anna M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA.
RP Breakefield, XO (reprint author), Harvard Univ, Massachusetts Gen Hosp, Mol Neurogenet Unit, Sch Med, E 13th St,Bldg 149, Charlestown, MA 02129 USA.
EM breakefield@hms.harvard.edu
RI huang, nqi/F-7238-2011
FU Children's Tumor Foundation [2007-01-043, 2005-01-004, NINDS NS24279,
NCI CA69246, CA86355]; Brain Tumor Society; American Brain Tumor
Society; Cancer League of Canton Zurich; Neurofibromatosis Inc.-New
England; S. Sydney De Young Foundation
FX We thank Anita Lal for meningioma cell lines SF4433 and SF4068. We also
thank Casey A. Maguire for critical reading of the manuscript, Arda
Mizrak for assistance, Suzanne McDavitt for skilled editorial
assistance, and Applied Biosystems for supplying the miRNA qRT-PCR
primers.
NR 46
TC 126
Z9 144
U1 1
U2 19
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 NOV 1
PY 2009
VL 29
IS 21
BP 5923
EP 5940
DI 10.1128/MCB.00332-09
PG 18
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 505SV
UT WOS:000270716800024
PM 19703993
ER
PT J
AU Jha, AR
Pillai, SK
York, VA
Sharp, ER
Storm, EC
Wachter, DJ
Martin, JN
Deeks, SG
Rosenberg, MG
Nixon, DF
Garrison, KE
AF Jha, Aashish R.
Pillai, Satish K.
York, Vanessa A.
Sharp, Elizabeth R.
Storm, Emily C.
Wachter, Douglas J.
Martin, Jeffrey N.
Deeks, Steven G.
Rosenberg, Michael G.
Nixon, Douglas F.
Garrison, Keith E.
TI Cross-Sectional Dating of Novel Haplotypes of HERV-K 113 and HERV-K 115
Indicate These Proviruses Originated in Africa before Homo sapiens
SO MOLECULAR BIOLOGY AND EVOLUTION
LA English
DT Article
DE insertion frequencies; haplotype; HERV-K113 and HERV-K115; hervotype;
human evolution; Homo erectus
ID ENDOGENOUS RETROVIRUS FAMILY; BREAST-CANCER PATIENTS; INSERTIONAL
POLYMORPHISMS; REVERSE-TRANSCRIPTASE; EVOLUTIONARY DYNAMICS;
RHEUMATOID-ARTHRITIS; SUBSTITUTION RATES; HUMAN-POPULATIONS; MOLECULAR
CLOCK; MIDDLE-AWASH
AB The human genome, human endogenous retroviruses (HERV), of which HERV-K 113 and HERV-K 115 are the only known full-length proviruses that are insertionally polymorphic. Although a handful of previously published papers have documented their prevalence in the global population; to date, there has been no report on their prevalence in the United States population. Here, we studied the geographic distribution of K113 and K115 among 156 HIV-1+ subjects from the United States, including African Americans, Hispanics, and Caucasians. In the individuals studied, we found higher insertion frequencies of K113 (21%) and K115 (35%) in African Americans compared with Caucasians (K113 9% and K115 6%) within the United States. We also report the presence of three single nucleotide polymorphism sites in the K113 5' long terminal repeats (LTRs) and four in the K115 5' LTR that together constituted four haplotypes for K113 Lind five haplotypes for K115. HERV insertion times can be estimated from the sequence differences between the 5' and 3' LTR of each insertion, but this dating method cannot be used with HERV-K115. We developed a method to estimate insertion times by applying coalescent inference to 5' LTR sequences within our study population and validated this approach using an independent estimate derived from the genetic distance between K113 5' and 3' LTR sequences. Using our method, we estimated the insertion dates of K113 and K115 to be it minimum of 800,000 and 1.1 million years ago, respectively. Both these insertion dates predate the emergence of anatomically modern Homo sapiens.
C1 [Jha, Aashish R.; York, Vanessa A.; Sharp, Elizabeth R.; Storm, Emily C.; Wachter, Douglas J.; Nixon, Douglas F.; Garrison, Keith E.] Univ Calif San Francisco, Div Expt Med, San Francisco, CA 94143 USA.
[Jha, Aashish R.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Pillai, Satish K.] Univ Calif San Francisco, Dept Med, San Francisco Vet Affairs Med Ctr, Div Infect Dis, San Francisco, CA USA.
[Martin, Jeffrey N.; Deeks, Steven G.] Univ Calif San Francisco, Dept Med, Div HIV AIDS, San Francisco Gen Hosp, San Francisco, CA USA.
[Rosenberg, Michael G.] Albert Einstein Coll Med, Jacobi Med Ctr, Bronx, NY 10467 USA.
[Garrison, Keith E.] St Marys Coll, Moraga, CA 94575 USA.
RP Jha, AR (reprint author), Univ Calif San Francisco, Div Expt Med, San Francisco, CA 94143 USA.
EM nepaliaashish@gmail.com
OI Nixon, Douglas/0000-0002-2801-1786
FU UCSF AIDS Research Institute; Pfizer, Inc.,; National Institutes of
Health [1KO1DA024654, A176059]; University of California San Francisco
AIDS Research Institute
FX This study was conducted in part from funds from the UCSF AIDS Research
Institute, a sponsored research agreement from Pfizer, Inc., and
National Institutes of Health grants 1KO1DA024654 (S.K.P.) and A176059
(D.F.N.). This study was conducted in part from funds from the
University of California San Francisco AIDS Research Institute, a
sponsored research agreement from Pfizer, Inc., and National Institutes
of Health grants 1KO1DA024654 (S.K.P.) and A176059 (D.F.N.).
NR 48
TC 19
Z9 19
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0737-4038
J9 MOL BIOL EVOL
JI Mol. Biol. Evol.
PD NOV
PY 2009
VL 26
IS 11
BP 2617
EP 2626
DI 10.1093/molbev/msp180
PG 10
WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
GA 514UX
UT WOS:000271422300020
PM 19666991
ER
PT J
AU Kong, TQ
Xu, DS
Yu, WF
Takakura, A
Boucher, I
Tran, M
Kreidberg, JA
Shah, J
Zhou, J
Denker, BM
AF Kong, Tianqing
Xu, Daosong
Yu, Wanfeng
Takakura, Ayumi
Boucher, Ilene
Tran, Mei
Kreidberg, Jordan A.
Shah, Jagesh
Zhou, Jing
Denker, Bradley M.
TI G alpha 12 Inhibits alpha 2 beta 1 Integrin-mediated Madin-Darby Canine
Kidney Cell Attachment and Migration on Collagen-I and Blocks
Tubulogenesis
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID FOCAL ADHESION KINASE; HETEROTRIMERIC G-PROTEINS; SRC TYROSINE KINASE;
BREAST-CANCER; BRANCHING MORPHOGENESIS; PHOSPHATASE-ACTIVITY;
EPITHELIAL-CELLS; BINDING PROTEIN; G(12) FAMILY; G12 FAMILY
AB Regulation of epithelial cell attachment and migration are essential for normal development and maintenance of numerous tissues. G proteins and integrins are critical signaling proteins regulating these processes, yet in polarized cells little is known about the interaction of these pathways. Herein, we demonstrate that G alpha 12 inhibits interaction of MDCK cells with collagen-I, the major ligand for alpha 2 beta 1 integrin. Activating G alpha 12 (QL point mutation or stimulating endogenous G alpha 12 with thrombin) inhibited focal adhesions and lamellipodia formation and led to impaired cell migration. Consistent with G alpha 12-regulated attachment to collagen-I, G alpha 12-silenced MDCK cells revealed a more adherent phenotype. Inhibiting Rho kinase completely restored normal attachment in G alpha 12-activated cells, and there was partial recovery with inhibition of Src and protein phosphatase pathways. G alpha 12 activation led to decreased phosphorylation of focal adhesion kinase and paxillin with displacement of alpha 2 integrin from the focal adhesion protein complex. Using the MDCK cell 3D-tubulogenesis assay, activated G alpha 12 inhibited tubulogenesis and led to the formation of cyst-like structures. Furthermore, G alpha 12-silenced MDCK cells were resistant to thrombin-stimulated cyst development. Taken together, these studies provide direct evidence for G alpha 12-integrin regulation of epithelial cell spreading and migration necessary for normal tubulogenesis.
C1 [Kong, Tianqing; Yu, Wanfeng; Takakura, Ayumi; Boucher, Ilene; Tran, Mei; Shah, Jagesh; Zhou, Jing; Denker, Bradley M.] Brigham & Womens Hosp, Div Renal, Harvard Inst Med, Boston, MA 02115 USA.
[Xu, Daosong] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kreidberg, Jordan A.] Childrens Hosp, Boston, MA 02115 USA.
RP Denker, BM (reprint author), Brigham & Womens Hosp, Div Renal, Harvard Inst Med, Boston, MA 02115 USA.
EM bdenker@rics.bwh.harvard.edu
RI yu, wanfeng/G-2915-2013
FU [P50 DK074030]; [R01 KD40703]; [R01 GM5223]; [K01 DK080179]
FX We thank members of the Harvard Polycystic Kidney Disease Center for
helpful comments and suggestions, Dr. Gunaratnam for providing G alpha
12-expressing PK1 cells, and Sarah Beaudry for her outstanding technical
assistance. This work was supported by Grants P50 DK074030 to J.Z. (PI)
and B.M.D. (Project 1). J.Z. is also supported by R01 KD40703 and B. M.
D. by R01 GM5223, and Grant K01 DK080179 to T. K.
NR 48
TC 12
Z9 12
U1 0
U2 3
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD NOV 1
PY 2009
VL 20
IS 21
BP 4596
EP 4610
DI 10.1091/mbc.E09-03-0220
PG 15
WC Cell Biology
SC Cell Biology
GA 514DL
UT WOS:000271374400012
PM 19776354
ER
PT J
AU Liu, BL
Ordonez-Ercan, D
Fan, ZY
Huang, XP
Edgerton, SM
Yang, XH
Thor, AD
AF Liu, Bolin
Ordonez-Ercan, Dalia
Fan, Zeying
Huang, Xiaoping
Edgerton, Susan M.
Yang, XiaoHe
Thor, Ann D.
TI Estrogenic Promotion of ErbB2 Tyrosine Kinase Activity in Mammary Tumor
Cells Requires Activation of ErbB3 Signaling
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID HUMAN-BREAST-CARCINOMA; MESSENGER RIBONUCLEIC-ACID; GROWTH-FACTOR
RECEPTOR; TRANSGENIC MICE; ENDOCRINE RESISTANCE; ADJUVANT THERAPY; NEU
ONCOGENE; CANCER CELLS; C-NEU; EXPRESSION
AB Increasing evidence suggests molecular interactions between erbB2 and other receptor tyrosine kinases, and estrogenic compounds and their cognate receptors. We have recently reported that downregulation of erbB3 abrogates erbB2-mediated tamoxifen resistance in breast cancer cells. On the basis of these data, we hypothesized that erbB3 may play a major role connecting these two sentinel pathways. Interactions were studied using mammary/breast cancer cell lines from wild-type rat c-neu gene transgenic mice and humans. Estradiol promoted cell proliferation and activated erbB2/neu tyrosine kinase, Akt, and mitogen-activated protein kinase signaling exclusively in mammary and breast epithelial cell lines with coexpression of both erbB2 and erbB3. Estradiol action was independent of the transgene promoter (MMTV-LTR) activity, both in vitro and in vivo, as well as c-neu transgene or endogenous erbB2 gene expression. Estrogen induction of cell growth promotion, erbB2/neu activation, and downstream signaling was abrogated by blockade of estrogen receptor (ER) with the pure ER antagonist ICI 182,780 or knockdown of erbB3 expression via specific siRNA. These data suggest that activation of both ER and erbB2/erbB3 signaling is requisite for estrogen-induced mitogenesis and erbB2/neu tyrosine kinase activation. (Mol Cancer Res 2009;7(11):1882-92)
C1 [Liu, Bolin; Fan, Zeying; Huang, Xiaoping; Edgerton, Susan M.; Thor, Ann D.] Univ Colorado, Dept Pathol, Denver Sch Med, Aurora, CO 80045 USA.
[Ordonez-Ercan, Dalia] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Yang, XiaoHe] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.
RP Thor, AD (reprint author), Univ Colorado, Dept Pathol, Denver Sch Med, MS B2116,POB 6511, Aurora, CO 80045 USA.
EM ann.thor@uchsc.edu
RI Yang, Jim/B-3776-2010
NR 45
TC 14
Z9 15
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 NOV
PY 2009
VL 7
IS 11
BP 1882
EP 1892
DI 10.1158/1541-7786.MCR-08-0509
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 522NZ
UT WOS:000272006300014
PM 19861407
ER
PT J
AU Joshi, MD
Ahmad, R
Yin, L
Raina, D
Rajabi, H
Bubley, G
Kharbanda, S
Kufe, D
AF Joshi, Maya Datt
Ahmad, Rehan
Yin, Li
Raina, Deepak
Rajabi, Hasan
Bubley, Glenn
Kharbanda, Surender
Kufe, Donald
TI MUC1 oncoprotein is a druggable target in human prostate cancer cells
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID RECEPTOR TRANSCRIPTIONAL ACTIVITY; EPIDERMAL-GROWTH-FACTOR;
ANDROGEN-RECEPTOR; BETA-CATENIN; SURVIVAL RESPONSE; OXIDATIVE STRESS;
CARCINOMA ANTIGEN; C-SRC; ACTIVATION; DEATH
AB Human prostate cancers are dependent on the androgen receptor for their progression. The MUC1 heterodimeric oncoprotein is aberrantly overexpressed in prostate cancers; however, it is not known if MUC1 is of functional importance to these tumors. To assess dependence on MUC1, we synthesized an inhibitor, designated GO-201, which interacts directly with the MUC1-C subunit at its oligomerization domain. Treatment of MUC1-positive DU145 and PC3 prostate cancer cells with GO-201, and not an altered version, resulted in inhibition of proliferation. GO-201 also induced necrotic cell death that was associated with increases in reactive oxygen species, loss of mitochondrial transmembrane potential, and depletion of ATP. By contrast, GO-201 had no effect against MUC1-negative LNCaP, CWR22Rv1, and MDA-PCa-2b prostate cancer cells. Significantly, GO-201 treatment of DU145 and PC3 xenografts growing in nude mice resulted in complete tumor regression and prolonged lack of recurrence. These findings indicate that certain prostate cancer cells are dependent on MUC1-C for growth and survival and that directly targeting MUC1-C results in their death in vitro and in tumor models. [Mol Cancer Ther 2009;(11):3056-65]
C1 [Joshi, Maya Datt; Ahmad, Rehan; Yin, Li; Rajabi, Hasan; Kufe, Donald] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Bubley, Glenn] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
RP Kufe, D (reprint author), Dana Farber Canc Inst, 44 Binney St,Dana 830, Boston, MA 02115 USA.
EM donald_kufe@dfci.harvard.edu
FU Dana-Farber/Harvard Cancer Center Nodal [2006-11-NN]; Department of
Defense Prostate Cancer Idea [W81XWH-08-1-0093]; National Cancer
Institute [CA97098, CA42802]
FX Dana-Farber/Harvard Cancer Center Nodal grant 2006-11-NN, Department of
Defense Prostate Cancer Idea Award W81XWH-08-1-0093, and National Cancer
Institute grants CA97098 and CA42802.
NR 50
TC 39
Z9 39
U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD NOV
PY 2009
VL 8
IS 11
BP 3056
EP 3065
DI 10.1158/1535-7163.MCT-09-0646
PG 10
WC Oncology
SC Oncology
GA 519XE
UT WOS:000271802100009
PM 19887552
ER
PT J
AU Ficicioglu, C
Mandell, R
Shih, VE
AF Ficicioglu, C.
Mandell, R.
Shih, V. E.
TI Argininosuccinate lyase deficiency: Longterm outcome of 13 patients
detected by newborn screening
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Argininosuccinate lyase deficiency; Argininosuccinic aciduria; Newborn
screening; Urea cycle disorder; Outcome; Hyperammonemia
ID DIETARY-MANAGEMENT; ACIDURIA; DISORDERS
AB Argininosuccinate lyase deficiency is a urea cycle disorder which can present in the neonatal period with hyperammonemic encephalopathy, or later in childhood with episodic vomiting, growth and developmental delay. Abnormal hair, hepatomegaly, and hepatic fibrosis are unique features of this disorder. Twelve patients with argininosuccinate lyase deficiency were ascertained between 4 and 6 weeks of age by urine amino acid screening. One infant in a previously identified family was diagnosed shortly after birth. Diagnosis was confirmed by enzyme assay in red blood cells and/or skin fibroblasts. At the time of last follow-up, patients had been followed for 13-33 years. All patients were asymptomatic at detection, 7 had slightly increased blood ammonia, and all were initially treated with low-protein diet. Utilization of (14)C-citrulline by intact skin fibroblasts measured by (14)C incorporation into macromolecules was 74-135% of the control mean for 7 of the 8 patients studied. Nine patients had normal development. 4 had learning disability, 6 had EEG abnormalities, 3 had seizure disorder. None had any episodes of hyperammonemic coma. None had hepatomegaly. Patients detected by screening had higher enzyme activity measured by the (14)C-citrulline incorporation assay than comparison groups of patients with neonatal-onset and with late-onset detected by clinical disease. The ability to utilize (14)C-citrulline by intact fibroblasts seems to correlate with clinical outcome and may have prognostic value. It is likely that early diagnosis and treatment contributed to the relatively mild clinical course of the study group. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Ficicioglu, C.; Mandell, R.; Shih, V. E.] Massachusetts Gen Hosp, Amino Acid Disorders Lab, Boston, MA 02114 USA.
RP Shih, VE (reprint author), Massachusetts Gen Hosp, Amino Acid Disorders Lab, 55 Fruit St,GRJ239, Boston, MA 02114 USA.
EM vshih@partners.org
OI Ficicioglu, Can/0000-0002-8331-9804
FU Massachusetts General Hospital
FX Supported in part by the Mary L. Efron Fund, Massachusetts General
Hospital.
NR 11
TC 22
Z9 23
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD NOV
PY 2009
VL 98
IS 3
BP 273
EP 277
DI 10.1016/j.ymgme.2009.06.011
PG 5
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 513BG
UT WOS:000271296400006
PM 19635676
ER
PT J
AU Zhong, Q
Simonis, N
Li, QR
Charloteaux, B
Heuze, F
Klitgord, N
Tam, S
Yu, HY
Venkatesan, K
Mou, D
Swearingen, V
Yildirim, MA
Yan, H
Dricot, A
Szeto, D
Lin, CW
Hao, T
Fan, CY
Milstein, S
Dupuy, D
Brasseur, R
Hill, DE
Cusick, ME
Vidal, M
AF Zhong, Quan
Simonis, Nicolas
Li, Qian-Ru
Charloteaux, Benoit
Heuze, Fabien
Klitgord, Niels
Tam, Stanley
Yu, Haiyuan
Venkatesan, Kavitha
Mou, Danny
Swearingen, Venus
Yildirim, Muhammed A.
Yan, Han
Dricot, Amelle
Szeto, David
Lin, Chenwei
Hao, Tong
Fan, Changyu
Milstein, Stuart
Dupuy, Denis
Brasseur, Robert
Hill, David E.
Cusick, Michael E.
Vidal, Marc
TI Edgetic perturbation models of human inherited disorders
SO MOLECULAR SYSTEMS BIOLOGY
LA English
DT Article
DE binary protein interaction; genotype-to-phenotype relationships; human
Mendelian disorders; network perturbation
ID PROTEIN-PROTEIN INTERACTIONS; BETA-ACTIN; CRYSTAL-STRUCTURE; STRUCTURAL
BASIS; HUMAN GENES; WEB TOOLS; DISEASE; DATABASE; GENOME; IMPROVEMENTS
AB Cellular functions are mediated through complex systems of macromolecules and metabolites linked through biochemical and physical interactions, represented in interactome models as 'nodes' and 'edges', respectively. Better understanding of genotype-to-phenotype relationships in human disease will require modeling of how disease-causing mutations affect systems or interactome properties. Here we investigate how perturbations of interactome networks may differ between complete loss of gene products ('node removal') and interaction-specific or edge-specific ('edgetic') alterations. Global computational analyses of similar to 50 000 known causative mutations in human Mendelian disorders revealed clear separations of mutations probably corresponding to those of node removal versus edgetic perturbations. Experimental characterization of mutant alleles in various disorders identified diverse edgetic interaction profiles of mutant proteins, which correlated with distinct structural properties of disease proteins and disease mechanisms. Edgetic perturbations seem to confer distinct functional consequences from node removal because a large fraction of cases in which a single gene is linked to multiple disorders can be modeled by distinguishing edgetic network perturbations. Edgetic network perturbation models might improve both the understanding of dissemination of disease alleles in human populations and the development of molecular therapeutic strategies. Molecular Systems Biology 5: 321; published online 3 November 2009; doi: 10.1038/msb.2009.80
C1 [Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Ctr Canc Syst Biol, Boston, MA 02115 USA.
[Zhong, Quan; Simonis, Nicolas; Li, Qian-Ru; Charloteaux, Benoit; Heuze, Fabien; Klitgord, Niels; Tam, Stanley; Yu, Haiyuan; Venkatesan, Kavitha; Mou, Danny; Swearingen, Venus; Yildirim, Muhammed A.; Yan, Han; Dricot, Amelle; Szeto, David; Lin, Chenwei; Hao, Tong; Fan, Changyu; Milstein, Stuart; Dupuy, Denis; Hill, David E.; Cusick, Michael E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Charloteaux, Benoit; Heuze, Fabien; Brasseur, Robert] Fac Univ Sci Agronom Gembloux, Ctr Biophys Mol Numer, Gembloux, Wallonia, Belgium.
RP Vidal, M (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Ctr Canc Syst Biol, 44 Binney St,Smith 858, Boston, MA 02115 USA.
EM marc_vidal@dfci.harvard.edu
RI Klitgord, Niels/B-5121-2009; Simonis, Nicolas/E-5124-2010; Hill,
David/B-6617-2011; Yildirim, Muhammed/J-3695-2014; Dupuy,
Denis/M-7299-2014
OI Yildirim, Muhammed/0000-0003-2826-1766;
FU Ellison Foundation; WM Keck Foundation (MV), NIH [R01-HG001715]; NHGRI
[U01-CA105423, U54-CA112952, R33-CA132073]; NCI; Institute Sponsored
Research funds from the DanaFarber Cancer Institute Strategic
Initiative; NIH NRSA training [T32-CA09361]; Belgian Program on
Interuniversity Attraction Poles initiated by the Federal Office for
Scientific, Technical and Cultural Affairs [IAPP6/19 PROFUSA]; Honorary
Research Associate' and 'Research Director'; Fonds de la Recherche
Scientifique (FRS-FNRS, French Community of Belgium)
FX We thank all members of the Vidal Lab and the Center for Cancer Systems
Biology (CCSB), Dr Patricia K Donahoe and Dr Roseann Mulloy for helpful
suggestions; Ines M Pinto for help with experiments. This study was
supported by the Ellison Foundation and the WM Keck Foundation (MV), NIH
grants R01-HG001715 from NHGRI (MVand F Roth), U01-CA105423 (PI, S
Orkin, project leader, MV), U54CA112952 (PI, J Nevins, subcontract, MV)
and R33-CA132073 (MV) from NCI, and by Institute Sponsored Research
funds from the DanaFarber Cancer Institute Strategic Initiative awarded
to CCSB. KV was supported by an NIH NRSA training grant fellowship
(T32-CA09361). BC was supported by the Belgian Program on
Interuniversity Attraction Poles initiated by the Federal Office for
Scientific, Technical and Cultural Affairs (IAPP6/19 PROFUSA). MVand RB
are 'Honorary Research Associate' and 'Research Director' from the Fonds
de la Recherche Scientifique (FRS-FNRS, French Community of Belgium),
respectively.
NR 37
TC 163
Z9 163
U1 1
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1744-4292
J9 MOL SYST BIOL
JI Mol. Syst. Biol.
PD NOV
PY 2009
VL 5
AR 321
DI 10.1038/msb.2009.80
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 526QY
UT WOS:000272308900005
PM 19888216
ER
PT J
AU Heinlen, LD
McClain, MT
Gross, T
Anderson, J
Pachner, A
Harley, JB
James, JA
AF Heinlen, Latisha D.
McClain, Micah T.
Gross, Tim
Anderson, Jourdan
Pachner, Andrew
Harley, John B.
James, Judith A.
TI Multiple sclerosis patients make antibodies against a unique sequence of
EBNA-1 that cross reacts with myelin basic protein
SO MULTIPLE SCLEROSIS
LA English
DT Meeting Abstract
CT 14th Annual Meeting of the
Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis/Cons
ortium-for-Multiple-Sclerosis-Centers
CY MAY 27-30, 2009
CL Atlanta, GA
SP Amer Comm Treatment & Res Multiple Sclerosis, Consortium Multiple Sclerosis Ctr
C1 [Heinlen, Latisha D.; McClain, Micah T.; Gross, Tim; Anderson, Jourdan; James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, Dept Clin Immunol, Oklahoma City, OK USA.
[Pachner, Andrew] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol & Neurosci, Newark, NJ 07103 USA.
[Harley, John B.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, Dept Arthrit & Immunol,US Dept Vet Affairs, Oklahoma City, OK USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
J9 MULT SCLER
JI Mult. Scler.
PD NOV
PY 2009
VL 15
IS 11
BP 1389
EP 1389
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 516IU
UT WOS:000271536400027
ER
PT J
AU Salameh, JS
Atassi, N
David, WS
AF Salameh, Johnny S.
Atassi, Nazem
David, William S.
TI SOD1 (A4V)-MEDIATED ALS PRESENTING WITH LOWER MOTOR NEURON FACIAL
DIPLEGIA AND UNILATERAL VOCAL CORD PARALYSIS
SO MUSCLE & NERVE
LA English
DT Article
DE amyotrophic lateral sclerosis; ALS; SOD1; A4V; motor neuron disease;
Madras motor neuron disease; Brown-Vialetto-Van Laere Syndrome; facial
diplegia
ID AMYOTROPHIC-LATERAL-SCLEROSIS; SUPEROXIDE-DISMUTASE GENE;
MUSCULAR-ATROPHY; DISEASE MMND; MUTATIONS
AB Amyotrophic lateral sclerosis (ALS) is a progressive degenerative neuromuscular disease that presents with upper and lower motor neuron signs. Although the majority of ALS cases are sporadic, 10% are familial, of which 20%-25% result from mutations in the superoxide dismutase (SOD1) gene. We describe a novel case of SOD1 (A4V)-mediated ALS that presented with lower motor neuron facial diplegia and unilateral vocal cord paralysis. This case expands the phenotypic expression of the A4V mutation. Muscle Nerve 40: 880-882, 2009
C1 [Salameh, Johnny S.; Atassi, Nazem; David, William S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Salameh, JS (reprint author), Massachusetts Gen Hosp, Dept Neurol, 165 Cambridge St,Suite 820, Boston, MA 02114 USA.
EM johnnysalameh@hotmail.com
NR 14
TC 5
Z9 6
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0148-639X
J9 MUSCLE NERVE
JI Muscle Nerve
PD NOV
PY 2009
VL 40
IS 5
BP 880
EP 882
DI 10.1002/mus.21321
PG 3
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 511OF
UT WOS:000271174400018
PM 19618436
ER
PT J
AU Chan, EM
Ratanasirintrawoot, S
Park, IH
Manos, PD
Loh, YH
Huo, HG
Miller, JD
Hartung, O
Rho, J
Ince, TA
Daley, GQ
Schlaeger, TM
AF Chan, Elayne M.
Ratanasirintrawoot, Sutheera
Park, In-Hyun
Manos, Philip D.
Loh, Yuin-Han
Huo, Hongguang
Miller, Justine D.
Hartung, Odelya
Rho, Junsung
Ince, Tan A.
Daley, George Q.
Schlaeger, Thorsten M.
TI Live cell imaging distinguishes bona fide human iPS cells from partially
reprogrammed cells
SO NATURE BIOTECHNOLOGY
LA English
DT Article
ID PLURIPOTENT STEM-CELLS; HUMAN SOMATIC-CELLS; DEFINED FACTORS;
FIBROBLASTS; GENERATION; EXPRESSION; SYSTEM; MOUSE
AB Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by enforced expression of transcription factors. Using serial live imaging of human fibroblasts undergoing reprogramming, we identified distinct colony types that morphologically resemble embryonic stem (ES) cells yet differ in molecular phenotype and differentiation potential. By analyzing expression of pluripotency markers, methylation at the OCT4 and NANOG promoters and differentiation into teratomas, we determined that only one colony type represents true iPS cells, whereas the others represent reprogramming intermediates. Proviral silencing and expression of TRA-1-60, DNMT3B and REX1 can be used to distinguish the fully reprogrammed state, whereas alkaline phosphatase, SSEA-4, GDF3, hTERT and NANOG are insufficient as markers. We also show that reprogramming using chemically defined medium favors formation of fully reprogrammed over partially reprogrammed colonies. Our data define molecular markers of the fully reprogrammed state and highlight the need for rigorous characterization and standardization of putative iPS cells.
C1 [Chan, Elayne M.; Ratanasirintrawoot, Sutheera; Park, In-Hyun; Manos, Philip D.; Loh, Yuin-Han; Huo, Hongguang; Miller, Justine D.; Hartung, Odelya; Rho, Junsung; Daley, George Q.; Schlaeger, Thorsten M.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
[Chan, Elayne M.; Ratanasirintrawoot, Sutheera; Park, In-Hyun; Manos, Philip D.; Loh, Yuin-Han; Huo, Hongguang; Miller, Justine D.; Hartung, Odelya; Rho, Junsung; Daley, George Q.; Schlaeger, Thorsten M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Chan, Elayne M.; Park, In-Hyun; Loh, Yuin-Han; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Ratanasirintrawoot, Sutheera; Manos, Philip D.; Huo, Hongguang; Miller, Justine D.; Hartung, Odelya; Daley, George Q.; Schlaeger, Thorsten M.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA.
[Ince, Tan A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Daley, George Q.; Schlaeger, Thorsten M.] Harvard Stem Cell Inst, Cambridge, MA USA.
[Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Daley, George Q.] Brigham & Womens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Daley, George Q.] Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA.
RP Daley, GQ (reprint author), Childrens Hosp, Div Pediat Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA.
EM george.daley@childrens.harvard.edu; schlaeger@enders.tch.harvard.edu
RI Loh, Yuin-Han/E-1096-2014
OI Loh, Yuin-Han/0000-0002-4715-6454
FU National Institutes of Health (NIH); Burroughs Wellcome Fund; Leukemia
and Lymphoma Society; Harvard Stem Cell Institute; Agency of Science,
Technology and Research International Fellowship; Institute of Medical
Biology, Singapore; Canadian Institutes of Health Research; Breast
Cancer Research Foundation, NY; Department of Defense; Congressionally
Directed Medical Research Programs (CDMRPs); Breast Cancer Research
Program (BCRP)
FX G. Q. D. was supported by grants from the National Institutes of Health
(NIH), the NIH Director's Pioneer Award of the NIH Roadmap for Medical
Research, and private funds contributed to the Harvard Stem Cell
Institute and the Children's Hospital Stem Cell Program. G. Q. D. is a
recipient of Clinical Scientist Awards in Translational Research from
the Burroughs Wellcome Fund and the Leukemia and Lymphoma Society, and
is an investigator of the Howard Hughes Medical Institute. T. M. S. was
supported by the Harvard Stem Cell Institute and the Children's Hospital
Stem Cell Program. Y.-H. L. is funded by the Agency of Science,
Technology and Research International Fellowship and the Institute of
Medical Biology, Singapore. E. M. C. was funded by The Canadian
Institutes of Health Research. T. A. I. was supported by Breast Cancer
Research Foundation, NY, and Department of Defense, Congressionally
Directed Medical Research Programs (CDMRPs) and Breast Cancer Research
Program (BCRP). We thank T. Woo (BWH) for her assistance with
immnuhistopathological stains of the teratoma sections.
NR 24
TC 284
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U1 1
U2 32
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD NOV
PY 2009
VL 27
IS 11
BP 1033
EP U100
DI 10.1038/nbt.1580
PG 6
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 516EM
UT WOS:000271524700024
PM 19826408
ER
PT J
AU Sun, YL
Jiang, XF
Xu, Y
Ayrapetov, MK
Moreau, LA
Whetstine, JR
Price, BD
AF Sun, Yingli
Jiang, Xiaofeng
Xu, Ye
Ayrapetov, Marina K.
Moreau, Lisa A.
Whetstine, Johnathan R.
Price, Brendan D.
TI Histone H3 methylation links DNA damage detection to activation of the
tumour suppressor Tip60
SO NATURE CELL BIOLOGY
LA English
DT Article
ID DOUBLE-STRAND BREAKS; ATM KINASE-ACTIVITY; CHROMATIN; ACETYLATION;
BINDING; GENOME; REPAIR; GENE; HETEROCHROMATIN; DEMETHYLASES
AB DNA double-strand break (DSB) repair involves complex interactions between chromatin and repair proteins, including Tip60, a tumour suppressor(1). Tip60 is an acetyltransferase that acetylates both histones(2-5) and ATM (ataxia telangiectasia mutated) kinase(6,7). Inactivation of Tip60 leads to defective DNA repair(2-4) and increased cancer risk(8-11). However, how DNA damage activates the acetyltransferase activity of Tip60 is not known. Here, we show that direct interaction between the chromodomain of Tip60 and histone H3 trimethylated on lysine 9 (H3K9me3) at DSBs activates the acetyltransferase activity of Tip60. Depletion of intracellular H3K9me3 blocks activation of the acetyltransferase activity of Tip60, resulting in defective ATM activation and widespread defects in DSB repair. In addition, the ability of Tip60 to access H3K9me3 is dependent on the DNA damage-induced displacement of HP1 beta (heterochromatin protein 1 beta) from H3K9me3. Finally, we demonstrate that the Mre11-Rad50-Nbs1 (MRN) complex targets Tip60 to H3K9me3, and is required to activate the acetyltransferase activity of Tip60. These results reveal a new function for H3K9me3 in coordinating activation of Tip60-dependent DNA repair pathways, and imply that aberrant patterns of histone methylation may contribute to cancer by altering the efficiency of DSB repair.
C1 [Sun, Yingli; Jiang, Xiaofeng; Xu, Ye; Ayrapetov, Marina K.; Moreau, Lisa A.; Price, Brendan D.] Harvard Univ, Sch Med, Div Genom Stabil & DNA Repair, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA.
[Whetstine, Johnathan R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
RP Price, BD (reprint author), Harvard Univ, Sch Med, Div Genom Stabil & DNA Repair, Dept Radiat Oncol,Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM brendan_price@dfci.harvard.edu
FU NCI [CA64585, CA93602]; DOD Breast Cancer Program; NIAID [U19AI067751];
[T32 CA09078]
FX We thank T. Jenuwein for providing Suv39h1/2 cells, D. Ferguson for
providing Rad50-deficient HCT116 cells, and H. Chan, J. Cote, D.
Chowdhury and A. D'Andrea for critical discussions and reading of the
manuscript. This work was supported by grants from the NCI (CA64585 and
CA93602) and the DOD Breast Cancer Program to B. D. P., and by NCI
training grants to Y.S. and M. K. A. (T32 CA09078). Y.X. is supported by
a U19 Center grant from NIAID (U19AI067751).
NR 38
TC 172
Z9 178
U1 2
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD NOV
PY 2009
VL 11
IS 11
BP 1376
EP U273
DI 10.1038/ncb1982
PG 18
WC Cell Biology
SC Cell Biology
GA 514WC
UT WOS:000271425800019
PM 19783983
ER
PT J
AU Yang, XHR
Ng, D
Alcorta, DA
Liebsch, NJ
Sheridan, E
Li, SF
Goldstein, AM
Parry, DM
Kelley, MJ
AF Yang, Xiaohong R.
Ng, David
Alcorta, David A.
Liebsch, Norbert J.
Sheridan, Eamonn
Li, Sufeng
Goldstein, Alisa M.
Parry, Dilys M.
Kelley, Michael J.
TI T (brachyury) gene duplication confers major susceptibility to familial
chordoma
SO NATURE GENETICS
LA English
DT Article
ID COPY-NUMBER VARIATION; GENOMIC REARRANGEMENTS; DISORDERS; PROTEIN;
DISEASE; LOCUS
AB Using high-resolution array-CGH, we identified unique duplications of a region on 6q27 in four multiplex families with at least three cases of chordoma, a cancer of presumed notochordal origin. The duplicated region contains only the T (brachyury) gene, which is important in notochord development and is expressed in most sporadic chordomas. Our findings highlight the value of screening for complex genomic rearrangements in searches for cancer-susceptibility genes.
C1 [Yang, Xiaohong R.; Ng, David; Goldstein, Alisa M.; Parry, Dilys M.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Alcorta, David A.; Li, Sufeng; Kelley, Michael J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Liebsch, Norbert J.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Sheridan, Eamonn] St James Univ Hosp, Leeds LS9 7TF, W Yorkshire, England.
[Li, Sufeng; Kelley, Michael J.] Durham Vet Affairs Med Ctr, Durham, NC USA.
RP Parry, DM (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM parryd@mail.nih.gov
OI Kelley, Michael/0000-0001-9523-6080
FU US National Cancer Institute, Division of Cancer Epidemiology and
Genetics; National Institutes of Health; Department of Veterans Affairs,
Veterans Health Administration; Office of Research and Development,
Biomedical Laboratory Research and Development program; Chordoma
Foundation
FX We thank D. Zametkin for her outstanding skills as a research nurse; G.
M. Glenn and M. L. McMaster for their careful clinical evaluations of
affected individuals and family members; N. J. Patronas for reviewing
the MRIs; A. Bergen and S. Chanock for SNP genotyping; K. Haque and D.
Maeder for technical assistance; and, especially, the affected
individuals and their families for their participation. This work was
supported by the intramural research program of the US National Cancer
Institute, Division of Cancer Epidemiology and Genetics, National
Institutes of Health; by the Department of Veterans Affairs, Veterans
Health Administration, Office of Research and Development, Biomedical
Laboratory Research and Development program; and by a grant from the
Chordoma Foundation (M. J. K.).
NR 13
TC 104
Z9 111
U1 0
U2 6
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 NOV
PY 2009
VL 41
IS 11
BP 1176
EP 1178
DI 10.1038/ng.454
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 512KM
UT WOS:000271247600008
PM 19801981
ER
PT J
AU Soranzo, N
Spector, TD
Mangino, M
Kuhnel, B
Rendon, A
Teumer, A
Willenborg, C
Wright, B
Chen, L
Li, MY
Salo, P
Voight, BF
Burns, P
Laskowski, RA
Xue, YL
Menzel, S
Altshuler, D
Bradley, JR
Bumpstead, S
Burnett, MS
Devaney, J
Doring, A
Elosua, R
Epstein, SE
Erber, W
Falchi, M
Garner, SF
Ghori, MJR
Goodall, AH
Gwilliam, R
Hakonarson, HH
Hall, AS
Hammond, N
Hengstenberg, C
Illig, T
Konig, IR
Knouff, CW
McPherson, R
Melander, O
Mooser, V
Nauck, M
Nieminen, MS
O'Donnell, CJ
Peltonen, L
Potter, SC
Prokisch, H
Rader, DJ
Rice, CM
Roberts, R
Salomaa, V
Sambrook, J
Schreiber, S
Schunkert, H
Schwartz, SM
Serbanovic-Canic, J
Sinisalo, J
Siscovick, DS
Stark, K
Surakka, I
Stephens, J
Thompson, JR
Volker, U
Volzke, H
Watkins, NA
Wells, GA
Wichmann, HE
Van Heel, DA
Tyler-Smith, C
Thein, SL
Kathiresan, S
Perola, M
Reilly, MP
Stewart, AFR
Erdmann, J
Samani, NJ
Meisinger, C
Greinacher, A
Deloukas, P
Ouwehand, WH
Gieger, C
AF Soranzo, Nicole
Spector, Tim D.
Mangino, Massimo
Kuehnel, Brigitte
Rendon, Augusto
Teumer, Alexander
Willenborg, Christina
Wright, Benjamin
Chen, Li
Li, Mingyao
Salo, Perttu
Voight, Benjamin F.
Burns, Philippa
Laskowski, Roman A.
Xue, Yali
Menzel, Stephan
Altshuler, David
Bradley, John R.
Bumpstead, Suzannah
Burnett, Mary-Susan
Devaney, Joseph
Doering, Angela
Elosua, Roberto
Epstein, Stephen E.
Erber, Wendy
Falchi, Mario
Garner, Stephen F.
Ghori, Mohammed J. R.
Goodall, Alison H.
Gwilliam, Rhian
Hakonarson, Hakon H.
Hall, Alistair S.
Hammond, Naomi
Hengstenberg, Christian
Illig, Thomas
Koenig, Inke R.
Knouff, Christopher W.
McPherson, Ruth
Melander, Olle
Mooser, Vincent
Nauck, Matthias
Nieminen, Markku S.
O'Donnell, Christopher J.
Peltonen, Leena
Potter, Simon C.
Prokisch, Holger
Rader, Daniel J.
Rice, Catherine M.
Roberts, Robert
Salomaa, Veikko
Sambrook, Jennifer
Schreiber, Stefan
Schunkert, Heribert
Schwartz, Stephen M.
Serbanovic-Canic, Jovana
Sinisalo, Juha
Siscovick, David S.
Stark, Klaus
Surakka, Ida
Stephens, Jonathan
Thompson, John R.
Voelker, Uwe
Voelzke, Henry
Watkins, Nicholas A.
Wells, George A.
Wichmann, H-Erich
Van Heel, David A.
Tyler-Smith, Chris
Thein, Swee Lay
Kathiresan, Sekar
Perola, Markus
Reilly, Muredach P.
Stewart, Alexandre F. R.
Erdmann, Jeanette
Samani, Nilesh J.
Meisinger, Christa
Greinacher, Andreas
Deloukas, Panos
Ouwehand, Willem H.
Gieger, Christian
TI A genome-wide meta-analysis identifies 22 loci associated with eight
hematological parameters in the HaemGen consortium
SO NATURE GENETICS
LA English
DT Article
ID CORONARY-HEART-DISEASE; MEAN PLATELET VOLUME; MYOCARDIAL-INFARCTION;
COMMON VARIANTS; NOONAN-SYNDROME; RISK; GENE; EXPRESSION; MUTATIONS;
SELECTION
AB The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.
C1 [Soranzo, Nicole; Xue, Yali; Bumpstead, Suzannah; Ghori, Mohammed J. R.; Gwilliam, Rhian; Hammond, Naomi; Potter, Simon C.; Rice, Catherine M.; Tyler-Smith, Chris; Deloukas, Panos; Ouwehand, Willem H.] Wellcome Trust Sanger Inst, Hinxton, England.
[Soranzo, Nicole; Spector, Tim D.; Mangino, Massimo; Falchi, Mario] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Kuehnel, Brigitte; Doering, Angela; Illig, Thomas; Wichmann, H-Erich; Meisinger, Christa; Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany.
[Rendon, Augusto; Burns, Philippa; Garner, Stephen F.; Sambrook, Jennifer; Serbanovic-Canic, Jovana; Stephens, Jonathan; Watkins, Nicholas A.; Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge, England.
[Rendon, Augusto; Burns, Philippa; Garner, Stephen F.; Sambrook, Jennifer; Serbanovic-Canic, Jovana; Stephens, Jonathan; Watkins, Nicholas A.; Ouwehand, Willem H.] Natl Hlth Serv Blood & Transplant, Cambridge, England.
[Teumer, Alexander; Voelker, Uwe] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Willenborg, Christina; Koenig, Inke R.] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany.
[Willenborg, Christina; Schunkert, Heribert; Erdmann, Jeanette] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany.
[Wright, Benjamin; Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
[Chen, Li; McPherson, Ruth; Roberts, Robert; Wells, George A.; Stewart, Alexandre F. R.] Univ Ottawa, Inst Heart, John & Jennifer Ruddy Canadian Cardiovasc Genet C, Ottawa, ON, Canada.
[Li, Mingyao] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Salo, Perttu; Peltonen, Leena; Salomaa, Veikko; Perola, Markus] Natl Inst Hlth & Welf, Helsinki, Finland.
[Salo, Perttu; Peltonen, Leena; Salomaa, Veikko; Surakka, Ida; Perola, Markus] Univ Helsinki, Inst Mol Med, FIN-00014 Helsinki, Finland.
[Voight, Benjamin F.; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Voight, Benjamin F.; Altshuler, David] MIT & Harvard, Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Laskowski, Roman A.] European Bioinformat Inst, Hinxton, England.
[Menzel, Stephan; Thein, Swee Lay] Kings Coll London, Dept Haematol, London WC2R 2LS, England.
[Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Altshuler, David; O'Donnell, Christopher J.; Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Bradley, John R.] Univ Cambridge, Sch Clin Med, Dept Med, Addenbrookes Hosp, Cambridge, England.
[Burnett, Mary-Susan; Devaney, Joseph; Epstein, Stephen E.] Washington Hosp Ctr, MedStar Res Inst, Cardiovasc Res Inst, Washington, DC 20010 USA.
[Elosua, Roberto] Inst Municipal Invest Med, E-08003 Barcelona, Spain.
[Elosua, Roberto] CIBER Epidemiol & Salud Publ, E-08003 Barcelona, Spain.
[Erber, Wendy] Cambridge Univ Hosp NHS Fdn Trust, Dept Haematol, Cambridge, England.
[Falchi, Mario] Univ London Imperial Coll Sci Technol & Med, Sect Genom Med, London, England.
[Goodall, Alison H.; Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Leicester, Leics, England.
[Hakonarson, Hakon H.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Hall, Alistair S.] Leeds Gen Infirm, BHF Heart Res Ctr, Leeds, W Yorkshire, England.
[Hengstenberg, Christian; Stark, Klaus] Univ Regensburg, Klin & Poliklin Innere Med 2, Regensburg, Germany.
[Knouff, Christopher W.; Mooser, Vincent] GlaxoSmithKline Inc, Div Genet, King Of Prussia, PA USA.
[Melander, Olle] Lund Univ, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo Univ Hosp, Malmo, Sweden.
[Nauck, Matthias] Ernst Moritz Arndt Univ Greifswald, Inst Klin Chem & Lab Med, Greifswald, Germany.
[Nieminen, Markku S.; Sinisalo, Juha] Univ Helsinki, Cent Hosp, Dept Med, Div Cardiol, Helsinki, Finland.
[O'Donnell, Christopher J.; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[O'Donnell, Christopher J.; Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Prokisch, Holger] Tech Univ Munich, Klinikum Rechts Isar, Dept Human Genet, D-8000 Munich, Germany.
[Prokisch, Holger] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.
[Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
[Schreiber, Stefan] Univ Kiel, Inst Klin Mol Biol, Kiel, Germany.
[Schwartz, Stephen M.; Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Schwartz, Stephen M.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
[Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Van Heel, David A.] Queen Mary Univ London, Inst Cell & Mol Sci, Barts & London Sch Med & Dent, London, England.
[Greinacher, Andreas] Ernst Moritz Arndt Univ Greifswald, Inst Immunol & Transfus Med, Greifswald, Germany.
RP Soranzo, N (reprint author), Wellcome Trust Sanger Inst, Genome Campus, Hinxton, England.
EM ns6@sanger.ac.uk
RI Konig, Inke/A-4544-2009; Erdmann, Jeanette/A-4417-2009; Erdmann,
Jeanette/P-7513-2014; Schreiber, Stefan/B-6748-2008; van Heel,
David/A-8005-2011; Altshuler, David/A-4476-2009; Voight,
Benjamin/F-1775-2011; Stark, Klaus/D-3813-2009; Stewart,
Alexandre/A-5677-2011; Falchi, Mario/F-5956-2013; Prokisch,
Holger/N-8964-2013; Erber, Wendy/A-1955-2012; Meisinger,
Christine/B-5358-2014; Willenborg, Christina/D-2668-2012; Spector,
Tim/F-6533-2012; Deloukas, Panos/B-2922-2013; mangino,
massimo/F-5134-2011
OI Bradley, John/0000-0002-7774-8805; Perola, Markus/0000-0003-4842-1667;
Sinisalo, Juha/0000-0002-0169-5137; Soranzo, Nicole/0000-0003-1095-3852;
Meisinger, Christa/0000-0002-9026-6544; ELOSUA,
ROBERTO/0000-0001-8235-0095; Rendon, Augusto/0000-0001-8994-0039; van
Heel, David/0000-0002-0637-2265; Stewart, Alexandre/0000-0003-2673-9164;
Erdmann, Jeanette/0000-0002-4486-6231; Gieger,
Christian/0000-0001-6986-9554; Laskowski, Roman/0000-0001-5528-0087;
Schreiber, Stefan/0000-0003-2254-7771; Altshuler,
David/0000-0002-7250-4107; Stark, Klaus/0000-0002-7832-1942; Willenborg,
Christina/0000-0001-5217-6882; Deloukas, Panos/0000-0001-9251-070X;
mangino, massimo/0000-0002-2167-7470
FU Wellcome Trust [UKBS-CC1]; EU [HEALTH-F2-2008-ENGAGE,
QLG2-CT-2002-01254, LSHM-CT-2006-037593]; National Institute for Health
Research of England (NIHR) (TwinsUK); Helmholtz Zentrum Munchen; German
Research Center for Environmental Health, Neuherberg, Germany; German
Federal Ministry of Education and Research (BMBF); German National
Genome Research Network (NGFN); Munich Center of Health Sciences (MC
Health) (KORA); Federal Ministry of Education and Research [01ZZ9603,
01ZZ0103, 01ZZ0403, 03ZIK012]; Ministry of Cultural Affairs, Social
Ministry of the Federal State of Mecklenburg-West Pomerania; Deutsche
Forschungsgemeinschaft [SFB TR 19]; Siemens Healthcare, Erlangen,
Germany; Federal State of Mecklenburg-West Pomerania (SHIP); NIHR,
CBMRC, NHSBT, (CBR); Deutsche Forschungsgemeinschaft; German Federal
Ministry of Education and Research (BMBF) [NGFN-2]; Leicester NIHR
Biomedical Research Unit in Cardiovascular Disease; EU-FP6
[LSHM-CT-2004-503485]; Cardiovascular Institute (University of
Pennsylvania); GlaxoSmithKline; MedSTAR Research Institute
(PennCATH/MedSTAR); US National Institutes of Health (NIH); National
Heart, Lung, and Blood Institute (STAMPEED); National Center for
Research Resource [U54 RR020278]; Canadian Institutes of Health Research
[MOP82810, NA6650, MOP77682]; Canada Foundation for Innovation and
Ontario Research Foundation [11966]; Finnish Foundation for
Cardiovascular Research, Sigrid Juselius Foundation (COROGENE); Juvenile
Diabetes Research Foundation/Wellcome Trust [T1D]
FX The Wellcome Trust, EU (HEALTH-F2-2008-ENGAGE, QLG2-CT-2002-01254),
National Institute for Health Research of England (NIHR) (TwinsUK); The
Wellcome Trust (UKBS-CC1); Helmholtz Zentrum Munchen, German Research
Center for Environmental Health, Neuherberg, Germany, the German Federal
Ministry of Education and Research (BMBF), the German National Genome
Research Network (NGFN), Munich Center of Health Sciences (MC Health)
(KORA); Federal Ministry of Education and Research (grants no. 01ZZ9603,
01ZZ0103 and 01ZZ0403), Ministry of Cultural Affairs, Social Ministry of
the Federal State of Mecklenburg-West Pomerania, Deutsche
Forschungsgemeinschaft (grant SFB TR 19), the Federal Ministry of
Education and Research (grant no. 03ZIK012); a joint grant from Siemens
Healthcare, Erlangen, Germany and the Federal State of Mecklenburg-West
Pomerania (SHIP); NIHR, CBMRC, NHSBT, (CBR); Deutsche
Forschungsgemeinschaft, the German Federal Ministry of Education and
Research (BMBF) (NGFN-2 and NGFN-plus), EU (LSHM-CT-2006-037593)
(GerMIFS I and II); BHF and the UK MRC, the Wellcome Trust, Leicester
NIHR Biomedical Research Unit in Cardiovascular Disease and EU-FP6
(LSHM-CT-2004-503485) (WTCCC-CAD); Cardiovascular Institute (University
of Pennsylvania), GlaxoSmithKline, MedSTAR Research Institute
(PennCATH/MedSTAR); US National Institutes of Health (NIH) and National
Heart, Lung, and Blood Institute (STAMPEED), National Center for
Research Resource (U54 RR020278) (MIGen); Canadian Institutes of Health
Research (MOP82810, NA6650 and MOP77682), Canada Foundation for
Innovation and Ontario Research Foundation (# 11966) (OHGS); Finnish
Foundation for Cardiovascular Research, Sigrid Juselius Foundation
(COROGENE); Juvenile Diabetes Research Foundation/Wellcome Trust (T1D).
NR 52
TC 288
Z9 298
U1 1
U2 19
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 NOV
PY 2009
VL 41
IS 11
BP 1182
EP U38
DI 10.1038/ng.467
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 512KM
UT WOS:000271247600010
PM 19820697
ER
PT J
AU Ganesh, SK
Zakai, NA
van Rooij, FJA
Soranzo, N
Smith, AV
Nalls, MA
Chen, MH
Kottgen, A
Glazer, NL
Dehghan, A
Kuhnel, B
Aspelund, T
Yang, Q
Tanaka, T
Jaffe, A
Bis, JCM
Verwoert, GC
Teumer, A
Fox, CS
Guralnik, JM
Ehret, GB
Rice, K
Felix, JF
Rendon, A
Eiriksdottir, G
Levy, D
Patel, KV
Boerwinkle, E
Rotter, JI
Hofman, A
Sambrook, JG
Hernandez, DG
Zheng, G
Bandinelli, S
Singleton, AB
Coresh, J
Lumley, T
Uitterlinden, AG
vanGils, JM
Launer, LJ
Cupples, LA
Oostra, BA
Zwaginga, JJ
Ouwehand, WH
Thein, SL
Meisinger, C
Deloukas, P
Nauck, M
Spector, TD
Gieger, C
Gudnason, V
van Duijn, CM
Psaty, BM
Ferrucci, L
Chakravarti, A
Greinacher, A
O'Donnell, CJ
Witteman, JCM
Furth, S
Cushman, M
Harris, TB
Lin, JP
AF Ganesh, Santhi K.
Zakai, Neil A.
van Rooij, Frank J. A.
Soranzo, Nicole
Smith, Albert V.
Nalls, Michael A.
Chen, Ming-Huei
Kottgen, Anna
Glazer, Nicole L.
Dehghan, Abbas
Kuhnel, Brigitte
Aspelund, Thor
Yang, Qiong
Tanaka, Toshiko
Jaffe, Andrew
Bis, Joshua C. M.
Verwoert, Germaine C.
Teumer, Alexander
Fox, Caroline S.
Guralnik, Jack M.
Ehret, Georg B.
Rice, Kenneth
Felix, Janine F.
Rendon, Augusto
Eiriksdottir, Gudny
Levy, Daniel
Patel, Kushang V.
Boerwinkle, Eric
Rotter, Jerome I.
Hofman, Albert
Sambrook, Jennifer G.
Hernandez, Dena G.
Zheng, Gang
Bandinelli, Stefania
Singleton, Andrew B.
Coresh, Josef
Lumley, Thomas
Uitterlinden, Andre G.
vanGils, Janine M.
Launer, Lenore J.
Cupples, L. Adrienne
Oostra, Ben A.
Zwaginga, Jaap-Jan
Ouwehand, Willem H.
Thein, Swee-Lay
Meisinger, Christa
Deloukas, Panos
Nauck, Matthias
Spector, Tim D.
Gieger, Christian
Gudnason, Vilmundur
van Duijn, Cornelia M.
Psaty, Bruce M.
Ferrucci, Luigi
Chakravarti, Aravinda
Greinacher, Andreas
O'Donnell, Christopher J.
Witteman, Jacqueline C. M.
Furth, Susan
Cushman, Mary
Harris, Tamara B.
Lin, Jing-Ping
TI Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BLOOD-PRESSURE; HEMOGLOBIN CONCENTRATION;
HEMOCHROMATOSIS GENE; HEREDITARY HEMOCHROMATOSIS;
CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; FETAL-HEMOGLOBIN;
CELIAC-DISEASE; C-MYB
AB Measurements of erythrocytes within the blood are important clinical traits and can indicate various hematological disorders. We report here genome-wide association studies (GWAS) for six erythrocyte traits, including hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red blood cell count (RBC). We performed an initial GWAS in cohorts of the CHARGE Consortium totaling 24,167 individuals of European ancestry and replication in additional independent cohorts of the HaemGen Consortium totaling 9,456 individuals. We identified 23 loci significantly associated with these traits in a meta-analysis of the discovery and replication cohorts (combined P values ranging from 5 x 10(-8) to 7 x 10(-86)). Our findings include loci previously associated with these traits (HBS1L-MYB, HFE, TMPRSS6, TFR2, SPTA1) as well as new associations (EPO, TFRC, SH2B3 and 15 other loci). This study has identified new determinants of erythrocyte traits, offering insight into common variants underlying variation in erythrocyte measures.
C1 [Ganesh, Santhi K.] NHGRI, Div Intramural Res, Bethesda, MD 20892 USA.
[Ganesh, Santhi K.; Fox, Caroline S.; Levy, Daniel] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[Ganesh, Santhi K.; Ehret, Georg B.; Chakravarti, Aravinda] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Zakai, Neil A.; Cushman, Mary] Univ Vermont, Dept Med, Burlington, VT USA.
[Zakai, Neil A.; Cushman, Mary] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA.
[van Rooij, Frank J. A.; Dehghan, Abbas; Verwoert, Germaine C.; Felix, Janine F.; Hofman, Albert; Uitterlinden, Andre G.; Oostra, Ben A.; van Duijn, Cornelia M.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[van Rooij, Frank J. A.; Dehghan, Abbas; Verwoert, Germaine C.; Felix, Janine F.; Hofman, Albert; Uitterlinden, Andre G.; Oostra, Ben A.; van Duijn, Cornelia M.; Witteman, Jacqueline C. M.] NCHA, NGI, Leiden, Netherlands.
[Soranzo, Nicole; Ouwehand, Willem H.; Deloukas, Panos] Wellcome Trust Sanger Inst, Hinxton, England.
[Soranzo, Nicole; Cupples, L. Adrienne; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Smith, Albert V.; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Hernandez, Dena G.] NIA, Intramural Res Program, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Chen, Ming-Huei; Yang, Qiong; Fox, Caroline S.; Levy, Daniel; Cupples, L. Adrienne; O'Donnell, Christopher J.] NHLBIs Framingham Heart Study, Framingham, MA USA.
[Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Kottgen, Anna; Jaffe, Andrew; Coresh, Josef] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Glazer, Nicole L.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA.
[Glazer, Nicole L.; Bis, Joshua C. M.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Kuhnel, Brigitte; Meisinger, Christa; Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany.
[Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Tanaka, Toshiko; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Tanaka, Toshiko] MedStar Res Inst, Hyattsville, MD USA.
[Verwoert, Germaine C.; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Teumer, Alexander] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Guralnik, Jack M.; Patel, Kushang V.; Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Ehret, Georg B.] Univ Hosp Geneva, Ctr Cardiol, Geneva, Switzerland.
[Rice, Kenneth; Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Rendon, Augusto; Sambrook, Jennifer G.; Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge, England.
[Rendon, Augusto; Sambrook, Jennifer G.; Ouwehand, Willem H.] Natl Hlth Serv Blood & Transplant, Cambridge, England.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Zheng, Gang; Lin, Jing-Ping] NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Bandinelli, Stefania] Geriatr Unit ASF, Florence, Italy.
[Uitterlinden, Andre G.] Erasmus MC, Dept Clin Chem, Rotterdam, Netherlands.
[Zwaginga, Jaap-Jan] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands.
[Oostra, Ben A.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
[Zwaginga, Jaap-Jan] Sanquin Res, Dept Expt Immunohematol, Amsterdam, Netherlands.
[Thein, Swee-Lay] Kings Coll London, Dept Haematol, London WC2R 2LS, England.
[Nauck, Matthias] Ernst Moritz Arndt Univ Greifswald, Inst Klin Chem & Lab Med, Greifswald, Germany.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA.
[Greinacher, Andreas] Ernst Moritz Arndt Univ Greifswald, Inst Immunol & Transfus Med, Greifswald, Germany.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Furth, Susan] Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD USA.
RP Ganesh, SK (reprint author), NHGRI, Div Intramural Res, Bethesda, MD 20892 USA.
EM ganeshs@mail.nih.gov; odonnellc@mail.nih.gov
RI Yang, Qiong/G-5438-2014; Gudnason, Vilmundur/K-6885-2015; Smith,
Albert/K-5150-2015; Singleton, Andrew/C-3010-2009; Aspelund,
Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; EHRET, Georg/A-9532-2009;
Kottgen, Anna/D-2920-2012; Spector, Tim/F-6533-2012; Rice,
Kenneth/A-4150-2013; Deloukas, Panos/B-2922-2013; Meisinger,
Christine/B-5358-2014
OI Felix, Janine/0000-0002-9801-5774; Rendon, Augusto/0000-0001-8994-0039;
Soranzo, Nicole/0000-0003-1095-3852; Gieger,
Christian/0000-0001-6986-9554; Meisinger, Christa/0000-0002-9026-6544;
Dehghan, Abbas/0000-0001-6403-016X; Gudnason,
Vilmundur/0000-0001-5696-0084; Smith, Albert/0000-0003-1942-5845;
Cupples, L. Adrienne/0000-0003-0273-7965; Aspelund,
Thor/0000-0002-7998-5433; EHRET, Georg/0000-0002-5730-0675; Rice,
Kenneth/0000-0001-5779-4495; Deloukas, Panos/0000-0001-9251-070X;
FU Medical Research Council [G0000111]; NHLBI NIH HHS [R01 HL086694, R01
HL086694-01A1, R01 HL086694-02, R01 HL086694-03]; NIDDK NIH HHS [P30
DK063491-049004, K24 DK078737, P30 DK063491, P30 DK063491-019004, P30
DK063491-029004, P30 DK063491-039004, P30 DK063491-05, U01 DK066174]
NR 65
TC 190
Z9 196
U1 2
U2 13
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 NOV
PY 2009
VL 41
IS 11
BP 1191
EP U48
DI 10.1038/ng.466
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 512KM
UT WOS:000271247600011
PM 19862010
ER
PT J
AU McCarthy, SE
Makarov, V
Kirov, G
Addington, AM
McClellan, J
Yoon, S
Perkins, DO
Dickel, DE
Kusenda, M
Krastoshevsky, O
Krause, V
Kumar, RA
Grozeva, D
Malhotra, D
Walsh, T
Zackai, EH
Kaplan, P
Ganesh, J
Krantz, ID
Spinner, NB
Roccanova, P
Bhandari, A
Pavon, K
Lakshmi, B
Leotta, A
Kendall, J
Lee, YH
Vacic, V
Gary, S
Iakoucheva, LM
Crow, TJ
Christian, SL
Lieberman, JA
Stroup, TS
Lehtimaki, T
Puura, K
Haldeman-Englert, C
Pearl, J
Goodell, M
Willour, VL
DeRosse, P
Steele, J
Kassem, L
Wolff, J
Chitkara, N
McMahon, FJ
Malhotra, AK
Potash, JB
Schulze, TG
Nothen, MM
Cichon, S
Rietschel, M
Leibenluft, E
Kustanovich, V
Lajonchere, CM
Sutcliffe, JS
Skuse, D
Gill, M
Gallagher, L
Mendell, NR
Craddock, N
Owen, MJ
O'Donovan, MC
Shaikh, TH
Susser, E
DeLisi, LE
Sullivan, PF
Deutsch, CK
Rapoport, J
Levy, DL
King, MC
Sebat, J
AF McCarthy, Shane E.
Makarov, Vladimir
Kirov, George
Addington, Anjene M.
McClellan, Jon
Yoon, Seungtai
Perkins, Diana O.
Dickel, Diane E.
Kusenda, Mary
Krastoshevsky, Olga
Krause, Verena
Kumar, Ravinesh A.
Grozeva, Detelina
Malhotra, Dheeraj
Walsh, Tom
Zackai, Elaine H.
Kaplan, Paige
Ganesh, Jaya
Krantz, Ian D.
Spinner, Nancy B.
Roccanova, Patricia
Bhandari, Abhishek
Pavon, Kevin
Lakshmi, B.
Leotta, Anthony
Kendall, Jude
Lee, Yoon-ha
Vacic, Vladimir
Gary, Sydney
Iakoucheva, Lilia M.
Crow, Timothy J.
Christian, Susan L.
Lieberman, Jeffrey A.
Stroup, T. Scott
Lehtimaki, Terho
Puura, Kaija
Haldeman-Englert, Chad
Pearl, Justin
Goodell, Meredith
Willour, Virginia L.
DeRosse, Pamela
Steele, Jo
Kassem, Layla
Wolff, Jessica
Chitkara, Nisha
McMahon, Francis J.
Malhotra, Anil K.
Potash, James B.
Schulze, Thomas G.
Noethen, Markus M.
Cichon, Sven
Rietschel, Marcella
Leibenluft, Ellen
Kustanovich, Vlad
Lajonchere, Clara M.
Sutcliffe, James S.
Skuse, David
Gill, Michael
Gallagher, Louise
Mendell, Nancy R.
Craddock, Nick
Owen, Michael J.
O'Donovan, Michael C.
Shaikh, Tamim H.
Susser, Ezra
DeLisi, Lynn E.
Sullivan, Patrick F.
Deutsch, Curtis K.
Rapoport, Judith
Levy, Deborah L.
King, Mary-Claire
Sebat, Jonathan
CA Wellcome Trust Case Control Consor
TI Microduplications of 16p11.2 are associated with schizophrenia
SO NATURE GENETICS
LA English
DT Article
ID PERVASIVE DEVELOPMENTAL DISORDERS; AUTISM SPECTRUM DISORDER; HEAD
CIRCUMFERENCE; RECURRENT REARRANGEMENTS; HUMAN GENOME; 1ST YEAR;
INDIVIDUALS; DISRUPTION; DELETIONS; GENES
AB Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders(1-3). We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 x 10(-5), OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia (P = 4.8 x 10(-7)), bipolar disorder (P = 0.017) and autism (P = 1.9 x 10(-7)). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 x 10(-13)). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007).
C1 [McCarthy, Shane E.; Makarov, Vladimir; Yoon, Seungtai; Kusenda, Mary; Malhotra, Dheeraj; Roccanova, Patricia; Bhandari, Abhishek; Pavon, Kevin; Lakshmi, B.; Leotta, Anthony; Kendall, Jude; Lee, Yoon-ha; Vacic, Vladimir; Gary, Sydney; Sebat, Jonathan] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
[Kirov, George; Grozeva, Detelina; Craddock, Nick; Owen, Michael J.; O'Donovan, Michael C.] Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Genom, Dept Psychol Med & Neurol,Sch Med, Cardiff, S Glam, Wales.
[Addington, Anjene M.; Rapoport, Judith] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
[McClellan, Jon] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA.
[Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Dickel, Diane E.; Walsh, Tom; King, Mary-Claire] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Kusenda, Mary] SUNY Stony Brook, Grad Program Genet, Stony Brook, NY 11794 USA.
[Krastoshevsky, Olga; Krause, Verena; Levy, Deborah L.] McLean Hosp, Psychol Res Lab, Belmont, MA 02178 USA.
[Kumar, Ravinesh A.; Christian, Susan L.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Zackai, Elaine H.; Krantz, Ian D.; Spinner, Nancy B.; Haldeman-Englert, Chad; Shaikh, Tamim H.] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA.
[Kaplan, Paige; Ganesh, Jaya] Childrens Hosp Philadelphia, Sect Biochem Genet, Philadelphia, PA 19104 USA.
[Lakshmi, B.] Ontario Inst Canc Res, Toronto, ON, Canada.
[Iakoucheva, Lilia M.] Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA.
[Crow, Timothy J.] Warneford Hosp, Prince Wales Int Ctr SANE Res, Oxford OX3 7JX, England.
[Lieberman, Jeffrey A.; Stroup, T. Scott; Susser, Ezra] Columbia Univ, Columbia Univ Coll Phys & Surg, New York, NY USA.
[Lieberman, Jeffrey A.] New York State Psychiat Hosp, New York, NY USA.
[Lehtimaki, Terho] Tampere Univ, Dept Clin Chem, FIN-33101 Tampere, Finland.
[Puura, Kaija] Tampere Univ, Dept Child Psychiat, FIN-33101 Tampere, Finland.
[Puura, Kaija] Univ Hosp, Tampere, Finland.
[Pearl, Justin; Steele, Jo; Kassem, Layla; Wolff, Jessica; McMahon, Francis J.; Schulze, Thomas G.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, NIH, Bethesda, MD 20892 USA.
[Goodell, Meredith; Willour, Virginia L.; Potash, James B.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA.
[DeRosse, Pamela; Chitkara, Nisha; Malhotra, Anil K.] Zucker Hillside Hosp, Dept Psychiat Res, Glen Oaks, NY USA.
[Schulze, Thomas G.; Rietschel, Marcella] Heidelberg Univ, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-6800 Mannheim, Germany.
[Noethen, Markus M.; Cichon, Sven] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany.
[Noethen, Markus M.; Cichon, Sven] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany.
[Rietschel, Marcella] Univ Bonn, Dept Psychiat & Psychotherapy, D-5300 Bonn, Germany.
[Leibenluft, Ellen] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Kustanovich, Vlad; Lajonchere, Clara M.] Autism Speaks, Autism Genet Resource Exchange, Los Angeles, CA USA.
[Sutcliffe, James S.] Vanderbilt Univ, Ctr Mol Neurosci, Nashville, TN USA.
[Skuse, David] UCL, Behav Sci Unit, Inst Child Hlth, London, England.
[Gill, Michael; Gallagher, Louise] Trinity Coll Dublin, Sch Med, Dept Psychiat, Dublin, Ireland.
[Mendell, Nancy R.] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA.
[DeLisi, Lynn E.; Deutsch, Curtis K.; Levy, Deborah L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[DeLisi, Lynn E.] VA Boston Healthcare Syst, Brockton, MA USA.
[Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Deutsch, Curtis K.] Univ Massachusetts, Sch Med, Eunice Kennedy Shriver Ctr, Waltham, MA USA.
RP Sebat, J (reprint author), Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA.
EM sebat@cshl.edu
RI Stroup, Thomas/F-9188-2014; turton, miranda/F-4682-2011; Schulze,
Thomas/H-2157-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014;
Sutcliffe, James/C-1348-2012;
OI Gallagher, Louise/0000-0001-9462-2836; Stroup,
Thomas/0000-0002-3123-0672; Gill, Michael/0000-0003-0206-5337; Vacic,
Vladimir/0000-0001-6571-2293; Cichon, Sven/0000-0002-9475-086X; Cichon,
Sven/0000-0002-9475-086X; Sutcliffe, James/0000-0001-5200-6007; Sebat,
Jonathan/0000-0002-9087-526X; Walsh, Tom/0000-0002-8875-0310; O'Donovan,
Michael/0000-0001-7073-2379; Iakoucheva, Lilia/0000-0002-4542-5219;
McMahon, Francis/0000-0002-9469-305X; Dickel, Diane/0000-0001-5497-6824;
Nothen, Markus/0000-0002-8770-2464
FU National Institute of Mental Health (NIMH) [R01 MH67257, R01 MH59588,
R01 MH59571, R01 MH59565, R01 MH59587, R01 MH60870, R01 MH59566, R01
MH59586, R01 MH61675, R01 MH60879, R01 MH81800, U01 MH46276, U01
MH46289, U01 MH46318, U01 MH79469, U01 MH79470]
FX Funding support for the genome-wide association of schizophrenia study
was provided by the National Institute of Mental Health (NIMH) (R01
MH67257, R01 MH59588, R01 MH59571, R01 MH59565, R01 MH59587, R01
MH60870, R01 MH59566, R01 MH59586, R01 MH61675, R01 MH60879, R01
MH81800, U01 MH46276, U01 MH46289, U01 MH46318, U01 MH79469 and U01
MH79470), and the genotyping of samples was provided through the genetic
association information network (GAIN). The datasets used for the
analyses described in this manuscript were obtained from the database of
genotype and phenotype (dbGaP) found at http://www.ncbi.nlm.nih.gov/gap
through dbGaP accession number phs000021.v2.p1. Samples and associated
phenotype data for the genome-wide association of schizophrenia study
were provided by the Molecular Genetics of Schizophrenia Collaboration
(PI: P. V. Gejman, Evanston Northwestern Healthcare (ENH) and
Northwestern University, Evanston, Illinois, USA).
NR 41
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Z9 352
U1 4
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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 NOV
PY 2009
VL 41
IS 11
BP 1223
EP U85
DI 10.1038/ng.474
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 512KM
UT WOS:000271247600015
PM 19855392
ER
PT J
AU Bass, AJ
Watanabe, H
Mermel, CH
Yu, SY
Perner, S
Verhaak, RG
Kim, SY
Wardwell, L
Tamayo, P
Gat-Viks, I
Ramos, AH
Woo, MS
Weir, BA
Getz, G
Beroukhim, R
O'Kelly, M
Dutt, A
Rozenblatt-Rosen, O
Dziunycz, P
Komisarof, J
Chirieac, LR
LaFargue, CJ
Scheble, V
Wilbertz, T
Ma, CQ
Rao, S
Nakagawa, H
Stairs, DB
Lin, L
Giordano, TJ
Wagner, P
Minna, JD
Gazdar, AF
Zhu, CQ
Brose, MS
Cecconello, I
Ribeiro, U
Marie, SK
Dahl, O
Shivdasani, RA
Tsao, MS
Rubin, MA
Wong, KK
Regev, A
Hahn, WC
Beer, DG
Rustgi, AK
Meyerson, M
AF Bass, Adam J.
Watanabe, Hideo
Mermel, Craig H.
Yu, Soyoung
Perner, Sven
Verhaak, Roel G.
Kim, So Young
Wardwell, Leslie
Tamayo, Pablo
Gat-Viks, Irit
Ramos, Alex H.
Woo, Michele S.
Weir, Barbara A.
Getz, Gad
Beroukhim, Rameen
O'Kelly, Michael
Dutt, Amit
Rozenblatt-Rosen, Orit
Dziunycz, Piotr
Komisarof, Justin
Chirieac, Lucian R.
LaFargue, Christopher J.
Scheble, Veit
Wilbertz, Theresia
Ma, Changqing
Rao, Shilpa
Nakagawa, Hiroshi
Stairs, Douglas B.
Lin, Lin
Giordano, Thomas J.
Wagner, Patrick
Minna, John D.
Gazdar, Adi F.
Zhu, Chang Qi
Brose, Marcia S.
Cecconello, Ivan
Ribeiro, Ulysses, Jr.
Marie, Suely K.
Dahl, Olav
Shivdasani, Ramesh A.
Tsao, Ming-Sound
Rubin, Mark A.
Wong, Kwok K.
Regev, Aviv
Hahn, William C.
Beer, David G.
Rustgi, Anil K.
Meyerson, Matthew
TI SOX2 is an amplified lineage-survival oncogene in lung and esophageal
squamous cell carcinomas
SO NATURE GENETICS
LA English
DT Article
ID FOREGUT ENDODERM; MOUSE TRACHEA; CANCER; GENE; EXPRESSION; REVEALS;
ADENOCARCINOMAS; DIFFERENTIATION; IDENTIFICATION; AMPLIFICATION
AB Lineage-survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development(1,2). Here we show that a peak of genomic amplification on chromosome 3q26.33 found in squamous cell carcinomas (SCCs) of the lung and esophagus contains the transcription factor gene SOX2, which is mutated in hereditary human esophageal malformations(3), is necessary for normal esophageal squamous development(4), promotes differentiation and proliferation of basal tracheal cells(5) and cooperates in induction of pluripotent stem cells(6-8). SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 here cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These characteristics identify SOX2 as a lineage-survival oncogene in lung and esophageal SCC.
C1 [Bass, Adam J.; Watanabe, Hideo; Mermel, Craig H.; Yu, Soyoung; Verhaak, Roel G.; Kim, So Young; Wardwell, Leslie; Ramos, Alex H.; Woo, Michele S.; Weir, Barbara A.; Beroukhim, Rameen; Dutt, Amit; Rozenblatt-Rosen, Orit; Dziunycz, Piotr; Komisarof, Justin; Shivdasani, Ramesh A.; Wong, Kwok K.; Hahn, William C.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Bass, Adam J.; Beroukhim, Rameen; Shivdasani, Ramesh A.; Wong, Kwok K.; Hahn, William C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Bass, Adam J.; Watanabe, Hideo; Mermel, Craig H.; Yu, Soyoung; Verhaak, Roel G.; Kim, So Young; Wardwell, Leslie; Ramos, Alex H.; Woo, Michele S.; Weir, Barbara A.; Beroukhim, Rameen; Dutt, Amit; Rozenblatt-Rosen, Orit; Hahn, William C.; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
[Bass, Adam J.; Watanabe, Hideo; Mermel, Craig H.; Verhaak, Roel G.; Tamayo, Pablo; Gat-Viks, Irit; Ramos, Alex H.; Woo, Michele S.; Weir, Barbara A.; Getz, Gad; Beroukhim, Rameen; O'Kelly, Michael; Dutt, Amit; Regev, Aviv; Hahn, William C.; Meyerson, Matthew] Broad Inst, Cambridge, MA USA.
[Perner, Sven; LaFargue, Christopher J.; Wagner, Patrick; Rubin, Mark A.] Cornell Univ, Dept Pathol, Weill Med Coll, New York, NY 10021 USA.
[Perner, Sven; Scheble, Veit; Wilbertz, Theresia] Univ Tubingen Hosp, Inst Pathol, Ctr Comprehens Canc, Tubingen, Germany.
[Chirieac, Lucian R.; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Ma, Changqing; Rao, Shilpa; Nakagawa, Hiroshi; Stairs, Douglas B.; Brose, Marcia S.; Rustgi, Anil K.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Nakagawa, Hiroshi; Stairs, Douglas B.; Rustgi, Anil K.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Lin, Lin; Beer, David G.] Univ Michigan, Dept Surg, Thorac Surg Sect, Ann Arbor, MI 48109 USA.
[Giordano, Thomas J.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Minna, John D.; Gazdar, Adi F.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Zhu, Chang Qi; Tsao, Ming-Sound] Univ Hlth Network, Toronto, ON, Canada.
[Zhu, Chang Qi; Tsao, Ming-Sound] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Brose, Marcia S.] Univ Penn, Dept Otorhinolaryngol, Philadelphia, PA 19104 USA.
[Cecconello, Ivan; Ribeiro, Ulysses, Jr.; Marie, Suely K.] Univ Sao Paulo, Sch Med, Bauru, SP, Brazil.
[Dahl, Olav] Univ Bergen, Sect Oncol, Bergen, Norway.
[Rustgi, Anil K.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM matthew_meyerson@dfci.harvard.edu
RI Meyerson, Matthew/E-7123-2012; Dutt, Amit/I-1911-2013; Marie,
Suely/D-1870-2012; Ribeiro Jr, Ulysses/G-5942-2012; Cecconello,
Ivan/A-3918-2013;
OI Rubin, Mark/0000-0002-8321-9950; Giordano, Thomas/0000-0003-0641-8873;
Dutt, Amit/0000-0002-1119-4774; Cecconello, Ivan/0000-0002-3535-4170;
Ribeiro Junior, Ulysses/0000-0003-1711-7347
FU Ruth L. Kirschstein NRSA; KWF Kankerbestrijding; US Department of
Defense; National Cancer Institute [K08CA134931, P50CA70907,
R33CA128625, R01CA071606-12, P01CA098101-05, R01CA109038, P50CA90578];
Genentech, Inc.; Sara Thomas Monopoli Lung Cancer Research Fund; Seaman
Corporation Fund for Lung Cancer Research
FX We thank J. Francis, J. Cho, A. Schinzel, R. Firestein, I. Guney and J.
Boehm for technical advice and discussions. A. J. B. is supported by the
Harvard Clinical Investigator Training Program and American Society of
Clinical Oncology. H. W. is supported by a Ruth L. Kirschstein NRSA T32
institutional training grant. R. G. V. is supported by the KWF
Kankerbestrijding. The Morphology, Molecular Biology and Cell Culture
Core of 5P01CA098101-05 (A. K. R.) provided tissue processing for this
project. This work was supported by US Department of Defense VITAL grant
(J. D. M, A. F. G.) and by National Cancer Institute grants K08CA134931
(A. J. B.), P50CA70907 (J. D. M, A. F. G.), R33CA128625 (W. C. H.),
R01CA071606-12 (D. G. B.), P01CA098101-05 (A. K. R.) and R01CA109038 and
P50CA90578 (M. M.). Funding for lung SCC SNP arrays was provided by
Genentech, Inc. Funding was provided by the Sara Thomas Monopoli Lung
Cancer Research Fund and the Seaman Corporation Fund for Lung Cancer
Research.
NR 38
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U1 1
U2 42
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 NOV
PY 2009
VL 41
IS 11
BP 1238
EP U105
DI 10.1038/ng.465
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 512KM
UT WOS:000271247600018
PM 19801978
ER
PT J
AU Wucherpfennig, KW
Gagnon, E
AF Wucherpfennig, Kai W.
Gagnon, Etienne
TI Positively selecting peptides: their job does not end in the thymus
SO NATURE IMMUNOLOGY
LA English
DT Editorial Material
ID T-CELL-RECEPTOR; SENSITIVITY
AB Peptides able to positively select major histocompatibility complex class II-restricted thymocytes have not yet been defined. Two new reports identify and ascribe important extrathymic functions to several positively selecting peptides for CD4(+) T cells.
C1 [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA.
RP Wucherpfennig, KW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA.
EM kai_wucherpfennig@dfci.harvard.edu
NR 10
TC 4
Z9 4
U1 0
U2 0
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 NOV
PY 2009
VL 10
IS 11
BP 1143
EP 1144
DI 10.1038/ni1109-1143
PG 3
WC Immunology
SC Immunology
GA 508SO
UT WOS:000270955900005
PM 19841646
ER
PT J
AU Geraldes, P
Hiraoka-Yamamoto, J
Matsumoto, M
Clermont, A
Leitges, M
Marette, A
Aiello, LP
Kern, TS
King, GL
AF Geraldes, Pedro
Hiraoka-Yamamoto, Junko
Matsumoto, Motonobu
Clermont, Allen
Leitges, Michael
Marette, Andre
Aiello, Lloyd P.
Kern, Timothy S.
King, George L.
TI Activation of PKC-delta and SHP-1 by hyperglycemia causes vascular cell
apoptosis and diabetic retinopathy
SO NATURE MEDICINE
LA English
DT Article
ID PROTEIN-KINASE-C; ENDOTHELIAL GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS;
MOTH-EATEN MICE; TYROSINE-PHOSPHATASE; INTENSIVE TREATMENT; FACTOR
RECEPTOR; BETA-INHIBITOR; COMPLICATIONS; GLUCOSE
AB Cellular apoptosis induced by hyperglycemia occurs in many vascular cells and is crucial for the initiation of diabetic pathologies. In the retina, pericyte apoptosis and the formation of acellular capillaries, the most specific vascular pathologies attributed to hyperglycemia, is linked to the loss of platelet-derived growth factor (PDGF)-mediated survival actions owing to unknown mechanisms. Here we show that hyperglycemia persistently activates protein kinase C-delta (PKC-delta, encoded by Prkcd) and p38 alpha mitogen-activated protein kinase (MAPK) to increase the expression of a previously unknown target of PKC-delta signaling, Src homology-2 domain-containing phosphatase-1 (SHP-1), a protein tyrosine phosphatase. This signaling cascade leads to PDGF receptor-beta dephosphorylation and a reduction in downstream signaling from this receptor, resulting in pericyte apoptosis independently of nuclear factor-kappa B (NF-kappa B) signaling. We observed increased PKC-delta activity and an increase in the number of acellular capillaries in diabetic mouse retinas, which were not reversible with insulin treatment that achieved normoglycemia. Unlike diabetic age-matched wild-type mice, diabetic Prkcd(-/-) mice did not show activation of p38 alpha MAPK or SHP-1, inhibition of PDGF signaling in vascular cells or the presence of acellular capillaries. We also observed PKC-delta, p38 alpha MAPK and SHP-1 activation in brain pericytes and in the renal cortex of diabetic mice. These findings elucidate a new signaling pathway by which hyperglycemia can induce PDGF resistance and increase vascular cell apoptosis to cause diabetic vascular complications.
C1 [Geraldes, Pedro; Hiraoka-Yamamoto, Junko; Matsumoto, Motonobu; Clermont, Allen; Aiello, Lloyd P.; King, George L.] Joslin Diabet Ctr, Dianne Nunnally Hoppes Lab Diabet Complicat, Boston, MA 02215 USA.
[Aiello, Lloyd P.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA.
[Leitges, Michael] Univ Oslo, Biotechnol Ctr Oslo, Oslo, Norway.
[Marette, Andre] Univ Laval, Dept Anat & Physiol, Quebec City, PQ, Canada.
[Aiello, Lloyd P.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Kern, Timothy S.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA.
[King, George L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP King, GL (reprint author), Joslin Diabet Ctr, Dianne Nunnally Hoppes Lab Diabet Complicat, Boston, MA 02215 USA.
EM george.king@joslin.harvard.edu
RI Marette, Andre/E-9342-2013
FU US National Eye Institute [5R01EY016150-02]; Canadian Institute of
Health Research [165453]
FX Prkcd-/- mice were provided by M. Leitges (University of
Oslo). Adenoviral vectors expressing dominant-negative p38 alpha and p38
beta MAPK were generously provided by Y. Wang (University of California,
Los Angeles). Adenoviral vector expressing dominant-negative of SHP-1
(Ad-DN SHP-1) was generously provided by A. Marette (University of
Laval). P. G. is a recipient of awards from the Juvenile Diabetes
Research Foundation. This study was supported by the US National Eye
Institute (grant 5R01EY016150-02 to G. L. K.) and by the Canadian
Institute of Health Research (grant 165453) to A. M. We thank W.-C. Li
and S. Bonner-Weir for the technical support on confocal microscopy
imaging.
NR 44
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U1 2
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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 NOV
PY 2009
VL 15
IS 11
BP 1298
EP U133
DI 10.1038/nm.2052
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 516LM
UT WOS:000271543700018
PM 19881493
ER
PT J
AU Cheng, ZY
Guo, SD
Copps, K
Dong, XC
Kollipara, R
Rodgers, JT
Depinho, RA
Puigserver, P
White, MF
AF Cheng, Zhiyong
Guo, Shaodong
Copps, Kyle
Dong, Xiaochen
Kollipara, Ramya
Rodgers, Joseph T.
Depinho, Ronald A.
Puigserver, Pere
White, Morris F.
TI Foxo1 integrates insulin signaling with mitochondrial function in the
liver
SO NATURE MEDICINE
LA English
DT Article
ID TRANSCRIPTION FACTOR FOXO1; HEPATIC GLUCOSE-PRODUCTION; HUMAN
SKELETAL-MUSCLE; LIFE-SPAN; MICE; DYSFUNCTION; RESISTANCE; INDUCTION;
OXIDATION; RECEPTOR
AB Type 2 diabetes is a complex disease that is marked by the dysfunction of glucose and lipid metabolism. Hepatic insulin resistance is especially pathogenic in type 2 diabetes, as it dysregulates fasting and postprandial glucose tolerance and promotes systemic dyslipidemia and nonalcoholic fatty liver disease(1,2). Mitochondrial dysfunction is closely associated with insulin resistance and might contribute to the progression of diabetes(3,4). Here we used previously generated mice(5) with hepatic insulin resistance owing to the deletion of the genes encoding insulin receptor substrate-1 (Irs-1) and Irs-2 (referred to here as double-knockout (DKO) mice) to establish the molecular link between dysregulated insulin action and mitochondrial function. The expression of several forkhead box O1 (Foxo1) target genes increased in the DKO liver, including heme oxygenase-1 (Hmox1), which disrupts complex III and IV of the respiratory chain and lowers the NAD(+)/NADH ratio and ATP production. Although peroxisome proliferator-activated receptor-gamma coactivator-1 gamma (Ppargc-1 alpha) was also upregulated in DKO liver, it was acetylated and failed to promote compensatory mitochondrial biogenesis or function. Deletion of hepatic Foxo1 in DKO liver normalized the expression of Hmox1 and the NAD(+)/NADH ratio, reduced Ppargc-1 alpha acetylation and restored mitochondrial oxidative metabolism and biogenesis. Thus, Foxo1 integrates insulin signaling with mitochondrial function, and inhibition of Foxo1 can improve hepatic metabolism during insulin resistance and the metabolic syndrome.
C1 [Cheng, Zhiyong; Guo, Shaodong; Copps, Kyle; Dong, Xiaochen; White, Morris F.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Div Endocrinol,Childrens Hosp Boston, Boston, MA 02115 USA.
[Kollipara, Ramya; Depinho, Ronald A.] Harvard Univ, Sch Med, Dept Med, Dept Med Oncol,Belfer Inst Appl Canc Sci, Boston, MA USA.
[Kollipara, Ramya; Depinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Rodgers, Joseph T.; Puigserver, Pere] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol,Dept Cell Biol, Boston, MA 02115 USA.
RP White, MF (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Div Endocrinol,Childrens Hosp Boston, Boston, MA 02115 USA.
EM morris.white@childrens.harvard.edu
FU US National Institutes of Health [DK38712, DK55326]; American Diabetes
Association [7-08-MN-63, JF-7-07-27]
FX We thank B. Spiegelman and L. M. Rohas for help with respiration assays,
S. Orkin for help with fluorescent assays and R. de Cabo for the
communication on flow cytometric assay. We are also grateful to Y. Long
for his valuable comments and discussion. This project was supported by
US National Institutes of Health grants DK38712 and DK55326 (M. F. W.),
American Diabetes Association Mentor-Based Postdoctoral Fellowship
7-08-MN-63 (M. F. W. and Z.C.) and American Diabetes Association Junior
Faculty Grant JF-7-07-27 (S. G.).
NR 34
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U1 4
U2 18
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 NOV
PY 2009
VL 15
IS 11
BP 1307
EP U105
DI 10.1038/nm.2049
PG 6
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 516LM
UT WOS:000271543700019
PM 19838201
ER
PT J
AU Dreze, M
Charloteaux, B
Milstein, S
Vidalain, PO
Yildirim, MA
Zhong, Q
Svrzikapa, N
Romero, V
Laloux, G
Brasseur, R
Vandenhaute, J
Boxem, M
Cusick, ME
Hill, DE
Vidal, M
AF Dreze, Matija
Charloteaux, Benoit
Milstein, Stuart
Vidalain, Pierre-Olivier
Yildirim, Muhammed A.
Zhong, Quan
Svrzikapa, Nenad
Romero, Viviana
Laloux, Geraldine
Brasseur, Robert
Vandenhaute, Jean
Boxem, Mike
Cusick, Michael E.
Hill, David E.
Vidal, Marc
TI 'Edgetic' perturbation of a C. elegans BCL2 ortholog
SO NATURE METHODS
LA English
DT Article
ID PROGRAMMED CELL-DEATH; REVERSE 2-HYBRID SYSTEM; PROTEIN-PROTEIN
INTERACTIONS; CAENORHABDITIS-ELEGANS; CED-3 ACTIVATION; GENETIC-CONTROL;
APOPTOSIS; YEAST; SELECTION; NETWORK
AB Genes and gene products do not function in isolation but within highly interconnected 'interactome' networks, modeled as graphs of nodes and edges representing macromolecules and interactions between them, respectively. We propose to investigate genotype-phenotype associations by methodical use of alleles that lack single interactions, while retaining all others, in contrast to genetic approaches designed to eliminate gene products completely. We describe an integrated strategy based on the reverse yeast two-hybrid system to isolate and characterize such edge-specific, or 'edgetic', alleles. We established a proof of concept with CED-9, a Caenorhabditis elegans BCL2 ortholog. Using ced-9 edgetic alleles, we uncovered a new potential functional link between apoptosis and a centrosomal protein. This approach is amenable to higher throughput and is particularly applicable to interactome network analysis in organisms for which transgenesis is straightforward.
C1 [Dreze, Matija; Charloteaux, Benoit; Milstein, Stuart; Vidalain, Pierre-Olivier; Yildirim, Muhammed A.; Zhong, Quan; Svrzikapa, Nenad; Romero, Viviana; Laloux, Geraldine; Boxem, Mike; Cusick, Michael E.; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, CCSB, Boston, MA 02115 USA.
[Dreze, Matija; Charloteaux, Benoit; Milstein, Stuart; Vidalain, Pierre-Olivier; Yildirim, Muhammed A.; Zhong, Quan; Svrzikapa, Nenad; Romero, Viviana; Laloux, Geraldine; Boxem, Mike; Cusick, Michael E.; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Dreze, Matija; Charloteaux, Benoit; Milstein, Stuart; Vidalain, Pierre-Olivier; Yildirim, Muhammed A.; Zhong, Quan; Svrzikapa, Nenad; Romero, Viviana; Laloux, Geraldine; Boxem, Mike; Cusick, Michael E.; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Dreze, Matija; Laloux, Geraldine; Vandenhaute, Jean] Fac Univ Notre Dame Paix, Unite Rech & Biol Mol, Namur, Wallonia, Belgium.
[Charloteaux, Benoit; Brasseur, Robert] Fac Univ Sci Agronom Gembloux, Ctr Biophys Mol Numer, Gembloux, Wallonia, Belgium.
RP Vidal, M (reprint author), Harvard Univ, Sch Med, CCSB, Boston, MA 02115 USA.
EM marc_vidal@dfci.harvard.edu
RI Boxem, Mike/B-8857-2011; Hill, David/B-6617-2011; Yildirim,
Muhammed/J-3695-2014;
OI Boxem, Mike/0000-0003-3966-4173; Yildirim, Muhammed/0000-0003-2826-1766;
, /0000-0001-7002-8488
FU US National Institutes of Health (NIH), National Human Genomics Research
Institute (NHGRI) and National Institute of General Medical Sciences
(NIGMS) [HG001715]; US National Cancer Institute (NCI) [R33 CA105405,
R33 CA132073, R21/R33 CA081658, U01 CA105423]; Dana-Farber Cancer
Institute Strategic Initiative; Fonds de la Recherche Scientifique
(FRS-FNRS, French Community of Belgium); Federal Office for Scientific,
Technical and Cultural Affairs [IAP P6/19 PROFUSA]; NIH National
Research Service [T32CA09361]; European Molecular Biology Organization
[61-2002]; Leukemia Research Foundation; 'Fonds de la Recherche
Scientifique (FRS-FNRS, French Community of Belgium)'
FX This paper is dedicated to the memory of Stan Korsmeyer. We thank the
members of the Vidal Lab and of the Dana-Farber Cancer Institute CCSB
and particularly A.-R. Carvunis for helpful discussions. This work was
supported by US National Institutes of Health (NIH) grants R01 HG001715
from the National Human Genomics Research Institute (NHGRI) and National
Institute of General Medical Sciences (NIGMS) and grants R33 CA105405,
R33 CA132073 and R21/R33 CA081658 from the US National Cancer Institute
(NCI) (M. V.), U01 CA105423 from the NCI (principal investigator, S.
Orkin; project leader, M. V.) and by Institute Sponsored Research funds
from the Dana-Farber Cancer Institute Strategic Initiative awarded to
CCSB. M. D. and G. L. were supported by a 'Research Fellow' fellowship
from the Fonds de la Recherche Scientifique (FRS-FNRS, French Community
of Belgium). B. C. was supported by the Belgian Program on
Interuniversity Attraction Poles initiated by the Federal Office for
Scientific, Technical and Cultural Affairs (IAP P6/19 PROFUSA). S. M.
was supported by an NIH National Research Service Award training grant
fellowship (T32CA09361). P.-O.V. was supported by a European Molecular
Biology Organization long-term fellowship 61-2002. Support was provided
by the Leukemia Research Foundation to M. B. M. V. and R. B. thank the
'Fonds de la Recherche Scientifique (FRS-FNRS, French Community of
Belgium)'. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the NCI, NHGRI,
NIGMS or the official views of the NCI, NHGRI, NIGMS or the NIH.
NR 44
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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 NOV
PY 2009
VL 6
IS 11
BP 843
EP U89
DI 10.1038/NMETH.1394
PG 10
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 512KI
UT WOS:000271247200019
PM 19855391
ER
PT J
AU Ruggiero, NJ
Jaff, MR
AF Ruggiero, Nicholas J.
Jaff, Michael R.
TI INTERVENTIONAL CARDIOLOGY Renal artery stenting-which patients will
benefit?
SO NATURE REVIEWS CARDIOLOGY
LA English
DT Editorial Material
ID STENOSIS; GUIDELINES; MANAGEMENT
C1 [Ruggiero, Nicholas J.; Jaff, Michael R.] Massachusetts Gen Hosp, Sect Vasc Med, Div Cardiovasc Med, Boston, MA 02114 USA.
RP Jaff, MR (reprint author), Jaff 55 Fruit St,GB 800, Boston, MA 02114 USA.
EM mjaff@partners.org
NR 7
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5002
J9 NAT REV CARDIOL
JI Nat. Rev. Cardiol.
PD NOV
PY 2009
VL 6
IS 11
BP 675
EP 676
DI 10.1038/nrcardio.2009.173
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 508RJ
UT WOS:000270950600002
PM 19851345
ER
PT J
AU Pillai, S
Cariappa, A
AF Pillai, Shiv
Cariappa, Annaiah
TI The follicular versus marginal zone B lymphocyte cell fate decision
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID NF-KAPPA-B; ANTIGEN RECEPTOR SIGNALS; IN-VIVO; BONE-MARROW;
IMMUNE-RESPONSES; CORROSION CASTS; MICROCIRCULATORY PATHWAYS; POSITIVE
SELECTION; SURVIVAL SIGNALS; DISTINCT ROLES
AB Bone marrow-derived B cells make an important cell fate choice to develop into either follicular B cells or marginal zone B cells in the spleen, which depends on signalling through the B cell receptor, Notch2, the receptor for B cell-activating factor and the canonical nuclear factor-kappa B pathway, as well as signals involved in the migration and anatomical retention of marginal zone B cells. Recent information discussed in this Review reconciles some of the controversies regarding the role of the B cell receptor in this cell fate decision and a clearer picture has also emerged regarding the anatomical location of ligands for Notch2 in the spleen. This cell fate decision could provide mechanistic insights that are relevant to other commitment events in lymphocytes.
C1 [Pillai, Shiv] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA.
Harvard Univ, Sch Med, Boston, MA 02129 USA.
RP Pillai, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA.
EM pillai@helix.mgh.harvard.edu
FU US National Institutes of Health. [AI064930, AO076505, AR058481]
FX This work was supported by grants AI064930, AO076505, and AR058481 from
the US National Institutes of Health.
NR 105
TC 195
Z9 201
U1 1
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD NOV
PY 2009
VL 9
IS 11
BP 767
EP 777
DI 10.1038/nri2656
PG 11
WC Immunology
SC Immunology
GA 510GG
UT WOS:000271075500010
PM 19855403
ER
PT J
AU Norden, AD
Drappatz, J
Wen, PY
AF Norden, Andrew D.
Drappatz, Jan
Wen, Patrick Y.
TI Antiangiogenic therapies for high-grade glioma
SO NATURE REVIEWS NEUROLOGY
LA English
DT Review
ID ENDOTHELIAL GROWTH-FACTOR; PHASE-II TRIAL; BEVACIZUMAB PLUS IRINOTECAN;
RECURRENT GLIOBLASTOMA-MULTIFORME; NEWLY-DIAGNOSED GLIOBLASTOMA; CANCER
STEM-CELLS; MALIGNANT GLIOMAS; TUMOR ANGIOGENESIS; BRAIN-TUMORS; IN-VIVO
AB High-grade gliomas (HGGs) are vascular tumors that represent attractive targets for antiangiogenic therapies. In this Review, we present the rationale and clinical trial evidence for targeting angiogenesis in HGGs, focusing predominantly on agents that target vascular endothelial growth factor (VEGF) and its receptors. Bevacizumab, a humanized monoclonal antibody against VEGF, was recently approved by the FDA for treatment of recurrent glioblastoma. Bevacizumab prolongs progress ion-free survival and controls peritumoral edema, but its effects on overall survival remain to be determined. Other inhibitors of VEGF, VEGF receptors and other proangiogenic signaling pathways are being evaluated. Antiangiogenic therapies are well tolerated, although potentially serious adverse events can occasionally occur, and resistance to antiangiogenic therapy inevitably develops. Mechanisms of resistance include upregulation of alternative proangiogenic pathways, and increased perivascular tumor growth. Tumor progression on antiangiogenic agents is a challenging problem for which no effective salvage therapy has been identified. Combining these agents with radiation therapy, cytotoxic chemotherapy, other targeted molecular agents, or anti-invasion therapies could be helpful. The international Response Assessment in Neuro-Oncology Working Group has developed consensus treatment response criteria for HGG that account for the complex effects of antiangiogenic drugs.
C1 [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Ctr Neurooncol, Dept Med Oncol, Boston, MA 02115 USA.
[Norden, Andrew D.; Drappatz, Jan; Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA.
RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Ctr Neurooncol, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM pwen@partners.org
NR 123
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U1 2
U2 21
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4758
J9 NAT REV NEUROL
JI Nat. Rev. Neurol.
PD NOV
PY 2009
VL 5
IS 11
BP 610
EP 620
DI 10.1038/nrneurol.2009.159
PG 11
WC Clinical Neurology
SC Neurosciences & Neurology
GA 512WJ
UT WOS:000271282100009
PM 19826401
ER
PT J
AU Li, XY
Sapp, E
Chase, K
Comer-Tierney, LA
Masso, N
Alexander, J
Reeves, P
Kegel, KB
Valencia, A
Esteves, M
Aronin, N
DiFiglia, M
AF Li, Xueyi
Sapp, Ellen
Chase, Kathryn
Comer-Tierney, Laryssa A.
Masso, Nicholas
Alexander, Jonathan
Reeves, Patrick
Kegel, Kimberly B.
Valencia, Antonio
Esteves, Miguel
Aronin, Neil
DiFiglia, Marian
TI Disruption of Rab11 activity in a knock-in mouse model of Huntington's
disease
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE Huntingtin; Knock-in mouse; Rab11
ID UBIQUITIN-PROTEASOME SYSTEM; GUANINE-NUCLEOTIDE-EXCHANGE; MUTANT
HUNTINGTIN; AXONAL-TRANSPORT; TRANSCRIPTIONAL REPRESSION; MITOCHONDRIAL
DYSFUNCTION; OXIDATIVE STRESS; NERVOUS-SYSTEM; AMPA RECEPTORS;
FRONTAL-CORTEX
AB The Huntington's disease (HD) mutation causes polyglutamine expansion in huntingtin (Htt) and neurodegeneration. Htt interacts with a complex containing Rab11GDP and is involved in activation of Rab11, which functions in endosomal recycling and neurite growth and long-term potentiation. Like other Rab proteins, Rab11GDP undergoes nucleotide exchange to Rab11 GTP for its activation. Here we show that striatal membranes of HD(140Q/140Q) knock-in mice are impaired in supporting conversion of Rab11GDP to Rab11GTP. Dominant negative Rab11 expressed in the striatum and cortex of normal mice caused neuropathology and motor dysfunction, suggesting that a deficiency in Rab11 activity is pathogenic in vivo. Primary cortical neurons from HD(140Q/140Q) Mice were delayed in recycling transferrin receptors back to the plasma membrane. Partial rescue from glutamate-induced cell death occurred in HD neurons expressing dominant active Rab11. We propose a novel mechanism of HD pathogenesis arising from diminished Rab11 activity at recycling endosomes. (C) 2009 Elsevier Inc. All rights reserved.
C1 [DiFiglia, Marian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cellular Neurobiol Lab,Dept Neurol, Charlestown, MA 02129 USA.
[Li, Xueyi; Sapp, Ellen; Comer-Tierney, Laryssa A.; Masso, Nicholas; Alexander, Jonathan; Reeves, Patrick; Kegel, Kimberly B.; Valencia, Antonio; Esteves, Miguel; DiFiglia, Marian] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Chase, Kathryn; Aronin, Neil] Univ Massachusetts, Sch Med, Dept Med & Cell Biol, Worcester, MA 01655 USA.
RP DiFiglia, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cellular Neurobiol Lab,Dept Neurol, Charlestown, MA 02129 USA.
EM xlil2@partners.org; difiglia@helix.mgh.harvard.edu
FU Hereditary Disease Foundation; High Q/CHDI Foundation; NIH [NS35711,
NS38194]
FX X.L. was supported by a John J. Wasmuth Postdoctoral Fellowship from the
Hereditary Disease Foundation. Other support included grants from High
Q/CHDI Foundation to M. D, Huntington's Disease Society of America to
M.D. and from NIH (NS35711 to M.D. and NS38194 to N.A.). We are indebted
to Dr. William E. Balch (The Scripps Research Institute, La Jolla, CA)
for his generous gift of GST-RabGDI.
NR 59
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U1 1
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0969-9961
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD NOV
PY 2009
VL 36
IS 2
BP 374
EP 383
DI 10.1016/j.nbd.2009.08.003
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 513AD
UT WOS:000271293000015
PM 19699304
ER
PT J
AU Chan, ST
Tang, SW
Tang, KW
Lee, WK
Lo, SS
Kwong, KK
AF Chan, Suk-tak
Tang, Sze-wing
Tang, Kwok-wing
Lee, Wing-kit
Lo, Shing-shun
Kwong, Kenneth K.
TI Hierarchical coding of characters in the ventral and dorsal visual
streams of Chinese language processing
SO NEUROIMAGE
LA English
DT Article
ID WORD FORM AREA; POSTERIOR PARIETAL CORTEX; HUMAN OBJECT AREAS;
EVENT-RELATED FMRI; FUNCTIONAL MRI; TOP-DOWN; DISCONNEXION SYNDROMES;
FUSIFORM GYRUS; BRAIN-FUNCTION; ACTIVATION
AB Functional and spatial hierarchical organization of increasingly language-like word forms has been proposed for alphabetic languages at the occipitotemporal cortex for visual word recognition. In the logographic Chinese language system, similar functional and spatial hierarchical presentations of brain responses to sublexical orthographic structure are beginning to be explored. In this study, we used whole-brain fMRI to show that a hierarchical coding of increasingly language-like character type is present in multiple Chinese language processing areas. Fluent Chinese readers were presented with Chinese synonyms/non-synonym pairs, identical/non-identical non-pronounceable pseudo-character pairs constructed with Chinese radicals, and identical/non-identical Korean character pairs. We observed the presence of a spatial gradient for increasing language-like character types in the ventral and dorsal visual streams of the cortex. At the left occipitotemporal cortex of the ventral visual stream, we observed a posterior-to-anterior gradient of character type selectivity with the anterior fusiform region being more selective for real Chinese characters and the posterior fusiform region being more selective for Korean characters. At the left and right intraparietal sulci of the dorsal visual stream, a medial-to-lateral gradient of character type selectivity was observed, with the lateral edge being more selective for real Chinese characters, the medial edge being more selective for pseudo-characters, and with less activation attributable to Korean characters. Spatial gradients of selecting character type were also identified in prefrontal cortex, dorsal striatum and lateral temporal cortex. The results suggest that the left occipitotemporal cortex and both left and right intraparietal sulci are tuned with a functional and spatial hierarchical sensitivity to the presence of semantic elements as well as different orthographic structures. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Chan, Suk-tak; Lee, Wing-kit] Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Hong Kong, Hong Kong, Peoples R China.
[Tang, Sze-wing] Hong Kong Polytech Univ, Dept Chinese & Bilingual Studies, Hong Kong, Hong Kong, Peoples R China.
[Tang, Kwok-wing] Queen Elizabeth Hosp, Dept Diagnost Radiol & Imaging, Hong Kong, Hong Kong, Peoples R China.
[Lo, Shing-shun] United Christian Hosp, Dept Radiol & Organ Imaging, Hong Kong, Hong Kong, Peoples R China.
[Kwong, Kenneth K.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
RP Chan, ST (reprint author), Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Hong Kong, Hong Kong, Peoples R China.
EM htphoebe@inet.polyu.edu.hk
RI Chan, Suk-tak/G-5846-2015
FU Hong Kong Research Grants Council [PolyU 5403/04M]; Hong Kong
Polytechnic University
FX This research was supported by the Hong Kong Research Grants Council
(PolyU 5403/04M) and The Hong Kong Polytechnic University. We thank the
radiographers at the United Christian Hospital and the Queen Elizabeth
Hospital for their assistance in data collection.
NR 80
TC 12
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U1 3
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD NOV 1
PY 2009
VL 48
IS 2
BP 423
EP 435
DI 10.1016/j.neuroimage.2009.06.078
PG 13
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 558EP
UT WOS:000274723900013
PM 19591947
ER
PT J
AU Costello, DJ
Eichler, AF
Eichler, FS
AF Costello, Daniel J.
Eichler, April F.
Eichler, Florian S.
TI Leukodystrophies Classification, Diagnosis, and Treatment
SO NEUROLOGIST
LA English
DT Review
DE leukodystrophy; X-linked adrenoleukodystrophy; metachromatic
leukodystrophy; vanishing white matter disease; Alexander disease;
Krabbe disease; magnetic resonance imaging
ID X-LINKED ADRENOLEUKODYSTROPHY; GLOBOID-CELL LEUKODYSTROPHY; VANISHING
WHITE-MATTER; PROTEOLIPID PROTEIN GENE; ADULT METACHROMATIC
LEUKODYSTROPHY; PELIZAEUS-MERZBACHER-DISEASE;
AICARDI-GOUTIERES-SYNDROME; MEGALENCEPHALIC LEUKOENCEPHALOPATHY;
SUBCORTICAL CYSTS; KRABBE-DISEASE
AB Background: The leukodystrophies are a heterogeneous group of diseases, which primarily affect white matter. Symptomatic patients are frequently misdiagnosed and the leukodystrophies are collectively under recognized. However, with ongoing research and increased availability of neuroimaging, our understanding of these diseases is increasing at a steady rate. Recent advances in the diagnosis and treatment of certain forms of leukodystrophy should prompt increased awareness of these diseases in clinical practice.
Review Summary: The clinical features, pathophysiology, and therapeutic approach to these diseases are described. Particular emphasis is placed on genetic and pathophysiologic mechanisms, imaging patterns, screening of other family members and, where available, treatment options and resources,
Conclusions: With more widespread use of neuroimaging, both pediatric and adult neurologists will increasingly be confronted with white matter disorders. Neurologists should have an approach to the recognition, diagnosis, and management of white matter diseases in general and the leukodystrophies in specific.
C1 [Costello, Daniel J.; Eichler, Florian S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Eichler, April F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA.
RP Eichler, FS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA.
EM feichler@partners.org
FU NINDS [1K08N552550-01A1]
FX Supported by NINDS, grant 1K08N552550-01A1 (to F.S.E).
NR 67
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U1 0
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1074-7931
J9 NEUROLOGIST
JI Neurologist
PD NOV
PY 2009
VL 15
IS 6
BP 319
EP 328
DI 10.1097/NRL.0b013e3181b287c8
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA 518KA
UT WOS:000271688900003
PM 19901710
ER
PT J
AU Schnyer, DM
Maddox, WT
Ell, S
Davis, S
Pacheco, C
Verfaellie, M
AF Schnyer, David M.
Maddox, W. Todd
Ell, Shawn
Davis, Sarah
Pacheco, Clenni
Verfaellie, Mieke
TI Prefrontal contributions to rule-based and information-integration
category learning
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Category learning; Prefrontal cortex; Feedback processing
ID CARD SORTING TEST; DECISION BOUND MODELS; BASAL GANGLIA; ORBITOFRONTAL
CORTEX; PERCEPTUAL PROCESSES; PARKINSONS-DISEASE; FRONTAL-CORTEX;
CATEGORIZATION; SYSTEMS; IDENTIFICATION
AB Previous research revealed that the basal ganglia play a critical role in category learning [Ell, S. W., Marchant, N. L., & Ivry, R. B. (2006). Focal putamen lesions impair learning in rule-based, but not information-integration categorization tasks. Neuropsychologia, 44(10),1737-1751; Maddox, W. T. & Filoteo, J. V. (2007). Modeling visual attention and category learning in amnesiacs, striatal-damaged patients and normal aging. In Advances in Clinical-cognitive science: formal modeling and assessment of processes and symptoms (pp. 113-146). Washington DC: American Psychological Association] but less is known about the specific role of prefrontal cortical (PFC) regions in category learning. The current study examined rule-based (RB) and information-integration (II) category learning in 13 patients with damage primarily to ventral PFC regions. After 600 learning trials with feedback, patients were significantly less accurate than matched controls on both RB and II learning. Model-based analysis identified subgroups of patients whose impaired performance in each task was due to the use of sub-optimal learning strategies. Those patients impaired at either II or RB learning, performed significantly worse on the Wisconsin Card Sorting Test, a test of abstract rule formation and the ability to shift and maintain rules. Lesion analysis pointed to damage in a fairly circumscribed region of ventral medial prefrontal cortex as common to the impaired group of patients and those patients without ventral PFC damage mostly performed normally. These results provide further evidence that the ventromedial prefrontal cortex is critically important for the ability to monitor and integrate feedback in order to select and maintain optimal learning strategies. (c) 2009 Elsevier Ltd. All rights reserved.
C1 [Schnyer, David M.; Maddox, W. Todd; Pacheco, Clenni] Univ Texas Austin, Dept Psychol, Inst Neurosci, Austin, TX 78712 USA.
[Ell, Shawn] Univ Maine, Dept Psychol, Grad Sch Biomed Sci, Orono, ME 04469 USA.
[Davis, Sarah] Univ Rochester, Dept Brain & Cognit Sci, Rochester, NY USA.
[Verfaellie, Mieke] VA Boston Healthcare Syst, Boston, MA USA.
[Verfaellie, Mieke] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Schnyer, DM (reprint author), Univ Texas Austin, Dept Psychol, Inst Neurosci, Austin, TX 78712 USA.
EM schnyer@psy.utexas.edu
OI Verfaellie, Mieke/0000-0001-5535-4584
FU NIMH [MH077708]; NINDS [NS047884, MH071783]; The University of Texas at
Austin [W911NF-07-2-0023]; Medical Research Service of the Department of
Veterans Affairs
FX We would like to thank Ginette Lafleche, Ph.D. and Michael Alexander,
M.D. for the neuropsychological testing and assessment of the patients.
We would also like to thank Caitlin Tenison, Natalie Dailey, Maria
Olivares, and Sasha Wolosin for their assistance in testing normal
control participants. This research was supported by NIMH grants
MH077708 to WTM, NINDS grant NS047884 to SWE, MH071783 to MV, and Army
grant #W911NF-07-2-0023 to DMS through the Center for Strategic and
Innovative Technologies at The University of Texas at Austin, and by the
Medical Research Service of the Department of Veterans Affairs.
NR 80
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD NOV
PY 2009
VL 47
IS 13
BP 2995
EP 3006
DI 10.1016/j.neuropsychologia.2009.07.011
PG 12
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 510DB
UT WOS:000271067100037
PM 19643119
ER
PT J
AU Walcott, BP
Bamber, NI
Anderson, DE
AF Walcott, Brian P.
Bamber, Norman I.
Anderson, Douglas E.
TI SUCCESSFUL TREATMENT OF CHRONIC PAROXYSMAL HEMICRANIA WITH POSTERIOR
HYPOTHALAMIC STIMULATION: TECHNICAL CASE REPORT
SO NEUROSURGERY
LA English
DT Article
DE Deep brain stimulation; Functional; Headache; Hypothalamus; Paroxysmal
hemicrania; Stereotactic; Target
AB OBJECTIVE: Chronic paroxysmal hemicrania (CPH) is a rare, unilateral primary headache syndrome. Recent studies suggest hypothalamic dysfunction as the likely cause of CPH. Therapeutic response to deep brain stimulation of the hypothalamus has been observed in the treatment of related trigeminal autonomic cephalgias. We explored the therapeutic effectiveness of posterior hypothalamic Stimulation for the treatment of CPH in a patient intolerant of medical management.
CLINICAL PRESENTATION: A 43-year-old woman with CPH reported acute onset of lancinating, unilateral headache pain focused about the right orbit. These debilitating headaches were accompanied by ipsilateral nasal congestion, conjunctival injection, tearing, and ptosis lasting minutes before resolving spontaneously. The patient exhausted attempts at medical management.
TECHNIQUE: A deep brain stimulator microelectrode was placed under stereotactic guidance. The posterior hypothalamic target was 3 mm posterior, 5 mm inferior, and 2 mm ipsilateral to the midcommissural point. The electrode was connected to a standard pulse generator and set to final amplitude of 1.5 V, a pulse width of 60 microseconds, and a frequency of 185 Hz.
CONCLUSION: The patient's headache symptoms were durably alleviated with intraoperative activation. NO complications were observed. This preliminary success suggests a role for posterior hypothalamic stimulation as a safe and effective treatment in patients with medically refractory CPH. As a therapeutic incremental innovation, this off-label use of technology for symptomatic therapy contributes to results of studies that support a central pathophysiological role for hypothalamic dysfunction in headaches classified among the trigeminal autonomic cephalgias.
C1 [Walcott, Brian P.] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA.
[Walcott, Brian P.] Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA USA.
[Bamber, Norman I.; Anderson, Douglas E.] Loyola Univ, Med Ctr, Dept Neurosurg, Maywood, IL 60153 USA.
RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA.
NR 0
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U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-396X
J9 NEUROSURGERY
JI Neurosurgery
PD NOV
PY 2009
VL 65
IS 5
BP 997
EP 997
DI 10.1227/01.NEU.0000345937.05186.73
PG 1
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 507SX
UT WOS:000270876100038
PM 19834392
ER
PT J
AU Ott, KM
Haddock, KS
Fox, SE
Shinn, JK
Walters, SE
Hardin, JW
Durand, K
Harris, JL
AF Ott, Karen M.
Haddock, K. Sue
Fox, Sandra E.
Shinn, Julie K.
Walters, Sandra E.
Hardin, James W.
Durand, Kerri
Harris, James L.
TI The Clinical Nurse Leader(SM): Impact On Practice Outcomes in the
Veterans Health Administration
SO NURSING ECONOMICS
LA English
DT Article
ID HEART-FAILURE
AB The Clinical Nurse Leader (CNL) role was designed to meet an identified need for expert clinical leadership at the point of care.
The Veterans Health Administration (VHA) became early adopters of the CNL role, foreseeing the value of this pivotal clinical leader at the point of care to meet the complex health care needs of America's veterans and shape health care delivery.
Impact data were collected and assimilated from seven Veterans Administration Medical Centers to support how CNLs impact the delivery of quality and safe patient care and how practice changes could be sustained.
Data collection and analyses resulted in many lessons learned.
The new CNL role was implemented in a variety of settings in the VHA system.
Integration of the CNL role in all areas of practice in every care setting has the promise of streamlining coordination of care for veterans across all spectrums in the provision of care.
C1 [Ott, Karen M.] Vet Hlth Adm, Natl CNL, Off Nursing Serv, Washington, DC USA.
[Haddock, K. Sue] Vet Hlth Adm, CNL Evaluat Program, Off Nursing Serv, Washington, DC USA.
[Haddock, K. Sue; Durand, Kerri] William Jennings Bryan Dorn VA Med Ctr, Columbia, SC USA.
[Fox, Sandra E.] VA Tennessee Valley Healthcare Syst, Surg Serv, Nashville, TN USA.
[Shinn, Julie K.] William S Middleton Mem Vet Adm Med Ctr, Inpatient Nursing Serv, Madison, WI USA.
[Walters, Sandra E.] VA Tennessee Valley Healthcare Syst, Educ Affiliat & Res, Nashville, TN USA.
[Hardin, James W.] Univ S Carolina, Biostat Collaborat Unit, Columbia, SC 29208 USA.
[Hardin, James W.] Univ S Carolina, Dept Epidemiol & Biostat, Columbia, SC 29208 USA.
RP Ott, KM (reprint author), Vet Hlth Adm, Natl CNL, Off Nursing Serv, Washington, DC USA.
RI Hardin, James/Q-7617-2016
OI Hardin, James/0000-0003-0506-5500
NR 19
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U1 0
U2 5
PU JANNETTI PUBLICATIONS, INC
PI PITMAN
PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA
SN 0746-1739
J9 NURS ECON
JI Nurs. Econ.
PD NOV-DEC
PY 2009
VL 27
IS 6
BP 363
EP +
PG 9
WC Nursing
SC Nursing
GA 531KJ
UT WOS:000272664600002
PM 20050486
ER
PT J
AU Buerhaus, PI
Donelan, K
DesRoches, C
Hess, R
AF Buerhaus, Peter I.
Donelan, Karen
DesRoches, Catherine
Hess, Robert
TI Registered Nurses' Perceptions of Nurse Staffing Ratios and New Hospital
Payment Regulations
SO NURSING ECONOMICS
LA English
DT Article
ID PATIENT OUTCOMES; CARE
AB Two regulatory initiatives weigh heavily on the nursing workforce: establishing minimum patient-to-nurse staffing ratios in hospitals and payment policy that eliminates payment to hospitals for negative consequences of care.
Although the majority of RNs favor ratios, results also indicate that a good number of RNs either do not support ratios or are unsure, which suggests that while strong support for ratios exists, the support is not universal.
With regard to the Centers for Medicare and Medicaid Services hospital payment regulations, while many RNs expect that this policy change will increase the emphasis on prevention and additional education and training, RNs also believe they will be blamed if adverse patient conditions occur.
A clear majority think that their work will increase, and only a small percentage of RNs think the regulations will lead to added respect, more staffing, higher pay, or raise their status.
Beyond affecting the clinical environment, both regulations will impact RNs' economic value in the eyes of the hospitals that employ them.
C1 [Buerhaus, Peter I.] Vanderbilt Univ, Med Ctr, Ctr Interdisciplinary Hlth Workforce Studies, Inst Med & Publ Hlth, Nashville, TN 37203 USA.
[DesRoches, Catherine] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA.
[Hess, Robert] Gannett Healthcare Grp, Falls Church, VA USA.
RP Buerhaus, PI (reprint author), Vanderbilt Univ, Med Ctr, Ctr Interdisciplinary Hlth Workforce Studies, Inst Med & Publ Hlth, Nashville, TN 37203 USA.
NR 14
TC 7
Z9 7
U1 0
U2 2
PU JANNETTI PUBLICATIONS, INC
PI PITMAN
PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA
SN 0746-1739
J9 NURS ECON
JI Nurs. Econ.
PD NOV-DEC
PY 2009
VL 27
IS 6
BP 372
EP 376
PG 5
WC Nursing
SC Nursing
GA 531KJ
UT WOS:000272664600003
PM 20050487
ER
PT J
AU Kong, A
Neuthouser, ML
Xiao, LR
Ulrich, CM
McTiernan, A
Foster-Schubert, KE
AF Kong, Angela
Neuthouser, Marian L.
Xiao, Liren
Ulrich, Cornelia M.
McTiernan, Anne
Foster-Schubert, Karen E.
TI Higher habitual intake of dietary fat and carbohydrates are associated
with lower leptin and higher ghrelin concentrations in overweight and
obese postmenopausal women with elevated insulin levels
SO NUTRITION RESEARCH
LA English
DT Article
DE Ghrelin; Leptin; Insulin; Dietary carbohydrates; Dietary fats; Dietary
habits; Obesity; Women
ID INCREASES FOOD-INTAKE; PLASMA LEPTIN; CIRCULATING GHRELIN; BODY-WEIGHT;
HEALTHY-MEN; GLUCOSE; SENSITIVITY; HUMANS; ENERGY; SECRETION
AB A highly regulated homeostatic system governs body weight; however, it is possible that this system might be impaired by the sustained intake of highly palatable foods. Short-term feeding studies suggest that the appetite-stimulating hormone ghrelin is suppressed less effectively by dietary fat intake, and diets high in sucrose decrease levels of the adipose hormone leptin. We hypothesized that higher habitual intake of dietary fat and carbohydrate (CHO) would be associated with elevated concentrations of circulating plasma ghrelin and lower circulating leptin in humans, a hormonal profile that could promote weight gain. To test our hypothesis, we examined the cross-sectional associations of ghrelin and leptin with the habitual macronutrient intake of 165 healthy overweight and obese sedentary women and tested the modifying role of insulin in these associations. We observed a significant inverse association between leptin concentrations and percentage energy from CHO independent of body mass index, percentage body fat, age, and intraabdominal fat (beta = -0.11 P = .04). No significant associations were observed between ghrelin and macronutrients or their subtypes among the total cohort. Among women with insulin concentrations at or greater than the median, we found a statistically significant positive association between intake of saturated fat and ghrelin concentrations, as well as additional statistically significant associations between leptin concentrations and macronutrients not observed among the total cohort. Our results provide some evidence that diets higher in fat and CHO are associated with a hormonal profile (ie, lower leptin and higher ghrelin concentrations), which could enhance weight gain, particularly among individuals with higher circulating insulin concentrations. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Foster-Schubert, Karen E.] Univ Washington, Dept Med, Seattle, WA 98109 USA.
[Foster-Schubert, Karen E.] VA Puget Sound Hlth Care Syst, Seattle, WA 98109 USA.
[Kong, Angela; Foster-Schubert, Karen E.] Univ Washington, Nutr Sci Program, Seattle, WA 98109 USA.
[Kong, Angela; Neuthouser, Marian L.; Xiao, Liren; Ulrich, Cornelia M.; McTiernan, Anne; Foster-Schubert, Karen E.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98109 USA.
RP Foster-Schubert, KE (reprint author), Univ Washington, Nutr Sci Program, Seattle, WA 98109 USA.
EM kfoster@u.washington.edu
FU Transdisciplinary Research in Energetics and Cancer [U54 CA116847];
National Cancer Institute [R25 CA94880, R01 CA69334]; National Center
for Research Resources [5 KL2 RR025015-03]
FX This study was supported by the Transdisciplinary Research in Energetics
and Cancer (U54 CA116847), National Cancer Institute (Grant R25
CA94880), National Cancer Institute (R01 CA69334), and National Center
for Research Resources (Grant 5 KL2 RR025015-03).
NR 50
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U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0271-5317
J9 NUTR RES
JI Nutr. Res.
PD NOV
PY 2009
VL 29
IS 11
BP 768
EP 776
DI 10.1016/j.nutres.2009.10.013
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 531KG
UT WOS:000272664300003
PM 19932865
ER
PT J
AU Kabrhel, C
Varraso, R
Goldhaber, SZ
Rimm, EB
Camargo, CA
AF Kabrhel, Christopher
Varraso, Raphaelle
Goldhaber, Samuel Z.
Rimm, Eric B.
Camargo, Carlos A.
TI Prospective Study of BMI and the Risk of Pulmonary Embolism in Women
SO OBESITY
LA English
DT Article
ID DEEP-VEIN THROMBOSIS; VENOUS THROMBOEMBOLISM; CARDIOVASCULAR RISK;
OLDER-ADULTS; OBESITY; HYPERTENSION; PREVALENCE; WEIGHT; EPIDEMIOLOGY;
OVERWEIGHT
AB Pulmonary embolism (PE) is common and associated with significant morbidity and mortality. An association between obesity and PE has been suggested, but the nature of the association has not been well defined. We performed a prospective cohort study of 87,226 women in the Nurses' Health Study (1984-2002) to define the association between BMI and the risk of incident PE. Primary exposure was BMI (<22.5, 22.5-24.9, 25.0-27.4, 27.5-29.9, 30.0-34.9, and >= 35.0kg/m(2)). Primary outcome was idiopathic PE (medical record confirmed cases of PE not associated with prior surgery, trauma, or malignancy). Secondary analysis of nonidiopathic PE was also performed. Multivariable Cox proportional hazards models were controlled for age, physical activity, caloric intake, smoking, pack-years, race, spouse's educational attainment, parity, menopause, nonaspirin nonsteroidal anti-inflammatory drugs, warfarin, multivitamin supplements, hypertension, coronary heart disease, and rheumatological disease. There were 157 incident idiopathic PE and 338 nonidiopathic PE. There was a strong positive association between BMI, the risk of idiopathic PE (relative risk (RR) = 1.08 (95% confidence interval (CI), 1.06-1.10) per 1 kg/m(2) increase in BMI, P < 0.001) and nonidiopathic PE (RR = 1.08 (95% Cl, 1.07-1.10), P < 0.001). The association was linear, and apparent even with modest increases in BMI (22.5-25kg/m(2)). The risk increased nearly sixfold among subjects with BMI >= 35kg/m(2), and was present in multiple subgroups. Increasing BMI has a strong, linear association with the development of PE in women. Clinicians should consider BMI when assessing the risk of PE in their patients.
C1 [Kabrhel, Christopher; Camargo, Carlos A.] Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
[Varraso, Raphaelle] Inst Municipal Invest Med, Ctr Res Environm Epidemiol, E-08003 Barcelona, Spain.
[Varraso, Raphaelle] Univ Paris Sud, Villejuif, France.
[Varraso, Raphaelle] INSERM, U780, Villejuif, France.
[Goldhaber, Samuel Z.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Div Cardiovasc,Med Sch, Boston, MA 02115 USA.
[Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Rimm, Eric B.; Camargo, Carlos A.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
RP Kabrhel, C (reprint author), Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
RI Varraso, Raphaelle/R-8740-2016;
OI Varraso, Raphaelle/0000-0002-3338-7825; Kabrhel,
Christopher/0000-0002-8699-7176
FU NIH [R21AG031079]
FX The Nurses' Health Study is coordinated at the Channing Laboratory.
Brigham and Women's Hospital, Boston, Massachusetts This work was
supported by NIH R21AG031079 (National Institute of Aging, National
Institutes of Health, Bethesda, Maryland)
NR 31
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U1 0
U2 0
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 NOV
PY 2009
VL 17
IS 11
BP 2040
EP 2046
DI 10.1038/oby.2009.92
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 512HT
UT WOS:000271237700013
PM 19373223
ER
PT J
AU Parikh, NI
Keyes, MJ
Larson, MG
Pou, KA
Hamburg, NA
Vita, JA
O'Donnell, CJ
Vasan, RS
Mitchell, GF
Hoffmann, U
Fox, CS
Benjamin, EJ
AF Parikh, Nisha I.
Keyes, Michelle J.
Larson, Martin G.
Pou, Karla A.
Hamburg, Naomi A.
Vita, Joseph A.
O'Donnell, Christopher J.
Vasan, Ramachandran S.
Mitchell, Gary F.
Hoffmann, Udo
Fox, Caroline S.
Benjamin, Emelia J.
TI Visceral and Subcutaneous Adiposity and Brachial Artery Vasodilator
Function
SO OBESITY
LA English
DT Article
ID FLOW-MEDIATED DILATION; CORONARY-HEART-DISEASE; METABOLIC RISK-FACTORS;
BODY-FAT DISTRIBUTION; C-REACTIVE PROTEIN; INSULIN-RESISTANCE;
ENDOTHELIAL DYSFUNCTION; JAPANESE-AMERICANS; TISSUE; WOMEN
AB Endothelial dysfunction may link obesity to cardiovascular disease (CVD). We tested the hypothesis that visceral abdominal tissue (VAT) as compared with subcutaneous adipose tissue (SAT) is more related to endothelium-dependent vasodilation. Among Framingham Offspring and Third Generation cohorts (n = 3,020, mean age 50 years, 47% women), we used multivariable linear regression adjusted for CVD and its risk factors to relate computed tomography (CT)-assessed VAT and SAT, BMI, and waist circumference (WC), with brachial artery measures. In multivariable-adjusted models, Bill WC, VAT, and SAT were positively related to baseline artery diameter and baseline mean flow velocity (all P < 0.001), but not hyperemic mean flow velocity. In multivariable-adjusted models, BMI (P = 0.002), WC (P = 0.001), and VAT (P = 0.01), but not SAT (P = 0.24) were inversely associated with percentage of flow-mediated dilation (FMD%). However, there was little incremental increase in the proportion of variability explained by VAT (R(2) = 0.266) as compared to SAT (R(2) = 0.265), above and beyond traditional risk factors. VAT, but not SAT was associated with FMD% after adjusting for clinical covariates. Nevertheless, the differential association with VAT as compared to SAT was minimal.
C1 [Parikh, Nisha I.; Keyes, Michelle J.; Larson, Martin G.; O'Donnell, Christopher J.; Vasan, Ramachandran S.; Fox, Caroline S.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Keyes, Michelle J.; Larson, Martin G.] Boston Univ, Sch Med, Math & Stat Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Pou, Karla A.; Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Hamburg, Naomi A.; Vita, Joseph A.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Cardiol Sect, Boston, MA 02118 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA.
[O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA.
[Mitchell, Gary F.] Cardiovasc Engn Inc, Holiston, MA USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Benjamin, EJ (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA.
OI Hamburg, Naomi/0000-0001-5504-5589; Vita, Joseph/0000-0001-5607-1797;
Larson, Martin/0000-0002-9631-1254; Ramachandran,
Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336
FU National Heart, Lung and Blood Institute's Framingham Heart Study
[N01-HC-25195, RO1 HL70100, 1 RO1 HL60040]; NHLBI/NIH [2K24HL04334]
FX This work was supported by the National Heart, Lung and Blood
Institute's Framingham Heart Study (N01-HC-25195, RO1 HL70100, 1 RO1
HL60040) Dr Vasan is supported in part by 2K24HL04334 (NHLBI/NIH).
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U1 0
U2 1
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 NOV
PY 2009
VL 17
IS 11
BP 2054
EP 2059
DI 10.1038/oby.2009.60
PG 6
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 512HT
UT WOS:000271237700015
PM 19282819
ER
PT J
AU Fowler-Brown, AG
Bennett, GG
Goodman, MS
Wee, CC
Corbie-Smith, GM
James, SA
AF Fowler-Brown, Angela G.
Bennett, Gary G.
Goodman, Melody S.
Wee, Christina C.
Corbie-Smith, Giselle M.
James, Sherman A.
TI Psychosocial Stress and 13-year BMI Change Among Blacks: The Pitt County
Study
SO OBESITY
LA English
DT Article
ID CORONARY-HEART-DISEASE; PERCEIVED STRESS; SOCIOECONOMIC POSITION; GENDER
DIFFERENCES; HEALTH BEHAVIORS; ALLOSTATIC LOAD; SOCIAL SUPPORT; LIFE
EVENTS; ADULTS; HYPERTENSION
AB Adverse psychosocial exposures may partially drive the high rates of obesity among blacks. The objective of this study was to prospectively examine the relationship between perceived psychosocial stress and percent change in BMI among adult black men and women. We used data from 756 women and 416 men who were participants in the Pitt County Study, a community-based, prospective cohort study of blacks in eastern North Carolina. Participants were aged 25-50 years of age on entry into the study in 1988 and follow-up was obtained in 2001. Using multivariable linear regression, we calculated the adjusted mean percentage change in BMI over the follow-up period for each tertile of baseline measures of the Perceived Stress Scale (low, medium, and high), adjusted for potential confounders. For black women, higher levels of psychosocial stress at baseline predicted higher adjusted percentage increase in BMI over the 13-year follow-up: low stress 12.0% (95% Cl 9.6-14.4), medium stress 16.3% (95% Cl 13.7-18.9), and high stress 15.5% (95% Cl 13.1-17.8). For black men, perceived stress was not associated with percent BMI change. These data suggest that interventions targeting obesity in black women should consider the potential impact of emotional stress on weight change.
C1 [Fowler-Brown, Angela G.; Wee, Christina C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care,Med Sch, Boston, MA 02215 USA.
[Bennett, Gary G.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Soc Human Dev & Hlth,Ctr Community Based Res, Boston, MA 02115 USA.
[Goodman, Melody S.] SUNY Stony Brook, Dept Prevent Med, Div Evaluat Sci, Med Ctr, Stony Brook, NY USA.
[Corbie-Smith, Giselle M.] Univ N Carolina, Dept Social Med, Chapel Hill, NC USA.
[James, Sherman A.] Duke Univ, Terry Sanford Inst Publ Policy, Durham, NC USA.
RP Fowler-Brown, AG (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care,Med Sch, Boston, MA 02215 USA.
RI Goodman, Melody/F-6768-2011
OI Goodman, Melody/0000-0001-8932-624X
FU National Institutes of Health (NIH) [R01 DK071083-01A1, HL 65645]
FX This work was primarily funded by an administrative supplement to
National Institutes of Health (NIH) grant R01 DK071083-01A1 (Dr
Fowler-Brown) Data collection for this study was supported by the NIH
(grant HL 65645).
NR 36
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U1 2
U2 11
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 NOV
PY 2009
VL 17
IS 11
BP 2106
EP 2109
DI 10.1038/oby.2009.130
PG 4
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 512HT
UT WOS:000271237700024
PM 19407807
ER
PT J
AU Broughton, DE
Beigi, RH
Switzer, GE
Raker, CA
Anderson, BL
AF Broughton, D. E.
Beigi, R. H.
Switzer, G. E.
Raker, C. A.
Anderson, B. L.
TI Obstetric Health Care Workers' Attitudes and Beliefs Regarding Influenza
Vaccination in Pregnancy
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID WOMEN; IMMUNIZATION; KNOWLEDGE
AB OBJECTIVE: To explore obstetric health care workers' attitudes and beliefs regarding influenza vaccination in pregnancy.
METHODS: A survey consisting of 16 multiple-choice questions was administered to nurses, medical and nursing assistants, receptionists, and clinical administrators in obstetric settings. Survey questions addressed general knowledge of influenza and recommendations for vaccination during pregnancy, as well as personal beliefs about the acceptability of the vaccine in the pregnant population. The study was conducted at two sites, Women & Infants Hospital in Providence, III, and Magee-Women's Hospital in Pittsburgh, PA. Variables were compared by Fisher exact test.
RESULTS: Two hundred sixty-seven completed surveys were available for analysis, with a completion rate of 85%. Almost one third of health care workers surveyed do not believe that vaccines are a safe and effective way to decrease infections (31%) and a minority believe that vaccines are safe in pregnancy (36%). just over half of health care workers know that pregnant women are at increased risk of complications from the flu (56.6%). Only 46% were able to correctly identify influenza symptoms, and only 65% would recommend influenza vaccination to a pregnant woman if indicated. A small percentage would be willing to give an avian influenza vaccine to pregnant women during a pandemic if it had not been tested in pregnancy (12.3%).
CONCLUSION: Many obstetric health care workers lack knowledge regarding the safety and importance of influenza vaccination during pregnancy. Misinformed or inadequately informed health care workers may represent a barrier to influenza vaccine coverage of pregnant women. This lack of knowledge among the health care workforce takes on added importance in the setting of the H1N1 2009 swine-origin influenza pandemic. (Obstet Gynecol 2009,114:981-7)
C1 [Broughton, D. E.] Brown Univ, Women & Infants Hosp, Alpert Med Sch, Dept Obstet & Gynecol, Providence, RI 02912 USA.
Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
Magee Womens Hosp, Pittsburgh, PA USA.
Univ Pittsburgh, Sch Med, Ctr Hlth Equ & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
RP Broughton, DE (reprint author), Brown Univ, Alpert Med Sch, MS3,Box 8191,75 Waterman St, Providence, RI 02912 USA.
EM darcy.e.broughton@gmail.com
FU Alpert Medical School Scholarly Concentration in Women's Reproductive
Health, Freedom Rights; Brown University Women's Reproductive Health
Research scholar program [5K12-HD050108-04]; Department of Obstetrics,
Gynecolog and Reproductive Sciences; Magee-Women's Hospital of the
University of Pittsburgh Medical Center
FX 1) Alpert Medical School Scholarly Concentration in Women's Reproductive
Health, Freedom & Rights; 2) Brown University Women's Reproductive
Health Research scholar program, 5K12-HD050108-04; and 3) Departmental
funding. Department of Obstetrics, Gynecolog and Reproductive Sciences,
Magee-Women's Hospital of the University of Pittsburgh Medical Center
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U1 0
U2 6
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 NOV
PY 2009
VL 114
IS 5
BP 981
EP 987
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 513AH
UT WOS:000271293500004
PM 20168097
ER
PT J
AU Cortot, AB
Janne, PA
AF Cortot, Alexis B.
Jaenne, Pasi A.
TI Histology... For Want of Anything Better?
SO ONCOLOGY-NEW YORK
LA English
DT Editorial Material
ID CELL LUNG-CANCER; THYMIDYLATE SYNTHASE; TUMOR CAVITATION; GEFITINIB;
THERAPY; ADENOCARCINOMA; CARBOPLATIN; PACLITAXEL; RESISTANCE; EXPRESSION
C1 [Cortot, Alexis B.; Jaenne, Pasi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol,Dept Med Oncol, Boston, MA 02115 USA.
RP Cortot, AB (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol,Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
NR 14
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 NOV
PY 2009
VL 23
IS 13
BP 1140
EP 1141
PG 2
WC Oncology
SC Oncology
GA V18PW
UT WOS:000208017700002
PM 20043462
ER
PT J
AU Gangaputra, S
Newcomb, CW
Liesegang, TL
Kacmaz, RO
Jabs, DA
Levy-Clarke, GA
Nussenblatt, RB
Rosenbaum, JT
Suhler, EB
Thorne, JE
Foster, CS
Kempen, JH
AF Gangaputra, Sapna
Newcomb, Craig W.
Liesegang, Teresa L.
Kacmaz, R. Oktay
Jabs, Douglas A.
Levy-Clarke, Grace A.
Nussenblatt, Robert B.
Rosenbaum, James T.
Suhler, Eric B.
Thorne, Jennifer E.
Foster, C. Stephen
Kempen, John H.
CA Systemic Immunosuppressive Therapy
TI Methotrexate for Ocular Inflammatory Diseases
SO OPHTHALMOLOGY
LA English
DT Article
ID LOW-DOSE METHOTREXATE; JUVENILE RHEUMATOID-ARTHRITIS;
CORTICOSTEROID-SPARING THERAPY; IDIOPATHIC ARTHRITIS; IMMUNOSUPPRESSIVE
THERAPY; INDUCED PNEUMONITIS; INTRAOCULAR LEVELS; OPTIC NEUROPATHY;
CHRONIC UVEITIS; TOXICITY
AB Purpose: To evaluate the outcome of treatment with methotrexate for noninfectious ocular inflammation.
Design: Retrospective cohort study.
Participants: Patients with noninfectious ocular inflammation managed at 4 tertiary ocular inflammation clinics in the United States observed to add methotrexate as a single, noncorticosteroid immunosuppressive agent to their treatment regimen, between 1979 and 2007, inclusive.
Methods: Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics, including dosage, route of administration of methotrexate, and main outcome measures, were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers.
Main Outcome Measures: Control of inflammation, corticosteroid-sparing effects, and incidence of and reason for discontinuation of therapy.
Results: Among 384 patients (639 eyes) observed from the point of addition of methotrexate to an anti-inflammatory regimen, 32.8%, 9.9%, 21.4%, 14.6%, 15.1%, and 6.3%, respectively, had anterior uveitis, intermediate uveitis, posterior or panuveitis, scleritis, ocular mucous membrane pemphigoid, and other forms of ocular inflammation. In these groups, complete suppression of inflammation sustained for 28 days was achieved within 6 months in 55.6%, 47.4%, 38.6%, 56.4%, 39.5%, and 76.7%, respectively. Corticosteroid-sparing success (sustained suppression of inflammation with prednisone <= 10 mg/d) was achieved within 6 months among 46.1%, 41.3%, 20.7%, 37.3%, 36.5%, and 50.9%, respectively. Overall, success within 12 months was 66% and 58.4% for sustained control and corticosteroid sparing (<= 10 mg), respectively. Methotrexate was discontinued within 1 year by 42% of patients. It was discontinued owing to ineffectiveness in 50 patients (13%); 60 patients (16%) discontinued because of side effects, which typically were reversible with dose reduction or discontinuation. Remission was seen in 43 patients, with 7.7% remitting within 1 year of treatment.
Conclusions: Our data suggest that adding methotrexate to an anti-inflammatory regimen not involving other noncorticosteroid immunosuppressive drugs is moderately effective for management of inflammatory activity and for achieving corticosteroid-sparing objectives, although many months may be required for therapeutic success. Methotrexate was well tolerated by most patients, and seems to convey little risk of serious side effects during treatment.
Financial Disclosure(s): The authors have no proprietary or commercial interests in any of the materials discussed in this article. Ophthalmology 2009,116:2188-2198 (C) 2009 by the American Academy of Ophthalmology.
C1 [Kempen, John H.] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA.
[Gangaputra, Sapna] Univ Wisconsin, Dept Ophthalmol, Fundus Photograph Reading Ctr, Madison, WI USA.
[Gangaputra, Sapna; Jabs, Douglas A.; Thorne, Jennifer E.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA.
[Jabs, Douglas A.; Thorne, Jennifer E.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Newcomb, Craig W.; Kempen, John H.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Newcomb, Craig W.; Kempen, John H.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Liesegang, Teresa L.; Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA.
[Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
[Kacmaz, R. Oktay; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA.
[Kacmaz, R. Oktay; Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA.
[Levy-Clarke, Grace A.] St Lukes Cataract & Laser Inst, Tarpon Springs, FL USA.
[Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA.
[Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA.
[Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA.
EM john.kempen@uphs.upenn.edu
FU National Eye Institute [EY014943]; Paul and Evanina Mackall Foundation;
Research to Prevent Blindness James S. Adams Special Scholar Award;
Senior Scientific Investigator Award; Prevent Blindness Harrington
Special Scholar Award
FX Supported primarily by National Eye Institute Grant EY014943 (JHK).
Additional support was provided by Research to Prevent Blindness and the
Paul and Evanina Mackall Foundation. Dr Kempen is a Research to Prevent
Blindness James S. Adams Special Scholar Award recipient. Drs Jabs and
Rosenbaum are Research to Prevent Blindness Senior Scientific
Investigator Award recipients. Dr Thorne is a Research to Prevent
Blindness Harrington Special Scholar Award recipient. Dr Levy-Clarke was
previously supported by and Dr Nussenblatt continues to be supported by
intramural funds of the National Eye Institute.
NR 49
TC 80
Z9 82
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2009
VL 116
IS 11
BP 2188
EP 2198
DI 10.1016/j.ophtha.2009.04.020
PG 11
WC Ophthalmology
SC Ophthalmology
GA 512ZQ
UT WOS:000271291600022
PM 19748676
ER
PT J
AU Lane, AM
Egan, KM
Harmon, D
Holbrook, A
Munzenrider, JE
Gragoudas, ES
AF Lane, Anne Marie
Egan, Kathleen M.
Harmon, David
Holbrook, Amy
Munzenrider, John E.
Gragoudas, Evangelos S.
TI Adjuvant Interferon Therapy for Patients with Uveal Melanoma at High
Risk of Metastasis
SO OPHTHALMOLOGY
LA English
DT Article
ID RENAL-CELL CARCINOMA; COOPERATIVE-ONCOLOGY-GROUP; DISSEMINATED
MALIGNANT-MELANOMA; LEUKOCYTE-A INTERFERON; OCULAR MELANOMA; C-MYC;
CUTANEOUS MELANOMA; RANDOMIZED-TRIAL; PHASE-II; RECOMBINANT
INTERFERON-ALPHA-2A
AB Purpose: To examine whether interferon (IFN)-alfa-2a treatment after radiation or enucleation reduces death rates in patients with uveal melanoma.
Design: Interventional, comparative case series.
Participants: Subjects were identified through the ocular oncology clinic of the Massachusetts Eye and Ear Infirmary. Patients eligible for the study were at increased risk of metastasis because of the presence of at least one of the following characteristics: age >= 65 years, largest tumor diameter (LTD) >= 15 mm, ciliary body involvement of the tumor, or extrascleral tumor extension.
Methods: Between May 1995 and June 1999, 121 patients with choroidal or ciliary body melanoma began a 2-year course of therapy (3 MIU IFN-alfa-2a subcutaneously 3 times per week), initiated within 3 years of primary therapy. All patients underwent regular monitoring for drug toxicity. To evaluate IFN-alfa-2a efficacy, we selected a series of historical controls frequency-matched (2:1) to IFN-alfa-2a-treated patients on age (+/-5 years), LTD (+/-3 mm), gender, and survival time between primary therapy and initiation of IFN therapy. Survival status was ascertained for all patients through December 2006.
Main Outcome Measures: Melanoma-related mortality, metastasis, IFN-related toxicities.
Results: Fifty-five patients (45%) completed therapy; the median dose for IFN-alfa-2a-treated patients was 792 MIU (85% of the theoretic dose). The median follow-up time in the IFN-alfa-2a-treated group was approximately 9 years. Treatment and control groups were similar with respect to age (P = 0.78), LTD (P = 0.38), and gender (P = 1.0). Of 363 patients, 108 developed metastasis under observation; 42 of these were IFN-alfa-2a-treated patients. Cumulative 5-year melanoma-related death rates were 17% in the radiation or enucleation-only group, 15% in those who completed the entire IFN-alfa-2a course, and 35% in those who discontinued IFN-alfa-2a therapy. In multivariate Cox regression, IFN-alfa-2a had no significant influence on melanoma-related mortality (rate ratio = 1.02, 95% confidence interval, 0.68-1.5, P = 0.91) or all-cause mortality (rate ratio = 0.84, 95% confidence interval, 0.58-1.2, P = 0.34).
Conclusions: Interferon-alfa-2a has no material influence on survival in patients with choroidal melanoma.
Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2009; 116:2206-2212 (C) 2009 by the American Academy of Ophthalmology.
C1 [Lane, Anne Marie; Holbrook, Amy; Gragoudas, Evangelos S.] Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA.
[Egan, Kathleen M.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[Harmon, David] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA.
[Munzenrider, John E.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Lane, AM (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA.
EM alane@meei.harvard.edu
FU Roche Laboratories; Nutley; New Jersey; Massachusetts Eye and Ear
Infirmary Melanoma Research Fund
FX Evangelos Gragoudas is a paid consultant for and has an equity ownership
in Jerini Ophthalmics. This research was conducted with funding from
Roche Laboratories, Nutley, New Jersey, and the Massachusetts Eye and
Ear Infirmary Melanoma Research Fund. The funding organization approved
the design of the study and the study manuscript. No other authors have
any financial interests to disclose.
NR 41
TC 21
Z9 21
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2009
VL 116
IS 11
BP 2206
EP 2212
DI 10.1016/j.ophtha.2009.04.044
PG 7
WC Ophthalmology
SC Ophthalmology
GA 512ZQ
UT WOS:000271291600024
PM 19744725
ER
PT J
AU Bouchard, C
Troulis, MJ
Kaban, LB
AF Bouchard, Carl
Troulis, Maria J.
Kaban, Leonard B.
TI Management of Obstructive Sleep Apnea: Role of Distraction Osteogenesis
SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Distraction osteogenesis; Obstructive sleep apnea; Orthognathic surgery;
Maxillomandibular advancement; Respiratory disturbance index
AB Distraction osteogenesis to expand the facial skeleton is an alternative to standard orthognathic surgery for selected patients with obstructive sleep apnea. For children with congenital micrognathia or midface hypoplasia, distraction osteogenesis allows large advancements without the need for bone grafting and with less risk of relapse. For later-onset obstructive sleep apnea, distraction osteogenesis may represent an alternative when acute bone movement is expected to be difficult (scarring from previous surgery or radiation therapy) or when the risk for inferior alveolar nerve damage is unacceptable (patients older than 40 years).
C1 [Bouchard, Carl; Troulis, Maria J.; Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
RP Bouchard, C (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
EM carlbouch@hotmail.com
FU AO Foundation (Berne, Switzerland); Synthes CMF (West Chester, PA); MGH
Department of OMFS Education Research; Hanson Foundation (Boston, MA)
FX This project was funded in part by the AO Foundation (Berne,
Switzerland); Synthes CMF (West Chester, PA); MGH Department of OMFS
Education & Research Fund; and the Hanson Foundation (Boston, MA).
NR 112
TC 10
Z9 10
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 1042-3699
J9 ORAL MAXIL SURG CLIN
JI Oral Maxillofac. Surg. Clin. N. Am.
PD NOV
PY 2009
VL 21
IS 4
BP 459
EP +
DI 10.1016/j.coms.2009.07.001
PG 18
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA V20LG
UT WOS:000208140900011
PM 19944346
ER
PT J
AU Marple, BF
Stringer, SP
Batra, PS
Bhattacharyya, N
Chiu, AG
Citardi, MJ
Han, JK
Kern, RC
Kingdom, TT
Lane, AP
Orlandi, RR
Ryan, MW
Senior, BA
Stewart, MG
AF Marple, Bradley F.
Stringer, Scott P.
Batra, Pete S.
Bhattacharyya, Neil
Chiu, Alexander G.
Citardi, Martin J.
Han, Joseph K.
Kern, Robert C.
Kingdom, Todd T.
Lane, Andrew P.
Orlandi, Richard R.
Ryan, Matthew W.
Senior, Brent A.
Stewart, Michael G.
CA Task Force Rhinology Paranasal Sin
TI Going to the next level: Health care's evolving expectations for
evidence
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Editorial Material
AB Rhinologic literature has historically relied oil lower levels of evidence to make prescriptive recommendations for use of new technology and procedures However, as the medical profession has moved to embrace the principles of evidence-based medicine, expectations for minimum standards of evidence have risen The resulting high-quality efficacy Outcomes data have become the linchpin of informed decision making by physicians, payers, and health care systems. While many challenges remain in this transition to higher evidence expectations, none are insurmountable. It has become the responsibility of the organized medical profession to play a role in influencing and supporting production of high-quality outcomes research (C) 2009 American Academy of Otolaryngology-Head and Neck Surgery Foundation All rights reserved
C1 [Marple, Bradley F.; Batra, Pete S.; Ryan, Matthew W.] Univ Texas SW Med Ctr Dallas, Dept Otolaryngol Head & Neck Surg, Dallas, TX 75390 USA.
[Stringer, Scott P.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Bhattacharyya, Neil] Dana Farber Brigham & Womens Canc Ctr, Head & Neck Oncol Program, Boston, MA USA.
[Chiu, Alexander G.] Hosp Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA.
[Citardi, Martin J.] Univ Texas Houston, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Houston, TX USA.
[Han, Joseph K.] E Virginia Med Sch, Dept Otolaryngol Head & Neck Surg, Norfolk, VA USA.
[Kern, Robert C.] Northwestern Univ, Sinus & Allergy Ctr, Chicago, IL 60611 USA.
[Kingdom, Todd T.] Univ Colorado, Hlth Sci Ctr, Dept Otolaryngol, Aurora, CO USA.
[Lane, Andrew P.] Johns Hopkins Univ Hosp, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA.
[Orlandi, Richard R.] Univ Utah, Dept Otolaryngol Head & Neck Surg, Salt Lake City, UT USA.
[Senior, Brent A.] Univ N Carolina, Sch Med, Dept Otolaryngol Head & Neck Surg, Chapel Hill, NC USA.
[Stewart, Michael G.] Cornell Univ, Dept Otorhinolaryngol, Weill Med Coll, New York, NY 10021 USA.
RP Marple, BF (reprint author), Univ Texas SW Med Ctr Dallas, Dept Otolaryngol Head & Neck Surg, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
RI Chiu, Alexander/J-1230-2014
OI Chiu, Alexander/0000-0002-7592-6575
NR 10
TC 3
Z9 3
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0194-5998
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD NOV
PY 2009
VL 141
IS 5
BP 551
EP 554
DI 10.1016/j.otohns.2009.07.013
PG 4
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 512DI
UT WOS:000271223300001
PM 19861188
ER
PT J
AU Morone, NE
Rollman, BL
Moore, CG
Qin, L
Weiner, DK
AF Morone, Natalia E.
Rollman, Bruce L.
Moore, Charity G.
Qin, Li
Weiner, Debra K.
TI A Mind-Body Program for Older Adults with Chronic Low Back Pain: Results
of a Pilot Study
SO PAIN MEDICINE
LA English
DT Article
DE Low Back Pain; Mindfulness; Meditation; Mind-Body; Aged
AB Objectives. Determine the impact of an 8-week mindfulness meditation program on disability, psychological function, and pain severity in community-dwelling older adults with chronic low back pain, and to test the education control program for feasibility.
Design. Randomized controlled trial.
Participants. Forty community-dwelling older adults with moderate low back pain or greater for at least the previous 3 months.
Intervention. Participants were randomized to an 8-week meditation program or an 8-week education control program.
Outcome Measures. Disability, psychological function, and pain severity were assessed. The same measures were obtained for both groups at baseline, at the end of the program, and 4 months after program completion.
Results. Sixteen participants (80%) completed the meditation program and 19 (95%) completed the education program. Both the meditation and control group improved on measures of disability, pain, and psychological function, both at program completion and 4-month follow-up. The differences between the two groups did not reach statistical significance. The meditation group practiced mindfulness meditation a mean of 5 days/week (range 1-7) and mean of 31 minutes/session (range 22-48). At 4 months follow-up 14/16 (88%) participants continued to meditate.
Conclusion. Both the intervention group and the education control group improved on outcome measures suggesting both programs had a beneficial effect. Participants continued to meditate on 4-month follow-up. The control program was feasible but not inert. Piloting the control program in mind-body research can inform the design of larger clinical trials.
C1 [Morone, Natalia E.; Rollman, Bruce L.; Moore, Charity G.; Qin, Li] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA.
[Weiner, Debra K.] Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA USA.
[Weiner, Debra K.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA.
[Weiner, Debra K.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA.
RP Morone, NE (reprint author), 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA.
EM moronene@upmc.edu
OI Moore, Charity/0000-0002-0060-0124
FU NIH [1KL2RR024154-04]; National Center for Research Resources (NCRR), a
component of the NIH [UL1RR024153]; NIH Roadmap for Medical Research
FX During the time of this work Dr. Morone was funded by the NIH Roadmap
Multidisciplinary Clinical Research Career Development Award Grant
(1KL2RR024154-04) from the National Institutes of Health (NIH). This
publication was also made possible by Grant Number UL1RR024153 from the
National Center for Research Resources (NCRR), a component of the NIH
and NIH Roadmap for Medical Research. Its contents are solely the
responsibility of the authors and do not necessarily represent the
official view of NCRR or NIH. Special thanks to Daniel Schenck, DC for
co-teaching the mindfulness meditation program and to Vinny Losasso for
assistance in data collection and preparation of the manuscript.
NR 37
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Z9 47
U1 3
U2 12
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1526-2375
J9 PAIN MED
JI Pain Med.
PD NOV-DEC
PY 2009
VL 10
IS 8
BP 1395
EP 1407
DI 10.1111/j.1526-4637.2009.00746.x
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA V20FE
UT WOS:000208125100008
PM 20021599
ER
PT J
AU Manchikanti, L
Derby, R
Wolfer, L
Singh, V
Datta, S
Hirsch, JA
AF Manchikanti, Laxmaiah
Derby, Richard
Wolfer, Lee
Singh, Vijay
Datta, Sukdeb
Hirsch, Joshua A.
TI Evidence-Based Medicine, Systematic Reviews, and Guidelines in
Interventional Pain Management: Part 7: Systematic Reviews and
Meta-Analyses of Diagnostic Accuracy Studies
SO PAIN PHYSICIAN
LA English
DT Review
DE Diagnostic accuracy studies; evidence-based medicine; systematic
reviews; meta-analysis; comparative effectiveness studies;
interventional pain management; Standards for the Reporting of
Diagnostic Accuracy Studies (STARD)
ID LOW-BACK-PAIN; FACET JOINT PAIN; RANDOMIZED CONTROLLED-TRIALS; CAUDAL
EPIDURAL INJECTIONS; CHRONIC SPINAL PAIN; LOCAL-ANESTHETIC BLOCKS;
MEDIAL BRANCH BLOCKS; 2000-2010 TASK-FORCE; RADIOFREQUENCY DENERVATION
SUCCESS; VERTEBRAL COMPRESSION FRACTURES
AB Appropriate diagnosis is essential in providing proper and effective therapy. The field of diagnostic accuracy tests is dynamic with new tests being developed at a fast pace along with improvement in technology of existing tests on a continuous basis. Well-designed diagnostic test accuracy studies can help in making appropriate health care decisions, provided that they transparently and fully report their participants, tests, methods, and results. Exaggerated and biased results from poorly designed and reported diagnostic test studies can trigger their premature dissemination and lead physicians into making incorrect treatment decisions. Consequently, a diagnostic test is useful only to the extent that it distinguishes between conditions or disorders that might otherwise be confused. Since it is unlikely that clinicians, patients, and policy makers have the time, skills, and resources to find, appraise, and interpret the evidence and incorporate it into their health care decisions, systematic reviews and meta-analysis provide an accurate and reliable synthesis of vast quantities of data.
A systematic review can identify what is known and what is unknown, giving guidance for future research. Systematic reviews have been considered as a vital link in the great chain of evidence that stretches from the laboratory to the bedside by helping to separate the insignificant, unsound, or redundant deadwood from the salient and critical studies that are worthy of reflection. A dangerous discrepancy exists between experts and evidence with all types of evidence.
Historically, it has been reported that in only 15% of all cases can a pathoanatomical explanation be found for patients with chronic low back pain of more than 3 months resulting in the assumption that very little can be done in our present state of ignorance to treat these patients and improve their natural histories. On the other end of the spectrum, due to lack of sound diagnostic information, excessive health care is utilized with exploding costs. The validity of all diagnostic techniques has been described with variable accuracy and reliability Lack of understanding of reference standards and their unavailability with interventional diagnostic techniques and misinterpretation secondary to interpretation bias may adversely influence the applicability of diagnostic interventions.
This manuscript provides a review of the literature, a checklist, and a flow diagram describing the preferred way to present the abstract, introduction, methods, results, and discussion sections of the report of an analysis in a systematic review of diagnostic accuracy studies.
C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA.
[Derby, Richard; Wolfer, Lee] Spinal Diagnost & Treatment Ctr, Daly City, CA USA.
[Datta, Sukdeb] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA.
[Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA.
RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA.
EM drlm@thepainmd.co
NR 298
TC 36
Z9 36
U1 1
U2 7
PU AM SOC INTERVENTIONAL PAIN PHYSICIANS
PI PADUCAH
PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA
SN 1533-3159
J9 PAIN PHYSICIAN
JI Pain Physician
PD NOV-DEC
PY 2009
VL 12
IS 6
BP 929
EP 963
PG 35
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA 537EQ
UT WOS:000273096200003
PM 19935980
ER
PT J
AU Warshaw, AL
AF Warshaw, Andrew L.
TI 2009 American Pancreatic Association Presidential Address On Our 40th
Birthday
SO PANCREAS
LA English
DT Editorial Material
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Warshaw, AL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,WHT506, Boston, MA 02114 USA.
EM awarshaw@partners.org
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2009
VL 38
IS 8
BP 844
EP 844
DI 10.1097/MPA.0b013e3181bd0fa9
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 512DZ
UT WOS:000271225300002
PM 19855230
ER
PT J
AU Thrower, EC
Wang, J
Cheriyan, S
Lugea, A
Kolodecik, TR
Yuan, JZ
Reeve, JR
Gorelick, FS
Pandol, SJ
AF Thrower, Edwin C.
Wang, Jeffrey
Cheriyan, Salim
Lugea, Aurelia
Kolodecik, Thomas R.
Yuan, Jingzhen
Reeve, Joseph R., Jr.
Gorelick, Fred S.
Pandol, Stephen J.
TI Protein Kinase C delta-Mediated Processes in
Cholecystokinin-8-Stimulated Pancreatic Acini
SO PANCREAS
LA English
DT Article
DE amylase secretion; genetic deletion; trypsinogen
ID DAMAGE-INDUCED APOPTOSIS; KAPPA-B ACTIVATION; PKC-DELTA; TYROSINE
PHOSPHORYLATION; AMYLASE RELEASE; CELLS; ROTTLERIN; EPSILON; MECHANISM;
ISOFORMS
AB Objectives: To define the role of protein kinase C delta (PKC delta) in acinar cell responses to the hormone cholecystokinin-8 (CCK) using isoform-specific inhibitors and a previously unreported genetic deletion model.
Methods: Pancreatic acinar cells were isolated from (1) rat, and pretreated with a PKC delta-specific inhibitor or (2) PKC delta-deficient and wild type mice. Isolated cells were stimulated with CCK (0.001-100 nmol/L) and cell responses were measured.
Results: The PKC delta inhibitor did not affect stimulated amylase secretion from rat pancreatic acinar cells. Cholecystokinin-8 stimulation induced a typical biphasic dose-response curve for amylase secretion in acinar cells isolated from both PKC delta(-/-) and wild type mice, with maximal stimulation at 10-pmol/L CCK. Cholecystokinin-8 (100 nmol/L) induced zymogen and nuclear factor kappa B activation in both PKC delta(-/-) and wild type mice, although it was up to 50% less in PKC delta(-/-).
Conclusions: In contrast to previous studies, this study has used specific and complementary approaches to examine PKC delta-mediated acinar cell responses. We could not confirm that it mediates amylase release but corroborated its role in the early stages of acute pancreatitis.
C1 [Thrower, Edwin C.; Cheriyan, Salim; Kolodecik, Thomas R.; Gorelick, Fred S.] Vet Adm Connecticut Healthcare, Sect Digest Dis, Dept Internal Med, West Haven, CT USA.
[Thrower, Edwin C.; Cheriyan, Salim; Kolodecik, Thomas R.; Gorelick, Fred S.] Yale Univ, Sch Med, New Haven, CT USA.
[Wang, Jeffrey; Lugea, Aurelia; Yuan, Jingzhen; Reeve, Joseph R., Jr.; Pandol, Stephen J.] Vet Affairs Greater Los Angeles Hlth Care Syst, Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA USA.
[Wang, Jeffrey; Lugea, Aurelia; Yuan, Jingzhen; Reeve, Joseph R., Jr.; Pandol, Stephen J.] Univ Calif Los Angeles, Los Angeles, CA USA.
RP Thrower, EC (reprint author), Vet Adm Med Ctr, 950 Campbell Ave,Bldg 4, West Haven, CT 06516 USA.
EM edwin.thrower@yale.edu
FU National Institutes of Health [R21 DK69702, RO1 DK33850, DK54021];
USC-UCLA Research Center for Alcoholic Liver and Pancreatic Injury [5
P60 AA11999]; Veterans Administration Merit and Senior Career
Development Award
FX This work was supported by a National Institutes of Health grant R21
(DK69702 to E. C. T.), National Institutes of Health Grants RO1 (DK33850
to J. R. R., Jr; DK54021 to F. S. G.), USC-UCLA Research Center for
Alcoholic Liver and Pancreatic Injury grant (5 P60 AA11999 from NIAAA;
Tsukamoto; to S. J. P.), and a Veterans Administration Merit and Senior
Career Development Award (to F. S. G.).
NR 34
TC 20
Z9 20
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2009
VL 38
IS 8
BP 930
EP 935
DI 10.1097/MPA.0b013e3181b8476a
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 512DZ
UT WOS:000271225300014
PM 19752773
ER
PT J
AU Boni, A
Thayer, SP
Ferrone, C
Bausch, D
Neyhard, N
Cogdill, A
Fernandez-del-Castillo, CF
Warshaw, AL
Wargo, JA
AF Boni, A.
Thayer, S. P.
Ferrone, C.
Bausch, D.
Neyhard, N.
Cogdill, A.
Fernandez-del-Castillo, C. F.
Warshaw, A. L.
Wargo, J. A.
TI Immunotherapeutic and Epigenetic Approaches Targeting Cancer-Testis
Antigens in the Treatment of Pancreatic Cancer
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Boni, A.; Thayer, S. P.; Ferrone, C.; Bausch, D.; Neyhard, N.; Cogdill, A.; Fernandez-del-Castillo, C. F.; Warshaw, A. L.; Wargo, J. A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2009
VL 38
IS 8
BP 985
EP 985
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 512DZ
UT WOS:000271225300045
ER
PT J
AU Correa-Gallego, C
Ferrone, C
Thayer, SP
Wargo, JA
Warshaw, AL
Fernandez-del Castillo, C
AF Correa-Gallego, C.
Ferrone, C.
Thayer, S. P.
Wargo, J. A.
Warshaw, A. L.
Fernandez-del Castillo, C.
TI Are Multifocal Pancreatic Cysts an Indolent Condition?
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Correa-Gallego, C.; Ferrone, C.; Thayer, S. P.; Wargo, J. A.; Warshaw, A. L.; Fernandez-del Castillo, C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2009
VL 38
IS 8
BP 991
EP 991
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 512DZ
UT WOS:000271225300072
ER
PT J
AU Correa-Gallego, C
Mino-Kenudson, M
Ferrone, C
Thayer, SP
Wargo, JA
Warshaw, AL
Fernandez-del Castillo, C
AF Correa-Gallego, C.
Mino-Kenudson, M.
Ferrone, C.
Thayer, S. P.
Wargo, J. A.
Warshaw, A. L.
Fernandez-del Castillo, C.
TI Non-Neoplastic Cysts Comprise 8% of Resected Pancreatic Cysts Presumed
to Be Neoplastic
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Correa-Gallego, C.; Ferrone, C.; Thayer, S. P.; Wargo, J. A.; Warshaw, A. L.; Fernandez-del Castillo, C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Mino-Kenudson, M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2009
VL 38
IS 8
BP 991
EP 991
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 512DZ
UT WOS:000271225300073
ER
PT J
AU Ferrone, CR
Konstantinidis, IT
Fernandez-del Castillo, C
Wargo, J
Thayer, SP
Warshaw, AL
AF Ferrone, C. R.
Konstantinidis, I. T.
Fernandez-del Castillo, C.
Wargo, J.
Thayer, S. P.
Warshaw, A. L.
TI Fifteen Years of the Warshaw Technique
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Ferrone, C. R.; Konstantinidis, I. T.; Fernandez-del Castillo, C.; Wargo, J.; Thayer, S. P.; Warshaw, A. L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2009
VL 38
IS 8
BP 995
EP 995
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 512DZ
UT WOS:000271225300094
ER
PT J
AU Furukawa, T
Hatori, T
Fujita, I
Yamamoto, M
Kobayashi, M
Ohike, N
Morohoshi, T
Egawa, S
Unno, M
Takao, S
Osako, M
Yonezawa, S
Mino-Kenudson, M
Lauwers, GY
Yamaguchi, H
Ban, S
Shimizu, M
AF Furukawa, T.
Hatori, T.
Fujita, I.
Yamamoto, M.
Kobayashi, M.
Ohike, N.
Morohoshi, T.
Egawa, S.
Unno, M.
Takao, S.
Osako, M.
Yonezawa, S.
Mino-Kenudson, M.
Lauwers, G. Y.
Yamaguchi, H.
Ban, S.
Shimizu, M.
TI Prognostic Relevance of Morphologic Types of Intraductal Papillary
Mucinous Neoplasms of the Pancreas
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Furukawa, T.] Tokyo Womens Med Univ, Int Res Edu Inst Integ Med Sci, Tokyo, Japan.
[Hatori, T.; Fujita, I.; Yamamoto, M.] Tokyo Womens Med Univ, Dept Surg, Inst Gastroenterol, Tokyo, Japan.
[Kobayashi, M.] Tokyo Womens Med Univ, Dept Path, Tokyo, Japan.
[Kobayashi, M.] Tokyo Womens Med Univ, Dept Surg Path, Tokyo, Japan.
[Ohike, N.; Morohoshi, T.] Showa Univ, Sch Med, Dept Path 1, Tokyo 142, Japan.
[Egawa, S.; Unno, M.] Tohoku Univ, Grad Sch Med, Div Hepbilpanc Surg, Sendai, Miyagi 980, Japan.
[Takao, S.] Kagoshima Univ, Front Sci Res Ctr, Kagoshima 890, Japan.
[Osako, M.] Kagoshima Shi Med Assoc Hosp, Dept Surg, Kagoshima, Japan.
[Yonezawa, S.] Kagoshima Univ, Grad Sch Med Dent Sci, Dept Hum Path, Kagoshima 890, Japan.
[Mino-Kenudson, M.; Lauwers, G. Y.] Massachusetts Gen Hosp, Dept Path, Boston, MA 02114 USA.
[Yamaguchi, H.; Ban, S.; Shimizu, M.] Saitama Med Univ, Int Med Ctr, Dept Path, Hidaka, Japan.
RI Unno, Michiaki/A-8633-2010
OI Unno, Michiaki/0000-0002-2145-6416
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2009
VL 38
IS 8
BP 998
EP 998
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 512DZ
UT WOS:000271225300106
ER
PT J
AU Hui, H
Tang, YG
Zhu, L
Khoury, N
Wang, KY
Perfetti, R
Pandol, SJ
Go, VLW
AF Hui, H.
Tang, Y. G.
Zhu, L.
Khoury, N.
Wang, K. Y.
Perfetti, R.
Pandol, S. J.
Go, V. L. W.
TI GLP-1 Directed Human Embryonic Stem Cells Differentiation Into Insulin
Producing Cells Via Hedgehog, CAMP, PI3K Pathways
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Hui, H.; Wang, K. Y.; Pandol, S. J.; Go, V. L. W.] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Ctr Excellence Pancreat Dis, Los Angeles, CA 90095 USA.
Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA.
[Hui, H.; Tang, Y. G.; Zhu, L.; Khoury, N.; Perfetti, R.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2009
VL 38
IS 8
BP 1005
EP 1005
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 512DZ
UT WOS:000271225300139
ER
PT J
AU Hui, H
Tang, YG
Wang, KY
Pandol, SJ
Go, VLW
AF Hui, H.
Tang, Y. G.
Wang, K. Y.
Pandol, S. J.
Go, V. L. W.
TI Inhibitory Effects of GLP-1 on Proliferation and Tumiorgenicisty of
Pancreatic Cancer Stem Cells In Vitro
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Hui, H.; Wang, K. Y.; Pandol, S. J.; Go, V. L. W.] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Ctr Excellence Pancreat Dis, Los Angeles, CA 90095 USA.
[Hui, H.; Pandol, S. J.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA.
[Tang, Y. G.] Cedars Sinai Med Ctr, Div Med Genet, Los Angeles, CA 90048 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2009
VL 38
IS 8
BP 1005
EP 1005
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 512DZ
UT WOS:000271225300138
ER
PT J
AU Mino-Kenudson, M
Warshaw, AL
Correa-Gallego, C
Muzikansky, A
Androutsopoulos, V
Deshpande, V
Pitman, MB
Thayer, SP
Lauwers, GY
Fernandez-del Castillo, C
AF Mino-Kenudson, M.
Warshaw, A. L.
Correa-Gallego, C.
Muzikansky, A.
Androutsopoulos, V.
Deshpande, V.
Pitman, M. B.
Thayer, S. P.
Lauwers, G. Y.
Fernandez-del Castillo, C.
TI Intraductal Papillary Mucinous Neoplasm - Associated Invasive Carcinoma
(IPMN-INV) Has Favorable Survival After Resection
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Mino-Kenudson, M.; Deshpande, V.; Pitman, M. B.; Lauwers, G. Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Warshaw, A. L.; Correa-Gallego, C.; Androutsopoulos, V.; Thayer, S. P.; Fernandez-del Castillo, C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Muzikansky, A.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2009
VL 38
IS 8
BP 1028
EP 1028
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 512DZ
UT WOS:000271225300246
ER
PT J
AU Sloss, CM
Wang, F
Palladino, M
Cusack, JC
AF Sloss, C. M.
Wang, F.
Palladino, M.
Cusack, J. C.
TI Proteasome Inhibition Activates EGFR in an HB-EGF Dependant Manner in
Pancreatic Cancer Cells
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Sloss, C. M.; Wang, F.; Cusack, J. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Palladino, M.] Nereus Pharmaceut, San Diego, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2009
VL 38
IS 8
BP 1049
EP 1049
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 512DZ
UT WOS:000271225300343
ER
PT J
AU Thrower, E
Yuan, J
Usmani, A
Jones, C
Ireson, C
Pandol, S
Guha, S
AF Thrower, E.
Yuan, J.
Usmani, A.
Jones, C.
Ireson, C.
Pandol, S.
Guha, S.
TI Protein Kinase D Regulates Secretagogue-Induced Amylase Secretion and
Zymogen Activation
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Thrower, E.; Usmani, A.; Jones, C.] VA Connecticut Healthcare, Sect Digest Dis, West Haven, CT USA.
[Thrower, E.; Usmani, A.; Jones, C.] Yale Univ, Sch Med, New Haven, CT 06520 USA.
[Yuan, J.; Pandol, S.] VA Greater LA Hlth Care Syst, Los Angeles, CA USA.
[Yuan, J.; Pandol, S.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA.
[Ireson, C.] Canc Res Technol, London, England.
[Guha, S.] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2009
VL 38
IS 8
BP 1056
EP 1056
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 512DZ
UT WOS:000271225300376
ER
PT J
AU Yuan, J
Liu, Y
Shalbueva, N
Tan, T
Gukovskaya, AS
Pandol, SJ
AF Yuan, J.
Liu, Y.
Shalbueva, N.
Tan, T.
Gukovskaya, A. S.
Pandol, S. J.
TI Protein Kinase C Epsilon Mediates Ethanol and Carbachol-Induced
Depolarization in Pancreatic Acinar Cells
SO PANCREAS
LA English
DT Meeting Abstract
C1 VA Greater LA Hlth Care Syst, Los Angeles, CA USA.
Univ Calif Los Angeles, Los Angeles, CA 90024 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2009
VL 38
IS 8
BP 1066
EP 1066
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 512DZ
UT WOS:000271225300424
ER
PT J
AU Yuan, J
Liu, Y
Pandol, SJ
Gukovskaya, AS
Tan, T
Thrower, E
Guha, S
AF Yuan, J.
Liu, Y.
Pandol, S. J.
Gukovskaya, A. S.
Tan, T.
Thrower, E.
Guha, S.
TI Protein Kinase D Regulates Cell Death Pathways in Acute Pancreatitis
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Yuan, J.; Pandol, S. J.; Gukovskaya, A. S.] VA Greater LA Hlth Care Syst, Los Angeles, CA USA.
[Yuan, J.; Pandol, S. J.; Gukovskaya, A. S.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA.
[Liu, Y.] Beijing Hosp, Beijing, Peoples R China.
[Thrower, E.] VA Connecticut Healthcare, West Haven, CT USA.
[Thrower, E.] Yale Univ, Sch Med, New Haven, CT 06520 USA.
[Guha, S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2009
VL 38
IS 8
BP 1066
EP 1066
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 512DZ
UT WOS:000271225300423
ER
PT J
AU Wolfe, J
AF Wolfe, Joanne
TI SYMPTOMS AND SUFFERING IN CHILDREN WITH CANCER AT THE END OF LIFE
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Wolfe, Joanne] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD NOV
PY 2009
VL 53
IS 5
BP 704
EP 704
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 499XS
UT WOS:000270260700009
ER
PT J
AU Kapoor, R
Hoffstad, O
Bilker, W
Margolis, DJ
AF Kapoor, Roger
Hoffstad, Ole
Bilker, Warren
Margolis, David J.
TI The Frequency and Intensity of Topical Pimecrolimus Treatment in
Children with Physician-Confirmed Mild to Moderate Atopic Dermatitis
SO PEDIATRIC DERMATOLOGY
LA English
DT Article
ID CALCINEURIN INHIBITORS; SKIN-CANCER; ASSOCIATION; EXPOSURE; DISEASES;
ASTHMA; RISK; AGE; PREVALENCE; CHILDHOOD
AB Atopic dermatitis (AD) is often treated with multiple modalities, including topical medications such as corticosteroids and topical calcineurin inhibitors (TCIs). The aim of this study was to describe the natural history of the utilization characteristics of topical treatment in those with AD. We conducted a longitudinal study of the first 4,105 children with physician-confirmed mild to moderate AD enrolled in an ongoing postmarketing safety study of pimecrolimus. Information was obtained from participants every six months using a questionnaire. Drug utilization was solely determined by the physician and patient. Over the three years of our study, an increasing number of individuals reported at least 6 months of complete control of their disease, without the continued use of a topical medication. While all study participants used pimecrolimus at the start of the study less than 40% continued to use it after 3 years of study participation. If an individual was still using a topical medication after three years of follow-up, it was most likely a topical corticosteroid. For those who continued to use pimecrolimus, the use was limited to about 60 grams of pimecrolimus in 6 months. Community-based use of topical pimecrolimus to treat AD is limited both with respect to the duration of exposure and amount or total dose of the exposure. If a topical therapy is persistent, it is most likely to a topical corticosteroid.
C1 [Kapoor, Roger] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA.
[Hoffstad, Ole; Bilker, Warren; Margolis, David J.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Margolis, David J.] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA.
RP Kapoor, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, 55 Fruit St, Boston, MA 02114 USA.
FU Novartis Pharmaceuticals
FX This study was sponsored by a grant from Novartis Pharmaceuticals to the
Trustees of the University of Pennsylvania.
NR 22
TC 9
Z9 9
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0736-8046
J9 PEDIATR DERMATOL
JI Pediatr. Dermatol.
PD NOV-DEC
PY 2009
VL 26
IS 6
BP 682
EP 687
DI 10.1111/j.1525-1470.2009.01013.x
PG 6
WC Dermatology; Pediatrics
SC Dermatology; Pediatrics
GA 535XZ
UT WOS:000273006600003
PM 20199441
ER
PT J
AU Tanaka, N
Thiele, EA
Madsen, JR
Bourgeois, BF
Stufflebeam, SM
AF Tanaka, Naoaki
Thiele, Elizabeth A.
Madsen, Joseph R.
Bourgeois, Blaise F.
Stufflebeam, Steven M.
TI Magnetoencephalographic Analysis in Patients With Vagus Nerve Stimulator
SO PEDIATRIC NEUROLOGY
LA English
DT Article
ID SIGNAL-SPACE SEPARATION; INTERFERENCE; ARTIFACTS; EPILEPSY; MEG
AB The objective of this study was to assess the feasibility of magnetoencephalography in epilepsy patients with a vagus nerve stimulator. Magnetoencephalography was performed in two patients with medically intractable epilepsy who had a vagus nerve stimulator. Because of the artifacts caused by the vagus nerve stimulator, no spikes could be identified in the original magnetoencephalographic data in either patient. The temporally extended signal space separation method was used to remove artifacts. After processing by this method, left temporoparietal spikes were clearly identified in patient 1. Equivalent current dipoles calculated from these spikes were localized in the left posterior-temporal and parietal lobes. The location of the dipoles was consistent with the spike distribution on intracranial electroencephalography. In patient 2, bilateral diffuse spikes were seen in the processed data. The contour maps demonstrated a bilateral pattern, not in agreement with a single focal source. These findings supported the diagnosis of symptomatic generalized epilepsy in this patient. Magnetoencephalography may thus be a useful option for evaluating patients with intractable epilepsy who have a vagus nerve stimulator. (C) 2009 by Elsevier Inc. All rights reserved.
C1 [Tanaka, Naoaki; Stufflebeam, Steven M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Pediat Epilepsy Program, Boston, MA 02114 USA.
[Madsen, Joseph R.] Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA.
[Bourgeois, Blaise F.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA.
RP Tanaka, N (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA.
EM naoro@nmr.mgh.harvard.edu
FU U.S. National Institutes of Health [P41RR14075, R01NS037462-07]; Mental
Illness and Neuroscience Discovery Institute; NARSAD
FX The authors thank Seppo P. Ahlfors, PhD, Matti S. Hamalainen, PhD, and
Samu Taulu, PhD, for their helpful comments on the manuscript. This work
was supported by U.S. National Institutes of Health (P41RR14075,
R01NS037462-07), Mental Illness and Neuroscience Discovery Institute,
and a NARSAD Young Investigatons Award.
NR 9
TC 10
Z9 10
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0887-8994
J9 PEDIATR NEUROL
JI Pediatr. Neurol.
PD NOV
PY 2009
VL 41
IS 5
BP 383
EP 387
DI 10.1016/j.pediatrneurol.2009.06.007
PG 5
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 510GY
UT WOS:000271077300013
PM 19818944
ER
PT J
AU Mansbach, JM
Ginde, AA
Camargo, CA
AF Mansbach, Jonathan M.
Ginde, Adit A.
Camargo, Carlos A., Jr.
TI Serum 25-Hydroxyvitamin D Levels Among US Children Aged 1 to 11 Years:
Do Children Need More Vitamin D?
SO PEDIATRICS
LA English
DT Article
DE vitamin D; deficiency; prevalence; supplementation
ID D DEFICIENCY; NUTRITIONAL RICKETS; HEALTHY-CHILDREN; EARLY-CHILDHOOD;
CANCER-RISK; INFANTS; ADOLESCENTS; SKIN; SUPPLEMENTATION; PREVALENCE
AB OBJECTIVE: Single-center studies have suggested that hypovitaminosis D is widespread. Our objective was to determine the serum levels of 25-hydroxyvitamin D (25[OH] D) in a nationally representative sample of US children aged 1 to 11 years.
METHODS: Data were obtained from the 2001-2004 National Health and Nutrition Examination Survey. Serum 25(OH) D levels were determined by radioimmunoassay and categorized as <25, <50, and <75 nmol/L. National estimates were obtained by using assigned patient visit weights and reported with 95% confidence intervals (CIs).
RESULTS: During the 2001-2004 time period, the mean serum 25(OH) D level for US children aged 1 to 11 years was 70 nmol/L (95% CI: 68-73). Children aged 6 to 11 years had lower mean levels of 25(OH) D ( 68 nmol/L [95% CI: 65-71]) compared with children aged 1 to 5 years (74 nmol/L [95% CI: 71-77]). Overall, the prevalence of levels at <25 nmol/L was 0.7% (95% CI: 0.4-1.3), <50 nmol/L was 15% (95% CI: 12-18), and <75 nmol/L was 65% (95% CI: 58-71). The prevalence of serum 25(OH) D levels of <75 nmol/L was higher among children aged 6 to 11 years (71%) compared with children aged 1 to 5 years (56%); girls (67%) compared with boys (62%); and non- Hispanic black (89%) and Mexican American (77%) children compared with non- Hispanic white children (54%).
CONCLUSIONS: On the basis of a nationally representative sample of US children aged 1 to 11 years, millions of children may have suboptimal levels of 25(OH) D, especially non- Hispanic black and Mexican American children. More data in children are needed not only to understand better the health implications of specific serum levels of 25(OH) D but also to determine the appropriate vitamin D supplement requirements for children. Pediatrics 2009; 124: 1404-1410
C1 [Mansbach, Jonathan M.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med, Boston, MA 02115 USA.
[Ginde, Adit A.] Univ Colorado Denver, Sch Med, Dept Emergency Med, Aurora, CO USA.
[Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA.
RP Mansbach, JM (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med, Main Clin Bldg 9 S 9157, Boston, MA 02115 USA.
EM jonathan.mansbach@childrens.harvard.edu
RI Siry, Bonnie/D-7189-2017
FU Massachusetts General Hospital Center for D-receptor Activation Research
( Boston, MA); [R01-HL84401]
FX Dr Camargo was supported by the Massachusetts General Hospital Center
for D-receptor Activation Research ( Boston, MA) and grant R01-HL84401 (
Bethesda, MD).
NR 52
TC 133
Z9 140
U1 1
U2 4
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 NOV
PY 2009
VL 124
IS 5
BP 1404
EP 1410
DI 10.1542/peds.2008-2041
PG 7
WC Pediatrics
SC Pediatrics
GA 510MH
UT WOS:000271092100020
PM 19951983
ER
PT J
AU Rudolph, JL
Babikian, VL
Treanor, P
Pochay, VE
Wigginton, JB
Crittenden, MD
Marcantonio, ER
AF Rudolph, James L.
Babikian, Viken L.
Treanor, Patrick
Pochay, Val E.
Wigginton, Jeremy B.
Crittenden, Michael D.
Marcantonio, Edward R.
TI Microemboli are not associated with delirium after coronary artery
bypass graft surgery
SO PERFUSION-UK
LA English
DT Article
DE microembolism; aged; delirium; coronary artery bypass graft; carotid
stenosis; transcranial doppler
ID CONFUSION ASSESSMENT METHOD; POSTOPERATIVE DELIRIUM; CARDIOPULMONARY
BYPASS; CARDIAC-SURGERY; TRANSCRANIAL DOPPLER; CEREBRAL MICROEMBOLI;
COGNITIVE CHANGE; PREDICTION RULE; PATIENT; VALIDATION
AB Delirium is an acute change in cognition which occurs frequently after coronary artery bypass graft (CABG) surgery. Cerebral microemboli, from plaque, air, or thrombus, have been hypothesized to contribute to delirium and cognitive decline after CABG. The purpose of this study was to determine if there was an association between cerebral microemboli and delirium after cardiac surgery. Non-delirious patients (n=68) were prospectively enrolled and underwent intraoperative monitoring of the middle cerebral arteries with transcranial Doppler (TCD). TCD signals were saved and analyzed postoperatively for microemboli manually, according to established criteria. Postoperatively, patients were assessed for delirium with a standardized battery. Thirty-three patients (48.5%) developed delirium after surgery. Microemboli counts (mean +/- SD) were not significantly different in those with and without delirium (303 +/- 449 vs. 299 +/- 350; p= 0.97). While intraoperative microemboli were not associated with delirium after CABG, further investigation into the source and composition of microemboli can further elucidate the long-term clinical impact of microemboli.
C1 [Rudolph, James L.] Boston VA Healthcare Syst, GRECC, Boston, MA 02130 USA.
[Babikian, Viken L.; Pochay, Val E.] Boston VA Healthcare Syst, Dept Neurol, Boston, MA 02130 USA.
[Treanor, Patrick; Crittenden, Michael D.] Boston VA Healthcare Syst, Div Cardiac Surg, Boston, MA 02130 USA.
[Wigginton, Jeremy B.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Crittenden, Michael D.] St Louis VA Med Ctr, Dept Surg, St Louis, MO USA.
[Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA.
[Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA.
[Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
[Babikian, Viken L.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
RP Rudolph, JL (reprint author), Boston VA Healthcare Syst, GRECC, JP-182 150 S Huntington Ave, Boston, MA 02130 USA.
EM jrudolph@partners.org
FU Harvard Older Americans Independence Center [AG08812-14, AG029861-02];
Harvard - Hartford Junior Faculty Development
FX Dr Rudolph is supported by a VA Rehabilitation Career Development Award.
This work was funded by the Harvard Older Americans Independence Center
AG08812-14 and AG029861-02. Additional support was provided by a Harvard
- Hartford Junior Faculty Development Grant and an American
NR 42
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Z9 15
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0267-6591
J9 PERFUSION-UK
JI Perfusion-UK
PD NOV
PY 2009
VL 24
IS 6
BP 409
EP 415
DI 10.1177/0267659109358207
PG 7
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 545XJ
UT WOS:000273770000007
PM 20093336
ER
PT J
AU Samie, MA
Grimm, C
Evans, JA
Curcio-Morelli, C
Heller, S
Slaugenhaupt, SA
Cuajungco, MP
AF Samie, Mohammad A.
Grimm, Christian
Evans, Jeffrey A.
Curcio-Morelli, Cyntia
Heller, Stefan
Slaugenhaupt, Susan A.
Cuajungco, Math P.
TI The tissue-specific expression of TRPML2 (MCOLN-2) gene is influenced by
the presence of TRPML1
SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
LA English
DT Article
DE TRP ion channel; TRPML2; Mucolipidosis type IV; Mucolipin-2; Lysosomal
storage disorder; TRPML1 knock out mouse
ID MUCOLIPIDOSIS TYPE-IV; ADENINE-DINUCLEOTIDE PHOSPHATE; VARITINT-WADDLER
PHENOTYPE; RECEPTOR POTENTIAL CHANNEL; NAADP MOBILIZES CALCIUM; CATION
CHANNEL; MEMBRANE-PROTEIN; RELEASE CHANNEL; T-LYMPHOCYTES; MUTATION
AB Mucolipidosis type IV is a lysosomal storage disorder caused by the loss or dysfunction of the mucolipin-1 (TRPML1) protein. It has been suggested that TRPML2 could genetically compensate (i.e., become upregulated) for the loss of TRPML1. We thus investigated this possibility by first studying the expression pattern of mouse TRPML2 and its basic channel properties using the varitint-waddler (Va) model. Here, we confirmed the presence of long variant TRPML2 (TRPML2lv) and short variant (TRPML2sv) isoforms. We showed for the first time that, heterologously expressed, TRPML2lv-Va is an active, inwardly rectifying channel. Secondly, we quantitatively measured TRPML2 and TRPML3 mRNA expressions in TRPML1(-/-) null and wild-type (Wt) mice. In wild-type mice, the TRPML2lv transcripts were very low while TRPML2sv and TRPML3 transcripts have predominant expressions in lymphoid and kidney organs. Significant reductions of TRPML2sv, but not TRPML2lv or TRPML3 transcripts, were observed in lymphoid and kidney organs of TRPML1(-/-) mice. RNA interference of endogenous human TRPML1 in HEK-293 cells produced a comparable decrease of human TRPML2 transcript levels that can be restored by overexpression of human TRPML1. Conversely, significant upregulation of TRPML2sv transcripts was observed when primary mouse lymphoid cells were treated with nicotinic acid adenine dinucleotide phosphate, or N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinoline sulfonamide, both known activators of TRPML1. In conclusion, our results indicate that TRPML2 is unlikely to compensate for the loss of TRPML1 in lymphoid or kidney organs and that TRPML1 appears to play a novel role in the tissue-specific transcriptional regulation of TRPML2.
C1 [Samie, Mohammad A.; Evans, Jeffrey A.; Cuajungco, Math P.] Calif State Univ Fullerton, Dept Biol Sci, Fullerton, CA 92831 USA.
[Samie, Mohammad A.; Evans, Jeffrey A.; Cuajungco, Math P.] Calif State Univ Fullerton, Ctr Appl Biotechnol Studies, Fullerton, CA 92831 USA.
[Grimm, Christian; Heller, Stefan] Stanford Univ, Sch Med, Dept Otolaryngol & Mol & Cellular Physiol, Stanford, CA 94305 USA.
[Curcio-Morelli, Cyntia; Slaugenhaupt, Susan A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Curcio-Morelli, Cyntia; Slaugenhaupt, Susan A.] Harvard Univ, Sch Med, Boston, MA USA.
[Cuajungco, Math P.] Mental Hlth Res Inst, Melbourne, Vic, Australia.
RP Cuajungco, MP (reprint author), Calif State Univ Fullerton, Dept Biol Sci, 800 N State Coll Blvd, Fullerton, CA 92831 USA.
EM mcuajungco@fullerton.edu
RI Cuajungco, Math/B-2647-2008; di Ronza, Alberto/H-7674-2016
OI Cuajungco, Math/0000-0003-0749-9564; di Ronza,
Alberto/0000-0002-9813-5143
FU Howard Hughes Medical Institute; California State University Program for
Education and Research in Biotechnology (CSUPERB); CSUF Junior Faculty
Intramural Research; CSUF Associated Students Inc.; Nagel-CSUPERB; NIH
[DC004563, NS39995]
FX We are grateful for the technical support given by Tony Ricci, Michael
Schnee, Simone Jors, and James Mull. We also thank Breck Wheelock for
his help on tissue dissection and primary mouse lymphoid cell culture.
We thank Dr. Rosa Puertollano (NIH/NHLBI) for providing the human TRPML2
expression plasmid and Dr. Kirill Kiselyov for the human anti-TRPML1
polyclonal antibodies. MPC is partly supported by the Howard Hughes
Medical Institute under the HHMI Undergraduate Research Program and a
recipient of the California State University Program for Education and
Research in Biotechnology (CSUPERB) Faculty-Student Collaborative
Research Grant and CSUF Junior Faculty Intramural Research Grant. M. A.
S. is a Coppel Graduate Student Science scholar and is a recipient of a
research grant from the CSUF Associated Students Inc. JAE is a
Howell-CSUPERB scholar, and a recipient of the Nagel-CSUPERB travel
award and the CSUF Associated Students Inc. research grant. SH is funded
by NIH grant (DC004563). SAS is funded by NIH grant (NS39995).
NR 65
TC 27
Z9 27
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0031-6768
J9 PFLUG ARCH EUR J PHY
JI Pflugers Arch.
PD NOV
PY 2009
VL 459
IS 1
BP 79
EP 91
DI 10.1007/s00424-009-0716-5
PG 13
WC Physiology
SC Physiology
GA 509OZ
UT WOS:000271028700008
PM 19763610
ER
PT J
AU Choi, WS
Mitsumoto, A
Kochevar, IE
AF Choi, Won Seon
Mitsumoto, Atsushi
Kochevar, Irene E.
TI Involvement of Reactive Oxygen Species in TGF-beta 1-induced
Tropoelastin Expression by Human Dermal Fibroblasts
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Article
ID GROWTH-FACTOR-BETA; HUMAN ELASTIN PROMOTER; GENE-EXPRESSION; NADPH
OXIDASE; HUMAN SKIN; SIGNAL-TRANSDUCTION; MESSENGER-RNA; IN-VITRO;
TRANSCRIPTION FACTORS; DEPENDENT MECHANISM
AB Chronic exposure to solar UV radiation causes marked changes in the dermal extracellular matrix that underlie the loss of resiliency and increased laxity observed in photoaged skin. In particular, the dermal elastin content increases substantially and the normal, well-organized elastic fibers are replaced by amorphous elastotic material. Transforming growth factor-beta 1 (TGF-beta 1) stimulates synthesis of elastin by dermal fibroblasts and may mediate the increase in elastin in chronically photo-damaged skin. We investigated pathways involved in the TGF-beta 1-induced increase in tropoelastin (TE), the soluble elastin monomer and assessed the role of reactive oxygen species (ROS) in the regulation of TE mRNA. Antioxidants and an inhibitor of NADPH oxidase blocked TGF-beta 1-induced TE mRNA increase even when added 1.5 h after TGF-beta 1, although ROS were detected for only 30 min. The TE mRNA increase required activation of Smad4, shown using Smad4 siRNA, and also involved the ERK1/2, p38 and JNK MAP kinases but not PI3K. ROS did not enhance signaling through Smad2 but did enhance activation of p38 and ERK1/2 at 10 min after TGF-beta 1. These results indicate that Smad and MAPK pathways mediate TGF-beta 1-induced TE expression and that ROS are required for both early signal transduction and later steps that increase elastin.
C1 [Choi, Won Seon; Mitsumoto, Atsushi; Kochevar, Irene E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02163 USA.
[Choi, Won Seon] MIT, Cambridge, MA 02139 USA.
RP Kochevar, IE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02163 USA.
EM kochevar@helix.mgh.harvard.edu
FU National Institutes of Health [RO1 AR43895]
FX We gratefully acknowledge support for this research by grant RO1 AR43895
from the National Institutes of Health.
NR 54
TC 10
Z9 11
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0031-8655
J9 PHOTOCHEM PHOTOBIOL
JI Photochem. Photobiol.
PD NOV-DEC
PY 2009
VL 85
IS 6
BP 1425
EP 1433
DI 10.1111/j.1751-1097.2009.00611.x
PG 9
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 509UX
UT WOS:000271045200018
PM 19709383
ER
PT J
AU Wooten, K
AF Wooten, Karen
TI Clinical Features and Electrodiagnosis of Diabetic Peripheral Neuropathy
in the Dysvascular Patient
SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
LA English
DT Article
DE Neuropathy; Electrodiagnosis; Diabetes; Dysvascular; Amputee; Diabetic
peripheral neuropathy; Polyneuropathy
ID DISTAL SYMMETRIC POLYNEUROPATHY; ACADEMY-OF-NEUROLOGY; AUTONOMIC
NEUROPATHY; NERVE-CONDUCTION; CLASSIFICATION; ASSOCIATION; MELLITUS;
CACHEXIA
AB Diabetic peripheral neuropathy (DPN) is a common disorder that can lead to limb loss and death. Up to 50% of DPN patients can be asymptomatic. This fact contributes to making DPN the leading cause of lower limb amputation. The degree of heterogeneity in the clinical manifestations of DPN makes diagnosing this condition difficult. This article reviews the characteristics, diagnosis, electrodiagnosis, classification, pathogenesis, and treatment of DPN.
C1 [Wooten, Karen] Vet Affairs Puget Sound Hlth Care Syst, Rehabilitat Care Serv S117, Seattle, WA 98108 USA.
[Wooten, Karen] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
RP Wooten, K (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Rehabilitat Care Serv S117, 1660 S Columbian Way, Seattle, WA 98108 USA.
EM Karen.wooten@va.gov
NR 35
TC 7
Z9 9
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 1047-9651
J9 PHYS MED REHABIL CLI
JI Phys. Med. Rehabil. Clin. N. Am.
PD NOV
PY 2009
VL 20
IS 4
BP 657
EP +
DI 10.1016/j.pmr.2009.06.011
PG 21
WC Rehabilitation
SC Rehabilitation
GA 509NI
UT WOS:000271024300006
PM 19781504
ER
PT J
AU Hakimi, KN
AF Hakimi, Kevin N.
TI Pre-Operative Rehabilitation Evaluation of the Dysvascular Patient Prior
to Amputation
SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
LA English
DT Article
DE Amputation; Rehabilitation; Diabetes mellitus; Diabetes complications;
Peripheral vascular diseases
ID LOWER-LIMB AMPUTATION; LOWER-EXTREMITY AMPUTATIONS; OUTCOMES; AMPUTEE;
10-YEAR
AB Lower-extremity amputation secondary to dysvascular disease, including diabetes and peripheral vascular disease, is a major health problem in the United States. Due to the increased comorbidities in this patient population, pre-operative rehabilitation evaluation by a multidisciplinary team is crucial to ensure optimal patient outcomes. This article discusses the key factors that may affect functional outcomes in this patient population and outlines important history and physical examination components that should be evaluated pre-operatively.
C1 [Hakimi, Kevin N.] VA Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA 98108 USA.
[Hakimi, Kevin N.] Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98159 USA.
RP Hakimi, KN (reprint author), VA Puget Sound Hlth Care Syst, Rehabil Care Serv, RCS 117,1660 S Columbian Way, Seattle, WA 98108 USA.
EM khakimi@u.washington.edu
NR 20
TC 5
Z9 5
U1 0
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1047-9651
J9 PHYS MED REHABIL CLI
JI Phys. Med. Rehabil. Clin. N. Am.
PD NOV
PY 2009
VL 20
IS 4
BP 677
EP +
DI 10.1016/j.pmr.2009.06.015
PG 13
WC Rehabilitation
SC Rehabilitation
GA 509NI
UT WOS:000271024300007
PM 19781505
ER
PT J
AU Won, S
Wilk, JB
Mathias, RA
O'Donnell, CJ
Silverman, EK
Barnes, K
O'Connor, GT
Weiss, ST
Lange, C
AF Won, Sungho
Wilk, Jemma B.
Mathias, Rasika A.
O'Donnell, Christopher J.
Silverman, Edwin K.
Barnes, Kathleen
O'Connor, George T.
Weiss, Scott T.
Lange, Christoph
TI On the Analysis of Genome-Wide Association Studies in Family-Based
Designs: A Universal, Robust Analysis Approach and an Application to
Four Genome-Wide Association Studies
SO PLOS GENETICS
LA English
DT Article
ID QUANTITATIVE TRAITS; UNIFIED APPROACH; GENERAL-CLASS; TESTS; POWER;
STRATIFICATION; REGRESSION; LINKAGE; ASTHMA
AB For genome-wide association studies in family-based designs, we propose a new, universally applicable approach. The new test statistic exploits all available information about the association, while, by virtue of its design, it maintains the same robustness against population admixture as traditional family-based approaches that are based exclusively on the within-family information. The approach is suitable for the analysis of almost any trait type, e. g. binary, continuous, time-to-onset, multivariate, etc., and combinations of those. We use simulation studies to verify all theoretically derived properties of the approach, estimate its power, and compare it with other standard approaches. We illustrate the practical implications of the new analysis method by an application to a lung-function phenotype, forced expiratory volume in one second (FEV1) in 4 genome-wide association studies.
C1 [Won, Sungho] Chung Ang Univ, Dept Stat, Seoul 156756, South Korea.
[Won, Sungho] Chung Ang Univ, Res Ctr Data Sci, Seoul 156756, South Korea.
[Wilk, Jemma B.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Mathias, Rasika A.] NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA.
[O'Donnell, Christopher J.] NHLBI, Bethesda, MD 20892 USA.
[O'Donnell, Christopher J.] Framingham Heart Dis Epidemiol Study, Bethesda, MD USA.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Silverman, Edwin K.; Weiss, Scott T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Silverman, Edwin K.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
[Barnes, Kathleen] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[O'Connor, George T.] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA.
[Weiss, Scott T.; Lange, Christoph] Brigham & Womens Hosp, Ctr Genom Med, Boston, MA 02115 USA.
[Lange, Christoph] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
RP Won, S (reprint author), Chung Ang Univ, Dept Stat, Seoul 156756, South Korea.
EM clange@hsph.harvard.edu
OI O'Connor, George/0000-0002-6476-3926
FU National Heart, Lung, and Blood Institute, National Institutes of Health
[U01 HL075419, U01 HL65899, P01 HL083069, R01 HL086601, T32 HL07427];
National Institutes of Health [R01MH081862]; Medic Research Council
[G00000934]; Wellcome Trust [068545/Z/02]
FX The CAMP Genetics Ancillary Study is supported by U01 HL075419, U01
HL65899, P01 HL083069, R01 HL086601, and T32 HL07427 from the National
Heart, Lung, and Blood Institute, National Institutes of Health. CL is
supported by the National Institutes of Health grant R01MH081862.
Framingham Heart Study genotype and phenotype data are publicly
available through the NHLBI's SNP Health Association Resource (SHARe)
initiative
(http://public.nhlbi.nih.gov/GeneticsGenomics/home/share.aspx). The
British 1958 Birth Cohort DNA collection is funded by the Medic Research
Council grant G00000934 and the Wellcome Trust grant 068545/Z/02. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 33
TC 26
Z9 27
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD NOV
PY 2009
VL 5
IS 11
AR e1000741
DI 10.1371/journal.pgen.1000741
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 528CW
UT WOS:000272419500036
PM 19956679
ER
PT J
AU Hammond, MC
AF Hammond, Margaret C.
TI Honoring Those Who Have Served
SO PM&R
LA English
DT Editorial Material
C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
RP Hammond, MC (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,128N, Seattle, WA 98108 USA.
EM margaret.hammond@va.gov
NR 7
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-1482
J9 PM&R
JI PM&R
PD NOV
PY 2009
VL 1
IS 11
BP 991
EP 992
DI 10.1016/j.pmrj.2009.10.009
PG 2
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA V24LO
UT WOS:000208412100001
PM 19942183
ER
PT J
AU Gaynes, BN
Warden, D
Trivedi, MH
Wisniewski, SR
Fava, M
Rush, AJ
AF Gaynes, Bradley N.
Warden, Diane
Trivedi, Madhukar H.
Wisniewski, Stephen R.
Fava, Maurizio
Rush, A. John
TI What Did STAR*D Teach Us? Results From a Large-Scale, Practical,
Clinical Trial for Patients With Depression
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID MEASUREMENT-BASED CARE; SEQUENCED TREATMENT ALTERNATIVES; FAILED
MEDICATION TREATMENTS; 2ND-STEP TREATMENTS; OUTPATIENTS; AUGMENTATION;
OUTCOMES; EPIDEMIOLOGY; MIRTAZAPINE; RATIONALE
AB The authors provide an overview of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (www.star-d.org), a large-scale practical clinical trial to determine which of several treatments are the most effective "next-steps" for patients with major depressive disorder whose symptoms do not remit or who cannot tolerate an initial treatment and, if needed, ensuing treatments. Entry criteria were broadly defined and inclusive, and patients were enrolled from psychiatric and primary care clinics. All participants began on citalopram and were managed by clinic physicians, who followed an algorithm-guided acute-phase treatment through five visits over 12 weeks. At the end of each sequence, patients whose depression had not fully remitted were eligible for subsequent randomized trials in a sequence of up to three clinical trials. In general, remission rates in the study clinics were lower than expected, suggesting the need for several steps to achieve remission for most patients. There was no clear medication "winner" for patients whose depression did not remit after one or more aggressive medication trials. Both switching and augmenting appeared to be reasonable options when an initial antidepressant treatment failed, although these two strategies could not be directly compared. Further, the likelihood of remission after two vigorous medication trials substantially decreased, and remission would likely require more complicated medication regimens for which the existing evidence base is quite thin. STAR*D demonstrated that inclusion of more real-world patients in clinical trials is both feasible and informative. Policy implications of the findings, as well as the study's limitations, are discussed. (Psychiatric Services 60: 1439-1445, 2009)
C1 [Gaynes, Bradley N.] Univ N Carolina, Dept Psychiat, Sch Med, Chapel Hill, NC 27599 USA.
[Warden, Diane; Trivedi, Madhukar H.; Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX USA.
[Wisniewski, Stephen R.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA.
[Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA.
RP Gaynes, BN (reprint author), Univ N Carolina, Dept Psychiat, Sch Med, CB 7160, Chapel Hill, NC 27599 USA.
EM bgaynes@med.unc.edu
OI Wisniewski, Stephen/0000-0002-3877-9860; Gaynes,
Bradley/0000-0002-8283-5030; Rush, Augustus/0000-0003-2004-2382
FU National Institute of Mental Health (NIMH) [N01MH90003]; Bristol-Myers
Squibb and Novartis; Targacept
FX Dr. Gaynes has received grants and research support from Bristol-Myers
Squibb and Novartis and has served as an advisor for Bristol-Myers
Squibb. Dr. Warden has owned stock in Pfizer in the past year. Dr.
Trivedi has received consulting fees from AstraZeneca, Bristol-Myers
Squibb, Cephalon, Inc., Eli Lilly and Company, Evotec, Fabre-Kramer
Pharmaceuticals, Forest Pharmaceuticals, GlaxoSmithKline, Janssen,
Johnson and Johnson, Medtronic, Neuronetics, Otsuka Pharmaceuticals,
Pfizer, Shire, and Wyeth-Ayerst Laboratories. He has received research
support from Targacept. Dr. Wisniewski has received consultant fees from
Cyberonics Inc. The other authors report no competing interests.
NR 27
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U1 0
U2 5
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD NOV
PY 2009
VL 60
IS 11
BP 1439
EP 1445
PG 7
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 514KM
UT WOS:000271393200006
PM 19880458
ER
PT J
AU Laje, G
Perlis, RH
Rush, AJ
McMahon, FJ
AF Laje, Gonzalo
Perlis, Roy H.
Rush, A. John
McMahon, Francis J.
TI Pharmacogenetics Studies in STAR*D: Strengths, Limitations, and Results
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID SEQUENCED TREATMENT ALTERNATIVES; FACTOR GENETIC-POLYMORPHISM; EMERGENT
SUICIDAL IDEATION; MAJOR DEPRESSIVE DISORDER; GENOME-WIDE ASSOCIATION;
ELEMENT-BINDING PROTEIN; ANTIDEPRESSANT TREATMENT; NEUROTROPHIC-FACTOR;
D COHORT; SEROTONIN TRANSPORTER
AB Several lines of evidence support an important genetic contribution to the wide individual variation in therapeutic response to antidepressant medications. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study provided the largest cohort assembled to date of DNA from patients with nonpsychotic major depressive disorder, uniformly treated with citalopram and followed prospectively for up to 12 weeks. This pivotal study changed the face of pharmacogenetics research by increasing the sample size by an order of magnitude as well as by providing detailed prospective information about antidepressant response and tolerability. Several groups have identified markers in genes and tested the replication of previous findings of genes associated with outcome and side effects of antidepressant treatment. Variants in HTR2A, GRIK4, and KCNK2 were associated with citalopram treatment outcome. Replication was achieved in markers in the FKBP5 gene. Other findings in PDE11A and BDNF were not successfully replicated, and reports of potential confounders in previous associations with serotonin transporter variation (SLC6A4) were identified. Polymorphisms in pharmacokinetic genes involved in metabolism and transmembrane transport were also not associated with antidepressant response. Adverse events were also tested. Treatment-emergent suicidal ideation was associated with GRIK2, GRIA3, PAPLN, IL28RA, and CREB1. Sexual dysfunction was linked with variation in GRIN3A, GRIA1 GRIA3, and GRIK2. Reported and future findings of pharmacogenetics studies in STAR*D could help elucidate pathways involved in major depression and those pertinent to antidepressant outcome and side effects. Replication of these findings in independent samples could lead to the development of new treatments and to optimization of available treatments. (Psychiatric Services 60: 1446-1457, 2009)
C1 [Laje, Gonzalo; McMahon, Francis J.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, Bethesda, MD 20892 USA.
[Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Rush, A. John] Duke Natl Univ Singapore, Singapore, Singapore.
RP Laje, G (reprint author), NIMH, Genet Basis Mood & Anxiety Disorders Unit, 35 Convent Dr,MSC 3719,Bldg 35-1A207, Bethesda, MD 20892 USA.
EM gonzalo.laje@nih.gov
RI Laje, Gonzalo/L-2654-2014;
OI Laje, Gonzalo/0000-0003-2763-3329; Rush, Augustus/0000-0003-2004-2382;
McMahon, Francis/0000-0002-9469-305X
FU NIMH [N01 MH-90003, K23MH67060]; National Institutes of Health (NIH);
U.S. Department of Health and Human Services (DHHS); NARSAD Young
Investigator/Sidney R. Baer Jr. Foundation; Bowman Family Foundation
FX STAR*D is supported by federal funds from NIMH under contract N01
MH-90003 to the University of Texas-Southwestern Medical Center at
Dallas (Dr. Rush, principal investigator). This study was funded by the
Intramural Research Program of NIMH, National Institutes of Health
(NIH), U.S. Department of Health and Human Services (DHHS), NIMH grant
K23MH67060, a NARSAD Young Investigator/Sidney R. Baer Jr. Foundation
Award, and a Bowman Family Foundation award. The content of this
publication does not necessarily reflect the views or policies of DHHS
nor does mention of trade names, commercial products, or organizations
imply endorsement by the U.S. government.
NR 67
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PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD NOV
PY 2009
VL 60
IS 11
BP 1446
EP 1457
PG 12
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 514KM
UT WOS:000271393200007
PM 19880459
ER
PT J
AU Ong, MK
Rubenstein, LV
AF Ong, Michael K.
Rubenstein, Lisa V.
TI Wishing Upon a STAR*D: The Promise of Ideal Depression Care by Primary
Care Providers
SO PSYCHIATRIC SERVICES
LA English
DT Editorial Material
ID DISSEMINATING QUALITY IMPROVEMENT; RANDOMIZED CONTROLLED-TRIAL;
COLLABORATIVE CARE; OUTCOMES; PREFERENCES; INCENTIVES; MANAGEMENT;
VISITS; IMPACT; TIME
AB The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial found that after initial treatment, depressed patients treated in primary care settings had the same or slightly better outcomes than those treated in specialty care settings. The authors describe challenges to using the STAR*D approach and protocols in usual primary care settings. These include inadequate availability of appointments, insufficient resources for care management and treatment monitoring, and lack of payment to primary care providers for providing mental health care. Substantial reengineering of payment and delivery systems is needed in order for the STAR*D approach to be viable in primary care clinics. (Psychiatric Services 60: 1460-1462, 2009)
C1 [Ong, Michael K.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA.
[Rubenstein, Lisa V.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA.
RP Ong, MK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, 911 Broxton Ave,1st Floor, Los Angeles, CA 90024 USA.
EM michael.ong@ucla.edu
RI Ong, Michael/F-7397-2013
FU NIMH NIH HHS [P30 MH068639, P30-MH082760, P30 MH082760]
NR 24
TC 3
Z9 3
U1 0
U2 0
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD NOV
PY 2009
VL 60
IS 11
BP 1460
EP 1462
PG 3
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 514KM
UT WOS:000271393200009
PM 19880461
ER
PT J
AU Cully, JA
Johnson, M
Moffett, ML
Khan, M
Deswal, A
AF Cully, Jeffrey A.
Johnson, Michael
Moffett, Maurice L.
Khan, Myrna
Deswal, Anita
TI Depression and Anxiety in Ambulatory Patients With Heart Failure
SO PSYCHOSOMATICS
LA English
DT Article
ID PRIMARY-CARE PATIENTS; QUALITY-OF-CARE; PULMONARY-DISEASE; COMPETING
DEMANDS; RISK; SYMPTOMS; PREVALENCE; PREDICTORS; OUTCOMES;
IDENTIFICATION
AB Background: Depression and anxiety are common in heart failure, but the prevalence, incidence, and relationship of these conditions to health service use and mortality remains uncertain. Objective: The authors sought to delineate these parameters and identify patient factors predicting hospitalizations for heart failure and mortality 12 months after their initial diagnosis of heart failure. Method: The authors utilized a retrospective database cohort of 12,028 ambulatory patients with newly diagnosed heart failure to examine diagnosed depression and anxiety and the relationship of these conditions to health service use and all-cause mortality. Results: Patients with diagnosed depression and/or anxiety (18% of the cohort) were frequently identified by providers within the first 30 days after a heart failure diagnosis. They subsequently utilized twice as many health services, but they did not show increased mortality risk. Discussion: Although mental health intervention data for heart failure patients are limited, the prevalence and impact of depression and anxiety in these patients suggest that assessment and intervention efforts appear warranted early in the heart failure process. (Psychosomatics 2009; 50: 592-598)
C1 Michael E DeBakey Vet Affairs Med Ctr, Hlth Serv Res & Dev Serv, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA.
Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
Vet Affairs S Cent Mental Illness Res Educ & Clin, Houston, TX USA.
Baylor Coll Med, Winters Ctr Heart Failure Res, Cardiol Sect, Houston, TX 77030 USA.
RP Cully, JA (reprint author), 2002 Holcombe 152, Houston, TX 77030 USA.
EM jcully@bcm.edu
NR 33
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U1 1
U2 3
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD NOV-DEC
PY 2009
VL 50
IS 6
BP 592
EP 598
PG 7
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 529AU
UT WOS:000272488900007
PM 19996230
ER
PT J
AU Nejad, SH
Gandhi, RT
Freudenreich, O
AF Nejad, Shamim Hashemi
Gandhi, Rajesh T.
Freudenreich, Oliver
TI Clozapine Use in HIV-Infected Schizophrenia Patients: A Case-Based
Discussion and Review
SO PSYCHOSOMATICS
LA English
DT Article
ID SERIOUS MENTAL-ILLNESS; ACQUIRED IMMUNODEFICIENCY SYNDROME;
PNEUMOCYSTIS-CARINII PNEUMONIA; TRIMETHOPRIM-SULFAMETHOXAZOLE;
ANTIRETROVIRAL THERAPY; DEPRESSIVE SYMPTOMS; METABOLIC SYNDROME;
CONTROLLED-TRIAL; DOUBLE-BLIND; HEPATITIS-C
AB Background: Schizophrenia is a common neuropsychiatric disorder that is associated with an increased risk for HIV infection. Because schizophrenia may affect the ability of HIV-infected patients to adhere to their antiretroviral regimen, optimal management of their mental illness is a high priority in such individuals. However, 20% to 30% of patients with schizophrenia are refractory to first-line antipsychotics. Objective: Given the frequency of comorbid HIV infection and schizophrenia, the authors investigated the potential role of clozapine, with the idea that this medication may be considered for use in this particular patient population. Method: The authors present histories of clozapine treatment in two patients with schizophrenia and comorbid HIV illness. The use of clozapine in this population, along with potential pharmacodynamic and pharmacokinetic drug interactions are discussed. Results: Management and information regarding the use of clozapine in patients with schizophrenia and comorbid HIV illness are presented. Discussion: Clozapine can be used successfully in HIV-infected individuals, with control of viral replication an achievable goal, particularly for those patients in whom there is some external oversight of medication adherence. A multidisciplinary approach must be adopted, with the consultation psychiatrist providing the best possible control of psychiatric problems so that infectious-disease doctors can achieve the goal of HIV replication control. (Psychosomatics 2009; 50: 626-632)
C1 [Nejad, Shamim Hashemi] Massachusetts Gen Hosp, Schizophrenia Program, Div Psychiat & Med, Div Infect Dis, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Schizophrenia Program, Partners AIDS Res Ctr, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Nejad, SH (reprint author), Massachusetts Gen Hosp, Schizophrenia Program, Div Psychiat & Med, Div Infect Dis, 55 Fruit St,WRN 605, Boston, MA 02114 USA.
EM snejad@partners.org
NR 50
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Z9 5
U1 2
U2 5
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD NOV-DEC
PY 2009
VL 50
IS 6
BP 626
EP 632
PG 7
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 529AU
UT WOS:000272488900012
PM 19996235
ER
PT J
AU Hennessey, KA
Bangsberg, DR
Weinbaum, C
Hahn, JA
AF Hennessey, Karen A.
Bangsberg, David R.
Weinbaum, Cindy
Hahn, Judith A.
TI Hepatitis A Seroprevalence and Risk Factors Among Homeless Adults in San
Francisco: Should Homelessness Be Included in the Risk-Based Strategy
for Vaccination?
SO PUBLIC HEALTH REPORTS
LA English
DT Article
ID INJECTION-DRUG USERS; VIRAL-HEPATITIS; POPULATION; INFECTION; VIRUS;
MEN; OUTBREAK
AB Objectives. Homeless adults have an increased risk of infectious diseases due to sexual and drug-related behaviors and substandard living conditions. We investigated the prevalence and risk factors for presence of hepatitis A virus (HAV) antibodies among homeless and marginally housed adults.
Methods. We analyzed serologic and questionnaire data from a study of marginally housed and homeless adults in San Francisco from April 1999 to March 2000. We tested seroprevalance for total antibodies to HAV (anti-HAV) and analyzed data using Chi-square tests and logistic regression.
Results. Of the 1,138 adults in the study, 52% were anti-HAV positive. The anti-HAV prevalence in this study population was 58% higher than the expected prevalence based on age-specific prevalence rates from the general population. Number of years of homelessness (<= 1, 2-4, and; >= 5 years) was associated with anti-HAV prevalence (46%, 50%, and 61%, respectively, p<0.001). We found other differences in anti-HAV prevalence (p<0.05) for ever having injected drugs (63% vs. 42% for non-injectors), being foreign-born (75% vs. 51% among U.S.-born), race/ethnicity (72%, 53%, and 45% for Hispanic, white, and black people, respectively), and increasing age (38%, 49%, and 62% among those aged <35, 35-45, and >45 years, respectively). These variables all remained significant in a multivariate model.
Conclusions. We found overall anti-HAV prevalence elevated in this San Francisco homeless population compared with the general U.S. population. These data show that anti-HAV was associated with homelessness independent of other known risk factors, such as being foreign-born, race/ethnicity, and injection drug use. This increase indicates an excess risk of HAV infection and the potential need to offer hepatitis A vaccination as part of homeless services.
C1 [Hennessey, Karen A.; Weinbaum, Cindy] Ctr Dis Control & Prevent, Div Viral Hepatitis, Atlanta, GA 30333 USA.
[Bangsberg, David R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Harvard Initiat Global Hlth, Cambridge, MA 02138 USA.
[Hahn, Judith A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Hennessey, KA (reprint author), Ctr Dis Control & Prevent, Div Viral Hepatitis, 1600 Clifton Rd,E-05, Atlanta, GA 30333 USA.
EM keh7@cdc.gov
FU NIDA NIH HHS [K01 DA023365, K01 DA023365-03]; NIMH NIH HHS [R01
MH054907]; PHS HHS [K-24 015287, R01-1 54907]
NR 18
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U1 0
U2 0
PU ASSOC SCHOOLS PUBLIC HEALTH
PI WASHINGTON
PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA
SN 0033-3549
J9 PUBLIC HEALTH REP
JI Public Health Rep.
PD NOV-DEC
PY 2009
VL 124
IS 6
BP 813
EP 817
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 504IG
UT WOS:000270608900008
PM 19894423
ER
PT J
AU Brown, CA
Cheng, EM
Hays, RD
Vassar, SD
Vickrey, BG
AF Brown, Carlos A.
Cheng, Eric M.
Hays, Ron D.
Vassar, Stefanie D.
Vickrey, Barbara G.
TI SF-36 includes less Parkinson Disease (PD)-targeted content but is more
responsive to change than two PD-targeted health-related quality of life
measures
SO QUALITY OF LIFE RESEARCH
LA English
DT Article
DE Health-related quality of life; Parkinson Disease; PDQUALIF; PDQ-39;
Responsiveness; SF-36
ID PATIENT-REPORTED OUTCOMES; MULTIPLE-SCLEROSIS; INSTRUMENTS; SCALE;
DISABILITY
AB To compare validity including responsiveness, and internal consistency reliability and scaling assumptions of a generic (SF-36) and Parkinson Disease (PD)-targeted (PDQ-39; PDQUALIF) health-related quality of life (HRQOL) measures.
Ninety-six PD patients were administered for all HRQOL measures by telephonic interview at baseline and 18 months. Relative efficiency and responsiveness were compared relative to four external criteria (self-ratings of PD's daily effects, global Quality of Life, PD symptom severity, and a depression screener). We examined whether PD-targeted measures explained unique variance beyond the SF-36 by regressing criterion variables on HRQOL scales/items. Adequacy of PD-targeted measures' original scaling was explored by item-scale correlations.
Relative efficiency estimates were similar for generic and PD-targeted measures across all criteria. Responsiveness analyses showed that the SF-36 yielded large (> 0.8) effect sizes (ES) for three of eight scales for each of two criterion variables, compared to only one large ES for any scale in either PD-targeted measure. Adjusted R (2) increased from 14 to 27% in regression models that included PD-targeted items compared to models with only SF-36 scales. Item-scale correlations showed significant cross-loading of items across scales of the PD-targeted measures.
SF-36 responsiveness was better than that of two PD-targeted measures, yet those measures had content that significantly explains PD patients' HRQOL.
C1 [Brown, Carlos A.; Cheng, Eric M.; Vassar, Stefanie D.; Vickrey, Barbara G.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA.
RP Cheng, EM (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA.
EM eric.cheng@va.gov
RI Hays, Ronald/D-5629-2013
FU Department of Veterans Affairs, Veterans Health Administration; VA
Health Services Research & Development Service [PDI 01-158]; NIH/NINDS
[NS038367]; NINDS [K23NS058571]
FX We acknowledge with thanks Michele Maines, MSG, Sunberri Murphy, and
Amelia Mittleman for bibliographic support, and Harvey Lopez and Jessika
Herrera for their administrative assistance. Erin Jacob assisted in the
data collection. We thank Drs. Jeff Bronstein, Yvette Bordelon, and Indu
Subramanian for recruitment of patients. The research presented here was
supported by the Department of Veterans Affairs, Veterans Health
Administration, VA Health Services Research & Development Service
project number PDI 01-158, and by NIH/NINDS NS038367 for the UCLA UDALL
Parkinson Disease Center of Excellence. Eric Cheng was supported by an
NINDS career development award (K23NS058571).
NR 34
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U1 1
U2 9
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
J9 QUAL LIFE RES
JI Qual. Life Res.
PD NOV
PY 2009
VL 18
IS 9
BP 1219
EP 1237
DI 10.1007/s11136-009-9530-y
PG 19
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 504XH
UT WOS:000270650900010
PM 19714487
ER
PT J
AU Catalano, OA
Sahani, DV
Forcione, DG
Czermak, B
Liu, CH
Soricelli, A
Arellano, RS
Mueller, PR
Hahn, PF
AF Catalano, Onofrio A.
Sahani, Dushyant V.
Forcione, David G.
Czermak, Benedikt
Liu, Chang-Hsien
Soricelli, Andrea
Arellano, Ronald S.
Mueller, Peter R.
Hahn, Peter F.
TI Biliary Infections: Spectrum of Imaging Findings and Management
SO RADIOGRAPHICS
LA English
DT Article
ID RECURRENT PYOGENIC CHOLANGITIS; HEPATOSPLENIC SCHISTOSOMIASIS-MANSONI;
MAGNETIC-RESONANCE CHOLANGIOGRAPHY; ACUTE SUPPURATIVE CHOLANGITIS;
BILE-DUCT STONES; LIVER-TRANSPLANTATION; RISK-FACTORS; NONSUPPURATIVE
CHOLANGITIS; SCLEROSING CHOLANGITIS; PERCUTANEOUS DRAINAGE
AB Infectious cholangitides encompass a wide spectrum of infectious processes affecting the biliary tree. They can have protean clinical and imaging appearances. Some manifest as an acute medical emergency with high mortality if not properly and emergently managed. Others are chronic processes that may predispose a patient to liver failure or cholangiocarcinoma. The clinical and imaging features and the subsequent therapy are dictated by the pathogens involved, the immune status of the host, and the degree and distribution of biliary obstruction. Bacteria cause most cases of infectious cholangitis in Western countries. In other parts of the world, parasites play an important role, either as causative agents or in predisposing the host to bacterial superinfection. Viral cholangitides primarily affect immunocompromised patients. The clinical and imaging features of cholangitis differ between immunocompetent and immunocompromised patients. Imaging plays a pivotal role in diagnosis of infectious cholangitis, helps identify predisposing causes, and demonstrates complications. Moreover, interventional radiology provides tools to treat acute life-threatening biliary infections, chronic entities, and complications. (C) RSNA, 2009.radiographics.rsna.org
C1 [Catalano, Onofrio A.; Sahani, Dushyant V.; Arellano, Ronald S.; Mueller, Peter R.; Hahn, Peter F.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA.
[Forcione, David G.] Harvard Univ, Sch Med, Dept Gastroenterol, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Czermak, Benedikt] Univ Innsbruck, Dept Radiol, Sch Med, A-6020 Innsbruck, Austria.
[Liu, Chang-Hsien] Tri Serv Gen Hosp, Dept Radiol, Taipei, Taiwan.
[Liu, Chang-Hsien] Natl Def Med Ctr, Taipei, Taiwan.
[Soricelli, Andrea] Univ Naples Parthenope, Dept Radiol, Naples, Italy.
[Soricelli, Andrea] SDN Fdn IRCCS, Naples, Italy.
RP Catalano, OA (reprint author), Harvard Univ, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA.
EM ocatalano@partners.org
RI soricelli, andrea/C-1133-2009
OI soricelli, andrea/0000-0001-7011-7667
NR 77
TC 21
Z9 24
U1 0
U2 0
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0271-5333
J9 RADIOGRAPHICS
JI Radiographics
PD NOV
PY 2009
VL 29
IS 7
BP 2059
EP U269
DI 10.1148/rg.297095051
PG 23
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 521UF
UT WOS:000271949200016
PM 19926762
ER
PT J
AU Levine, D
Bankier, AA
Halpern, EF
AF Levine, Deborah
Bankier, Alexander A.
Halpern, Elkan F.
TI Submissions to Radiology: Our Top 10 List of Statistical Errors
SO RADIOLOGY
LA English
DT Editorial Material
ID SAMPLE-SIZE ESTIMATION; DIAGNOSTIC-ACCURACY; PROPORTIONS; REGRESSION;
AGREEMENT; QUALITY
C1 [Levine, Deborah; Bankier, Alexander A.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA.
[Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
RP Levine, D (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA.
EM dlevine@bidmc.harvard.edu
OI Levine, Deborah/0000-0001-7761-6493
NR 23
TC 9
Z9 9
U1 0
U2 3
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 NOV
PY 2009
VL 253
IS 2
BP 288
EP 290
DI 10.1148/radiol.2532090759
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 512UH
UT WOS:000271275800003
ER
PT J
AU Sistrom, CL
Dreyer, KJ
Dang, PP
Weilburg, JB
Boland, GW
Rosenthal, DI
Thrall, JH
AF Sistrom, Christopher L.
Dreyer, Keith J.
Dang, Pragya P.
Weilburg, Jeffrey B.
Boland, Giles W.
Rosenthal, Daniel I.
Thrall, James H.
TI Recommendations for Additional Imaging in Radiology Reports:
Multifactorial Analysis of 5.9 Million Examinations
SO RADIOLOGY
LA English
DT Article
ID P-VALUE FALLACY; CT; COST
AB Purpose: To quantify the rates of recommendation for additional imaging (RAI) in a large number of radiology reports of different modalities and to estimate the effects of 11 clinically relevant factors.
Materials and Methods: This HIPAA compliant research was approved by the institutional review board under an expedited protocol for analyzing anonymous aggregated radiology data. All diagnostic imaging examinations (n = 5 948 342) interpreted by radiologists between 1995 and 2008 were studied. A natural language processing technique specifically designed to extract information about any recommendations from radiology report texts was used. The analytic data set included three quantitative variables: the interpreting radiologist's experience, the year of study, and patient age. Categoric variables described patient location (inpatient, outpatient, emergency department), whether a resident dictated the case, patient sex, modality, body area studied, ordering service, radiologist's specialty division, and whether the examination result was positive. A multivariable logistic regression model was used to determine the effect of each of these factors on likelihood of RAI while holding all others equal.
Results: Recommendations increased during the 13 years of study, with the unadjusted rate rising from roughly 6% to 12%. After accounting for all other factors, the odds of any one examination resulting in an RAI increased by 2.16 times (95% confidence interval: 2.12, 2.21) from 1995 to 2008. As radiologist experience increased, the odds of an RAI decreased by about 15% per decade. Studies that had positive findings were more likely (odds ratio = 5.03; 95% confidence interval: 4.98, 5.07) to have an RAI. The remaining factors also had significant effects on the tendency for an RAI.
Conclusion: The likelihood of RAI increased by 15% for each decade of radiologist experience and roughly doubled over 13 years of study. (C) RSNA, 2009
C1 [Sistrom, Christopher L.; Dreyer, Keith J.; Dang, Pragya P.; Boland, Giles W.; Rosenthal, Daniel I.; Thrall, James H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Weilburg, Jeffrey B.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
RP Sistrom, CL (reprint author), Univ Florida, Ctr Hlth, Dept Radiol, POB 100374, Gainesville, FL 32610 USA.
EM sistrc@radiology.ufl.edu
NR 16
TC 50
Z9 51
U1 0
U2 1
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 NOV
PY 2009
VL 253
IS 2
BP 453
EP 461
DI 10.1148/radiol.2532090200
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 512UH
UT WOS:000271275800021
PM 19710005
ER
PT J
AU Holloway, CL
Racine, ML
Cormack, RA
O'Farrell, DA
Viswanathan, AN
AF Holloway, Caroline L.
Racine, Marie-Lynn
Cormack, Robert A.
O'Farrell, Desmond A.
Viswanathan, Akila N.
TI Sigmoid dose using 3D imaging in cervical-cancer brachytherapy
SO RADIOTHERAPY AND ONCOLOGY
LA English
DT Article
DE Cervical cancer; Brachytherapy; Normal tissue dose
ID INTRACAVITARY BRACHYTHERAPY; VOLUME PARAMETERS; UTERINE CERVIX;
RADIATION-THERAPY; CARCINOMA; RADIOTHERAPY; BLADDER; RECTUM;
RECOMMENDATIONS; COMPLICATIONS
AB Background and Purpose: To evaluate the proximity. variance, predictors of dose, and complications to the sigmoid in cervical-cancer brachytherapy using 3D planning.
Materials and methods: Over 36 months, 50 patients were treated for cervical cancer with either low-dose-rate (LDR) or high-dose-rate (HDR) brachytherapy. The distance from the central tandem to the sigmoid, the D0.1cc and the D2cc to the sigmoid, rectum and bladder doses, and toxicity were analyzed.
Results: The median sigmoid EQD2 D0.1cc and D2cc were 84 Gy and 68.3 Gy for HDR versus 71.1 Gy and 65.9 Gy for LDR (p = 0.02 and 0.98, respectively). Twenty percent of the HDR fractions required manipulation of the superior dwell positions to decrease the sigmoid dose. The median distance from the sigmoid to the tandem was 1.7 cm (range [rg], 0.1-6.16 cm) for HDR and 2.7 cm (rg, 1.17-4.52 cm) for LDR; from the sigmoid to the 100% isodose region the median distances were -0.1 cm (rg, -1.4 to 2.5 cm) and 0.44 cm (rg. -0.73-5.2 cm), respectively. The proximity of the sigmoid to the tandem is significantly related to sigmoid dose (p<0.0001). Within-patient (among-fraction) variation in sigmoid-to-tandem distance during HDR was substantial (coefficient of variation =40%). No grade 3-4 sigmoid toxicity was seen after a median 31-month follow-up period.
Conclusions: 3D imaging in cervical-cancer brachytherapy shows the sigmoid in close proximity to the tandem. The sigmoid-to-tandem distance varies substantially between fractions, indicating the importance of sigmoid dose-volume evaluation with each fraction. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 93 (2009) 307-310
C1 [Holloway, Caroline L.; Racine, Marie-Lynn; Cormack, Robert A.; O'Farrell, Desmond A.; Viswanathan, Akila N.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St,L2, Boston, MA 02115 USA.
EM aviswanathan@lroc.harvard.edu
OI Cormack, Robert/0000-0001-5553-9984
FU NCI NIH HHS [K07 CA117979-01, K07 CA117979-04, K07 CA117979-03, K07
CA117979, K07 CA117979-02]
NR 30
TC 27
Z9 29
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-8140
J9 RADIOTHER ONCOL
JI Radiother. Oncol.
PD NOV
PY 2009
VL 93
IS 2
BP 307
EP 310
DI 10.1016/j.radonc.2009.06.032
PG 4
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 523RT
UT WOS:000272092900025
PM 19665244
ER
PT J
AU Huang, CYC
Pelaez, D
Bendala, JD
Garcia-Godoy, F
Cheung, HS
AF Huang, C-Y Charles
Pelaez, Daniel
Bendala, Juan Dominguez
Garcia-Godoy, Franklin
Cheung, Herman S.
TI Plasticity of stem cells derived from adult periodontal ligament
SO REGENERATIVE MEDICINE
LA English
DT Article
DE adult stem cells; neural crest; periodontal ligament; pluripotent stem
cells
ID CARDIAC NEURAL CREST; HUMAN SOMATIC-CELLS; IN-VITRO; PROGENITOR CELLS;
ENDOCRINE PANCREAS; HUMAN FIBROBLASTS; DEFINED FACTORS; SELF-RENEWAL;
BONE-MARROW; DIFFERENTIATION
AB Background: The neural crest contains pluripotent cells that can give rise to neurons and glial cells of the peripheral nervous system, endocrine cells, connective tissue cells, muscle cells and pigment cells during embryonic development. Stem cells derived from the neural crest may still reside in neural crest derivatives including the periodontal ligament (PDL). However, the pluripotency of PDL-derived stem cells has not been investigated. Aim: To identify subpopulations of stem cells from the adult PDL and study their pluripotency. Human PDLs were harvested from impacted wisdom teeth (patients aged 19-22 years). Results: This study demonstrated that subpopulations of PDL cells expressed embryonic stem cell markers (Oct4, Sox2, Nanog and Klf4) and a subset of neural crest markers (Nestin, Slug, p75 and Sox10). Such PDL cell subpopulations exhibited the potential to differentiate into neurogenic, cardiomyogenic, chondrogenic and osteogenic lineages. Furthermore, preliminary evidence suggesting insulin production of PDL cells might be indicative of the generation of cells of the endodermal lineage. Conclusion: These findings suggest that the PDL may contain pluripotent stem cells that originate from the neural crest. Our observations open the door to prospective autologous therapeutic applications for a variety of conditions.
C1 [Huang, C-Y Charles; Pelaez, Daniel; Cheung, Herman S.] Univ Miami, Dept Biomed Engn, Coral Gables, FL 33124 USA.
[Huang, C-Y Charles] Nova SE Univ, Craniofacial Res Lab, Coll Dent Med, Ft Lauderdale, FL 33314 USA.
[Pelaez, Daniel; Cheung, Herman S.] Miami VA Med Ctr, Miami, FL 33125 USA.
[Bendala, Juan Dominguez] Univ Miami, Sch Med, Diabet Res Inst, Miami, FL USA.
[Garcia-Godoy, Franklin] Univ Miami, Biosci Res Ctr, Coll Dent, Coral Gables, FL 33124 USA.
[Garcia-Godoy, Franklin] Forsyth Inst, Boston, MA USA.
RP Cheung, HS (reprint author), Univ Miami, Dept Biomed Engn, Coral Gables, FL 33124 USA.
EM hcheung@med.miami.edu
NR 59
TC 63
Z9 65
U1 0
U2 6
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1746-0751
J9 REGEN MED
JI Regen. Med.
PD NOV
PY 2009
VL 4
IS 6
BP 809
EP 821
DI 10.2217/RME.09.55
PG 13
WC Cell & Tissue Engineering; Engineering, Biomedical
SC Cell Biology; Engineering
GA 522PJ
UT WOS:000272010000008
PM 19903001
ER
PT J
AU Hausmann, LRM
Ye, FF
Schofield, JW
Woods, RL
AF Hausmann, Leslie R. M.
Ye, Feifei
Schofield, Janet Ward
Woods, Rochelle L.
TI Sense of Belonging and Persistence in White and African American
First-Year Students
SO RESEARCH IN HIGHER EDUCATION
LA English
DT Article
DE Sense of belonging; Persistence; Intentions; Intervention
ID CAMPUS RACIAL CLIMATE; REDUCING INTERGROUP BIAS; COLLEGE-STUDENTS;
PREDOMINANTLY WHITE; MINORITY-STUDENTS; HIGHER-EDUCATION; SOCIAL
INTEGRATION; THEORETICAL-MODEL; ETHNIC-MINORITY; CAUSAL MODEL
AB The authors argue for the inclusion of students' subjective sense of belonging in an integrated model of student persistence (Cabrera et al., J Higher Educ 64:123-139, 1993). The effects of sense of belonging and a simple intervention designed to increase sense of belonging are tested in the context of this model. The intervention increased sense of belonging for white students, but not for African American students. However, sense of belonging had direct effects on institutional commitment and indirect effects on intentions to persist and actual persistence behavior for both white and African American students.
C1 [Hausmann, Leslie R. M.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA.
[Ye, Feifei] Univ Pittsburgh, Dept Educ Psychol, Pittsburgh, PA USA.
[Schofield, Janet Ward] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA.
[Schofield, Janet Ward] Univ Pittsburgh, Ctr Learning Res & Dev, Pittsburgh, PA 15260 USA.
[Woods, Rochelle L.] Univ Michigan, Off Acad Multicultural Initiat, Ann Arbor, MI 48109 USA.
RP Hausmann, LRM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr 151C H, Pittsburgh, PA 15206 USA.
EM leslie.hausmann@gmail.com
NR 56
TC 24
Z9 26
U1 7
U2 19
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0361-0365
J9 RES HIGH EDUC
JI Res. High. Educ.
PD NOV
PY 2009
VL 50
IS 7
BP 649
EP 669
DI 10.1007/s11162-009-9137-8
PG 21
WC Education & Educational Research
SC Education & Educational Research
GA 480YQ
UT WOS:000268773600002
ER
PT J
AU MacDonald, AW
Thermenos, HW
Barch, DM
Seidman, LJ
AF MacDonald, Angus W., III
Thermenos, Heidi W.
Barch, Deanna M.
Seidman, Larry J.
TI Imaging Genetic Liability to Schizophrenia: Systematic Review of fMRI
Studies of Patients' Nonpsychotic Relatives
SO SCHIZOPHRENIA BULLETIN
LA English
DT Review
DE schizophrenia; neuroimaging; fMRI; relatives; family study; cognitive
control; working memory; memory; language; review
ID DORSOLATERAL PREFRONTAL CORTEX; WORKING-MEMORY PERFORMANCE;
EVENT-RELATED FMRI; 1ST-DEGREE RELATIVES; VERBAL FLUENCY; LANGUAGE
LATERALIZATION; BRAIN ACTIVATION; FUNCTIONAL MRI; UNAFFECTED RELATIVES;
THALAMIC ACTIVATION
AB There is a growing literature on brain activity in the non-psychotic first-degree relatives of patients with schizophrenia as measured using functional imaging. This systematic review examined 20 studies in 4 domains of cognition, including cognitive control (7 samples), working memory (5 samples), long-term memory (4 samples), and language (4 samples). While the literature was widely divergent, these studies did consistently find activation differences between patients' relatives and controls. The most consistent increases in activation within hemisphere were found in right ventral prefrontal cortex (PFC) and right parietal cortex. Abnormal activity, defined as significant increases or decreases in activation relative to controls irrespective of hemisphere, was found in about two-thirds of contrasts in the cerebellum, dorsal prefrontal, lateral temporal, and parietal cortices, and thalamus, with basal ganglia and ventral PFC showing abnormalities in approximately half of those contrasts. Anterior cingulate was generally spared in patients' relatives. The diversity of findings in studies of patients' relatives may derive from differences between the cognitive demands across studies. We identify avenues for building a more accurate and cumulative literature, including symmetrical inclusion criteria for relatives and controls, recording in-scanner responses, using both a priori and whole-brain tests, explicitly reporting threshold values, reporting main effects of task, reporting effect sizes, and quantifying the risk of false negatives. While functional imaging in the relatives of schizophrenia patients remains a promising methodology for understanding the impact of the unexpressed genetic liability to schizophrenia, no single region or mechanism of abnormalities has yet emerged.
C1 [MacDonald, Angus W., III] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
[MacDonald, Angus W., III] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA.
[Thermenos, Heidi W.; Seidman, Larry J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Psychiat,Med Sch, Massachusetts Mental Hlth Ctr,Publ Psychiat Div, Cambridge, MA 02138 USA.
[Thermenos, Heidi W.; Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
[Thermenos, Heidi W.; Seidman, Larry J.] MIT, MGH, HMS, Athinoula A Martinos Ctr Funct & Struct Biomed Im, Cambridge, MA 02139 USA.
[Barch, Deanna M.] Washington Univ, Dept Psychol, St Louis, MO 63130 USA.
[Barch, Deanna M.] Washington Univ, Dept Psychiat, St Louis, MO 63130 USA.
[Barch, Deanna M.] Washington Univ, Dept Radiol, St Louis, MO 63130 USA.
RP MacDonald, AW (reprint author), Univ Minnesota, Dept Psychol, N218 Elliott Hall,75 E River Rd, Minneapolis, MN 55455 USA.
EM angus@umn.edu
RI Barch, Deanna/G-8638-2013; MacDonald, Angus/M-9855-2016
OI MacDonald, Angus/0000-0003-4588-931X
FU National Alliance for Research in Schizophrenia and Affective Disorders;
University of Minnesota's McKnight-Land Grant Fellowship; National
Institute of Mental Health [MH 18269, MH 79262]; National Institute of
Mental Health Conte Center [MH 71616]; Commonwealth Research Center of
the Massachusetts Department of Mental Health and National Institute of
Mental Health [MH 43518, MH 63951, MH 65562]; Center grant [P50
MH080272]
FX National Alliance for Research in Schizophrenia and Affective Disorders
(to A.W.M. III, D.M.B., and L.J.S.); the University of Minnesota's
McKnight-Land Grant Fellowship and National Institute of Mental Health
(grants MH 18269 and MH 79262 to A.W.M. 111); National Institute of
Mental Health Conte Center (grant MH 71616 to D.M.B.); the Commonwealth
Research Center of the Massachusetts Department of Mental Health and
National Institute of Mental Health (grants MH 43518. MH 63951, and MH
65562); Center grant (P50 MH080272 to H.W.T. and L.J.S.).
NR 113
TC 78
Z9 78
U1 1
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0586-7614
J9 SCHIZOPHRENIA BULL
JI Schizophr. Bull.
PD NOV
PY 2009
VL 35
IS 6
BP 1142
EP 1162
DI 10.1093/schbul/sbn053
PG 21
WC Psychiatry
SC Psychiatry
GA 518UG
UT WOS:000271719200014
PM 18556667
ER
PT J
AU Walker, EF
Cornblatt, BA
Addington, J
Cadenhead, KS
Cannon, TD
McGlashan, TH
Perkins, DO
Seidman, LJ
Tsuang, MT
Woods, SW
Heinssen, R
AF Walker, Elaine F.
Cornblatt, Barbara A.
Addington, Jean
Cadenhead, Kristin S.
Cannon, Tyrone D.
McGlashan, Thomas H.
Perkins, Diana O.
Seidman, Larry J.
Tsuang, Ming T.
Woods, Scott W.
Heinssen, Robert
TI The relation of antipsychotic and antidepressant medication with
baseline symptoms and symptom progression: A naturalistic study of the
North American Prodrome Longitudinal Sample
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Psychosis; Prodrome; Medication
ID RANDOMIZED CONTROLLED-TRIAL; ULTRA-HIGH RISK; SCHIZOPHRENIA PRODROME;
FOLLOW-UP; PSYCHOSIS; PEOPLE; PHASE; NEURODEVELOPMENT; INTERVENTIONS;
OLANZAPINE
AB A substantial number of patients who meet criteria for a prodromal syndrome for first psychosis are treated with antipsychotic and/or antidepressant medications. There is suggestive evidence that both classes of medication may reduce prodromal symptoms. This longitudinal study examined the relation of antipsychotic and antidepressant medication with prodromal symptom severity at baseline and 6-month follow-up. Participants met Structured Interview for Prodromal Syndromes (SIPS) criteria for the prodrome, and were evaluated at eight centers as part of the North American Prodrome Longitudinal Study (NAPLS). Symptom ratings (positive, negative, disorganized and general) and data on antipsychotics, SSRIs, and other antidepressant medications were obtained at baseline and 6-month follow-up. Analyses revealed that all symptom dimensions declined in severity over time, but there were differences in the magnitude of the decline as a function of antipsychotic medication. Those never on antipsychotics showed less reduction in positive and disorganized symptoms over time. SSRIs and other antidepressants were not linked with declines in symptom severity. Consistent with findings from small-sample, clinical trials, the present results suggest that atypical antipsychotics may be effective in reducing the severity of attenuated positive symptoms associated with the prodrome to psychotic disorders. Limitations of the present study are noted, including the fact that it is not a randomized trial, and data on duration and dosage of medication and 2-year follow-up were not available for most participants. The results are discussed in light of the relative risks and benefits of preventive interventions, both medication and cognitive therapies, and the importance of future clinical trials. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA.
[Walker, Elaine F.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA.
[Cornblatt, Barbara A.] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA.
[Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada.
[Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA.
[Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
[McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Seidman, Larry J.; Tsuang, Ming T.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Psychiat, Boston, MA 02215 USA.
[Seidman, Larry J.; Tsuang, Ming T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Cadenhead, Kristin S.; Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Heinssen, Robert] NIMH, Schizophrenia Spectrum Res Program, Div Adult Translat Res, Bethesda, MD 20892 USA.
RP Walker, EF (reprint author), Emory Univ, Dept Psychol, 36 Eagle Row, Atlanta, GA 30322 USA.
EM psyefw@emory.edu
FU NCATS NIH HHS [UL1 TR000454]; NIMH NIH HHS [K24 MH076191-05, R01
MH060720, U01 MH081944, U01 MH081944-05, R01 MH060720-10, U01 MH081988,
U01 MH081988-02, K24 MH076191, U01 MH081988-01A1, K23 MH001905]
NR 22
TC 33
Z9 34
U1 5
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD NOV
PY 2009
VL 115
IS 1
BP 50
EP 57
DI 10.1016/j.schres.2009.07.023
PG 8
WC Psychiatry
SC Psychiatry
GA 518JD
UT WOS:000271686400008
PM 19709859
ER
PT J
AU Asif, A
Salman, L
Carrillo, RG
Garisto, JD
Lopera, G
Barakat, U
Lenz, O
Yevzlin, A
Agarwal, A
Gadalean, F
Sachdeva, B
Vachharajani, TJ
Wu, S
Maya, ID
Abreo, K
AF Asif, Arif
Salman, Loay
Carrillo, Roger G.
Garisto, Juan D.
Lopera, Gustavo
Barakat, Urwa
Lenz, Oliver
Yevzlin, Alexander
Agarwal, Anil
Gadalean, Florin
Sachdeva, Bharat
Vachharajani, Tushar J.
Wu, Steven
Maya, Ivan D.
Abreo, Ken
TI Patency Rates for Angioplasty in the Treatment of Pacemaker-Induced
Central Venous Stenosis in Hemodialysis Patients: Results of a
Multi-Center Study
SO SEMINARS IN DIALYSIS
LA English
DT Article
ID SUBCLAVIAN VEIN STENOSIS; TRANSVENOUS PACEMAKER; FOLLOW-UP; OCCLUSION;
OBSTRUCTION; FISTULA; WALLSTENTS; PLACEMENT; INSERTION; SALVAGE
AB While hemodialysis access ligation has been used to manage pacemaker (PM) and implantable cardioverter-defibrillator (ICD) lead-induced central venous stenosis (CVS), percutaneous transluminal balloon angioplasty (PTA) has also been employed to manage this complication. The advantages of PTA include minimal invasiveness and preservation of arteriovenous access for hemodialysis therapy. In this multi-center study we report the patency rates for PTA to manage lead-induced CVS. Consecutive PM/ICD chronic hemodialysis patients with an arteriovenous access referred for signs and symptoms of CVS due to lead-induced CVS were included in this analysis. PTA was performed using the standard technique. Technical and clinical success was examined. Technical success was defined as the ability to successfully perform the procedure. Clinical success was defined as the ability to achieve amelioration of the signs and symptoms of CVS. Both primary and secondary patency rates were also analyzed. Twenty-eight consecutive patients underwent PTA procedure. Technical success was 95%. Postprocedure clinical success was achieved in 100% of the cases where the procedure was successful. The primary patency rates were 18% and 9% at 6 and 12 months, respectively. The secondary patency rates were 95%, 86%, and 73% at 6, 12, and 24 months, respectively. On average, 2.1 procedures/year were required to maintain secondary patency. There were no procedure-related complications. This study finds PTA to be a viable option in the management of PM/ICD lead-induced CVS. Additional studies with appropriate design and sample size are required to conclusively establish the role of PTA in the management of this problem.
C1 [Asif, Arif; Salman, Loay; Carrillo, Roger G.; Garisto, Juan D.; Lopera, Gustavo; Barakat, Urwa; Lenz, Oliver] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Yevzlin, Alexander] Univ Wisconsin, Madison, WI USA.
[Agarwal, Anil] Ohio Univ, Columbus, OH USA.
[Gadalean, Florin] Nephrol Associates Cent Florida, Intervent Nephrol, Orlando, FL USA.
[Sachdeva, Bharat; Abreo, Ken] Louisiana State Univ, Shreveport, LA 71105 USA.
[Vachharajani, Tushar J.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
[Wu, Steven] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Maya, Ivan D.] Univ Alabama, Birmingham, AL USA.
RP Asif, A (reprint author), 1600 NW 10th Ave R 7168, Miami, FL 33136 USA.
EM aasif@med.miami.edu
RI Carrillo, Roger/C-2231-2015; Lenz, Oliver/M-4672-2016
OI Carrillo, Roger/0000-0002-0443-8689; Lenz, Oliver/0000-0003-2997-3976
NR 27
TC 20
Z9 22
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0894-0959
J9 SEMIN DIALYSIS
JI Semin. Dial.
PD NOV-DEC
PY 2009
VL 22
IS 6
BP 671
EP 676
DI 10.1111/j.1525-139X.2009.00636.x
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 528NO
UT WOS:000272452800014
PM 19799756
ER
PT J
AU Choudhury, D
Tuncel, M
Levi, M
AF Choudhury, Devasmita
Tuncel, Meryem
Levi, Moshe
TI Disorders of Lipid Metabolism and Chronic Kidney Disease in the Elderly
SO SEMINARS IN NEPHROLOGY
LA English
DT Review
DE Lipid disorder; elderly; chronic kidney disease; end-stage renal
disease; dyslipidemia
ID CHRONIC-RENAL-FAILURE; CORONARY-HEART-DISEASE; HMG-COA REDUCTASE;
AGE-RELATED HYPERCHOLESTEROLEMIA; NUTRITION EXAMINATION SURVEY;
ELEMENT-BINDING PROTEINS; WHITE ADIPOSE-TISSUE; 3RD NATIONAL-HEALTH;
CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION
C1 [Choudhury, Devasmita] Univ Texas SW Med Ctr Dallas, Inctr & Home Dialysis, Dallas VA Med Ctr, Dallas, TX 75390 USA.
[Tuncel, Meryem] Texas Tech Univ, Hlth Sci Ctr, Dept Hypertens & Nephrol, Lubbock, TX 79430 USA.
[Levi, Moshe] Univ Colorado, Dept Med, Denver VA Med Ctr, Denver, CO USA.
RP Levi, M (reprint author), 12700 E 19th Ave,Res 2,Room 7002, Aurora, CO 80045 USA.
EM moshe.levi@UCHSC.edu
OI Levi, Moshe/0000-0002-6225-946X
FU NIA NIH HHS [R01 AG026529-01A2, R01 AG026529]
NR 90
TC 5
Z9 7
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 0270-9295
J9 SEMIN NEPHROL
JI Semin. Nephrol.
PD NOV
PY 2009
VL 29
IS 6
BP 610
EP 620
DI 10.1016/j.semnephrol.2009.07.006
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA 617CD
UT WOS:000279257500009
PM 20006793
ER
PT J
AU Li, YQ
Liu, BL
Zhao, H
Sailhamer, EA
Fukudome, EY
Zhang, XB
Kheirbek, T
Finkelstein, RA
Velmahos, GC
deMoya, M
Hales, CA
Alam, HB
AF Li, Yongqing
Liu, Baoling
Zhao, Hang
Sailhamer, Elizabeth A.
Fukudome, Eugene Y.
Zhang, Xiaobo
Kheirbek, Tareq
Finkelstein, Robert A.
Velmahos, George C.
deMoya, Marc
Hales, Charles A.
Alam, Hasan B.
TI PROTECTIVE EFFECT OF SUBEROYLANILIDE HYDROXAMIC ACID AGAINST LPS-INDUCED
SEPTIC SHOCK IN RODENTS
SO SHOCK
LA English
DT Article; Proceedings Paper
CT 94th Annual Clinical Congress of the American-College-of-Surgeons/63rd
Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical
Problems
CY OCT 12-16, 2008
CL San Francisco, CA
SP Amer Coll Surg
DE Septic shock; acetylation; LPS; suberoylanilide hydroxamic acid;
histone; survival; lung; macrophage
ID HISTONE DEACETYLASE INHIBITOR; ACUTE LUNG INJURY; RESUSCITATION
STRATEGIES; HEMORRHAGIC-SHOCK; CARDIAC HISTONES; GENE-EXPRESSION;
VALPROIC ACID; ACETYLATION; RECEPTOR; RECRUITMENT
AB We have recently found that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, improves survival in a lethal model of hemorrhagic shock in rats. The purpose of the present study was to determine whether SAHA treatment would prevent LPS-induced septic shock and improve the survival in a murine model. C57BL/6J mice were randomly divided into two groups. Experimental mice were given intraperitoneal SAHA (50 mg/kg) in vehicle dimethyl sulfoxide fluid (n = 10). The control mice (n = 10) received vehicle dimethyl sulfoxide only. They were injected with LIDS (20 mg/kg, i.p.) 2 h later, and the animals from the treatment group were given a second dose of SAHA. Survival was monitored during the next 7 days. In a parallel study, mice treated with or without SAHA were subjected to LPS insult while normal (sham) mice serviced as controls. 1) Lungs were harvested at 3 and 48 h for analysis of gene expression and pathologic changes, respectively; 2) spleens were isolated for analysis of neutrophilic cell population. In addition, RAW264.7 mouse macrophages were cultured to assess the effects of SAHA on LPS-induced inflammation in vitro. All mice in the control group that were subjected to LIDS challenge died in less than 48 h. However, SAHA-treated animals displayed a significantly higher 1-week survival rate (87.5%) compared with the control group (0%). Moreover, LPS insult decreased the acetylation of histone proteins (H2A, H2B, and H3), elevated the levels of TNF-alpha in vivo (circulation) and in vitro (culture medium), increased the neutrophilic cell population in the spleen, enhanced the expression of TNF-alpha and IL-1 beta genes in lung tissue, and augmented the pulmonary neutrophil infiltration. In contrast, SAHA treatment markedly attenuated all of these LPS-induced alterations. We report for the first time that administration of SAHA (50 mg/kg) significantly attenuates a variety of inflammatory markers and improves long-term survival after a lethal LPS insult.
C1 [Li, Yongqing; Liu, Baoling; Sailhamer, Elizabeth A.; Fukudome, Eugene Y.; Kheirbek, Tareq; Finkelstein, Robert A.; Velmahos, George C.; deMoya, Marc; Alam, Hasan B.] Harvard Univ, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp, Dept Surg,Med Sch, Boston, MA 02114 USA.
[Zhao, Hang; Hales, Charles A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA 02114 USA.
[Zhang, Xiaobo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA.
[Finkelstein, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Div Crit Care, Boston, MA 02114 USA.
RP Alam, HB (reprint author), Harvard Univ, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp, Dept Surg,Med Sch, 165 Cambridge St,Suite 810, Boston, MA 02114 USA.
EM hbalam@partners.org
FU NHLBI NIH HHS [R01 HL039150]
NR 30
TC 41
Z9 43
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1073-2322
J9 SHOCK
JI Shock
PD NOV
PY 2009
VL 32
IS 5
BP 517
EP 523
DI 10.1097/SHK.0b013e3181a44c79
PG 7
WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease
SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System
& Cardiology
GA 514QJ
UT WOS:000271409700010
PM 19295477
ER
PT J
AU Torriani, M
Gupta, R
Donahue, DM
AF Torriani, Martin
Gupta, Rajiv
Donahue, Dean M.
TI Sonographically guided anesthetic injection of anterior scalene muscle
for investigation of neurogenic thoracic outlet syndrome
SO SKELETAL RADIOLOGY
LA English
DT Article
DE Thoracic outlet syndrome; Anterior scalene; Brachial plexus; Ultrasound;
Percutaneous block
ID CLINICAL-SIGNIFICANCE; BRACHIAL-PLEXUS
AB To describe the technique and complications of sonographically guided anesthetic injection of the anterior scalene muscle in patients being investigated for neurogenic thoracic outlet syndrome.
Subjects were identified via a retrospective review of medical records. For the procedure a 25-gauge needle was introduced into the anterior scalene muscle under real-time ultrasound guidance followed by injection of local anesthetic. The procedures were evaluated for technical success, which was defined as satisfactory identification of anterior scalene muscle, intramuscular needle placement, and intramuscular delivery of medication. There was a short-term follow-up to determine procedure-related complications and rate of unintended brachial plexus (BP) block, manifested by upper extremity paresthesias and/or weakness.
Twenty-six subjects with suspected neurogenic thoracic outlet syndrome underwent 29 injections (three subjects received bilateral injections). Technical success was achieved in all procedures. The mean duration of the procedure was 30 min, and there were no cases of intravascular needle placement or neurogenic pain during the injection. No major complications occurred. Temporary symptoms of partial BP block occurred after nine injections (9/29, 31%), and a temporary complete BP block occurred after one injection (1/29, 3%).
Sonographically guided anesthetic injection of the anterior scalene muscle is a safe and well-tolerated diagnostic test for patients being investigated for neurogenic thoracic outlet syndrome.
C1 [Torriani, Martin] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, Boston, MA 02114 USA.
[Torriani, Martin; Gupta, Rajiv; Donahue, Dean M.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Donahue, Dean M.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA.
RP Torriani, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, 55 Fruit St,YAW 6048, Boston, MA 02114 USA.
EM mtorriani@hms.harvard.edu
NR 9
TC 13
Z9 13
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-2348
J9 SKELETAL RADIOL
JI Skeletal Radiol.
PD NOV
PY 2009
VL 38
IS 11
BP 1083
EP 1087
DI 10.1007/s00256-009-0714-x
PG 5
WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging
SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging
GA 500TB
UT WOS:000270326700009
PM 19440705
ER
PT J
AU Gray, ST
Chen, YL
Lin, DT
AF Gray, Stacey Tutt
Chen, Yen-Lin
Lin, Derrick T.
TI Efficacy of Proton Beam Therapy in the Treatment of Ewing's Sarcoma of
the Paranasal Sinuses and Anterior Skull Base
SO SKULL BASE-AN INTERDISCIPLINARY APPROACH
LA English
DT Article
CT 7th International Conference on Head and Neck Cancer
CY JUL 19-23, 2008
CL San Francisco, CA
SP Amer Head & Neck Soc
DE Ewing's sarcoma; anterior skull base; proton beam; endoscopic surgery
ID SARCOMA/PRIMITIVE NEUROECTODERMAL TUMOR; COMBINED-MODALITY THERAPY;
TERM-FOLLOW-UP; ADJUVANT CHEMOTHERAPY; MULTIMODAL THERAPY;
RADIATION-THERAPY; MAXILLARY SINUS; NASAL FOSSA; NO BENEFIT; BONE
AB Ewing's sarcoma involving the sinonasal cavity and anterior skull base is very rare. The purpose of this article is to present our experience with two such cases, which were both treated with combined chemotherapy and proton beam radiation therapy. The patients were selected from a retrospective medical record analysis that was conducted of all patients who were diagnosed with Ewing's sarcoma of the sinonasal cavity at the Massachusetts Eye & Ear Infirmary/Massachusetts General Hospital Cranial Base Center from 2004 to 2008. One of the patients underwent pretreatment endoscopic subtotal resection to facilitate proton beam radiation therapy. Response to treatment was assessed, post-treatment endoscopic biopsies were performed to assure eradication of disease, and treatment complications were recorded. Both patients completed chemotherapy and proton beam radiation therapy without complication. One patient completed treatment in December 2006 and remains disease free. The second patient completed treatment in March 2007 and remains disease free. Both patients developed headaches accompanied by frontal sinus opacification after treatment that required endoscopic drainage. After endoscopic drainage, the opacification and symptoms resolved.
C1 [Gray, Stacey Tutt; Lin, Derrick T.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA.
[Chen, Yen-Lin] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Gray, ST (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA.
EM stacey_gray@meei.harvard.edu
NR 35
TC 12
Z9 13
U1 0
U2 1
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1531-5010
J9 SKULL BASE-INTERD AP
JI Skull Base-Interdiscip. Appr.
PD NOV
PY 2009
VL 19
IS 6
BP 409
EP 416
DI 10.1055/s-0029-1220207
PG 8
WC Clinical Neurology; Otorhinolaryngology; Surgery
SC Neurosciences & Neurology; Otorhinolaryngology; Surgery
GA 521EX
UT WOS:000271904200004
PM 20436842
ER
PT J
AU Collins, ME
Block, SD
Arnold, RM
Christakis, NA
AF Collins, Molly E.
Block, Susan D.
Arnold, Robert M.
Christakis, Nicholas A.
TI On the prospects for a blame-free medical culture
SO SOCIAL SCIENCE & MEDICINE
LA English
DT Article
DE USA; Blame-free culture; Medical errors; Physicians; Palliative care
ID PATIENT SAFETY; MISTAKES; ERRORS; PHYSICIANS; DOCTORS; DEATHS; VICTIM;
IMPACT
AB Official policy-making bodies and experts in medical error have called for a shift in perspective to a blame-free culture within medicine, predicated on the basis that errors are largely attributable to systems rather than individuals. However, little is known about how the lived experience of blame in medical care relates to prospects for such a shift. In this essay we explore the benefits and costs of blame in medical culture. Our observations are informed by our clinical experience and supported by interview data from a study in which 163 American physicians were interviewed about caring for a total of 66 dying patients in two institutions. We observe three ways in which blame is invoked: (1) self-blame, (2) blame of impersonal forces or the "system," and (3) blame of others. Physicians articulate several important functions of blame: as a stimulus for learning and improvement; as a way to empathically allow physicians to forgive mistakes when others accept responsibility using self-blame; and as a way to achieve control over clinical outcomes. We argue that, since error is viewed as a personal failing and tends to evoke substantial self-blame, physicians do not tend to think of errors in a systems context. Given that physicians' ideology of self-blame is ingrained, accompanied by benefits, and limits a systems perspective on error, it may subvert attempts to establish a blame-free culture. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Collins, Molly E.] Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Block, Susan D.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA.
[Block, Susan D.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA.
[Block, Susan D.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Block, Susan D.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA.
[Arnold, Robert M.] Univ Pittsburgh, Inst Doctor Patient Commun, Pittsburgh, PA 15260 USA.
[Christakis, Nicholas A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Christakis, Nicholas A.] Mt Auburn Hosp, Dept Med, Boston, MA USA.
[Christakis, Nicholas A.] Harvard Univ, Dept Sociol, Boston, MA 02115 USA.
RP Collins, ME (reprint author), Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
EM molly_collins@post.harvard.edu
RI Christakis, Nicholas/C-3205-2009
NR 33
TC 13
Z9 15
U1 0
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0277-9536
J9 SOC SCI MED
JI Soc. Sci. Med.
PD NOV
PY 2009
VL 69
IS 9
BP 1287
EP 1290
DI 10.1016/j.socscimed.2009.08.033
PG 4
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 518LU
UT WOS:000271694700001
PM 19766373
ER
PT J
AU Collins, ME
Block, SD
Arnold, RM
Christakis, NA
AF Collins, Molly E.
Block, Susan D.
Arnold, Robert M.
Christakis, Nicholas A.
TI Responsibility and reflection: Understanding our responses to perceived
errors. A response to Woodward, Lemer and Wu
SO SOCIAL SCIENCE & MEDICINE
LA English
DT Editorial Material
DE Blame-free culture; Medical errors; USA; Physicians
ID MISTAKES
C1 [Collins, Molly E.] Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Block, Susan D.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA.
[Block, Susan D.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA.
[Block, Susan D.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Block, Susan D.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA.
[Arnold, Robert M.] Inst Enhance Palliat Care, Sect Palliat Care & Med Eth, Div Gen Internal Med, Pittsburgh, PA USA.
[Arnold, Robert M.] Univ Pittsburgh, Inst Doctor Patient Commun, Pittsburgh, PA USA.
[Christakis, Nicholas A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Christakis, Nicholas A.] Mt Auburn Hosp, Dept Med, Cambridge, MA USA.
[Christakis, Nicholas A.] Harvard Univ, Dept Sociol, Cambridge, MA 02138 USA.
RP Collins, ME (reprint author), Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
EM molly_collins@post.harvard.edu
RI Christakis, Nicholas/C-3205-2009
NR 6
TC 1
Z9 1
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0277-9536
J9 SOC SCI MED
JI Soc. Sci. Med.
PD NOV
PY 2009
VL 69
IS 9
BP 1294
EP 1295
DI 10.1016/j.socscimed.2009.08.007
PG 2
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 518LU
UT WOS:000271694700003
PM 19766370
ER
PT J
AU Hinton, DE
Rasmussen, A
Nou, L
Pollack, MH
Good, MJ
AF Hinton, Devon E.
Rasmussen, Andrew
Nou, Leakhena
Pollack, Mark H.
Good, Mary-Jo
TI Anger, PTSD, and the nuclear family: A study of Cambodian refugees
SO SOCIAL SCIENCE & MEDICINE
LA English
DT Article
DE Anger; PTSD; Family; Catastrophic cognitions; Cambodian refugees;
Acculturation; USA
ID POSTTRAUMATIC-STRESS-DISORDER; ANXIETY DISORDERS; PSYCHOMETRIC
PROPERTIES; COMBAT VETERANS; MENTAL-HEALTH; PANIC-ATTACKS; SOCIAL
COURSE; TRAUMA; SCALE; WAR
AB This study profiles the family-directed anger of traumatized Cambodian refugees, all survivors of the Pol Pot genocide (1975-1979), who were patients at a psychiatric clinic in Lowell, MA, USA. We focus on the nuclear family (NF) unit, the NF unit defined as the patient's "significant other" (i.e. spouse or boyfriend/girlfriend) and children. Survey data were collected from a convenience sample of 143 Cambodian refugee patients from October 2006 to August 2007. The study revealed that 48% (68/143) of the patients had anger directed toward a NF member in the last month, with anger directed toward children being particularly common (64 of the 143 patients, or 49% [64/131] of the patients with children). NF-type anger was severe, for example, almost always resulting in somatic arousal (e.g., causing palpitations in 91% [62/68] of the anger episodes) and often in trauma recall and fears of bodily dysfunction. Responses to open-ended questions revealed the causes of anger toward a significant other and children, the content of anger-associated trauma recall, and what patients did to gain relief from anger. A type of cultural gap, namely, a linguistic gap (i.e., the parent's lack of English language skills and the child's lack of Khmer language skills), seemingly played a role in generating conflict and anger. NF-type anger was associated with PTSD presence. The effect of anger on PTSD severity resulted in part from anger-associated trauma recall and fears of bodily dysfunction, with 54% of the variance in PTSD severity explained by that regression model. The study: 1) suggests that among traumatized refugees, family-related anger is a major clinical concern; 2) illustrates how family-related anger may be profiled and investigated in trauma-exposed populations; and 3) gives insights into how family-related anger is generated in such populations. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Hinton, Devon E.; Pollack, Mark H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Hinton, Devon E.] Arbour Counseling, SE Asian Clin, Lowell, MA USA.
[Rasmussen, Andrew] NYU, Sch Med, Div Gen Internal Med, New York, NY 10003 USA.
[Nou, Leakhena] Calif State Univ Long Beach, Dept Sociol, Long Beach, CA 90840 USA.
[Good, Mary-Jo] Harvard Univ, Cambridge, MA 02138 USA.
RP Hinton, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02115 USA.
EM devon_hinton@hms.harvard.edu
FU NIMH NIH HHS [R01 MH079032, R01 MH079032-01A1, R01 MH094312]
NR 42
TC 36
Z9 36
U1 2
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0277-9536
J9 SOC SCI MED
JI Soc. Sci. Med.
PD NOV
PY 2009
VL 69
IS 9
BP 1387
EP 1394
DI 10.1016/j.socscimed.2009.08.018
PG 8
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 518LU
UT WOS:000271694700015
PM 19748169
ER
PT J
AU Stowell, CP
Jones, SC
Enny, C
Langholff, W
Leitz, G
AF Stowell, Christopher P.
Jones, Stanley C.
Enny, Christopher
Langholff, Wayne
Leitz, Gerhard
TI An Open-Label, Randomized, Parallel-Group Study of Perioperative Epoetin
Alfa Versus Standard of Care for Blood Conservation in Major Elective
Spinal Surgery Safety Analysis
SO SPINE
LA English
DT Article
DE erythropoietin; epoetin alfa; surgery; deep vein thrombosis;
thrombovascular events
ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; VENOUS THROMBOEMBOLISM; REPLACEMENT;
OUTCOMES; HIP
AB Study Design. Prospective, open-label, randomized, parallel-group study at 80 centers.
Objective. To demonstrate there is no clinically important additional risk for deep vein thrombosis with perioperative use of epoetin alfa versus standard of care in spine surgery without prophylactic anticoagulation.
Summary of Background Data. Trials of epoetin alfa in orthopedic surgery that demonstrated no additional risk of thrombovascular events included perioperative pharmacologic anticoagulation.
Methods. Subjects received epoetin alfa 600 U/kg subcutaneously once weekly starting 3 weeks before spinal surgery plus standard of care for blood conservation, or standard of care alone. Perioperative anticoagulation therapy was not permitted; mechanical deep vein thrombosis prophylaxis was allowed. Doppler imaging for deep vein thrombosis was done on postoperative day 4 (or day of discharge), or for suspected deep vein thrombosis. Deep vein thrombosis was diagnosed by Doppler result or adverse event report. The criterion for no additional risk of deep vein thrombosis was a 1-sided 97.5% upper confidence limit <= 4% between groups.
Results. Of the 680 subjects analyzed (340 in each treatment group), 16 (4.7%) in the epoetin alfa group and 7 (2.1%) in the standard of care group had a diagnosis of deep vein thrombosis either by Doppler or by adverse event report with normal Doppler. The between-group difference was 2.6% (97.5% upper confidence limit, 5.4%). Deep vein thrombosis confirmed by Doppler (4.1% vs. 2.1%), other clinically relevant thrombovascular events (1.5% vs. 0.9%), and all adverse events combined (76.5% vs. 73.2%) occurred with similar frequency in the 2 treatment groups.
Conclusion. This study documented a higher incidence of deep vein thrombosis and similar rates of other clinically relevant thrombovascular events with epoetin alfa versus standard of care for blood conservation in subjects who did not receive prophylactic anticoagulation before spinal surgery. Antithrombotic prophylaxis should be considered when erythropoietin is used in the surgical setting.
C1 [Stowell, Christopher P.] Harvard Univ, Sch Med, Blood Transfus Serv, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Jones, Stanley C.] Spine Care, Houston, TX USA.
[Enny, Christopher; Langholff, Wayne; Leitz, Gerhard] Centocor Ortho Biotech Serv LLC, Med Affairs, Bridgewater, NJ USA.
RP Stowell, CP (reprint author), Harvard Univ, Sch Med, Blood Transfus Serv, Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM cstowell@partners.org
FU Centocor Ortho Biotech Services LLC [PR97-19-002]
FX Supported by Centocor Ortho Biotech Services LLC (Protocol
#PR97-19-002).
NR 18
TC 45
Z9 46
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0362-2436
J9 SPINE
JI SPINE
PD NOV 1
PY 2009
VL 34
IS 23
BP 2479
EP 2485
DI 10.1097/BRS.0b013e3181bd163f
PG 7
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA 515CT
UT WOS:000271444900001
PM 19927096
ER
PT J
AU Kim, JH
Deasy, BM
Seo, HY
Studer, RK
Vo, NV
Georgescu, HI
Sowa, GA
Kang, JD
AF Kim, Joo Han
Deasy, Bridget M.
Seo, Hyoung Yeon
Studer, Rebecca K.
Vo, Nam V.
Georgescu, Helga I.
Sowa, Gwendolyn A.
Kang, James D.
TI Differentiation of Intervertebral Notochordal Cells Through Live
Automated Cell Imaging System In Vitro
SO SPINE
LA English
DT Article
DE notochordal cells; chondrocyte-like cells; live automated cell imager;
(35)S sulfate incorporation; RT-PCR
ID NUCLEUS PULPOSUS; EXTRACELLULAR-MATRIX; CULTURE SYSTEM; DISC;
EXPRESSION; PROLIFERATION; CHONDROCYTES; SOX9
AB Study Design. We demonstrated the differentiation of notochordal cells by direct observation using a live automated cell imaging system. We also hypothesized that notochordal cells have characteristics of chondrocyte-like cells.
Objective. To determine characteristics of notochordal cells by matrix protein expression and their differentiation using a live automated cell imager.
Summary of Background Data. Although notochordal cells are critical to homeostasis of intervertebral disc, their fate has not been extensively studied and there is little evidence of notochordal cells as progenitors.
Methods. Notochordal cells purified from rabbit nucleus pulposus were isolated after serial filtration. Notochordal cells in 3-dimensional culture were compared to chondrocyte-like cells by (35)S sulfate incorporation into proteoglycan and reverse transcription polymerase chain reaction for gene expression(collagen II and aggrecan). Notochordal cells in 2-D culture were used for immunocytochemical staining (collagen II, aggrecan, and SOX9) and time-lapsed cell tracking study.
Results. Notochordal cells were capable of proteoglycan production at a rate comparable to chondrocyte-like cells (108% +/- 22.6% to chondrocyte-like cells) and expressed collagen II, aggrecan, and SOX9. In time- lapsed cell tracking analysis, notochordal cells were slower in population doubling time than chondrocyte-like cells and differentiated into 3 morphologically distinct cell types: vacuolated cells (area: 2392 +/- 507.1 mu m(2), velocity: 0.09 +/- 0.01 mu m/min); giant cells (area: 12678 +/- 1637.0 mu m(2), velocity: 0.08 +/- 0.01 mu m/min) which grew rapidly without cell division; polygonal cells (area: 3053 +/- 751.2 mu m(2), 0.14 +/- 0.01 mu m/min) morphologically similar to typical differentiation type of chondrocyte-like cells ( area: 2671 +/- 235.6 mu m(2), 0.19 +/- 0.01 mu m/min). Rarely, notochordal cells formed clusters analogous to that observed in vivo.
Conclusion. These studies demonstrate a chondrocyte phenotype of notochordal cells and are the first direct evidence of notochordal cell differentiation, suggesting that they may act as progenitor cells, which has the potential to lead to their use in novel approaches to regeneration of degenerative intervertebral disc.
C1 [Sowa, Gwendolyn A.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA 15261 USA.
[Kim, Joo Han; Deasy, Bridget M.; Vo, Nam V.; Georgescu, Helga I.; Kang, James D.] Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Pittsburgh, PA 15261 USA.
[Kim, Joo Han] Korea Univ, Coll Med, Dept Neurosurg, Seoul 136705, South Korea.
[Seo, Hyoung Yeon] Chonnam Natl Univ, Dept Orthopaed Surg, Coll Med, Kwangju, South Korea.
[Studer, Rebecca K.] Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA.
RP Sowa, GA (reprint author), Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, 200 Lothrop St,E1658,Biomed Sci Tower, Pittsburgh, PA 15261 USA.
EM sowaga@upmc.edu
RI Kim, Joo Han/B-8129-2014
OI Kim, Joo Han/0000-0002-4747-9763
FU Pittsburgh Foundation at Department of Orthopedic Surgery; University of
Pittsburgh
FX Supported by the Pittsburgh Foundation at Department of Orthopedic
Surgery, University of Pittsburgh.
NR 26
TC 35
Z9 40
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0362-2436
J9 SPINE
JI SPINE
PD NOV 1
PY 2009
VL 34
IS 23
BP 2486
EP 2493
DI 10.1097/BRS.0b013e3181b26ed1
PG 8
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA 515CT
UT WOS:000271444900002
PM 19841610
ER
PT J
AU Sims, JR
Lee, SW
Topalkara, K
Qiu, JH
Xu, J
Zhou, ZP
Moskowitz, MA
AF Sims, John R.
Lee, Sae-Won
Topalkara, Kamil
Qiu, Jianhua
Xu, Jian
Zhou, Zhipeng
Moskowitz, Michael A.
TI Sonic Hedgehog Regulates Ischemia/Hypoxia-Induced Neural Progenitor
Proliferation
SO STROKE
LA English
DT Article
DE brain ischemia; dentate gyrus; gene expression; Sonic hedgehog; stem
cell
ID ADULT BRAIN; IN-VIVO; CELLS; DIFFERENTIATION; EXPRESSION; NEUROGENESIS
AB Background and Purpose - Sonic hedgehog (Shh) protein is required for the maintenance of neural progenitor cells (NPCs) in the embryonic and adult hippocampus. Brain ischemia causes increased proliferation of hippocampal NPCs. We therefore examined whether Shh regulates the increase in proliferation of NPCs after ischemia/hypoxia.
Methods - Male SV129 mice were exposed to a 20-minute middle cerebral artery occlusion; hippocampi were then analyzed for Shh mRNA and protein expression by real-time polymerase chain reaction, immunoblot, and immunohistochemistry. Primary cell cultures of neurons, astrocytes, and NPCs were exposed to 16 hours of hypoxia (1% O-2) and analyzed by real-time polymerase chain reaction and immunoblot for Shh expression. Proliferation of NPCs, in vivo and in vitro, was measured by bromodeoxyuridine incorporation.
Results - Among the cell types examined in vitro, only NPC and neurons increased Shh mRNA under hypoxic conditions. Furthermore, hypoxia increased proliferation of NPCs and this proliferation was enhanced by the addition of recombinant Shh or blocked by the pathway- specific inhibitor, cyclopamine. Middle cerebral artery occlusion was associated with a transient 2-fold increase in the mRNA encoding both Shh and its transcription factor, Gli1, 0.5 days after ischemia. Within the hippocampus, Shh protein was increased approximately 3-fold 3 and 7 days after ischemia and was observed predominantly within cells in the CA3 and hilar regions. Shh was expressed only in mature neurons. In vivo, cyclopamine suppressed ischemia- induced proliferation of subgranular NPCs.
Conclusion - The Shh pathway plays a role in the proliferation of NPCs induced by ischemia/hypoxia and might participate in injury remodeling. (Stroke. 2009; 40: 3618- 3626.)
C1 [Sims, John R.; Lee, Sae-Won; Topalkara, Kamil; Qiu, Jianhua; Zhou, Zhipeng; Moskowitz, Michael A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab,Dept Radiol, Charlestown, MA 02129 USA.
[Sims, John R.; Lee, Sae-Won; Topalkara, Kamil; Qiu, Jianhua; Zhou, Zhipeng; Moskowitz, Michael A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab,Neurosci Ctr, Charlestown, MA 02129 USA.
[Sims, John R.; Xu, Jian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab,Dept Neurol, Charlestown, MA 02129 USA.
[Sims, John R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab,Dept Neurosurg, Charlestown, MA 02129 USA.
RP Sims, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab,Dept Radiol, CNY149 Room 6403, Charlestown, MA 02129 USA.
EM jsims@partners.org
FU National Institutes of Health (NIH) [NS045776, P30 NS045776, K08
NS04924]; Cardiovascular Foundation; Craig H. Neilsen Foundation;
American Heart Association, National Scientist Development [0335154N,
0535138N]; NIH Interdepartmental Stroke Program [5 P50 NS10828]
FX Real-time polymerase chain reaction work was supported by a National
Institutes of Health (NIH) Nucleic Acid Quantitation Core Grant
NS045776. Image analysis data obtained with NIH core grant support P30
NS045776. This work was supported by grants from the Stanely J. Sarnoff
Cardiovascular Foundation (J. R. S.), Craig H. Neilsen Foundation (J. R.
S.), American Heart Association, National Scientist Development Grants,
0335154N (J. Q.) and 0535138N (J. R. S.), National Institutes of Health
(NIH) K08 NS049241 (J. R. S.), and NIH Interdepartmental Stroke Program
Project 5 P50 NS10828 (M. A. M.).
NR 23
TC 68
Z9 87
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD NOV
PY 2009
VL 40
IS 11
BP 3618
EP 3626
DI 10.1161/STROKEAHA.109.561951
PG 9
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 511JM
UT WOS:000271160300035
PM 19762700
ER
PT J
AU Schwaitzberg, SD
Kochman, ML
Hawes, RH
Rattner, DW
AF Schwaitzberg, Steven D.
Kochman, Michael L.
Hawes, Robert H.
Rattner, David W.
TI Natural orifice translumenal endoscopic surgery (NOTES): Is it time for
introduction to clinical practice?
SO SURGERY
LA English
DT Editorial Material
C1 [Schwaitzberg, Steven D.] Cambridge Hlth Alliance, Dept Surg, Boston, MA USA.
[Kochman, Michael L.] Univ Penn Hlth Syst, Div Gastroenterol, Philadelphia, PA USA.
[Hawes, Robert H.] Med Univ S Carolina, Div Gastroenterol & Hepatol, Charleston, SC 29425 USA.
[Rattner, David W.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Schwaitzberg, SD (reprint author), Cambridge Hlth Alliance, 1493 Cambridge St, Cambridge, MA 02139 USA.
EM sschwaitzberg@challiance.org
NR 2
TC 5
Z9 5
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD NOV
PY 2009
VL 146
IS 5
BP 841
EP 842
DI 10.1016/j.surg.2009.06.015
PG 2
WC Surgery
SC Surgery
GA 514TX
UT WOS:000271419600002
PM 19744446
ER
PT J
AU Mekel, M
Stephen, AE
Gaz, RD
Perry, ZH
Hodin, RA
Parangi, S
AF Mekel, Michal
Stephen, Antonia E.
Gaz, Randall D.
Perry, Zvi H.
Hodin, Richard A.
Parangi, Sareh
TI Thyroid surgery in octogenarians is associated with higher complication
rates
SO SURGERY
LA English
DT Article
ID ELDERLY-PATIENTS; MALE GENDER; OUTCOMES; CANCER; MANAGEMENT; MORBIDITY;
NODULES; DISEASE; RISK; AGE
AB Background. The incidence of thyroid nodules increases with age and little information is available regarding the risks of thyroid surgery in elderly patients. The aim of this study was to determine whether thyroid surgery in patients : 80 is associated with higher complication rates.
Methods. Out of 3,568 patients undergoing thyroid surgery between July 2001 and October 2007 at a single institution., the records of 90 consecutive patients 80 years were reviewed retrospectively and compared with a cohort of 242 randomly selected patients aged 18-79, who underwent thyroid surgery during the same time period. Clinical variables included age, gender, pre-operative diagnosis, substernal component, previous surgery, final pathology, length of stay, comorbidities, American Society of Anesthesiologists (ASA) score, body mass index, postoperative complications, and mortality.
Results. Preoperative indications for surgery included benign disease in 51% vs 39%, suspected malignancy in 19% vs 26%, and suspected follicular neoplasms in 30% vs 35% in the octogenarian patient group (>= 80 years old) vs the younger patient cohort (P = NS). Octogenarians had 20% significant malignancy on final pathology vs 27% in the younger cohort (P = NS). The overall complication rate in the octogenarian group was 24% vs 9% in the younger cohort (P < .001). Male gender and ASA >= 3 were found to be independent fisk factors for Perioperative complications after thyroid surgery, while age alone was not.
Conclusion. Age >= 80 is associated with higher morbidity after thyroid surgery, although not independently. Earlier operative intervention may be advised in those at high risk for disease progression, whereas follow-up strategies without operation may be advised for others. (Surgery 2009;146:913-21.)
C1 [Mekel, Michal; Stephen, Antonia E.; Gaz, Randall D.; Hodin, Richard A.; Parangi, Sareh] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Mekel, Michal; Stephen, Antonia E.; Gaz, Randall D.; Hodin, Richard A.; Parangi, Sareh] Massachusetts Gen Hosp, Endocrine Surg Unit, Boston, MA 02114 USA.
[Mekel, Michal; Stephen, Antonia E.; Gaz, Randall D.; Hodin, Richard A.; Parangi, Sareh] Harvard Univ, Sch Med, Boston, MA USA.
[Perry, Zvi H.] Tufts Med Ctr, Surg Res Lab, Boston, MA USA.
RP Parangi, S (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,Wang ACC 460, Boston, MA 02114 USA.
EM sparangi@partners.org
OI Perry, Zvi/0000-0002-1131-5230
FU NCI NIH HHS [R01 CA149738]
NR 25
TC 16
Z9 17
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD NOV
PY 2009
VL 146
IS 5
BP 913
EP 921
DI 10.1016/j.surg.2009.05.004
PG 9
WC Surgery
SC Surgery
GA 514TX
UT WOS:000271419600011
PM 19744461
ER
PT J
AU Livhits, M
Mercado, C
Yermilov, I
Parikh, JA
Dutson, E
Mehran, A
Ko, CY
Gibbons, MM
AF Livhits, Masha
Mercado, Cheryl
Yermilov, Irina
Parikh, Janak A.
Dutson, Erik
Mehran, Amir
Ko, Clifford Y.
Gibbons, Melinda Maggard
TI Does weight loss immediately before bariatric surgery improve outcomes:
a systematic review
SO SURGERY FOR OBESITY AND RELATED DISEASES
LA English
DT Review
DE Bariatric surgery; Predictors; Weight loss; Preoperative weight loss;
Outcomes
AB Background: Preoperative weight loss before bariatric surgery has been proposed as a predictive factor for improved patient compliance and the degree of excess weight loss achieved after surgery. In the present study, we sought to determine the effect of preoperative weight loss on postoperative outcomes.
Methods: A search of MEDLINE was completed to identify the patient factors associated with weight loss after bariatric surgery. Of the 909 screened reports, 15 had reported on preoperative weight loss and the degree of postoperative weight loss achieved. A meta-analysis was performed that compared the postoperative weight loss and perioperative outcomes in patients who had lost weight preoperatively compared to those who had not.
Results: Of the 15 articles (n = 3404 patients) identified, 5 found a positive effect of preoperative weight loss on postoperative weight loss, 2 found a positive short-term effect that was not sustained long term, 5 did not find an effect difference, and 1 found a negative effect. A meta-analysis revealed a significant increase in the 1-year postoperative weight loss (mean difference of 5% EWL, 95% confidence interval 2.68-7.32) for patients who had lost weight preoperatively. A meta-analysis of other outcomes revealed a decreased operative time for patients who had lost weight preoperatively (mean difference 23.3 minutes, 95% confidence interval 13.8-32.8).
Conclusion: Preoperative weight loss before bariatric surgery appears to be associated with greater weight loss postoperatively and might help to identify patients who would have better compliance after surgery. (C) 2009 American Society for Metabolic and Bariatric Surgery. All rights reserved.
C1 [Livhits, Masha; Mercado, Cheryl; Yermilov, Irina; Parikh, Janak A.; Dutson, Erik; Mehran, Amir; Ko, Clifford Y.; Gibbons, Melinda Maggard] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA.
[Livhits, Masha; Yermilov, Irina; Parikh, Janak A.; Ko, Clifford Y.; Gibbons, Melinda Maggard] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA.
[Gibbons, Melinda Maggard] Olive View Univ Calif, Dept Surg, Sylmar, CA USA.
RP Livhits, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 LeComte Ave,72-215 CHS, Los Angeles, CA 90095 USA.
EM mlivhits@mednet.ucla.edu
NR 35
TC 45
Z9 47
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1550-7289
EI 1878-7533
J9 SURG OBES RELAT DIS
JI Surg. Obes. Relat. Dis.
PD NOV-DEC
PY 2009
VL 5
IS 6
BP 713
EP 721
DI 10.1016/j.soard.2009.08.014
PG 9
WC Surgery
SC Surgery
GA V30LE
UT WOS:000208816700017
PM 19879814
ER
PT J
AU Izci, Y
Seckin, H
Ates, O
Baskaya, MK
AF Izci, Yusuf
Seckin, Hakan
Ates, Oezkan
Baskaya, Mustafa K.
TI Supracerebellar transtentorial transcollateral sulcus approach to the
atrium of the lateral ventricle: microsurgical anatomy and surgical
technique in cadaveric dissections
SO SURGICAL NEUROLOGY
LA English
DT Article
DE Atrium; Collateral sulcus; Lateral ventricle; Supracerebellar approach
ID ARTERIOVENOUS-MALFORMATIONS; TEMPORAL-LOBE; FIBER DISSECTION; TUMORS
AB Background: Access to lesions located in the atrium of the lateral ventricle without causing neurologic deficit can be challenging. Here, we demonstrate the supracerebellar transtentorial transcollateral sulcus (STTS) approach as an alternative route to the atrium of the lateral ventricle using anatomical dissections in cadavers.
Methods: Suboccipital craniotomy with extension above the transverse sinus was performed in 5 arterial and venous latex-injected cadaveric heads (10 hemispheres). After the dural opening, arachnoidal dissection of the supracerebellar space was performed, and the tentorium cerebelli was cut from lateral to medial. This revealed the parahippocampal and fusiform gyri and collateral sulcus (CS). The distance from the CS to the atrium was measured.
Results: The atrium of the lateral ventricle was entered through the CS in each specimen. The cerebral hemispheres were removed from each cadaveric specimen, and dissections were performed. The distance from the CS to the atrium was 1.30 cm on the right side and 1.31 cm on the left. The CS was bifurcated in 62% of the hemispheres, whereas it was single in 38%. Through this approach, only the "u" fibers of the CS were damaged, and the fibers of the optic radiation in the inferolateral wall of the atrium were preserved.
Conclusion: The STTS approach may be an effective alternative approach to lesions located in the medioposterior aspect of the atrium of the lateral ventricle in selected cases. Further clinical studies to evaluate the safety and efficacy of this approach are needed. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Baskaya, Mustafa K.] Univ Wisconsin, Dept Neurol Surg, Madison, WI 53792 USA.
William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53792 USA.
RP Baskaya, MK (reprint author), Univ Wisconsin, Dept Neurol Surg, Madison, WI 53792 USA.
EM m.baskaya@neurosurg.wisc.edu
NR 16
TC 12
Z9 14
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0090-3019
J9 SURG NEUROL
JI Surg. Neurol.
PD NOV
PY 2009
VL 72
IS 5
BP 509
EP 514
DI 10.1016/j.surneu.2009.01.025
PG 6
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 616TX
UT WOS:000279233800014
PM 19328525
ER
PT J
AU Carty, SE
Cooper, DS
Doherty, GM
Duh, QY
Kloos, RT
Mandel, SJ
Randolph, GW
Stack, BC
Steward, DL
Terris, DJ
Thompson, GB
Tufano, RP
Tuttle, RM
Udelsman, R
AF Carty, Sally E.
Cooper, David S.
Doherty, Gerard M.
Duh, Quan-Yang
Kloos, Richard T.
Mandel, Susan J.
Randolph, Gregory W.
Stack, Brendan C., Jr.
Steward, David L.
Terris, David J.
Thompson, Geoffrey B.
Tufano, Ralph P.
Tuttle, R. Michael
Udelsman, Robert
CA Amer Thyroid Assoc Surg Working Gr
TI Consensus Statement on the Terminology and Classification of Central
Neck Dissection for Thyroid Cancer
SO THYROID
LA English
DT Review
ID SURGERY; ACADEMY; HEAD
AB Background: The primary goals of this interdisciplinary consensus statement are to review the relevant anatomy of the central neck compartment, to identify the nodal subgroups within the central compartment commonly involved in thyroid cancer, and to define a consistent terminology relevant to the central compartment neck dissection.
Summary: The most commonly involved central lymph nodes in thyroid carcinoma are the prelaryngeal (Delphian), pretracheal, and the right and left paratracheal nodal basins. A central neck dissection includes comprehensive, compartment-oriented removal of the prelaryngeal and pretracheal nodes and at least one paratracheal lymph node basin. A designation should be made as to whether a unilateral or bilateral dissection is performed and on which side (left or right) in unilateral cases. Lymph node "plucking" or "berry picking" implies removal only of the clinically involved nodes rather than a complete nodal group within the compartment and is not recommended. A therapeutic central compartment neck dissection implies that nodal metastasis is apparent clinically (preoperatively or intraoperatively) or by imaging (clinically N1a). A prophylactic/elective central compartment dissection implies nodal metastasis is not detected clinically or by imaging (clinically N0).
Conclusion: Central neck dissection at a minimum should consist of removal of the prelaryngeal, pretracheal, and paratracheal lymph nodes. The description of a central neck dissection should include both the indication (therapeutic vs. prophylactic/elective) and the extent of the dissection (unilateral or bilateral).
C1 [Steward, David L.] Univ Cincinnati, Coll Med, Dept Otolaryngol Head & Neck Surg, Cincinnati, OH 45267 USA.
[Carty, Sally E.] Univ Pittsburgh, Sch Med, Dept Surg, Sect Endocrine Surg, Pittsburgh, PA USA.
[Cooper, David S.] Johns Hopkins Univ, Sch Med, Div Endocrinol & Metab, Baltimore, MD USA.
[Doherty, Gerard M.] Univ Michigan Hlth Syst, Dept Surg, Ann Arbor, MI USA.
[Duh, Quan-Yang] Vet Affairs Med Ctr, Surg Serv, San Francisco, CA 94121 USA.
[Duh, Quan-Yang] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Kloos, Richard T.] Ohio State Univ, Arthur G James Canc Hosp, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA.
[Kloos, Richard T.] Ohio State Univ, Arthur G James Canc Hosp, Div Nucl Med, Columbus, OH 43210 USA.
[Kloos, Richard T.] Ohio State Univ, Arthur G James Canc Hosp, Dept Internal Med, Columbus, OH 43210 USA.
[Kloos, Richard T.] Ohio State Univ, Arthur G James Canc Hosp, Dept Radiol, Columbus, OH 43210 USA.
[Kloos, Richard T.] Ohio State Univ, Richard J Solove Res Inst, Columbus, OH 43210 USA.
[Kloos, Richard T.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Mandel, Susan J.] Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
[Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Stack, Brendan C., Jr.] Univ Arkansas Med Sci, Dept Otolaryngol Head & Neck Surg, Little Rock, AR 72205 USA.
[Terris, David J.] Med Coll Georgia, Dept Otolaryngol Head & Neck Surg, Augusta, GA 30912 USA.
[Thompson, Geoffrey B.] Mayo Clin, Rochester, MN USA.
[Tufano, Ralph P.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA.
[Tuttle, R. Michael] Mem Sloan Kettering Canc Ctr, Dept Endocrinol, New York, NY 10021 USA.
[Udelsman, Robert] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA.
RP Steward, DL (reprint author), Univ Cincinnati, Coll Med, Dept Otolaryngol Head & Neck Surg, 231 Albert B Sabin Way, Cincinnati, OH 45267 USA.
EM david.steward@uc.edu
OI Doherty, Gerard/0000-0002-1685-9552
NR 5
TC 156
Z9 170
U1 2
U2 16
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 NOV
PY 2009
VL 19
IS 11
BP 1153
EP 1158
DI 10.1089/thy.2009.0159
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 515BB
UT WOS:000271440100005
ER
PT J
AU Yagi, H
Parekkadan, B
Suganuma, K
Soto-Gutierrez, A
Tompkins, RG
Tilles, AW
Yarmush, ML
AF Yagi, Hiroshi
Parekkadan, Biju
Suganuma, Kazuhiro
Soto-Gutierrez, Alejandro
Tompkins, Ronald G.
Tilles, Arno W.
Yarmush, Martin L.
TI Long-Term Superior Performance of a Stem Cell/Hepatocyte Device for the
Treatment of Acute Liver Failure
SO TISSUE ENGINEERING PART A
LA English
DT Article
ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; FULMINANT HEPATIC-FAILURE;
BIOARTIFICIAL LIVER; IN-VITRO; PORCINE HEPATOCYTES; SUPPORT-SYSTEMS;
PHASE-I; CELLS; EXPRESSION; RATS
AB Cell-based technologies to support/restore organ function represent one of the most promising avenues in the treatment of acute liver failure (ALF). Recently, mesenchymal stem cells (MSCs) have been reported as a new therapeutic for inflammatory conditions. Here, we demonstrate the efficacy of MSCs, when cocultured with hepatocytes, to provide combination hepatic and antiinflammatory therapy in the setting of ALF. MSCs were shown to have multiple beneficial effects in vitro that were relevant in a therapeutic context, including (1) hepatocellular functional support, (2) secretion of molecules that inhibit hepatocyte apoptosis, and (3) modulation of an acute phase response by hepatocytes cultured in ALF-induced serum. In addition, we show that the MSC secretome is dynamically changed in response to serum exposure from ALF rats. We then conducted a therapeutic trial of liver assist devices (LADs). LADs containing cocultures of MSCs and hepatocytes provided a greater survival benefit compared to other coculture and monocellular control LADs. Treatment with MSC-hepatocyte devices was associated with specific improvements in hepatic functional and histological parameters as well as decreasing inflammatory serum cytokine levels, validating a combined therapeutic effect. Moreover, MSC coculture reduced the overall cell mass of the device by an order of magnitude. These findings demonstrate the importance of nonparenchymal cells in the cellular composition of LADs, and strongly support the integration of MSCs into hepatocyte-coculture-based LADs as a potential destination therapy for ALF.
C1 [Yagi, Hiroshi; Parekkadan, Biju; Soto-Gutierrez, Alejandro; Tompkins, Ronald G.; Tilles, Arno W.; Yarmush, Martin L.] Massachusetts Gen Hosp, Ctr Engn Med, Shriners Hosp Children, Boston, MA 02114 USA.
[Yagi, Hiroshi; Parekkadan, Biju; Soto-Gutierrez, Alejandro; Tompkins, Ronald G.; Tilles, Arno W.; Yarmush, Martin L.] Massachusetts Gen Hosp, Surg Serv, Shriners Hosp Children, Boston, MA 02114 USA.
[Yagi, Hiroshi; Parekkadan, Biju; Soto-Gutierrez, Alejandro; Tompkins, Ronald G.; Tilles, Arno W.; Yarmush, Martin L.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Yagi, Hiroshi; Suganuma, Kazuhiro] Keio Univ, Sch Med, Dept Surg, Tokyo 160, Japan.
RP Yarmush, ML (reprint author), Massachusetts Gen Hosp, Ctr Engn Med, Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA.
EM ireis@sbi.org
FU Shriners Hospitals for Children; National Institutes of Health [R01
DK43371, K08 DK66040]
FX The authors acknowledge the technical assistance of Carley Shulman for
isolation of hepatocytes, Don Poulsen for help with illustrations, and
Bob Crowther for preparing histological slides. We are grateful to Dr.
Richard Hurley and Angela Heiser (Center for Comparative Medicine,
Massachusetts General Hospital, Charlestown, MA) for their assistance in
animal care. Also we thank Dr. Yaakov Nahmias and Dr. Srivatsan Kidambi
(Center for Engineering in Medicine, Massachusetts General Hospital,
Boston, MA) for assistance in Cytochrome P450 assay. This work was
partially supported by grants from Shriners Hospitals for Children and
National Institutes of Health (contract grant numbers: R01 DK43371 and
K08 DK66040).
NR 37
TC 34
Z9 36
U1 0
U2 6
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD NOV
PY 2009
VL 15
IS 11
BP 3377
EP 3388
DI 10.1089/ten.tea.2008.0681
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 519EC
UT WOS:000271746800016
PM 19397469
ER
PT J
AU Dennis, JW
Lau, KS
Demetriou, M
Nabi, IR
AF Dennis, James W.
Lau, Ken S.
Demetriou, Michael
Nabi, Ivan R.
TI Adaptive Regulation at the Cell Surface by N-Glycosylation
SO TRAFFIC
LA English
DT Review
DE N-glycosylation; Golgi; endocytosis; galectins; signaling; computational
modeling
ID GROWTH-FACTOR RECEPTOR; PLASMA-MEMBRANE; BREAST-CANCER; EGF RECEPTORS;
TUMOR-CELLS; ACETYLGLUCOSAMINYLTRANSFERASE-V; REDOX REGULATION;
ENZYMATIC BASIS; DOWN-REGULATION; LIGAND-BINDING
AB The association of receptors and solute transporters with components of the endocytic machinery regulates their surface levels, and thereby cellular sensitivity to cytokines, ligands and nutrients in the extracellular environment. Most transmembrane receptors and solute transporters are glycoproteins, and the Asn (N)-linked oligosaccharides (N-glycans) can bind animal lectins, forming multivalent lattices or microdomains that regulate glycoprotein mobility in the plane of membrane. The N-glycan number (sequence-encoded NXS/T) and context-dependent Golgi N-glycan branching cooperate to regulate glycoprotein affinities for the galectin family of lectins. Galectin-3 binding reduces EGF receptor trafficking into clathrin-coated pits and caveolae lipid rafts, decreases ligand-independent receptor activation and promotes alpha 5 beta 1 integrin remodelling in focal adhesions. N-glycan branching in the medial Golgi increases glycan affinity for galectins, and the Golgi pathway is sensitive to uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) supply, in turn hexosamine pathway metabolites (fructose-6-P, glutamine and acetyl-CoA). Thus, lattice avidity and cellular responsiveness to extracellular cues are regulated in an adaptive manner by metabolism and Golgi modification to glycoproteins. Computational modelling of the hexosamine/Golgi/lattice has provided new insight on cell surface adaptation in cancer and autoimmune disease.
C1 [Dennis, James W.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Dennis, James W.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada.
[Dennis, James W.] Univ Toronto, Dept Lab Med & Pathol, Toronto, ON M5S 1A1, Canada.
[Lau, Ken S.] Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA USA.
[Demetriou, Michael] Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA.
[Demetriou, Michael] Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA.
[Nabi, Ivan R.] Univ British Columbia, Inst Life Sci, Dept Cellular & Physiol Sci, Vancouver, BC V5Z 1M9, Canada.
RP Dennis, JW (reprint author), Mt Sinai Hosp, Samuel Lunenfeld Res Inst, 600 Univ Ave R988, Toronto, ON M5G 1X5, Canada.
EM dennis@mshri.on.ca
RI Dennis, James/E-7268-2013;
OI Lau, Ken/0000-0001-8438-0319
FU Genome Canada through the OGI; CIHR [MOP-79405, MOP-62975, MOP-43938]
FX Research was supported by grants from Genome Canada through the OGI, and
funding from CIHR (MOP-79405 and MOP-62975), and to J. W. D. and I. R.
N. (MOP-43938).
NR 96
TC 98
Z9 100
U1 1
U2 19
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-9219
J9 TRAFFIC
JI Traffic
PD NOV
PY 2009
VL 10
IS 11
BP 1569
EP 1578
DI 10.1111/j.1600-0854.2009.00981.x
PG 10
WC Cell Biology
SC Cell Biology
GA 505CH
UT WOS:000270665300002
PM 19761541
ER
PT J
AU Liu, YY
Liao, SK
Huang, CC
Tsai, YH
Quinn, DA
Li, LF
AF Liu, Yung-Yang
Liao, Shuen-Kuei
Huang, Chung-Chi
Tsai, Ying-Huang
Quinn, Deborah A.
Li, Li-Fu
TI Role for nuclear factor-kappa B in augmented lung injury because of
interaction between hyperoxia and high stretch ventilation
SO TRANSLATIONAL RESEARCH
LA English
DT Article
ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; NECROSIS-FACTOR-ALPHA;
RESPIRATORY-DISTRESS-SYNDROME; CONTROLLED ANIMAL-EXPERIMENT; LOWER TIDAL
VOLUMES; MECHANICAL VENTILATION; ENDOTHELIAL-CELLS; PAI-1 EXPRESSION;
TISSUE FACTOR; NITRIC-OXIDE
AB High-tidal-volume mechanical ventilation and hyperoxia used in patients with acute lung injury (ALI) can induce alveolar coagulopathy and fibrin depositions within the airways. Hyperoxia has been shown to increase ventilator-induced lung injury (VILI), but the mechanisms that regulate interaction between high-tidal-volume mechanical ventilation and hyperoxia are unclear. We hypothesized that mechanical stretch with hyperoxia synergistically augmented neutrophil infiltration and production of plasminogen activator inhibitor-1 (PAI-1) via the nuclear factor-kappa B (NF-kappa B) pathway. C57BL/6 mice (n = 5 per group) were exposed to high-tidal-volume (30mL/kg) or low-tidal-volume (6mL/kg) mechanical ventilation with room air or hyperoxia for 1 to 5h after 2-mu g/g NF-kappa B inhibitor (SN-50) administration. Nonventilated mice with room air or hyperoxia served as control groups. Evans blue dye, myeloperoxidase, electrophoretic mobility shifting of nuclear protein, and inflammatory cytokine were measured. The expression of tumor necrosis factor-alpha (TNF-alpha) and PAI-1 were studied by immunohistochemistry. The addition of hyperoxia to high-tidal-volume ventilation-augmented lung injury, as demonstrated by increased microvascular leak, neutrophil migration into the lung, TNF-alpha and active PAI-1 production, DNA binding activity of NF-kappa B, and NF-kappa B activation. No statistically significant increase of neutrophil infiltration and inflammatory cytokine production was found in the mice ventilated at 6mL/kg using hyperoxia. Hyperoxia-induced augmentation of VILI was attenuated in mice with pharmacologic inhibition of NF-kappa B activity by SN-50. We conclude that hyperoxia increased high-tidal-volume-induced cytokine production and neutrophil influx through activation of the NF-kappa B pathway. (Translational Research 2009; 154:228-240)
C1 [Huang, Chung-Chi; Tsai, Ying-Huang; Li, Li-Fu] Chang Gung Mem Hosp, Div Pulm & Crit Care Med, Tao Yuan 333, Taiwan.
[Liu, Yung-Yang] Taipei Vet Gen Hosp, Chest Dept, Taipei, Taiwan.
[Liu, Yung-Yang] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan.
[Liao, Shuen-Kuei] Chang Gung Univ, Grad Inst Clin Med Sci, Tao Yuan, Taiwan.
[Huang, Chung-Chi; Tsai, Ying-Huang; Li, Li-Fu] Chang Gung Mem Hosp, Dept Resp Therapy, Tao Yuan 333, Taiwan.
[Quinn, Deborah A.] Massachusetts Gen Hosp, Dept Med, Pulm Unit, Boston, MA 02114 USA.
[Quinn, Deborah A.] Massachusetts Gen Hosp, Dept Med, Crit Care Unit, Boston, MA 02114 USA.
[Quinn, Deborah A.] Harvard Univ, Sch Med, Boston, MA USA.
[Quinn, Deborah A.] Novartis Inst Biomed Res, Cambridge, MA USA.
[Huang, Chung-Chi; Tsai, Ying-Huang; Li, Li-Fu] Chang Gung Univ, Taoyuan, Taiwan.
RP Li, LF (reprint author), Chang Gung Mem Hosp, Div Pulm & Crit Care Med, 5 Fu Hsing St, Tao Yuan 333, Taiwan.
EM lfp3434@adm.cgmh.org.tw
FU Chang Gung Medical Research [MRPG361412]
FX Supported by Grant MRPG361412 from the Chang Gung Medical Research
Project.
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U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1931-5244
EI 1878-1810
J9 TRANSL RES
JI Transl. Res.
PD NOV
PY 2009
VL 154
IS 5
BP 228
EP 240
DI 10.1016/j.trsl.2009.06.006
PG 13
WC Medical Laboratory Technology; Medicine, General & Internal; Medicine,
Research & Experimental
SC Medical Laboratory Technology; General & Internal Medicine; Research &
Experimental Medicine
GA 515QA
UT WOS:000271485900003
PM 19840764
ER
PT J
AU Messmer-Blust, A
An, XJ
Li, J
AF Messmer-Blust, Angela
An, Xiaojin
Li, Jian
TI Hypoxia-Regulated Angiogenic Inhibitors
SO TRENDS IN CARDIOVASCULAR MEDICINE
LA English
DT Review
ID ENDOTHELIAL GROWTH-FACTOR; CELL-DEATH; APOPTOSIS; HIF-1-ALPHA;
EXPRESSION; ENDOSTATIN; GENE; VEGF; P53; ANGIOPOIETIN-2
AB The regulation of angio genesis by hypoxia is an essential homeostatic mechanism that depends on a precise balance between positive and negative angiogenic regulatory molecules. Proangiogenic factors are well characterized; however, several in vivo and in vitro studies indicate that there are feedback mechanisms in place to inhibit angiogenesis during hypoxia. Understanding the signaling pathways leading to the negative feedback of angiogenesis will undoubtedly provide important tools to develop novel therapeutic strategies not only to enhance the angiogenic response in coronary artery disease but also to hinder deregulated angiogenesis in tumorigenesis. (Trends Cardiovasc Med 2009;19:252-256) 2009, Elsevier Inc.
C1 [Messmer-Blust, Angela; An, Xiaojin; Li, Jian] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA.
RP Li, J (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, 3 Blackfan Circle, Boston, MA 02115 USA.
EM jli@bidmc.harvard.edu
FU National Institutes of Health [HLR01082837, HL007917]
FX The authors thank Ms. Brittany L. Cully for editing the manuscript. This
work was supported by National Institutes of Health grants HLR01082837
(Li) and T32 training award HL007917 (Messmer-Blust).
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U1 0
U2 3
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1050-1738
J9 TRENDS CARDIOVAS MED
JI Trends Cardiovasc. Med.
PD NOV
PY 2009
VL 19
IS 8
BP 252
EP 256
AR PII S1050-1738(10)00008-3
DI 10.1016/j.tcm.2010.02.006
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 596PY
UT WOS:000277698500002
PM 20447566
ER
PT J
AU Kirchhausen, T
AF Kirchhausen, Tom
TI Imaging endocytic clathrin structures in living cells
SO TRENDS IN CELL BIOLOGY
LA English
DT Review
ID RECEPTOR-MEDIATED ENDOCYTOSIS; MEMBRANE-ASSOCIATED CLATHRIN; INTERACTING
PROTEIN-1 HIP1; POLARIZED EPITHELIAL-CELLS; COATED PITS; FLUORESCENCE
MICROSCOPY; ACTIN CYTOSKELETON; PLASMA-MEMBRANE; ELECTRON
CRYOMICROSCOPY; MAMMALIAN-CELLS
AB Our understanding of the clathrin-dependent endocytic pathway owes much to new visualization techniques. Budding coated pits and clathrin-coated structures are transient molecular machines with distinctive morphological characteristics, and fluorescently labeled versions of a variety of marker proteins have given us a tantalizing glimpse of the dynamics of the system in living cells. Recent live-cell imaging studies have revealed unexpected modes of coat assembly, with distinct kinetics, distinct recruitment of associated proteins, distinct requirements for the participation of actin and its accessory proteins, and apparently distinct mechanisms of membrane deformation. A crucial issue is to connect the events detected by light microscopy with the structures and properties of the molecular constituents. Here, I outline descriptions of coat assembly in different circumstances that are consistent with what is known from X-ray crystallography and electron microscopy.
C1 Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, W Alpert Bldg Room 128,200 Longwood Ave, Boston, MA 02115 USA.
EM kirchhausen@crystal.harvard.edu
FU NIH [GM075252]; NERCE [U54 A1057159]
FX I thank the members of my laboratory, current and past, for helping
create and sustain a stimulating environment. I thank my colleagues,
Stephen C. Harrison in particular, for the opportunity to share good
science and for many enlightening discussions. Our visualization efforts
have been supported by NIH grants GM075252 and NERCE U54 A1057159.
Finally, I apologize to colleagues whose work I have inadvertently
failed to quote.
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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 NOV
PY 2009
VL 19
IS 11
BP 596
EP 605
DI 10.1016/j.tcb.2009.09.002
PG 10
WC Cell Biology
SC Cell Biology
GA 523FM
UT WOS:000272057500006
PM 19836955
ER
PT J
AU Bar, M
AF Bar, Moshe
TI A cognitive neuroscience hypothesis of mood and depression
SO TRENDS IN COGNITIVE SCIENCES
LA English
DT Review
ID TREATMENT-RESISTANT DEPRESSION; DEEP BRAIN-STIMULATION;
POSTTRAUMATIC-STRESS-DISORDER; CONSCIOUS RESTING STATE; MAJOR
DEPRESSION; HIPPOCAMPAL NEUROGENESIS; ANTIDEPRESSANT TREATMENT; NEGATIVE
MOOD; THOUGHT SPEED; MEMORY
AB Although mood has a direct impact on mental and physical health, our understanding of the mechanisms underlying mood regulation is limited. Here, I propose that there is a direct reciprocal relation between the cortical activation of associations and mood regulation, whereby positive mood promotes associative processing, and associative processing promotes positive mood. This relation might stem from an evolutionary pressure for learning and predicting. Along these lines, one can think of mood as a reward mechanism that guides individuals to use their brains in the most productive manner. The proposed framework has many implications, most notably for diagnosing and treating mood disorders such as depression; for elucidating the role of inhibition in the regulation of mood; for contextualizing adult hippocampal neurogenesis; and for a general, non-invasive improvement of well-being.
C1 Harvard Univ, Sch Med, Martinos Ctr, Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
RP Bar, M (reprint author), Harvard Univ, Sch Med, Martinos Ctr, Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA.
EM bar@nmr.mgh.harvard.edu
FU NIH [R01NS050615]
FX I thank L. Barrett, L. Barsalou, D. Carney, J. Denninger, M. Fava, M.
Fenske, D. Gilbert, A. Harvey, M. Mason, J. Matthews, H. Mayberg, K.
Shepherd, C. Thomas and D. Wegner for stimulating discussions,
constructive comments and help with the article. I was supported by NIH
grant R01NS050615.
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PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1364-6613
J9 TRENDS COGN SCI
JI TRENDS COGN. SCI.
PD NOV
PY 2009
VL 13
IS 11
BP 456
EP 463
DI 10.1016/j.tics.2009.08.009
PG 8
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 522MT
UT WOS:000272002900002
PM 19819753
ER
PT J
AU Lerner, LB
Tyson, MD
AF Lerner, Lori B.
Tyson, Mark D.
TI Holmium Laser Applications of the Prostate
SO UROLOGIC CLINICS OF NORTH AMERICA
LA English
DT Article
DE Holmium laser enucleation of the prostate; Holmium; Laser; Prostate;
Surgery; Laser physics
ID RANDOMIZED PROSPECTIVE TRIAL; TRANSURETHRAL RESECTION; LEARNING-CURVE;
CLINICAL-EXPERIENCE; SEXUAL FUNCTION; FOLLOW-UP; ENUCLEATION;
HYPERPLASIA; ADENOMA; ELECTROCAUTERY
AB The high-powered holmium laser is an excellent tool for the surgical treatment of benign prostatic hyperplasia. This article discusses the background of holmium use in the prostate and describes the surgical techniques of holmium laser ablation of the prostate and holmium laser enucleation of the prostate. Operative challenges are reviewed with suggestions as to how to avoid these problems or deal with them when they arise. Surgical outcomes and a thorough literature review are both presented.
C1 [Lerner, Lori B.] Boston Univ, Sch Med, Boston, MA 02043 USA.
[Tyson, Mark D.] Dartmouth Med Sch, Hanover, NH 03755 USA.
[Lerner, Lori B.] VA Boston Healthcare Syst, Urol Sect, Boston, MA USA.
RP Lerner, LB (reprint author), Boston Univ, Sch Med, 12 Water St, Boston, MA 02043 USA.
EM lerner_lori@hotmail.com
FU Lumenis, Inc; Preceptor, Consultant; Boston Scientific, Inc
FX Financial Disclosures: Dr Lerner has the following financial
disclosures: Lumenis, Inc: Preceptor, Consultant; Boston Scientific,
Inc:
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PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0094-0143
J9 UROL CLIN N AM
JI Urol. Clin. N. Am.
PD NOV
PY 2009
VL 36
IS 4
BP 485
EP +
DI 10.1016/j.ucl.2009.07.005
PG 12
WC Urology & Nephrology
SC Urology & Nephrology
GA 617CK
UT WOS:000279258200008
PM 19942047
ER
PT J
AU Lu, B
Maqsodi, B
Yang, W
McMaster, GK
Perner, S
Regan, M
Bubley, GJ
Balk, SP
Rubin, M
Sanda, MG
AF Lu, Bin
Maqsodi, Botoul
Yang, Wen
McMaster, Gary K.
Perner, Sven
Regan, Meredith
Bubley, Glenn J.
Balk, Steven P.
Rubin, Mark
Sanda, Martin G.
TI Detection of TMPRSS2-ERG Fusion Gene Expression in Prostate Cancer
Specimens by a Novel Assay Using Branched DNA
SO UROLOGY
LA English
DT Article
ID OVEREXPRESSION; TRANSCRIPTS
AB OBJECTIVES To develop a novel assay that uses branched DNA technology to measure TMPRSS2-ERG fusion, as genetic rearrangement of TMPRSS2 regulatory sequences and coding sequences of the ERG gene has been detected in nearly half of prostate cancers, but quantitative assays to detect Such TMPRSS2-ERG gene fusion have been limited to real-time polymerase chain reaction (PCR) techniques that rely on reverse transcriptase-based amplification.
METHODS Branched DNA probes were designed to detect TMPRSS2-ERG gene fusion in prostate cancer cell lines. Nonquantitative nested reverse transcription (RT)-PCR and fluorescence in situ hybridization (FISH) were used to ascertain TMPRSS2-ERG gene fusion status in prostate tissues.
RESULTS The branched DNA assay detected TMPRSS2-ERG gene fusion from less than 200 pg of prostate cancer RNA, whereas more than 600 pg of RNA was required for fusion gene detection by one step real-time RT-PCR. In evaluation of clinical prostatectomy specimens, the branched DNA assay showed a concordant detectable fusion signal in all 9 clinical samples that had fusion detected by nested RT-PCR or FISH. Moreover, branched DNA detected gene fusion in 2 of 16 prostate cancer tissue specimens that was not detected by FISH or nested RT-PCR.
CONCLUSIONS Our findings demonstrate a branched DNA assay that is effective for detection of TMPRSS2-ERG gene fusion in prostate cancer clinical specimens, thus providing an alternative method to ascertain TMPRSS2-ERG gene fusion in human prostate cancer tissue. UROLOGY 74: 1156-1162, 2009. (C) 2009 Elsevier Inc.
C1 [Sanda, Martin G.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Urol, Boston, MA 02115 USA.
Affymetrix Inc, Fremont, CA USA.
Cornell Univ, Dept Pathol & Lab Med, New York, NY 10021 USA.
Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA.
Univ Hosp Ulm, Dept Pathol, Ulm, Germany.
RP Sanda, MG (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Urol, Rabb 440,330 Brookline Ave, Boston, MA 02115 USA.
EM msanda@bidmc.harvard.edu
RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015;
OI Rubin, Mark/0000-0002-8321-9950
FU NIH-NCI Early Detection Research Network [UO1-CA11391]
FX Funded by NIH-NCI Early Detection Research Network Grant UO1-CA11391.
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U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0090-4295
J9 UROLOGY
JI Urology
PD NOV
PY 2009
VL 74
IS 5
BP 1156
EP 1161
DI 10.1016/j.urology.2009.01.087
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 522IZ
UT WOS:000271992400080
PM 19647299
ER
PT J
AU Johnson, ML
Crown, W
Martin, BC
Dormuth, CR
Siebert, U
AF Johnson, Michael L.
Crown, William
Martin, Bradley C.
Dormuth, Colin R.
Siebert, Uwe
TI Good Research Practices for Comparative Effectiveness Research: Analytic
Methods to Improve Causal Inference from Nonrandomized Studies of
Treatment Effects Using Secondary Data Sources: The ISPOR Good Research
Practices for Retrospective Database Analysis Task Force Report-Part III
SO VALUE IN HEALTH
LA English
DT Article
DE causal inference; comparative effectiveness; nonrandomized studies;
research methods; secondary databases
ID MARGINAL STRUCTURAL MODELS; INSTRUMENTAL VARIABLE REGRESSION; PROPENSITY
SCORE METHODS; SAMPLE SELECTION; SENSITIVITY-ANALYSIS; HEALTH; OUTCOMES;
BIAS; HETEROGENEITY; ADJUSTMENTS
AB Objectives:
Most contemporary epidemiologic studies require complex analytical methods to adjust for bias and confounding. New methods are constantly being developed, and older more established methods are yet appropriate. Careful application of statistical analysis techniques can improve causal inference of comparative treatment effects from nonrandomized studies using secondary databases. A Task Force was formed to offer a review of the more recent developments in statistical control of confounding.
Methods:
The Task Force was commissioned and a chair was selected by the ISPOR Board of Directors in October 2007. This Report, the third in this issue of the journal, addressed methods to improve causal inference of treatment effects for nonrandomized studies.
Results:
The Task Force Report recommends general analytic techniques and specific best practices where consensus is reached including: use of stratification analysis before multivariable modeling, multivariable regression including model performance and diagnostic testing, propensity scoring, instrumental variable, and structural modeling techniques including marginal structural models, where appropriate for secondary data. Sensitivity analyses and discussion of extent of residual confounding are discussed.
Conclusions:
Valid findings of causal therapeutic benefits can be produced from nonrandomized studies using an array of state-of-the-art analytic techniques. Improving the quality and uniformity of these studies will improve the value to patients, physicians, and policymakers worldwide.
C1 [Johnson, Michael L.] Univ Houston, Coll Pharm, Dept Clin Sci & Adm, Houston, TX 77030 USA.
[Johnson, Michael L.] Michael E DeBakey VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Dept Vet Affairs, Houston, TX USA.
[Crown, William] i3 Innovus, Waltham, MA USA.
[Martin, Bradley C.] Univ Arkansas Med Sci, Div Pharmaceut Evaluat & Policy, Coll Pharm, Little Rock, AR 72205 USA.
[Dormuth, Colin R.] Univ British Columbia, Dept Anesthesiol Pharmacol & Therapeut, Vancouver, BC V5Z 1M9, Canada.
[Siebert, Uwe] Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Informat Syst & Hlth Technol Asses, Hall In Tirol, Austria.
[Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA.
[Siebert, Uwe] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Dormuth, Colin R.] Therapeut Initiat, Pharmacoepidemiol Grp, Vancouver, BC, Canada.
RP Johnson, ML (reprint author), Univ Houston, Coll Pharm, Dept Clin Sci & Adm, Houston, TX 77030 USA.
EM mikejohnson@uh.edu
FU Department of Veteran Affairs [HFP020-90]
FX This work was supported in part by the Department of Veteran Affairs
Health Services Research and Development grant HFP020-90. The views
expressed are those of the authors and do not necessarily reflect the
views of the Department of Veteran Affairs.
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PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-3015
EI 1524-4733
J9 VALUE HEALTH
JI Value Health
PD NOV-DEC
PY 2009
VL 12
IS 8
BP 1062
EP 1073
DI 10.1111/j.1524-4733.2009.00602.x
PG 12
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA 515TH
UT WOS:000271495300005
PM 19793071
ER
PT J
AU Chami, HA
Keyes, MJ
Vita, JA
Mitchell, GF
Larson, MG
Fan, SX
Vasan, RS
O'Connor, GT
Benjamin, EJ
Gottlieb, DJ
AF Chami, Hassan A.
Keyes, Michelle J.
Vita, Joseph A.
Mitchell, Gary F.
Larson, Martin G.
Fan, Shuxia
Vasan, Ramachandran S.
O'Connor, George T.
Benjamin, Emelia J.
Gottlieb, Daniel J.
TI Brachial artery diameter, blood flow and flow-mediated dilation in
sleep-disordered breathing
SO VASCULAR MEDICINE
LA English
DT Article
DE epidemiology; obstructive sleep apnea; vascular endothelium; vascular
remodeling
ID POSITIVE AIRWAY PRESSURE; VASCULAR ENDOTHELIAL FUNCTION; HEART HEALTH;
CARDIOVASCULAR-DISEASE; SHEAR-STRESS; APNEA; ASSOCIATION; COMMUNITY;
ATHEROSCLEROSIS; HYPERTENSION
AB Clinic-based, case-control studies linked sleep-disordered breathing (SDB) to markers of endothelial dysfunction. We attempted to validate this association in a large community-based sample, and evaluate the relation of SDB to arterial diameter and peripheral blood flow. This community-based, cross-sectional observational study included 327 men and 355 women, aged 42-83 years, from the Framingham Heart Study site of the Sleep Heart Health Study. The polysomnographically derived apnea-hypopnea index and the hypoxemia index (percent sleep time with oxyhemoglobin saturation below 90%) were used to quantify the severity of SDB. Brachial artery ultrasound measurements included baseline diameter, percent flow-mediated dilation, and baseline and hyperemic flow velocity and volume. The baseline brachial artery diameter was significantly associated with both the apnea-hypopnea index and the hypoxemia index. The association was diminished by adjustment for body mass index, but remained significant for the apnea-hypopnea index. Age-, sex-, race-and body mass index-adjusted mean diameters were 4.32, 4.33, 4.33, 4.56, 4.53 mm for those with apnea-hypopnea index < 1.5, 1.5-4.9, 5-14.9, 15-29.9, = 30, respectively; p = 0.03. Baseline flow measures were associated with the apnea-hypopnea index but this association was non-significant after adjusting for body mass index. No significant association was observed between measures of SDB and percent flow-mediated dilation or hyperemic flow in any model. In conclusion, this study supports a moderate association of SDB and larger baseline brachial artery diameter, which may reflect SDB-induced vascular remodeling. This study does not support a link between SDB and endothelial dysfunction as measured by brachial artery flow-mediated dilation.
C1 [Chami, Hassan A.] Boston Univ, Sch Med, Ctr Pulm, Dept Med, Boston, MA 02118 USA.
[Chami, Hassan A.; Gottlieb, Daniel J.] VA Boston Healthcare Syst, Boston, MA USA.
[Keyes, Michelle J.; Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Math & Stat, Boston, MA 02118 USA.
[Keyes, Michelle J.; Larson, Martin G.; Fan, Shuxia; Vasan, Ramachandran S.; Benjamin, Emelia J.] NHLBIs Framingham Heart Study, Framingham, MA USA.
[Vita, Joseph A.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
RP Chami, HA (reprint author), Boston Univ, Sch Med, Ctr Pulm, Dept Med, 715 Albany St,R-304, Boston, MA 02118 USA.
EM hchami@bu.edu
OI Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254;
Chami, Hassan/0000-0002-9239-2528; O'Connor, George/0000-0002-6476-3926;
Ramachandran, Vasan/0000-0001-7357-5970; Benjamin,
Emelia/0000-0003-4076-2336
FU National Heart, Lung and Blood Institute's Framingham Heart Study
[N01-HC 25195, HL60040, HL70100, K24-HL-04334]; National Heart, Lung and
Blood Institute's Sleep Heart Health Study [U01-HL53941]; Donald W.
Reynolds Foundation
FX This work was supported by the National Heart, Lung and Blood
Institute's Framingham Heart Study N01-HC 25195, HL60040, HL70100,
K24-HL-04334(RSV), the National Heart, Lung and Blood Institute's Sleep
Heart Health Study U01-HL53941 and the Donald W. Reynolds Foundation.
Cardiovascular Engineering provided image capture software.
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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 NOV
PY 2009
VL 14
IS 4
BP 351
EP 360
DI 10.1177/1358863X09105132
PG 10
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 503NZ
UT WOS:000270544900008
PM 19808720
ER
PT J
AU Islam, MA
Rosenfield, K
Maree, AO
Patel, PM
Jaff, MR
AF Islam, M. Ashequl
Rosenfield, Kenneth
Maree, Andrew O.
Patel, Pranav M.
Jaff, Michael R.
TI Percutaneous revascularization of occluded renal arteries in the setting
of acute renal failure
SO VASCULAR MEDICINE
LA English
DT Article
DE renal angioplasty; stenting
ID ATHEROSCLEROTIC RENOVASCULAR DISEASE; DEPENDENT ISCHEMIC NEPHROPATHY;
NATURAL-HISTORY; DIALYSIS; STENOSIS; HYPERTENSION; MANAGEMENT;
OCCLUSION; RECANALIZATION; INSUFFICIENCY
AB We report the case of a 60-year-old patient with acute renal failure and occluded bilateral renal arteries presenting with acute pulmonary edema and non-ST segment elevation myocardial infarction. The patient required renal replacement therapy with hemodialysis and was subsequently successfully treated with bilateral renal artery stent placement. Marked improvement in renal function was noted within 1 week with freedom from the need for renal replacement therapy at 4 months of follow-up.
C1 [Rosenfield, Kenneth; Jaff, Michael R.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Islam, M. Ashequl] Baystate Med Ctr, Div Cardiol, Springfield, MA 01199 USA.
[Rosenfield, Kenneth] Massachusetts Gen Hosp, Div Cardiovasc Med, Boston, MA 02114 USA.
[Maree, Andrew O.] Boston Univ, Med Ctr, Div Cardiol, Boston, MA 02215 USA.
[Patel, Pranav M.] Univ Calif Irvine, Div Cardiol, Irvine, CA USA.
[Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Boston, MA 02114 USA.
RP Jaff, MR (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA.
EM mjaff@partners.org
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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 NOV
PY 2009
VL 14
IS 4
BP 365
EP 369
DI 10.1177/1358863X09103200
PG 5
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 503NZ
UT WOS:000270544900010
PM 19808722
ER
PT J
AU Zamani, P
Kaufman, J
Kinlay, S
AF Zamani, Payman
Kaufman, James
Kinlay, Scott
TI Ischemic steal syndrome following arm arteriovenous fistula for
hemodialysis
SO VASCULAR MEDICINE
LA English
DT Article
DE angioplasty; fistula; gangrene; ischemia; peripheral vascular diseases;
subclavian artery; vascular fistula
ID REVASCULARIZATION-INTERVAL LIGATION; VASCULAR ACCESS; DIALYSIS ACCESS;
MONOMELIC NEUROPATHY; HAND ISCHEMIA; LIMB SALVAGE; EXTREMITY;
ANGIOACCESS; MAINTENANCE; MANAGEMENT
AB Arteriovenous fistulae in the arm are commonly used for hemodialysis in end-stage renal disease. Although physiological steal with reverse flow in the artery distal to the fistula is common, hand ischemia or infarction are rare. The ischemic steal syndrome (hand or forearm ischemia) is usually a result of arterial disease proximal or distal to the fistula and/or poor collateral supply to the hand. The diagnosis is primarily clinical; however, markedly reduced digital pressures and pulse volume recordings support the diagnosis. Management requires imaging for focal stenoses or disease in arteries proximal and distal to the fistula from the aorta to the hand. We present a case caused by subclavian artery occlusion that was initially missed due to focusing investigation only on the fistula. We describe the percutaneous treatments and surgical revisions that attempt to restore flow to the hand without compromising the fistula.
C1 [Kinlay, Scott] VA Boston Healthcare Syst, Div Cardiovasc, Cardiac Catheterizat Lab & Vasc Med, W Roxbury, MA 02132 USA.
[Zamani, Payman; Kinlay, Scott] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Zamani, Payman; Kinlay, Scott] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Kaufman, James] VA Boston Healthcare Syst, Div Renal, W Roxbury, MA 02132 USA.
[Kaufman, James] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Kinlay, Scott] VA Boston Healthcare Syst, Div Cardiovasc, W Roxbury, MA 02132 USA.
RP Kinlay, S (reprint author), VA Boston Healthcare Syst, Div Cardiovasc, Cardiac Catheterizat Lab & Vasc Med, 1400 VFW Pkwy, W Roxbury, MA 02132 USA.
EM scott.kinlay@va.gov
NR 33
TC 11
Z9 13
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 NOV
PY 2009
VL 14
IS 4
BP 371
EP 376
DI 10.1177/1358863X09102293
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 503NZ
UT WOS:000270544900011
PM 19808723
ER
PT J
AU Honings, J
Gaissert, HA
Ruangchira-Urai, R
Wain, JC
Wright, CD
Mathisen, DJ
Mark, EJ
AF Honings, Jimmie
Gaissert, Henning A.
Ruangchira-Urai, Ruchira
Wain, John C.
Wright, Cameron D.
Mathisen, Douglas J.
Mark, Eugene J.
TI Pathologic characteristics of resected squamous cell carcinoma of the
trachea: prognostic factors based on an analysis of 59 cases
SO VIRCHOWS ARCHIV
LA English
DT Article
DE Trachea; Squamous cell carcinoma; Airway resection; Pathologic staging;
Histologic features of invasion
ID TUMORS
AB While squamous cell carcinoma (SCC) is the most common tracheal malignancy, few reports describe the pathologic considerations that may guide intraoperative decisions and prognostic assessment. We reviewed 59 tracheal SCC treated between 1985 and 2008 by segmental resection of the trachea, including resection of the carina in 24% and inferior larynx in 14%. We classified these tumors by grading histologic differentiation and microscopic features used in SCC of other sites. Of 59 tumors, 24% (14 of 59) were well differentiated, 49% (29 of 59) were moderately differentiated, and 27% (16 of 59) were poorly differentiated. Unfavorable prognostic factors were tumor extension into the thyroid gland (all of five so-afflicted patients died of tumor progression within 3 years) and lymphatic invasion (mean survival 4.6 versus 7.6 years). Keratinization, dyskeratosis, acantholysis, necrosis, and tumor thickness did not predict prognosis. As surgical resection is the only curative treatment; the surgeon should establish clean lines of resection using, as appropriate, intraoperative frozen section. The pathologist can provide additional important prognostic information, including tumor differentiation and extent, invasion of surgical margins, and extension into the thyroid.
C1 [Honings, Jimmie; Gaissert, Henning A.; Wain, John C.; Wright, Cameron D.; Mathisen, Douglas J.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA.
[Honings, Jimmie; Gaissert, Henning A.; Wain, John C.; Wright, Cameron D.; Mathisen, Douglas J.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Ruangchira-Urai, Ruchira; Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Gaissert, HA (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, 32 Fruit St,Blake 1570, Boston, MA 02114 USA.
EM hgaissert@partners.org
RI Honings, Jimmie/B-3639-2016
OI Honings, Jimmie/0000-0001-5077-3472
NR 7
TC 6
Z9 6
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0945-6317
J9 VIRCHOWS ARCH
JI Virchows Arch.
PD NOV
PY 2009
VL 455
IS 5
BP 423
EP 429
DI 10.1007/s00428-009-0843-6
PG 7
WC Pathology
SC Pathology
GA 514RQ
UT WOS:000271413100003
PM 19838727
ER
PT J
AU Butt, MU
Velmahos, GC
Zacharias, N
Alam, HB
de Moya, M
King, DR
AF Butt, Muhammad U.
Velmahos, George C.
Zacharias, Nikos
Alam, Hasan B.
de Moya, Marc
King, David R.
TI Adhesional Small Bowel Obstruction in the Absence of Previous
Operations: Management and Outcomes
SO WORLD JOURNAL OF SURGERY
LA English
DT Article
ID INTESTINAL-OBSTRUCTION; SURGERY; BAND
AB Background The majority of small bowel obstructions (SBO) are the result of adhesions caused by a previous abdominal operation. On rare occasions, adhesional SBO occurs in the absence of such an operation. Our objective was to describe the management, findings, and outcomes of unexplained adhesional SBO (UA-SBO) and examine whether preoperative diagnostic uncertainty leads to delays in therapy and complications.
Methods The medical records of all adhesional SBO patients admitted to the Massachusetts General Hospital between January 1, 1997 and December 31, 2007 were screened. UA-SBO records were reviewed in detail. Each UA-SBO patient was matched with an adhesional SBO patient with abdominal surgical history (SH-SBO) according to gender, age (+/- 7 years), white blood cell count (+/- 3000/mm(3)), time interval from the onset of symptoms to the time of admission (+/- 24 h), and year of admission (+/- 4 years). Outcomes included time from admission to operation, morbidity, mortality, and length of hospital stay.
Results Of 1,036 patients with adhesional SBO, 34 (3.3%) had UA-SBO. Adhesiolysis was sufficient in 31 patients, whereas 3 required an enterectomy. UA-SBO patients were similar in terms of demographics, clinical presentation, and initial laboratory tests with SH-SBO patients. There was no difference in any of the outcomes between the two groups.
Conclusions In this study of UA-SBO, diagnostic delays were not found and patient outcomes were similar to those of patients with SH-SBO.
C1 [Butt, Muhammad U.; Velmahos, George C.; Zacharias, Nikos; Alam, Hasan B.; de Moya, Marc; King, David R.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
[Butt, Muhammad U.; Velmahos, George C.; Zacharias, Nikos; Alam, Hasan B.; de Moya, Marc; King, David R.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA.
EM gvelmahos@partners.org
OI King, David/0000-0003-1028-1478
NR 10
TC 5
Z9 6
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-2313
J9 WORLD J SURG
JI World J.Surg.
PD NOV
PY 2009
VL 33
IS 11
BP 2368
EP 2371
DI 10.1007/s00268-009-0200-6
PG 4
WC Surgery
SC Surgery
GA 505HE
UT WOS:000270682200016
PM 19756860
ER
PT J
AU Nellore, A
Fishman, J
AF Nellore, Anoma
Fishman, Jay
TI Pandemic Swine Flu 2009
SO XENOTRANSPLANTATION
LA English
DT Editorial Material
ID INFLUENZA-A VIRUSES; TRANSPLANT RECIPIENTS; VACCINATION; RESPONSES; PIGS
C1 [Nellore, Anoma; Fishman, Jay] Massachusetts Gen Hosp, Transplant Infect Dis Program, Boston, MA 02114 USA.
RP Nellore, A (reprint author), Massachusetts Gen Hosp, Transplant Infect Dis Program, 55 Fruit St,GRJ 504, Boston, MA 02114 USA.
EM jfishman@partners.org
NR 21
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0908-665X
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD NOV-DEC
PY 2009
VL 16
IS 6
BP 463
EP 465
DI 10.1111/j.1399-3089.2009.00559.x
PG 3
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA 535YH
UT WOS:000273007400001
PM 20042043
ER
PT J
AU Schuetz, C
Lee, KM
Eliades, P
Machaidze, Z
Tokiya, A
Bautista, P
Yagi, Y
Deng, SP
Markmann, JF
AF Schuetz, Christian
Lee, Kang Mi
Eliades, Philip
Machaidze, Zurab
Tokiya, Abe
Bautista, Pinky
Yagi, Yukako
Deng, Shaoping
Markmann, James F.
TI Diabetogenic immunosuppression: effects of drugs commonly used in islet
transplantation
SO XENOTRANSPLANTATION
LA English
DT Meeting Abstract
CT Joint Meeting of the
International-Pancreas-and-Islet-Transplant-Association/International-Xe
notransplanation-Association
CY OCT 12-16, 2009
CL Venice, ITALY
SP Absorber AB, Astellas Pharma, Biorep Technol, Biotest Italia SRL, Natl Transplant Ctr, Covidien, Daibetes Wellness & Res Fdn, Ethicon, Fond L Incremento Trapianti Organo E Di Tessuti, Genzyne Transplant Europe, GTI ITALIA SRL, Johnson & Johnson Med, Juvenile Diabetes Res Fdn, Lagitre s r l, Novartis, One Lambda Inc, Prodo Lab, Roche, Serva Electrophores GMBH, SRT Transplantat Reg Syst, Storz Med, Trumpf MRD Italia, VitaCyte LLC, Wisepress, Wyeth Italia, Zaccanti SPA
C1 Massachusetts Gen Hosp, Transplant Surg Ctr, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RI Schuetz, Christian/K-5234-2013
OI Schuetz, Christian/0000-0002-6828-4543
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0908-665X
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD NOV-DEC
PY 2009
VL 16
IS 6
BP 541
EP 542
PG 2
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA 535YH
UT WOS:000273007400014
ER
PT J
AU Wong, J
Sibani, S
Lokko, NN
LaBaer, J
Anderson, KS
AF Wong, Jessica
Sibani, Sahar
Lokko, Naa Norkor
LaBaer, Joshua
Anderson, Karen S.
TI Rapid detection of antibodies in sera using multiplexed self-assembling
bead arrays
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE Autoantibodies; Tumor antigen; Biomarker; Luminex; Multiplex
immunoassay; EBV
ID EPSTEIN-BARR-VIRUS; PROTEIN MICROARRAYS; BREAST-CANCER; NEUTRALIZING
EPITOPES; IMMUNOLOGICAL STATUS; RESPONSES; ASSAY; IMMUNOASSAY;
OPTIMIZATION; DIAGNOSIS
AB Rapid detection of antibody immunity in serum or plasma, whether to pathogenic antigens, tumor antigens, or autoimmune antigens, is critical for diagnosis, monitoring, and biomarker assessment of the immune response. Individual or multiplexed ELISAs that use purified recombinant proteins are dependent on a prior! protein purification, a labor-intensive process that may take months to obtain proteins of sufficient purity and stability for serologic assays. We developed a programmable multiplexed immunoassay for the rapid monitoring of humoral immunity using the Luminex suspension bead array platform. In this approach, epitope-tagged antigens (GST- or FLAG-tagged) are expressed using in vitro transcription and translation, and captured onto anti-epitope-coupled Luminex SeroMap beads. The antigen-loaded beads are mixed, serum is added, and human IgG is detected with standard secondary detection reagents. By coupling high-throughput DNA preparation of cDNA ORFs with antigen expression/capture, we demonstrate that 71/72 (98.6%) of GST-tagged proteins can be expressed and specifically detected on the bead ELISA. Detection of antibodies to the test viral antigen EBNA-I in human sera is highly reproducible, with intra-assay variation of 3-8%, inter-assay variation of 5%, and with stability over I I months. The specificity and limits of detection of the bead ELISAs for the tumor antigen p53 are comparable to both standard protein ELISAs and plate-based programmable (RAPID) ELISAs, and are also comparable to the detection of directly-conjugated p53 protein. Multiplexing a panel of analytes does not impair the sensitivity of antibody detection. Immunity to a panel of EBV-derived antigens (EBNA-1, EBNA-3A, EBNA-3B, and LMP-2) is specifically and differentially detected within healthy donor sera. This method allows for rapid conversion of ORFeome-derived cDNAs to a multiplexed bead ELISA to detect antibody immunity to both infectious and tumor antigens. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Wong, Jessica; Lokko, Naa Norkor; Anderson, Karen S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA.
[Sibani, Sahar; LaBaer, Joshua] Harvard Univ, Sch Med, Harvard Inst Prote, Cambridge, MA 02138 USA.
[Anderson, Karen S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Anderson, KS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, HIM416,77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM kanderson@partners.org
FU NCI Early Detection Research Network [5U01CA117374-02]
FX We thank Dr. Niroshan Ramachandran for assistance in setting up the
Luminex system. This study was supported by a research grant from the
NCI Early Detection Research Network 5U01CA117374-02.
NR 30
TC 36
Z9 37
U1 0
U2 18
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD OCT 31
PY 2009
VL 350
IS 1-2
BP 171
EP 182
DI 10.1016/j.jim.2009.08.013
PG 12
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 519JA
UT WOS:000271761100020
PM 19732778
ER
PT J
AU Kotagal, M
Lee, P
Habiyakare, C
Dusabe, R
Kanama, P
Epino, HM
Rich, ML
Farmer, PE
AF Kotagal, Meera
Lee, Patrick
Habiyakare, Caste
Dusabe, Raymond
Kanama, Philibert
Epino, Henry M.
Rich, Michael L.
Farmer, Paul E.
TI Quality Improvement Report Improving quality in resource poor settings:
observational study from rural Rwanda
SO BRITISH MEDICAL JOURNAL
LA English
DT Article
ID HEALTH; PROGRAM
AB Problem Hospitals in rural Africa, such as in Rwanda, often lack electricity, supplies, and staff. In our setting, basic care processes, such monitoring vital signs, giving drugs, and laboratory testing, were performed unreliably, resulting in delays in treatment owing to lack of information needed for clinical decision making.
Design Simple quality improvement tools, including plan-do-study-act cycles and process maps, were used to improve system level processes in a stepwise fashion; resources were augmented where necessary.
Setting 50 bed district hospital in rural Rwanda.
Measurement of improvement Three key indicators ( percentage of vital signs taken by 9 am, drugs given as prescribed, and laboratory tests performed and documented) were tracked daily. Data were collected from a random sample of 25 charts from six inpatient wards.
Strategy for change Our intervention had two components: staff education on quality improvement and routine care processes, and stepwise implementation of system level interventions. Real time performance data were reported to staff daily, with a goal of 95% performance for each indicator within two weeks. A Rwandan quality improvement team was trained to run the hospital's quality improvement initiatives.
Effects of changes Within two weeks, all indicators achieved the 95% goal. The data for the three objectives were analysed by using time series analysis. Progress was compared against time by using run chart rules for statistical significance of improvement, showing significant improvement for all indicators. Doctors and nurses subjectively reported improved patient care and higher staff morale.
Lessons learnt Four lessons are highlighted: making data visible and using them to inform subsequent interventions can promote change in resource poor settings; improvements can be made in advance of resource inputs, but sustained change in resource poor settings requires additional resources; local leadership is essential for success; and early successes were crucial for encouraging staff and motivating buy-in.
C1 [Kotagal, Meera; Lee, Patrick; Epino, Henry M.; Farmer, Paul E.] Partners Hlth, Boston, MA 02215 USA.
[Farmer, Paul E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA.
[Lee, Patrick] Newton Wellesley Hosp, Newton, MA 02462 USA.
[Habiyakare, Caste; Dusabe, Raymond; Kanama, Philibert] Partners Hlth, Rwanda Minist Hlth, Kirehe Dist Hosp, Kigali, Rwanda.
[Epino, Henry M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Farmer, Paul E.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA.
RP Kotagal, M (reprint author), Univ Washington, Dept Surg, Box 356410, Seattle, WA 98195 USA.
EM mkotagal@post.harvard.edu
FU Harvard University Committee on General Scholarships; Sinclair Kennedy
travelling fellowship
FX Harvard University Committee on General Scholarships; MK received a
Sinclair Kennedy travelling fellowship.
NR 20
TC 14
Z9 14
U1 1
U2 7
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0959-8146
J9 BRIT MED J
JI Br. Med. J.
PD OCT 30
PY 2009
VL 339
AR b3488
DI 10.1136/bmj.b3488
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 514AQ
UT WOS:000271366100001
PM 19880528
ER
PT J
AU Srinivasan, L
Sasaki, Y
Calado, DP
Zhang, BC
Paik, JH
DePinho, RA
Kutok, JL
Kearney, JF
Otipoby, KL
Rajewsky, K
AF Srinivasan, Lakshmi
Sasaki, Yoshiteru
Calado, Dinis Pedro
Zhang, Baochun
Paik, Ji Hye
DePinho, Ronald A.
Kutok, Jeffrey L.
Kearney, John F.
Otipoby, Kevin L.
Rajewsky, Klaus
TI PI3 Kinase Signals BCR-Dependent Mature B Cell Survival
SO CELL
LA English
DT Article
ID NF-KAPPA-B; FOXO TRANSCRIPTION FACTORS; CLASS-SWITCH RECOMBINATION;
ANTIGEN RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; MARGINAL ZONE; POSITIVE
SELECTION; CRITICAL ROLES; LYMPHOCYTES; ACTIVATION
AB Previous work has shown that mature B cells depend upon survival signals delivered to the cells by their antigen receptor (BCR). To identify the molecular nature of this survival signal, we have developed a genetic approach in which ablation of the BCR is combined with the activation of specific, BCR dependent signaling cascades in mature B cells in vivo. Using this system, we provide evidence that the survival of BCR deficient mature B cells can be rescued by a single signaling pathway downstream of the BCR, namely PI3K signaling, with the FOXO1 transcription factor playing a central role.
C1 [Srinivasan, Lakshmi; Sasaki, Yoshiteru; Calado, Dinis Pedro; Zhang, Baochun; Otipoby, Kevin L.; Rajewsky, Klaus] Harvard Univ, Sch Med, Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Srinivasan, Lakshmi; Sasaki, Yoshiteru; Calado, Dinis Pedro; Zhang, Baochun; Otipoby, Kevin L.; Rajewsky, Klaus] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Paik, Ji Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kutok, Jeffrey L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Kearney, John F.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
RP Rajewsky, K (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
EM rajewsky@idi.harvard.edu
OI Zhang, Baochun/0000-0003-1759-1161
FU NIH [AI054636, CA092625, AI014782-31]; Leukemia and Lymphoma Society;
European Union through MUGEN; Hematology and Transfusion Medicine at
Harvard Medical School; Portuguese Foundation for Science and
Technology; Robert A. and Renee E. Belfer Foundation
FX We thank D. Ghitza, A. Pellerin, A. Monti, A. Tetreault, J. Grundy, J.
Wang, J. Xia and W. F. Jia for expert technical assistance; E. Derudder
for reagents; all Rajewsky lab members for discussions; and M. Janz for
critical reading of the manuscript; A. Klippel for the MP110* cDNA; and
K. Kaibuchi for Rac1DA cDNA. K. R. is supported by NIH grants AI054636
and CA092625, the Leukemia and Lymphoma Society and the European Union
through MUGEN; L. S. by the T32 training grant of the Joint Program in
Hematology and Transfusion Medicine at Harvard Medical School; J. F. K.
by NIH grant AI014782-31; D. P. C. by a postdoctoral fellowship from the
Portuguese Foundation for Science and Technology (FCT-MCES); B. Z. by a
postdoctoral fellowship of the Leukemia and Lymphoma Society; and RAD by
the NIH and the Robert A. and Renee E. Belfer Foundation.
NR 58
TC 271
Z9 276
U1 0
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD OCT 30
PY 2009
VL 139
IS 3
BP 573
EP 586
DI 10.1016/j.cell.2009.08.041
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 512ON
UT WOS:000271259600021
PM 19879843
ER
PT J
AU Palijan, A
Fernandes, I
Bastien, Y
Tang, LQ
Verway, M
Kourelis, M
Tavera-Mendoza, LE
Li, Z
Bourdeau, V
Mader, S
Yang, XJ
White, JH
AF Palijan, Ana
Fernandes, Isabelle
Bastien, Yolande
Tang, Liqun
Verway, Mark
Kourelis, Maria
Tavera-Mendoza, Luz E.
Li, Zhi
Bourdeau, Veronique
Mader, Sylvie
Yang, Xiang Jiao
White, John H.
TI Function of Histone Deacetylase 6 as a Cofactor of Nuclear Receptor
Coregulator LCoR
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BREAST-CANCER CELLS; TRANSCRIPTIONAL REPRESSION; HORMONE-RECEPTORS;
GENE-EXPRESSION; CO-REPRESSOR; N-COR; COREPRESSOR; RECRUITMENT; HDAC6;
ALPHA
AB Ligand-dependent corepressor LCoR was identified as a protein that interacts with the estrogen receptor alpha(ER alpha) ligand binding domain in a hormone-dependent manner. LCoR also interacts directly with histone deacetylase 3 (HDAC3) and HDAC6. Notably, HDAC6 has emerged as a marker of breast cancer prognosis. However, although HDAC3 is nuclear, HDAC6 is cytoplasmic in many cells. We found that HDAC6 is partially nuclear in estrogen-responsive MCF7 cells, colocalizes with LCoR, represses transactivation of estrogen- inducible reporter genes, and augments corepression by LCoR. In contrast, no repression was observed upon HDAC6 expression in COS7 cells, where it is exclusively cytoplasmic. LCoR binds to HDAC6 in vitro via a central domain, and repression by LCoR mutants lacking this domain was attenuated. Kinetic chromatin immunoprecipitation assays revealed hormone-dependent recruitment of LCoR to promoters of ER alpha-induced target genes in synchrony with ER alpha. HDAC6 was also recruited to these promoters, and repeat chromatin immunoprecipitation experiments confirmed the corecruitment of LCoR with ER alpha and with HDAC6. Remarkably, however, although we find evidence for corecruitment of LCoR and ER alpha on genes repressed by the receptor, LCoR and HDAC6 failed to coimmunoprecipitate, suggesting that they are part of distinct complexes on these genes. Although small interfering RNA-mediated knockdown of LCoR or HDAC6 augmented expression of an estrogen-sensitive reporter gene in MCF7 cells, unexpectedly their ablation led to reduced expression of some endogenous estrogen target genes. Taken together, these data establish that HDAC6 can function as a cofactor of LCoR but suggest that they may act in enhance expressing some target genes.
C1 [Palijan, Ana; Fernandes, Isabelle; Bastien, Yolande; Tang, Liqun; Verway, Mark; Kourelis, Maria; Li, Zhi; White, John H.] McGill Univ, Dept Physiol, Montreal, PQ H3G 1Y6, Canada.
[Yang, Xiang Jiao; White, John H.] McGill Univ, Dept Med, Montreal, PQ H3G 1Y6, Canada.
[Tavera-Mendoza, Luz E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
[Bourdeau, Veronique; Mader, Sylvie] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada.
[Bourdeau, Veronique; Mader, Sylvie] Univ Montreal, Dept Biochem, Montreal, PQ H3C 3J7, Canada.
RP White, JH (reprint author), McGill Univ, Dept Physiol, 3655 Drummond St, Montreal, PQ H3G Y6, Canada.
EM john.white@mcgill.ca
OI White, John/0000-0002-4785-2687
FU Canadian Institutes of Health [MT-11704]; Canadian Cancer Society
[018362]
FX This work was supported by Canadian Institutes of Health Research Grant
MT-11704 ( to J.H.W.) and a grant from the Canadian Cancer Society
(018362 to X.J.Y.).
NR 52
TC 26
Z9 28
U1 2
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 30
PY 2009
VL 284
IS 44
BP 30264
EP 30274
DI 10.1074/jbc.M109.045526
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 510LM
UT WOS:000271090000030
PM 19744931
ER
PT J
AU Palijan, A
Fernandes, I
Verway, M
Kourelis, M
Bastien, Y
Tavera-Mendoza, LE
Sacheli, A
Bourdeau, V
Mader, S
White, JH
AF Palijan, Ana
Fernandes, Isabelle
Verway, Mark
Kourelis, Maria
Bastien, Yolande
Tavera-Mendoza, Luz E.
Sacheli, Aaron
Bourdeau, Veronique
Mader, Sylvie
White, John H.
TI Ligand-dependent Corepressor LCoR Is an Attenuator of
Progesterone-regulated Gene Expression
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TERMINAL BINDING-PROTEIN; RECEPTOR-INTERACTING PROTEIN; BOUND NUCLEAR
RECEPTORS; TRANSCRIPTIONAL COREPRESSOR; PIPSQUEAK PROTEIN;
STEROID-HORMONES; TARGET GENES; CANCER-CELLS; ESTROGEN; CTBP
AB Ligand-dependent corepressor LCoR interacts with the progesterone receptor (PR) and estrogen receptor ER alpha in the presence of hormone. LCoR contains tandem N-terminal PXDLS motifs that recruit C-terminal-binding protein (CtBP) corepressors as well as a C-terminal helix-turn-helix (HTH) domain. Here, we analyzed the function of these domains in coregulation of PR- and ER alpha-regulated gene expression. LCoR and CtBP1 colocalize in nuclear bodies that also contain CtBP-interacting protein CtIP and polycomb group repressor complex marker BMI1. Coexpression of CtBP1 in MCF7 or T47D breast cancer cells augmented corepression by LCoR, whereas coexpression of CtIP did not, consistent with direct interaction of LCoR with CtBP1, but not CtIP. The N-terminal region containing the PXDLS motifs is necessary and sufficient for CTBP1 recruitment and essential for full corepression. However, LCoR function was also strongly dependent on the helix-turn-helix domain, as its deletion completely abolished corepression. LCoR, CtBP, and CtIP were recruited to endogenous PR- and ER alpha-stimulated genes in a hormone-dependent manner. Similarly, LCoR was recruited to estrogen-repressed genes, whereas hormone treatment reduced CtBP1 binding. Small interfering RNA-mediated knockdown of LCoR or CtBP1 augmented expression of progesterone- and estrogen-stimulated reporter genes as well as endogenous progesterone- stimulated target genes. In contrast, their ablation had gene-specific effects on ER alpha-regulated transcription that generally led to reduced gene expression. Taken together, these results show that multiple domains contribute to LCoR function. They also reveal a role for LCoR and CtBP1 as attenuators of progesterone-regulated transcription but suggest that LCoR and CtBP1 can act to enhance transcription of some genes.
C1 [Palijan, Ana; Fernandes, Isabelle; Verway, Mark; Kourelis, Maria; Bastien, Yolande; Sacheli, Aaron; White, John H.] McGill Univ, Dept Physiol, Montreal, PQ H3G 1Y6, Canada.
[White, John H.] McGill Univ, Dept Med, Montreal, PQ H3G 1Y6, Canada.
[Tavera-Mendoza, Luz E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
[Bourdeau, Veronique; Mader, Sylvie] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada.
[Bourdeau, Veronique; Mader, Sylvie] Univ Montreal, Dept Biochem, Montreal, PQ H3C 3J7, Canada.
RP White, JH (reprint author), McGill Univ, Dept Physiol, 3655 Drummond St, Montreal, PQ H3G 1Y6, Canada.
EM john.white@mcgill.ca
OI White, John/0000-0002-4785-2687
FU Canadian Institutes of Health [MT-11704]
FX This work was supported by Canadian Institutes of Health Research Grant
MT-11704 (to J. H. W.).
NR 54
TC 14
Z9 14
U1 1
U2 9
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 30
PY 2009
VL 284
IS 44
BP 30275
EP 30287
DI 10.1074/jbc.M109.051201
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 510LM
UT WOS:000271090000031
PM 19744932
ER
PT J
AU Zhuang, J
Jiang, GC
Willers, H
Xia, F
AF Zhuang, Jing
Jiang, Guochun
Willers, Henning
Xia, Fen
TI Exonuclease Function of Human Mre11 Promotes Deletional Nonhomologous
End Joining
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID STRAND-BREAK REPAIR; DEPENDENT PROTEIN-KINASE; DNA END; CELL-CYCLE;
HOMOLOGOUS RECOMBINATION; CHECKPOINT CONTROL; MAMMALIAN-CELLS; COMPLEX;
MECHANISMS; NUCLEASE
AB DNAdouble-stranded breaks (DSBs) are lethal if not repaired and are highly mutagenic if misrepaired. Nonhomologous end joining (NHEJ) is one of the major DSB repair pathways and can rejoin the DSB ends either precisely or with mistakes. Recent evidence suggests the existence of two NHEJ subpathways: conservative NHEJ (C-NHEJ), which does not require microhomology and can join ends precisely; and deletional NHEJ (D-NHEJ), which utilizes microhomology to join the ends with small deletions. Little is known about how these NHEJ subpathways are regulated. Mre11 has been implicated in DNA damage response, thus we investigated whether Mre11 function also extended to NHEJ. We utilized an intrachromosomal NHEJ substrate in which DSBs are generated by the I-SceI to address this question. The cohesive ends are fully complementary and were either repaired by C-NHEJ or D-NHEJ with similar efficiency. We found that disruption of Mre11 by RNA interference in human cells led to a 10-fold decrease in the frequency of D-NHEJ compared with cells with functional Mre11. Interestingly, C-NHEJ was not affected by Mre11 status. Expression of wild type but not exonuclease-defective Mre11 mutants was able to rescue D-NHEJ in Mre11-deficient cells. Further mutational analysis suggested that additional mechanisms associated with methylation of Mre11 at the C-terminal glycine-arginine-rich domain contributed to the promotion of D-NHEJ by Mre11. This study provides new insights into the mechanisms by which Mre11 affects the accuracy of DSB end joining specifically through control of the D-NHEJ subpathway, thus illustrating the complexity of the Mre11 role in maintaining genomic stability.
C1 [Zhuang, Jing; Jiang, Guochun; Xia, Fen] Vanderbilt Univ, Dept Radiat Oncol, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA.
[Zhuang, Jing; Jiang, Guochun; Xia, Fen] Vanderbilt Univ, Dept Canc Biol, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA.
[Willers, Henning] Massachusetts Gen Hosp, Lab Cellular & Mol Radiat Oncol, Ctr Canc, Boston, MA 02114 USA.
RP Xia, F (reprint author), Vanderbilt Univ, Dept Radiat Oncol, Med Ctr, Nashville, TN 37232 USA.
EM fen.xia@vanderbilt.edu
RI Xia, Fen/G-3708-2013
FU National Institutes of Health [R01 CA118158-02]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant R01 CA118158-02 ( to F. X.).
NR 47
TC 37
Z9 38
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 30
PY 2009
VL 284
IS 44
BP 30565
EP 30573
DI 10.1074/jbc.M109.059444
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 510LM
UT WOS:000271090000059
PM 19744924
ER
PT J
AU De Rosa, L
Antonini, D
Ferone, G
Russo, MT
Yu, PB
Han, R
Missero, C
AF De Rosa, Laura
Antonini, Dario
Ferone, Giustina
Russo, Monia T.
Yu, Paul B.
Han, Rong
Missero, Caterina
TI p63 Suppresses Non-epidermal Lineage Markers in a Bone Morphogenetic
Protein-dependent Manner via Repression of Smad7
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID OSTEOGENIC PROTEIN-1; HAIR FOLLICLE; SIGNALING PATHWAYS;
GENE-EXPRESSION; I RECEPTORS; P53 HOMOLOG; STEM-CELLS; MOUSE;
DIFFERENTIATION; TARGET
AB p63, a p53 family member, plays an essential role in epidermal development by regulating its transcriptional program. Here we report a previously uncovered role of p63 in controlling bone morphogenetic protein (BMP) signaling, which is required for maintaining low expression levels of several non-epidermal genes. p63 represses transcription of the inhibitory Smad7 and activates Bmp7, thereby sustaining BMP signaling. In the absence of p63, compromised BMP signaling leads to inappropriate non-epidermal gene expression in postnatal mouse keratinocytes and in embryonic epidermis. Reactivation of BMP signaling by Smad7 knockdown and/or, to a lesser extent, by BMP treatment suppresses expression of non-epidermal genes in the absence of p63. Canonical BMP/Smad signaling is essential for control of non-epidermal genes as use of a specific inhibitor, or simultaneous knockdown of Smad1 and Smad5 counteract suppression of non-epidermal genes. Our data indicate that p63 prevents ectopic expression of non-epidermal genes by a mechanism involving Smad7 repression and, to a lesser extent, Bmp7 induction, with consequent enhancement of BMP/Smad signaling.
C1 [De Rosa, Laura; Antonini, Dario; Ferone, Giustina; Russo, Monia T.; Missero, Caterina] CEINGE Biotecnol Avanzate, I-80145 Naples, Italy.
[De Rosa, Laura; Missero, Caterina] IRCCS Fdn SDN, I-80143 Naples, Italy.
[Yu, Paul B.] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Han, Rong] Harvard Univ, Cutaneous Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA.
RP Missero, C (reprint author), CEINGE Biotecnol Avanzate, Via Comunale Margherita 482, I-80145 Naples, Italy.
EM missero@ceinge.unina.it
RI russo, monia /Q-5774-2016; De Rosa, Laura/H-7504-2015;
OI russo, monia /0000-0003-2001-5384; Han, Rong/0000-0002-5766-8277; De
Rosa, Laura/0000-0001-9020-8451; Missero, Caterina/0000-0003-0905-5123;
Yu, Paul/0000-0003-2145-4944
FU Italian Telethon Foundation [GGP06243]; National Foundation for
Ectodermal Dysplasia
FX This work was supported in part by Italian Telethon Foundation Grant
GGP06243 and the National Foundation for Ectodermal Dysplasia.
NR 54
TC 20
Z9 20
U1 2
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 30
PY 2009
VL 284
IS 44
BP 30574
EP 30582
DI 10.1074/jbc.M109.049619
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 510LM
UT WOS:000271090000060
PM 19717565
ER
PT J
AU Kuter, DJ
Mufti, GJ
Bain, BJ
Hasserjian, RP
Davis, W
Rutstein, M
AF Kuter, David J.
Mufti, Ghulam J.
Bain, Barbara J.
Hasserjian, Robert P.
Davis, Wende
Rutstein, Mark
TI Evaluation of bone marrow reticulin formation in chronic immune
thrombocytopenia patients treated with romiplostim
SO BLOOD
LA English
DT Article
ID FAMILIAL ESSENTIAL THROMBOCYTHEMIA; LONG-TERM TREATMENT; PURPURA ITP;
IN-VITRO; THROMBOPOIETIN GENE; OPEN-LABEL; MICE; GROWTH; MEGAKARYOCYTES;
MYELOFIBROSIS
AB Romiplostim is a thrombopoietin receptor agonist that increases platelet counts in patients with chronic immune thrombocytopenia (ITP). Thrombopoietin receptor agonists are reported to increase the risk for reticulin fiber deposition within bone marrow. This report describes bone marrow findings from romiplostim-treated rats, a retrospective analysis of reticulin observed in romiplostim ITP clinical trials, and a prospective clinical study of the effects of romiplostim on bone marrow morphology. In rats, romiplostim produced a dose-dependent increase in bone marrow fibrosis that resolved after treatment withdrawal. Of 271 ITP patients in romiplostim clinical trials, 10 were reported to have reticulin deposition; reticulin grade was increased in 4 of 5 patients with both pretreatment and on-treatment bone marrow results. Reticulin grade often decreased soon after romiplostim discontinuation. In the prospective study, reticulin grade during romiplostim treatment remained within the normal range for all patients and was increased in only 1 of 6 patients with pretreatment and on-treatment bone marrow results. This report suggests that romiplostim produces reversible, dose-dependent bone marrow changes in rats and produces modest increases in bone marrow reticulin in some ITP patients that decrease when therapy is discontinued. These studies were registered at www.clinicaltrials.gov as # NCT00102323, # NCT00102336, # NCT00861224, and # NCT00116688. (Blood. 2009; 114: 3748-3756)
C1 [Kuter, David J.; Hasserjian, Robert P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Mufti, Ghulam J.] Kings Coll Hosp, London, England.
[Bain, Barbara J.] St Marys Hosp, London, England.
[Davis, Wende; Rutstein, Mark] Amgen Inc, Thousand Oaks, CA 91320 USA.
RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM kuter.david@MGH.harvard.edu
FU Amgen Inc.
FX This work was supported by Amgen Inc. In collaboration with the
investigators, Amgen designed the studies and conducted statistical
analyses. Writing assistance was provided by Amy Lindsay, who was funded
by Amgen Inc. Animal pathology specimens were analyzed by Margarita
Gruebbel, Experimental Pathology Laboratories Inc.
NR 44
TC 84
Z9 88
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 29
PY 2009
VL 114
IS 18
BP 3748
EP 3756
DI 10.1182/blood-2009-05-224766
PG 9
WC Hematology
SC Hematology
GA 512RO
UT WOS:000271268100008
PM 19671919
ER
PT J
AU van der Linden, MH
Valsecchi, MG
De Lorenzo, P
Moricke, A
Janka, G
Leblanc, TM
Felice, M
Biondi, A
Campbell, M
Hann, I
Rubnitz, JE
Stary, J
Szczepanski, T
Vora, A
Ferster, A
Hovi, L
Silverman, LB
Pieters, R
AF van der Linden, Marieke H.
Valsecchi, Maria Grazia
De Lorenzo, Paola
Moericke, Anja
Janka, Gritta
Leblanc, Thierry M.
Felice, Maria
Biondi, Andrea
Campbell, Myriam
Hann, Ian
Rubnitz, Jeffrey E.
Stary, Jan
Szczepanski, Tomasz
Vora, Ajay
Ferster, Alina
Hovi, Liisa
Silverman, Lewis B.
Pieters, Rob
TI Outcome of congenital acute lymphoblastic leukemia treated on the
Interfant-99 protocol
SO BLOOD
LA English
DT Article
ID ONCOLOGY-GROUP; PROGNOSTIC-FACTORS; INFANTS; EXPERIENCE; THERAPY; TRIAL
AB Acute lymphoblastic leukemia (ALL) diagnosed in the first month of life (congenital ALL) is very rare. Although congenital ALL is often assumed to be fatal, no studies have been published on outcome except for case reports. The present study reports the outcome of 30 patients with congenital ALL treated with the uniform Interfant-99 protocol, a hybrid regimen combining ALL treatment with elements designed for treatment of acute myeloid leukemia. Congenital ALL was characterized by a higher white blood cell count and a strong trend for higher incidence of MLL rearrangements and CD10-negative B-lineage ALL compared with older infants. Induction failure rate was 13% and not significantly different from that in older infants (7%, P = .14), but relapse rate was significantly higher in congenital ALL patients (2-year cumulative incidence [SE] was 60.0 [9.3] vs 34.2 [2.3], P < .001). Two-year event-free survival and survival of congenital ALL patients treated with this protocol was 20% (SE 9.1%). Early death in complete remission and treatment delays resulting from toxicity were not different. The survival of 17% after last follow-up, combined with a toxicity profile comparable with that in older infants, justifies treating congenital ALL with curative intent. This trial was registered at www.clinicaltrials.gov as no. NCT 00015873, and at www.controlled-trials.com as no. ISRCTN24251487. (Blood. 2009; 114: 3764-3768)
C1 [Pieters, Rob] Erasmus MC Sophia Childrens Hosp, Dept Paediat Oncol & Haematol, NL-3015 GJ Rotterdam, Netherlands.
[Valsecchi, Maria Grazia; De Lorenzo, Paola] Univ Milano Bicocca, Dept Clin Med & Prevent, Milan, Italy.
[Moericke, Anja] Univ Med Ctr Schleswig Holstein, Kiel, Germany.
[Janka, Gritta] Univ Hosp Hamburg Eppendorf, Cooperat Study Grp Treatment ALL, Hamburg, Germany.
[Leblanc, Thierry M.] Hop St Louis, French ALL Grp, Paris, France.
[Felice, Maria] Argentina Hosp Pediat, Buenos Aires, DF, Argentina.
[Biondi, Andrea] Univ Milano Bicocca, Assoc Italiana Ematol Oncol Pediat, Monza, Italy.
[Campbell, Myriam] Hosp Roberto Del Rio, Programa Infantil Nacl Drogas Antineplasicas, Santiago, Chile.
[Hann, Ian] Great Ormond St Hosp Sick Children, UK Childrens Canc Study Grp, London WC1N 3JH, England.
[Rubnitz, Jeffrey E.] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Stary, Jan] Charles Univ Prague, Czech Paediat Haematol, Univ Hosp Motol, Prague, Czech Republic.
[Stary, Jan] Charles Univ Prague, Sch Med 2, Prague, Czech Republic.
[Szczepanski, Tomasz] Med Univ Silesia, Polish Paediat Leukemia & Lymphoma Study Grp, Zabrze, Poland.
[Vora, Ajay] Sheffield Childrens Hosp, Sheffield, S Yorkshire, England.
[Ferster, Alina] Hop Univ Enfants Reine Fabiola, Childrens Leukemia Grp, Brussels, Belgium.
[Hovi, Liisa] Univ Helsinki, Nord Soc Paediat Haematol & Oncol, Helsinki, Finland.
[Silverman, Lewis B.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Pieters, Rob] Dutch Childhood Oncol Grp, The Hague, Netherlands.
RP Pieters, R (reprint author), Erasmus MC Sophia Childrens Hosp, Dept Paediat Oncol & Haematol, Dr Molewaterpl 60, NL-3015 GJ Rotterdam, Netherlands.
EM rob.pieters@erasmusmc.nl
FU KiKa; Associazione Italiana Ricerca sul Cancro Regional [Cod 1105];
Fondazione Tettamanti and Comitato MM Verga; Polish Ministry of Science
and Higher Education [2 P054 095 30]; Czech Ministry of Education
[MSM0021620813]; Deutsche Krebshilfe
FX M. H. v. d. L. is supported by KiKa. The many participating institutes
of all study groups are acknowledged for their support. This study in
Associazione Italiana Ematologia Oncologia Pediatrica is partially
supported by Associazione Italiana Ricerca sul Cancro Regional Grant Cod
1105 (to A. B. and M. G. V.). The international study operating center
was partially supported by Fondazione Tettamanti and Comitato MM Verga
(to M. G. V. and P. D. L.). T. S. was supported by the Polish Ministry
of Science and Higher Education (grant 2 P054 095 30). Czech Paediatric
Haematology was supported by the Czech Ministry of Education (grant
MSM0021620813). Berlin-Frankfurt-Munster Germany was supported by
Deutsche Krebshilfe.
NR 20
TC 32
Z9 33
U1 0
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 29
PY 2009
VL 114
IS 18
BP 3764
EP 3768
DI 10.1182/blood-2009-02-204214
PG 5
WC Hematology
SC Hematology
GA 512RO
UT WOS:000271268100010
PM 19657114
ER
PT J
AU Beekman, JM
Verhagen, LP
Geijsen, N
Coffer, PJ
AF Beekman, Jeffrey M.
Verhagen, Liesbeth P.
Geijsen, Niels
Coffer, Paul J.
TI Regulation of myelopoiesis through syntenin-mediated modulation of IL-5
receptor output
SO BLOOD
LA English
DT Article
ID COLONY-STIMULATING FACTOR; EOSINOPHIL DIFFERENTIATION;
FUNCTIONAL-PROPERTIES; SIGNAL-TRANSDUCTION; CYTOKINE RECEPTORS;
CRYSTAL-STRUCTURE; CELL-DEVELOPMENT; BONE-MARROW; PDZ TANDEM; B-1 CELLS
AB The granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin (IL)-3/IL-5 receptor family regulates the production and function of myeloid cells. These cytokines signal through receptor complexes that consist of unique ligand-binding alpha-chains and common signaling beta-chains. IL-5 is distinct from IL-3 and GM-CSF in its capacity to induce eosinophil development, however, the molecular mechanisms that generate functional diversity within this receptor family are mostly unknown. Here, we characterized the selective IL-5R alpha-binding adapter protein syntenin in IL-5R function. Syntenin and IL-5R alpha colocalize at the plasma membrane and in early endosomal compartments. Manipulation of syntenin expression by ectopic expression or knockdown selectively modulated IL-5R but not GM-CSF receptor signaling, and severely affected IL-5-induced eosinophil differentiation from primary human CD34(+) hematopoietic progenitor cells. We found syntenin upregulated during eosinophilopoiesis but down-regulated during neutropoiesis. Syntenin forms complexes with multiple IL-5R alpha chains, suggesting that syntenin-enhanced IL-5R output may result from stabilization of an IL-5-induced oligomeric receptor complex. These data demonstrate that cytokine-specific functions can be transduced by unique receptor alpha-chain-associating adapter proteins. (Blood. 2009;114:3917-3927)
C1 [Beekman, Jeffrey M.; Verhagen, Liesbeth P.; Coffer, Paul J.] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Mol Immunol Lab, Dept Immunol, NL-3584 EA Utrecht, Netherlands.
[Beekman, Jeffrey M.; Coffer, Paul J.] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Dept Pediat Immunol, NL-3584 EA Utrecht, Netherlands.
[Geijsen, Niels] Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA 02114 USA.
RP Coffer, PJ (reprint author), Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Mol Immunol Lab, Dept Immunol, Lundlaan 6, NL-3584 EA Utrecht, Netherlands.
EM p.j.coffer@umcutrecht.nl
RI Beekman, Jeffrey/I-7781-2014
OI Beekman, Jeffrey/0000-0003-4886-3756
FU Dutch Scientific Organization (NWO) [917.36.316]
FX J.M.B. was supported by a grant from the Dutch Scientific Organization
(NWO 917.36.316).
NR 54
TC 11
Z9 11
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD OCT 29
PY 2009
VL 114
IS 18
BP 3917
EP 3927
DI 10.1182/blood-2009-03-208850
PG 11
WC Hematology
SC Hematology
GA 512RO
UT WOS:000271268100027
PM 19654410
ER
PT J
AU Meems, H
Meijer, AB
Cullinan, DB
Mertens, K
Gilbert, GE
AF Meems, Henriet
Meijer, Alexander B.
Cullinan, David B.
Mertens, Koen
Gilbert, Gary E.
TI Factor VIII C1 domain residues Lys 2092 and Phe 2093 contribute to
membrane binding and cofactor activity
SO BLOOD
LA English
DT Article
ID COAGULATION-FACTOR-VIII; VON-WILLEBRAND-FACTOR; HEMOPHILIA-A; C2 DOMAIN;
FACTOR-X; FACTOR-IXA; PHOSPHOLIPID-MEMBRANES; FACTOR-V; ACTIVATION;
COMPLEX
AB Binding of factor VIII to membranes containing phosphatidyl-L-serine (Ptd-L-Ser) is mediated, in part, by a motif localized to the C2 domain. We evaluated a putative membrane-binding role of the C1 domain using an anti-C1 antibody fragment, KM33(scFv), and factor VIII mutants with an altered KM33 epitope. We prepared a dual mutant Lys2092/Phe2093 -> Ala/Ala (fVIII(YFP) (2092/93)) and 2 single mutants Lys2092 -> Ala and Phe2093 -> Ala. KM33(scFv) inhibited binding of fluorescein-labeled factor VIII to synthetic membranes and inhibited at least 95% of factor Xase activity. fVIII(YFP 2092/93) had 3-fold lower affinity for membranes containing 15% Ptd-L-Ser but more than 10-fold reduction in affinity for membranes with 4% Ptd-L-Ser. In a microtiter plate, KM33(scFv) was additive with an anti-C2 antibody for blocking binding to vesicles of 15% Ptd-L-Ser, whereas either antibody blocked binding to vesicles of 4% Ptd-L-Ser. KM33(scFv) inhibited binding to platelets and fVIII(YFP 2092/93) had reduced binding to A23187-stimulated platelets. fVIII(YFP 2092) exhibited normal activity at various Ptd-L-Ser concentrations, whereas fVIII(YFP 2093) showed a reduction of activity with Ptd-L-Ser less than 12%. fVIII(YFP 2092/93) had a greater reduction of activity than either single mutant. These results indicate that Lys 2092 and Phe 2093 are elements of a membrane-binding motif on the factor VIII C1 domain. (Blood. 2009;114:3938-3946)
C1 [Cullinan, David B.; Gilbert, Gary E.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Dept Med, W Roxbury, MA 02132 USA.
[Cullinan, David B.; Gilbert, Gary E.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Dept Res, W Roxbury, MA 02132 USA.
[Cullinan, David B.; Gilbert, Gary E.] Harvard Univ, Sch Med, Boston, MA USA.
[Meijer, Alexander B.; Mertens, Koen] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands.
[Meems, Henriet; Mertens, Koen] UMC Utrecht & Sanquin, Creveld Lab, Amsterdam, Netherlands.
[Meems, Henriet; Meijer, Alexander B.; Mertens, Koen] Dept Plasma Prot, Amsterdam, Netherlands.
RP Gilbert, GE (reprint author), Brigham & Womens Hosp, VA Boston Healthcare Syst, Dept Med, 1400 VFW Pkwy, W Roxbury, MA 02132 USA.
EM Gary_Gilbert@hms.harvard.edu
NR 45
TC 39
Z9 40
U1 1
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD OCT 29
PY 2009
VL 114
IS 18
BP 3938
EP 3946
DI 10.1182/blood-2009-01-197707
PG 9
WC Hematology
SC Hematology
GA 512RO
UT WOS:000271268100030
PM 19687511
ER
PT J
AU Koreth, J
Stevenson, KE
Kim, HT
Garcia, M
Ho, VT
Armand, P
Cutler, C
Ritz, J
Antin, JH
Soiffer, RJ
Alyea, EP
AF Koreth, John
Stevenson, Kristen E.
Kim, Haesook T.
Garcia, Michael
Ho, Vincent T.
Armand, Philippe
Cutler, Corey
Ritz, Jerome
Antin, Joseph H.
Soiffer, Robert J.
Alyea, Edwin P., III
TI Bortezomib, tacrolimus, and methotrexate for prophylaxis of
graft-versus-host disease after reduced-intensity conditioning
allogeneic stem cell transplantation from HLA-mismatched unrelated
donors
SO BLOOD
LA English
DT Article
ID NF-KAPPA-B; PROTEASOME INHIBITOR BORTEZOMIB; ACTIVATION; DEPLETION;
GROWTH; GVHD
AB Graft-versus-host disease (GVHD) is a significant complication of allogeneic stem cell transplantation (alloSCT). The proteasome inhibitor bortezomib has immunomodulatory properties of potential benefit for GVHD control. We undertook a phase 1 trial of bortezomib, tacrolimus, and methotrexate for GVHD prophylaxis after reduced-intensity conditioning alloSCT using human leukocyte antigen-mismatched unrelated donors. Twenty-three patients were enrolled. Bortezomib dose levels of 1, 1.3, and 1.5 mg/m(2) were evaluated with 5, 3, and 5 patients, respectively. Ten additional patients were accrued at the 1.3 mg/m(2) bortezomib dose level. Bortezomib-related toxicity was minimal. With a 12-month median follow-up, grade II-IV acute GVHD occurred in 3 patients, a 180-day cumulative incidence of 13%. Chronic GVHD occurred in 9 patients, a 1-year cumulative incidence of 41%. At 1-year, the nonrelapse mortality was zero, cumulative incidence of relapse/progression was 29%, and overall, progression-free, and event-free survival were 75%, 64%, and 59%, respectively. Bortezomib is a promising novel immunomodulatory agent in allogeneic transplantation. This study was registered at http://www.clinicaltrials.gov as # NCT00369226. (Blood. 2009;114:3956-3959)
C1 [Koreth, John; Garcia, Michael; Ho, Vincent T.; Armand, Philippe; Cutler, Corey; Ritz, Jerome; Antin, Joseph H.; Soiffer, Robert J.; Alyea, Edwin P., III] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
[Stevenson, Kristen E.; Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
RP Koreth, J (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA.
EM jkoreth@partners.org
FU Millennium Pharmaceuticals Inc; National Institutes of Health [P01
CA142106]
FX This study was supported in part by Millennium Pharmaceuticals Inc and
by the National Institutes of Health (P01 CA142106).
NR 14
TC 52
Z9 53
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 29
PY 2009
VL 114
IS 18
BP 3956
EP 3959
DI 10.1182/blood-2009-07-231092
PG 4
WC Hematology
SC Hematology
GA 512RO
UT WOS:000271268100032
PM 19713456
ER
PT J
AU Parikh, JR
Askenazi, M
Ficarro, SB
Cashorali, T
Webber, JT
Blank, NC
Zhang, Y
Marto, JA
AF Parikh, Jignesh R.
Askenazi, Manor
Ficarro, Scott B.
Cashorali, Tanya
Webber, James T.
Blank, Nathaniel C.
Zhang, Yi
Marto, Jarrod A.
TI multiplierz: an extensible API based desktop environment for proteomics
data analysis
SO BMC BIOINFORMATICS
LA English
DT Article
ID TANDEM MASS-SPECTROMETRY; NEXT-GENERATION; IDENTIFICATION; ALGORITHM;
PEPTIDES; SPECTRA
AB Background: Efficient analysis of results from mass spectrometry-based proteomics experiments requires access to disparate data types, including native mass spectrometry files, output from algorithms that assign peptide sequence to MS/MS spectra, and annotation for proteins and pathways from various database sources. Moreover, proteomics technologies and experimental methods are not yet standardized; hence a high degree of flexibility is necessary for efficient support of high-and low-throughput data analytic tasks. Development of a desktop environment that is sufficiently robust for deployment in data analytic pipelines, and simultaneously supports customization for programmers and non-programmers alike, has proven to be a significant challenge.
Results: We describe multiplierz, a flexible and open-source desktop environment for comprehensive proteomics data analysis. We use this framework to expose a prototype version of our recently proposed common API (mzAPI) designed for direct access to proprietary mass spectrometry files. In addition to routine data analytic tasks, multiplierz supports generation of information rich, portable spreadsheet-based reports. Moreover, multiplierz is designed around a "zero infrastructure" philosophy, meaning that it can be deployed by end users with little or no system administration support. Finally, access to multiplierz functionality is provided via high-level Python scripts, resulting in a fully extensible data analytic environment for rapid development of custom algorithms and deployment of high-throughput data pipelines.
Conclusion: Collectively, mzAPI and multiplierz facilitate a wide range of data analysis tasks, spanning technology development to biological annotation, for mass spectrometry-based proteomics research.
C1 [Askenazi, Manor; Ficarro, Scott B.; Cashorali, Tanya; Webber, James T.; Blank, Nathaniel C.; Zhang, Yi; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Parikh, Jignesh R.] Boston Univ, Bioinformat Program, Boston, MA 02115 USA.
[Askenazi, Manor; Ficarro, Scott B.; Cashorali, Tanya; Webber, James T.; Blank, Nathaniel C.; Zhang, Yi; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA.
[Askenazi, Manor; Ficarro, Scott B.; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Askenazi, Manor] Hebrew Univ Jerusalem, Dept Biol Chem, IL-91904 Jerusalem, Israel.
RP Marto, JA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St,Smith 1158A, Boston, MA 02115 USA.
EM jparikh@bu.edu; manor_askenazi@dfci.harvard.edu;
scott_ficarro@dfci.harvard.edu; tanya@gnsbiotech.com;
jamest_webber@dfci.harvard.edu; nate.blank@centre.edu;
yi_zhang@dfci.harvard.edu; jarrod_marto@dfci.harvard.edu
OI Webber, James/0000-0001-8594-9888
FU NHGRI NIH HHS [P50 HG004233, P50HG004233]
NR 29
TC 36
Z9 36
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD OCT 29
PY 2009
VL 10
AR 364
DI 10.1186/1471-2105-10-364
PG 16
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 519KN
UT WOS:000271765400002
PM 19874609
ER
PT J
AU Maslowski, KM
Vieira, AT
Ng, A
Kranich, J
Sierro, F
Yu, D
Schilter, HC
Rolph, MS
Mackay, F
Artis, D
Xavier, RJ
Teixeira, MM
Mackay, CR
AF Maslowski, Kendle M.
Vieira, Angelica T.
Ng, Aylwin
Kranich, Jan
Sierro, Frederic
Yu, Di
Schilter, Heidi C.
Rolph, Michael S.
Mackay, Fabienne
Artis, David
Xavier, Ramnik J.
Teixeira, Mauro M.
Mackay, Charles R.
TI Regulation of inflammatory responses by gut microbiota and
chemoattractant receptor GPR43
SO NATURE
LA English
DT Article
ID CHAIN FATTY-ACIDS; DISTAL ULCERATIVE-COLITIS; NF-KAPPA-B;
FUNCTIONAL-CHARACTERIZATION; INTESTINAL MICROBIOTA; BOWEL-DISEASE; MICE;
EOSINOPHILS; IRRIGATION; INHIBITION
AB The immune system responds to pathogens by a variety of pattern recognition molecules such as the Toll-like receptors (TLRs), which promote recognition of dangerous foreign pathogens. However, recent evidence indicates that normal intestinal microbiota might also positively influence immune responses, and protect against the development of inflammatory diseases(1,2). One of these elements may be short-chain fatty acids (SCFAs), which are produced by fermentation of dietary fibre by intestinal microbiota. A feature of human ulcerative colitis and other colitic diseases is a change in 'healthy' microbiota such as Bifidobacterium and Bacteriodes(3), and a concurrent reduction in SCFAs(4). Moreover, increased intake of fermentable dietary fibre, or SCFAs, seems to be clinically beneficial in the treatment of colitis(5-9). SCFAs bind the G-protein-coupled receptor 43 (GPR43, also known as FFAR2)(10,11), and here we show that SCFA-GPR43 interactions profoundly affect inflammatory responses. Stimulation of GPR43 by SCFAs was necessary for the normal resolution of certain inflammatory responses, because GPR43-deficient (Gpr43(-/-)) mice showed exacerbated or unresolving inflammation in models of colitis, arthritis and asthma. This seemed to relate to increased production of inflammatory mediators by Gpr43(-/-) immune cells, and increased immune cell recruitment. Germ-free mice, which are devoid of bacteria and express little or no SCFAs, showed a similar dysregulation of certain inflammatory responses. GPR43 binding of SCFAs potentially provides a molecular link between diet, gastrointestinal bacterial metabolism, and immune and inflammatory responses.
C1 [Maslowski, Kendle M.; Vieira, Angelica T.; Kranich, Jan; Sierro, Frederic; Yu, Di; Schilter, Heidi C.; Rolph, Michael S.; Mackay, Fabienne; Mackay, Charles R.] St Vincents Hosp, Garvan Inst Med Res, Darlinghurst, NSW 2010, Australia.
[Maslowski, Kendle M.; Kranich, Jan; Schilter, Heidi C.; Rolph, Michael S.; Mackay, Charles R.] Cooperat Res Ctr Asthma & Airways, Camperdown, NSW 2050, Australia.
[Maslowski, Kendle M.; Schilter, Heidi C.; Mackay, Charles R.] Univ New S Wales, St Vincents Clin Sch, Sydney, NSW 2010, Australia.
[Vieira, Angelica T.; Teixeira, Mauro M.] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Biochem & Immunol, BR-31270901 Belo Horizonte, MG, Brazil.
[Ng, Aylwin; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Ng, Aylwin; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Ng, Aylwin; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Mackay, Fabienne; Mackay, Charles R.] Monash Univ, Fac Med, Clayton, Vic 3800, Australia.
[Artis, David] Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA.
[Xavier, Ramnik J.] MIT, Broad Inst, Cambridge, MA 02142 USA.
[Xavier, Ramnik J.] Harvard Univ, Cambridge, MA 02142 USA.
RP Mackay, CR (reprint author), St Vincents Hosp, Garvan Inst Med Res, 384 Victoria St, Darlinghurst, NSW 2010, Australia.
EM charles.mackay@med.monash.edu.au
RI Mackay, Charles/A-9673-2008; Sierro, Frederic/B-9742-2009; Yu,
Di/C-2163-2009; Mackay, Fabienne/B-7440-2008; Vieira,
Angelica/A-6227-2015; Osborne, Nicholas/N-4915-2015;
OI Mackay, Charles/0000-0002-6338-7340; Sierro,
Frederic/0000-0001-5004-8414; Yu, Di/0000-0003-1721-8922; Mackay,
Fabienne/0000-0002-6074-2693; Vieira, Angelica/0000-0002-4556-7671;
Osborne, Nicholas/0000-0002-6700-2284; Maslowski,
Kendle/0000-0003-1995-5424
FU Australian NHMRC; CRC for Asthma and Airways; Crohn's and Colitis
Foundation of America; Cancer Institute NSW
FX The authors thank P. Silvera and S. Tangye for supply of certain
Genechip data sets, L. Tsai for help with heatmaps, and D. Kobuley, J.
Nicoli and M. Abt for help in the germ-free animal facilities. K. M. M.
and C. R. M. are supported by the Australian NHMRC, and the CRC for
Asthma and Airways. A. N. is a recipient of a Fellowship award from the
Crohn's and Colitis Foundation of America. F. S. and D. Y. are Cancer
Institute NSW Fellows.
NR 44
TC 800
Z9 834
U1 26
U2 206
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 29
PY 2009
VL 461
IS 7268
BP 1282
EP U119
DI 10.1038/nature08530
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 511TF
UT WOS:000271190800049
PM 19865172
ER
PT J
AU Taylor, CR
Gandhi, RT
Handwerker, J
Duncan, LM
AF Taylor, Charles R.
Gandhi, Rajesh T.
Handwerker, Jason
Duncan, Lyn M.
TI A Man with Sore Throat, Fever, and Rash PLEVA (pityriasis lichenoides et
varioliformis acuta)
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID MUCHA-HABERMANN-DISEASE; ARCANOBACTERIUM-HAEMOLYTICUM
C1 [Taylor, Charles R.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Gandhi, Rajesh T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Handwerker, Jason] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Duncan, Lyn M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Taylor, Charles R.] Harvard Univ, Sch Med, Dept Dermatol, Cambridge, MA 02138 USA.
[Gandhi, Rajesh T.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA.
[Handwerker, Jason] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA.
[Duncan, Lyn M.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA.
RP Taylor, CR (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
FU Tibotec
FX Dr. Gandhi reports receiving lecture fees from GlaxoSmithKline and grant
support from Tibotec. No other potential conflict of interest relevant
to this article was reported.
NR 19
TC 1
Z9 2
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 29
PY 2009
VL 361
IS 18
BP 1787
EP 1796
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 511RY
UT WOS:000271185600013
PM 19864678
ER
PT J
AU Yotsumoto, Y
Chang, LH
Watanabe, T
Sasaki, Y
AF Yotsumoto, Yuko
Chang, Li-hung
Watanabe, Takeo
Sasaki, Yuka
TI Interference and feature specificity in visual perceptual learning
SO VISION RESEARCH
LA English
DT Article
DE Perceptual learning; Roving; Interference; Feature specificity
ID HUMAN MOTOR MEMORY; TIME-COURSE; CONTRAST DISCRIMINATION;
TEXTURE-DISCRIMINATION; MOTION DISCRIMINATION; SPATIAL-FREQUENCY;
CONSOLIDATION; ORIENTATION; SLEEP; TASK
AB Perceptual learning (PL) often shows specificity to a trained feature. We investigated whether feature specificity is related to disruption in PL using the texture discrimination task (TDT), which shows learning specificity to background element but not to target element. Learning was disrupted when orientations of background elements were changed in two successive training sessions (interference) but not in a random order from trial to trial (roving). The presentation of target elements seemed to have reversed effect; learning occurred in two-parts training but not with roving. These results suggest that interference in TDT is feature specific while disruption by roving is not. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Yotsumoto, Yuko; Chang, Li-hung; Sasaki, Yuka] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA.
[Yotsumoto, Yuko; Chang, Li-hung; Watanabe, Takeo] Boston Univ, Dept Psychol, Boston, MA 02215 USA.
[Yotsumoto, Yuko; Sasaki, Yuka] Harvard Univ, Sch Med, Dept Radiol, Charlestown, MA 02129 USA.
RP Sasaki, Y (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA.
EM yuka@nmr.mgh.harvard.edu
FU NIH [EY01 9466, EY01 5980]; Japan Society for the Promotion of Science;
ERATO
FX This work was supported by NIH (EY01 9466 and EY01 5980) to TW. YY is
supported by Japan Society for the Promotion of Science. YS is supported
by ERATO Shimojo Implicit brain function project, Japan Science
Technology. We thank Nichole Eusemann for her careful editing our
manuscript.
NR 43
TC 17
Z9 18
U1 1
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
J9 VISION RES
JI Vision Res.
PD OCT 29
PY 2009
VL 49
IS 21
BP 2611
EP 2623
DI 10.1016/j.visres.2009.08.001
PG 13
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA 517GE
UT WOS:000271600500011
PM 19665036
ER
PT J
AU Carlson, BA
Yoo, MH
Sano, Y
Sengupta, A
Kim, JY
Irons, R
Gladyshev, VN
Hatfield, DL
Park, JM
AF Carlson, Bradley A.
Yoo, Min-Hyuk
Sano, Yasuyo
Sengupta, Aniruddha
Kim, Jin Young
Irons, Robert
Gladyshev, Vadim N.
Hatfield, Dolph L.
Park, Jin Mo
TI Selenoproteins regulate macrophage invasiveness and extracellular
matrix-related gene expression
SO BMC IMMUNOLOGY
LA English
DT Article
ID SELENOCYSTEINE TRANSFER-RNA; SIGNAL-TRANSDUCTION; INNATE IMMUNITY;
KAPPA-B; ACTIVATION; SELENIUM; MICE; INHIBITION; TRSP
AB Background: Selenium, a micronutrient whose deficiency in diet causes immune dysfunction and inflammatory disorders, is thought to exert its physiological effects mostly in the form of selenium-containing proteins (selenoproteins). Incorporation of selenium into the amino acid selenocysteine (Sec), and subsequently into selenoproteins is mediated by Sec tRNA([Ser]Sec).
Results: To define macrophage-specific selenoprotein functions, we generated mice with the Sec tRNA([Ser]Sec) gene specifically deleted in myeloid cells. These mutant mice were devoid of the "selenoproteome" in macrophages, yet exhibited largely normal inflammatory responses. However, selenoprotein deficiency led to aberrant expression of extracellular matrix-related genes, and diminished migration of macrophages in a protein gel matrix.
Conclusion: Selenium status may affect immune defense and tissue homeostasis through its effect on selenoprotein expression and the trafficking of tissue macrophages.
C1 [Carlson, Bradley A.; Yoo, Min-Hyuk; Sengupta, Aniruddha; Kim, Jin Young; Irons, Robert; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Sano, Yasuyo; Park, Jin Mo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
[Sano, Yasuyo; Park, Jin Mo] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA.
RP Hatfield, DL (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
EM carlsonb@mail.nih.gov; yoom@mail.nih.gov;
yasuyo.sano@cbrc2.mgh.harvard.edu; sengupta@mail.nih.gov;
glory80@snu.ac.kr; robert@veirons.com; vgladysh@unlnotes.unl.edu;
hatfield@mail.nih.gov; jmpark@cbrc2.mgh.harvard.edu
RI Gladyshev, Vadim/A-9894-2013
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, and 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, and in addition, a specific grant from the Office of
Dietary Supplements, NCI, NIH and the Cutaneous Biology Research Center
through the Massachusetts General Hospital/Shiseido Co. Ltd. Agreement
to JMP and NIH grants awarded to VNG.
NR 26
TC 35
Z9 36
U1 1
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2172
J9 BMC IMMUNOL
JI BMC Immunol.
PD OCT 28
PY 2009
VL 10
AR 57
DI 10.1186/1471-2172-10-57
PG 12
WC Immunology
SC Immunology
GA 521LY
UT WOS:000271924100001
PM 19863805
ER
PT J
AU Kastrinos, F
Mukherjee, B
Tayob, N
Wang, F
Sparr, J
Raymond, VM
Bandipalliam, P
Stoffel, EM
Gruber, SB
Syngal, S
AF Kastrinos, Fay
Mukherjee, Bhramar
Tayob, Nabihah
Wang, Fei
Sparr, Jennifer
Raymond, Victoria M.
Bandipalliam, Prathap
Stoffel, Elena M.
Gruber, Stephen B.
Syngal, Sapna
TI Risk of Pancreatic Cancer in Families With Lynch Syndrome
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID NONPOLYPOSIS COLORECTAL-CANCER; MSH2 MUTATION CARRIERS;
PEUTZ-JEGHERS-SYNDROME; MISMATCH REPAIR GENE; MEDULLARY CARCINOMA;
ENDOMETRIAL CANCER; HISTORY; ACCURACY; HNPCC; INDIVIDUALS
AB Context Lynch syndrome is an inherited cause of colorectal cancer caused by mutations of DNA mismatch repair (MMR) genes. A number of extracolonic tumors have been associated with the disorder, including pancreatic cancer; however, the risk of pancreatic cancer in Lynch syndrome is uncertain and not quantified.
Objective To estimate pancreatic cancer risk in families with germline MMR gene mutations.
Design, Setting, and Patients Cancer histories of probands and their relatives were evaluated in MMR gene mutation carriers in the familial cancer registries of the Dana-Farber Cancer Institute (n=80), Boston, Massachusetts, and University of Michigan Comprehensive Cancer Center (n=67), Ann Arbor, Michigan. Families enrolled before the study start date ( June 2008) were eligible. Age-specific cumulative risks and hazard ratio estimates of pancreatic cancer risk were calculated and compared with the general population using modified segregation analysis, with correction for ascertainment.
Main Outcome Measures Age-specific cumulative risks and hazard ratio estimates of pancreatic cancer risk.
Results Data on 6342 individuals from 147 families with MMR gene mutations were analyzed. Thirty-one families (21.1%) reported at least 1 case of pancreatic cancer. Forty-seven pancreatic cancers were reported ( 21 men and 26 women), with no sex-related difference in age of diagnosis (51.5 vs 56.5 years for men and women, respectively). The cumulative risk of pancreatic cancer in these families with gene mutations was 1.31% (95% confidence interval [CI], 0.31%-2.32%) up to age 50 years and 3.68% ( 95% CI, 1.45%-5.88%) up to age 70 years, which represents an 8.6-fold increase ( 95% CI, 4.7-15.7) compared with the general population.
Conclusions Among 147 families with germline MMR gene mutations, the risk of pancreatic cancer was increased compared with the US population. Individuals with MMR gene mutations and a family history of pancreatic cancer are appropriate to include in studies to further define the risk of premalignant and malignant pancreatic neoplasms and potential benefits and limitations of surveillance. JAMA. 2009; 302(16):1790-1795 www.jama.com
C1 [Sparr, Jennifer; Bandipalliam, Prathap; Stoffel, Elena M.; Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA.
[Kastrinos, Fay; Stoffel, Elena M.; Syngal, Sapna] Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA.
[Kastrinos, Fay] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY USA.
[Mukherjee, Bhramar; Tayob, Nabihah; Wang, Fei] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Raymond, Victoria M.; Gruber, Stephen B.] Univ Michigan, Sch Publ Hlth, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Gruber, Stephen B.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol & Human Genet, Ann Arbor, MI 48109 USA.
RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Populat Sci, 1 Jimmy Fund Way,SM 209, Boston, MA 02115 USA.
EM sgruber@med.umich.edu; ssyngal@partners.org
FU National Cancer Institute [R01CA81488, K24CA113433, R01CA97075,
5P30CA46592]; The Karp Family; H. H. & M. Metals Inc Fund; Leake Gift
for Pancreatic Cancer Research
FX This work was supported in part by the grants R01CA81488, K24CA113433,
R01CA97075, and 5P30CA46592 from the National Cancer Institute, The Karp
Family, H. H. & M. Metals Inc Fund, and the Leake Gift for Pancreatic
Cancer Research.
NR 38
TC 143
Z9 145
U1 1
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD OCT 28
PY 2009
VL 302
IS 16
BP 1790
EP 1795
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 511FW
UT WOS:000271150300022
PM 19861671
ER
PT J
AU Ross, JS
Detsky, AS
AF Ross, Joseph S.
Detsky, Allan S.
TI Health Care Choices and Decisions in the United States and Canada
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Detsky, Allan S.] Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada.
[Detsky, Allan S.] Univ Toronto, Dept Hlth Policy, Toronto, ON, Canada.
[Detsky, Allan S.] Univ Toronto, Dept Management, Toronto, ON, Canada.
[Detsky, Allan S.] Univ Toronto, Dept Evaluat & Med, Toronto, ON, Canada.
[Detsky, Allan S.] Univ Hlth Network, Toronto, ON, Canada.
[Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr, New York, NY USA.
[Ross, Joseph S.] Mt Sinai Sch Med, Dept Palliat Care & Med, New York, NY USA.
[Ross, Joseph S.] James J Peters Vet Adm Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, Bronx, NY USA.
[Ross, Joseph S.] James J Peters Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA.
RP Detsky, AS (reprint author), Mt Sinai Hosp, Dept Med, 429-600 Univ Ave, Toronto, ON M5G 1X5, Canada.
EM adetsky@mtsinai.on.ca
FU NIA NIH HHS [K08 AG032886-01, K08 AG032886]
NR 8
TC 3
Z9 3
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD OCT 28
PY 2009
VL 302
IS 16
BP 1803
EP 1804
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 511FW
UT WOS:000271150300024
PM 19861673
ER
PT J
AU Campbell, EG
Rosenthal, M
AF Campbell, Eric G.
Rosenthal, Meredith
TI Reform of Continuing Medical Education Investments in Physician Human
Capital
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Campbell, Eric G.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA.
[Rosenthal, Meredith] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
RP Campbell, EG (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Stanford St,9th Floor, Boston, MA 02114 USA.
EM ecampbell@partners.org
OI Rosenthal, Meredith/0000-0003-3410-0184
NR 8
TC 6
Z9 6
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD OCT 28
PY 2009
VL 302
IS 16
BP 1807
EP 1808
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 511FW
UT WOS:000271150300026
PM 19861675
ER
PT J
AU Ran, CZ
Xu, XY
Raymond, SB
Ferrara, BJ
Neal, K
Bacskai, BJ
Medarova, Z
Moore, A
AF Ran, Chongzhao
Xu, Xiaoyin
Raymond, Scott B.
Ferrara, Brian J.
Neal, Krista
Bacskai, Brian J.
Medarova, Zdravka
Moore, Anna
TI Design, Synthesis, and Testing of Difluoroboron-Derivatized Curcumins as
Near-Infrared Probes for in Vivo Detection of Amyloid-beta Deposits
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID PITTSBURGH COMPOUND-B; ALZHEIMERS-DISEASE; MOUSE MODEL; TRANSGENIC MICE;
CONTRAST AGENT; ZUR KENNTNIS; PLAQUES; BRAIN; PHOSPHORESCENCE;
FLUORESCENCE
AB Amyloid-beta (A beta) deposits have been identified as key players in the progression of Alzheimer's disease (AD). Recent evidence indicates that the deposits probably precede and induce the neuronal atrophy. Therefore, methods that enable monitoring the pathology before clinical symptoms are observed would be beneficial for early AD detection. Here, we report the design, synthesis, and testing of a curcumin-derivatized near-infrared (NIR) probe, CRANAD-2. Upon interacting with A beta aggregates, CRANAD-2 undergoes a range of changes, which include a 70-fold fluorescence intensity increase, a 90 nm blue shift (from 805 to 715 nm), and a large increase in quantum yield. Moreover, this probe also shows a high affinity for A beta aggregates (K(d) = 38.0 nM), a reasonable log P value (log P = 3), considerable stability in serum, and a weak interaction with albumin. After intravenous injection of this probe, 19-month-old Tg2576 mice exhibited significantly higher relative signal than that of the control mice over the same period of time. In summary, CRANAD-2 meets all the requirements for a NIR contrast agent for the detection of A beta plaques both in vitro and in vivo. Our data point toward the feasibility of monitoring the progress of the disease by NIR imaging with CRANAD-2. In addition, we believe that our probe could be potentially used as a tool for drug screening.
C1 [Ran, Chongzhao; Medarova, Zdravka; Moore, Anna] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Mol Imaging Lab,Dept Radio, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA.
[Xu, Xiaoyin] Brigham & Womens Hosp, Dept Radiol, Opt Imaging Lab, Boston, MA 02115 USA.
[Raymond, Scott B.; Ferrara, Brian J.; Neal, Krista; Bacskai, Brian J.] Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Unit, Boston, MA 02114 USA.
RP Moore, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Mol Imaging Lab,Dept Radio, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Room 2301,Bldg 149, Charlestown, MA 02129 USA.
EM amoore@helix.mgh.harvard.edu
OI Raymond, Scott/0000-0001-7008-8974
FU NIH [AG026240, CA113672]
FX This work was partially supported by the NIH Program Project Grants
AG026240 (B.J.B.) and CA113672 (A.M.).
NR 39
TC 131
Z9 134
U1 8
U2 64
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD OCT 28
PY 2009
VL 131
IS 42
BP 15257
EP 15261
DI 10.1021/ja9047043
PG 5
WC Chemistry, Multidisciplinary
SC Chemistry
GA 512SX
UT WOS:000271272000044
PM 19807070
ER
PT J
AU Lim, LY
Vidnovic, N
Ellisen, LW
Leong, CO
AF Lim, L. Y.
Vidnovic, N.
Ellisen, L. W.
Leong, C-O
TI Mutant p53 mediates survival of breast cancer cells
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE p53; breast cancer; gain of function; p63; p73; apoptosis
ID LI-FRAUMENI-SYNDROME; WILD-TYPE P53; TUMOR-SUPPRESSOR P53;
GAIN-OF-FUNCTION; P73-DEPENDENT APOPTOSIS; FUNCTION MUTATIONS; TP53
GENOTYPE; P73; P63; FAMILY
AB BACKGROUND: p53 is the most commonly mutated tumour-suppressor gene in human cancers. Unlike other tumour-suppressor genes, most p53 cancer mutations are missense mutations within the core domain, leading to the expression of a full-length mutant p53 protein. Accumulating evidence has indicated that p53 cancer mutants not only lose tumour suppression activity but also gain new oncogenic activities to promote tumourigenesis.
METHODS: The endogenous mutant p53 function in human breast cancer cells was studied using RNA interference (RNAi). Gene knockdown was confirmed by quantitative PCR and western blotting. Apoptosis was evaluated by morphological changes of cells, their PARP cleavage and annexin V staining.
RESULTS: We show that cancer-associated p53 missense mutants are required for the survival of breast cancer cells. Inhibition of endogenous mutant p53 by RNAi led to massive apoptosis in two mutant p53-expressing cell lines, T47D and MDA-MB-468, but not in the wild-type p53-expressing cells, MCF-7 and MCF-10A. Reconstitution of an RNAi-insensitive mutant p53 in MDA-MB-468 cells completely abolished the apoptotic effects after silencing of endogenous mutant p53, suggesting the specific survival effects of mutant p53. The apoptotic effect induced by mutant p53 ablation, however, is independent of p63 or p73 function.
CONCLUSION: These findings provide clear evidence of a pro-survival 'gain-of-function' property of a subset of p53 cancer mutants in breast cancer cells. British Journal of Cancer ( 2009) 101, 1606-1612. doi: 10.1038/sj.bjc.6605335 www.bjcancer.com Published online 22 September 2009 (C) 2009 Cancer Research UK
C1 [Lim, L. Y.; Leong, C-O] Int Med Univ, Kuala Lumpur 57000, Malaysia.
[Vidnovic, N.; Ellisen, L. W.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
RP Leong, CO (reprint author), Int Med Univ, 126 Jalan 19-155B,Bukit Jalil, Kuala Lumpur 57000, Malaysia.
EM cheeonn_leong@imu.edu.my
FU MAKNA Cancer Research Award, Malaysia; Ministry of Science, Technology
and Innovation, Malaysia [02-02-09-SF0010]; International Medical
University Research Fund [IMU-168-2008, BMS I02-2008(03)]
FX This work was supported by a grant from the MAKNA Cancer Research Award,
Malaysia, and by-Science Fund 02-02-09-SF0010 from the Ministry of
Science, Technology and Innovation, Malaysia (to COL); and by the
International Medical University Research Fund IMU-168-2008 (to COL) and
BMS I02-2008(03) ( to LYL). No sponsors of this work had any function in
the design or conduct of the study, in the collection, analysis, and
interpretation of data, or in the preparation, review, or approval of
the paper.
NR 51
TC 61
Z9 62
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD OCT 27
PY 2009
VL 101
IS 9
BP 1606
EP 1612
DI 10.1038/sj.bjc.6605335
PG 7
WC Oncology
SC Oncology
GA 512KO
UT WOS:000271247800017
PM 19773755
ER
PT J
AU Thatte, HS
Rousou, L
Hussaini, BE
Lu, XG
Treanor, PR
Khuri, SF
AF Thatte, Hemant S.
Rousou, Laki
Hussaini, Bader E.
Lu, Xiu-Gui
Treanor, Patrick R.
Khuri, Shukri F.
TI Development and Evaluation of a Novel Solution, Somah, for the
Procurement and Preservation of Beating and Nonbeating Donor Hearts for
Transplantation
SO CIRCULATION
LA English
DT Article
DE endothelium; myocytes; nitric oxide synthase; transplantation
ID GAP-JUNCTIONAL HEMICHANNELS; SAPHENOUS-VEIN; GLUCOSE-METABOLISM; ATP;
CARDIOPROTECTION; DICHLOROACETATE; REPERFUSION; GLYCOLYSIS; PHYSIOLOGY;
INSULIN
AB Background-Injury to myocytes, endocardium, and the coronary endothelium during harvesting and storage can compromise outcomes after heart transplantation. Safeguarding of structure and function of cardiomyocytes and endothelium in donor hearts may lead to improved patient survival after transplantation. Information gained from porcine hearts stored in standard transplant solution was used to design a superior preservation solution that would optimally protect and maintain organs from beating heart and/or nonbeating heart donors during long-term storage.
Methods and Results-Multiphoton microscopy was used to image deep within cardiac biopsies and coronary artery tissue harvested from porcine hearts obtained from beating heart and nonbeating heart donors for analysis of myocyte and endothelial cell structure and function. Cell structural integrity and viability, calcium mobilization, and nitric oxide generation were determined with fluorescence viability markers, immunofluorescence, and Western blots. During hypothermic storage in standard preservation solution, Celsior, myocyte, and endothelial viability was markedly attenuated in hearts obtained from beating heart donors. In contrast, hearts from beating and nonbeating heart donors stored in the newly formulated Somah solution demonstrated an increase in high-energy phosphate levels, protection of cardiac myocyte viability, mitochondrial membrane polarization, and structural proteins. Similarly, coronary artery endothelial organization and function, calcium mobilization, and nitric oxide generation were well maintained during temporal storage in Somah.
Conclusions-The Celsior preservation solution in clinical use today has led to a profound decline in cardiomyocyte and endothelial cell viability, whereas the newly designed Somah solution has safeguarded myocyte and endothelial integrity and function during organ storage. Use of Somah as a storage medium may lead to optimized graft function and long-term patient survival after transplantation. (Circulation. 2009;120:1704-1713.)
C1 Harvard Univ, Sch Med, Dept Surg, Cardiothorac Div,VA Boston Healthcare Syst, Boston, MA 02115 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Thatte, HS (reprint author), VA Boston Healthcare Syst, Dept Surg 112, 1400 VFW Pkwy, W Roxbury, MA 02132 USA.
EM Hemant_thatte@hms.harvard.edu
FU National Institutes of Health [T32]
FX This work was supported by grants from DoD/ONR (Dr Thatte) and VA
Medical Research Service (Drs Khuri and Thatte). Dr Rousou was supported
by the T32 National Institutes of Health training grant.
NR 40
TC 15
Z9 16
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 27
PY 2009
VL 120
IS 17
BP 1704
EP 1713
DI 10.1161/CIRCULATIONAHA.108.808907
PG 10
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 511HB
UT WOS:000271153500010
PM 19822811
ER
PT J
AU Saam, T
Raya, JG
Cyran, CC
Bochmann, K
Meimarakis, G
Dietrich, O
Clevert, DA
Frey, U
Yuan, C
Hatsukami, TS
Werf, A
Reiser, MF
Nikolaou, K
AF Saam, Tobias
Raya, Jose G.
Cyran, Clemens C.
Bochmann, Katja
Meimarakis, Georgios
Dietrich, Olaf
Clevert, Dirk A.
Frey, Ute
Yuan, Chun
Hatsukami, Thomas S.
Werf, Abe
Reiser, Maximilian F.
Nikolaou, Konstantin
TI High resolution carotid black-blood 3T MR with parallel imaging and
dedicated 4-channel surface coils
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
ID RISK-ASSESSMENT STRATEGIES; MAGNETIC-FIELD STRENGTHS; RICH NECROTIC
CORE; IN-VIVO; ATHEROSCLEROTIC PLAQUE; QUANTITATIVE ASSESSMENT;
VULNERABLE PATIENT; LESIONS; REPRODUCIBILITY; ULTRASOUND
AB Background: Most of the carotid plaque MR studies have been performed using black-blood protocols at 1.5 T without parallel imaging techniques. The purpose of this study was to evaluate a multi-sequence, black-blood MR protocol using parallel imaging and a dedicated 4-channel surface coil for vessel wall imaging of the carotid arteries at 3 T.
Materials and methods: 14 healthy volunteers and 14 patients with intimal thickening as proven by duplex ultrasound had their carotid arteries imaged at 3 T using a multi-sequence protocol (time-of-flight MR angiography, pre-contrast T1w-, PDw- and T2w sequences in the volunteers, additional post-contrast T1w- and dynamic contrast enhanced sequences in patients). To assess intrascan reproducibility, 10 volunteers were scanned twice within 2 weeks.
Results: Intrascan reproducibility for quantitative measurements of lumen, wall and outer wall areas was excellent with Intraclass Correlation Coefficients >0.98 and measurement errors of 1.5%, 4.5% and 1.9%, respectively. Patients had larger wall areas than volunteers in both common carotid and internal carotid arteries and smaller lumen areas in internal carotid arteries (p < 0.001). Positive correlations were found between wall area and cardiovascular risk factors such as age, hypertension, coronary heart disease and hypercholesterolemia (Spearman's r = 0.45-0.76, p < 0.05). No significant correlations were found between wall area and body mass index, gender, diabetes or a family history of cardiovascular disease.
Conclusion: The findings of this study indicate that high resolution carotid black-blood 3 T MR with parallel imaging is a fast, reproducible and robust method to assess carotid atherosclerotic plaque in vivo and this method is ready to be used in clinical practice.
C1 [Saam, Tobias; Raya, Jose G.; Dietrich, Olaf] Univ Munich, Dept Clin Radiol, Josef Lissner Lab Biomed Imaging, Munich, Germany.
[Meimarakis, Georgios; Frey, Ute] Univ Munich, Dept Surg, Munich, Germany.
[Yuan, Chun] Univ Washington, Dept Radiol, Seattle, WA 98195 USA.
[Hatsukami, Thomas S.] VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98108 USA.
[Hatsukami, Thomas S.] Univ Washington, Dept Surg, Seattle, WA 98195 USA.
[Werf, Abe] Machnet BV, Td Eelde, Netherlands.
RP Saam, T (reprint author), Univ Munich, Dept Clin Radiol, Josef Lissner Lab Biomed Imaging, Grosshadern Campus, Munich, Germany.
EM Tobias.Saam@med.uni-muenchen.de; Jose.Raya@med.uni-muenchen.de;
Clemens.Cyran@med.uni-muenchen.de; katja.bochmann@med.uni-muenchen.de;
Georgios.Meimarakis@med.uni-muenchen.de;
Olaf.Dietrich@med.uni-muenchen.de; Dirk.Clevert@med.uni-muenchen.de;
Ute.Frey@med.uni-muenchen.de; cyuan@u.washington.edu;
tomhat@u.washington.edu; avanderwerf@machnet.nl;
Maximilian.Reiser@med.uni-muenchen.de; Nikolaou@med.uni-muenchen.de
RI Dietrich, Olaf/C-4696-2014;
OI Dietrich, Olaf/0000-0001-6182-5039; Nikolaou,
Konstantin/0000-0003-2668-7325; Clevert, Dirk Andre/0000-0003-3889-5447
NR 30
TC 25
Z9 26
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1097-6647
J9 J CARDIOVASC MAGN R
JI J. Cardiov. Magn. Reson.
PD OCT 27
PY 2009
VL 11
AR 41
DI 10.1186/1532-429X-11-41
PG 12
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 516FY
UT WOS:000271528700001
PM 19860875
ER
PT J
AU Qureshi, AH
Chaoji, V
Maiguel, D
Faridi, MH
Barth, CJ
Salem, SM
Singhal, M
Stoub, D
Krastins, B
Ogihara, M
Zaki, MJ
Gupta, V
AF Qureshi, Amir H.
Chaoji, Vineet
Maiguel, Dony
Faridi, Mohd Hafeez
Barth, Constantinos J.
Salem, Saeed M.
Singhal, Mudita
Stoub, Darren
Krastins, Bryan
Ogihara, Mitsunori
Zaki, Mohammed J.
Gupta, Vineet
TI Proteomic and Phospho-Proteomic Profile of Human Platelets in Basal,
Resting State: Insights into Integrin Signaling
SO PLOS ONE
LA English
DT Article
ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; FLOW-CYTOMETRIC ANALYSIS; ACTIVATED
PLATELETS; MASS-SPECTROMETRY; THREONINE PHOSPHORYLATION;
AFFINITY-CHROMATOGRAPHY; PROTEIN INTERACTIONS; INTERACTION NETWORKS;
IDENTIFICATION; INTERACTOME
AB During atherogenesis and vascular inflammation quiescent platelets are activated to increase the surface expression and ligand affinity of the integrin alpha IIb beta 3 via inside-out signaling. Diverse signals such as thrombin, ADP and epinephrine transduce signals through their respective GPCRs to activate protein kinases that ultimately lead to the phosphorylation of the cytoplasmic tail of the integrin alpha IIb beta 3 and augment its function. The signaling pathways that transmit signals from the GPCR to the cytosolic domain of the integrin are not well defined. In an effort to better understand these pathways, we employed a combination of proteomic profiling and computational analyses of isolated human platelets. We analyzed ten independent human samples and identified a total of 1507 unique proteins in platelets. This is the most comprehensive platelet proteome assembled to date and includes 190 membrane-associated and 262 phosphorylated proteins, which were identified via independent proteomic and phospho-proteomic profiling. We used this proteomic dataset to create a platelet protein-protein interaction (PPI) network and applied novel contextual information about the phosphorylation step to introduce limited directionality in the PPI graph. This newly developed contextual PPI network computationally recapitulated an integrin signaling pathway. Most importantly, our approach not only provided insights into the mechanism of integrin alpha IIb beta 3 activation in resting platelets but also provides an improved model for analysis and discovery of PPI dynamics and signaling pathways in the future.
RP Qureshi, AH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA 02115 USA.
EM vgupta2@med.miami.edu
OI Zaki, Mohammed/0000-0003-4711-0234; Gupta, Vineet/0000-0001-6987-2550
FU NIBIB NIH HHS [1R01EB0080161]; NIDDK NIH HHS [K01 DK068253,
K01DK068253]; NINDS NIH HHS [R03 NS053659, R03NS053659]
NR 67
TC 54
Z9 57
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 27
PY 2009
VL 4
IS 10
AR e7627
DI 10.1371/journal.pone.0007627
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 511ET
UT WOS:000271147400019
PM 19859549
ER
PT J
AU Chaturvedi, CP
Hosey, AM
Palii, C
Perez-Iratxeta, C
Nakatani, Y
Ranish, JA
Dilworth, FJ
Brand, M
AF Chaturvedi, Chandra-Prakash
Hosey, Alison M.
Palii, Carmen
Perez-Iratxeta, Carolina
Nakatani, Yoshihiro
Ranish, Jeffrey A.
Dilworth, F. Jeffrey
Brand, Marjorie
TI Dual role for the methyltransferase G9a in the maintenance of
beta-globin gene transcription in adult erythroid cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE chromatin; histone methylation; UTX; NF-E2
ID LOCUS-CONTROL REGION; HISTONE H3; LYSINE-9 METHYLATION; HUMAN GENOME;
CHROMATIN; DIFFERENTIATION; RECRUITMENT; ACTIVATION; COMPLEX; PROTEIN
AB Using a proteomics screen, we have identified the methyltransferase G9a as an interacting partner of the hematopoietic activator NF-E2. We show that G9a is recruited to the beta-globin locus in a NF-E2-dependent manner and spreads over the entire locus. While G9a is often regarded as a corepressor, knocking down this protein in differentiating adult erythroid cells leads to repression of the adult beta(maj) globin gene and aberrant reactivation of the embryonic beta-like globin gene E(y). While in adult cells G9a maintains E(y) in a repressed state via dimethylation of histone H3 at lysines 9 and 27, it activates beta(maj) transcription in a methyltransferase-independent manner. Interestingly, the demethylase UTX is recruited to the beta(maj) (but not the Ey) promoter where it antagonizes G9a-dependent H3K27 dimethylation. Collectively, these results reveal a dual role for G9a in maintaining proper expression (both repression and activation) of the beta-globin genes in differentiating adult erythroid cells.
C1 [Chaturvedi, Chandra-Prakash; Hosey, Alison M.; Palii, Carmen; Perez-Iratxeta, Carolina; Dilworth, F. Jeffrey; Brand, Marjorie] Ottawa Hosp, Res Inst, Regenerat Med Program, Sprott Ctr Stem Cell Res, Ottawa, ON K1H 8L6, Canada.
[Nakatani, Yoshihiro] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Ranish, Jeffrey A.] Inst Syst Biol, Seattle, WA 98103 USA.
[Dilworth, F. Jeffrey; Brand, Marjorie] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8L6, Canada.
RP Brand, M (reprint author), Ottawa Hosp, Res Inst, Regenerat Med Program, Sprott Ctr Stem Cell Res, Ottawa, ON K1H 8L6, Canada.
EM mbrand@ohri.ca
FU Canadian Institutes of Health Research; Terry Fox Foundation (Canadian
Cancer Society Research Institute); CIHR/Thalassemia Foundation of
Canada fellowship
FX We thank A. Dean and M. Lorincz for critically reading the manuscript;
P. Chambon, S. Pradhan, P. Rakopoulos (The Sprott Center for Stem Cell
Research, Regenerative Medicine Program, Ottawa Hospital Research
Institute, Ottawa, ON Canada), Y. Shinkai, and L. Tora for providing
reagents; A. Desjardins for technical help; G. Palidwor for microarray
data analysis; and F. Dumas for Edman sequencing. This project was
funded with grants from the Canadian Institutes of Health Research and
the Terry Fox Foundation (Canadian Cancer Society Research Institute)
(to to M. B.) and a CIHR/Thalassemia Foundation of Canada fellowship (to
C-P. C.). M. B. holds the Canadian Research Chair in the regulation of
gene expression.
NR 35
TC 43
Z9 43
U1 1
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 27
PY 2009
VL 106
IS 43
BP 18303
EP 18308
DI 10.1073/pnas.0906769106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 512DB
UT WOS:000271222500048
PM 19822740
ER
PT J
AU Zhang, HM
Liu, JH
Yang, W
Springer, T
Shimaoka, M
Wang, JH
AF Zhang, Hongmin
Liu, Jin-huan
Yang, Wei
Springer, Timothy
Shimaoka, Motomu
Wang, Jia-huai
TI Structural basis of activation-dependent binding of ligand-mimetic
antibody AL-57 to integrin LFA-1
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cell adhesion; crystal structure; ICAM-1
ID I-DOMAIN; HIGH-AFFINITY; CRYSTAL-STRUCTURE; DISULFIDE BOND; COMPLEX;
ICAM-1; CONFORMATION; RECOGNITION; CD11B/CD18; ADHESION
AB The activity of integrin LFA-1 (alpha(L)beta(2)) to its ligand ICAM-1 is regulated through the conformational changes of its ligand-binding domain, the I domain of alpha(L) chain, from an inactive, low-affinity closed form (LA), to an intermediate-affinity form (IA), and then finally, to a high-affinity open form (HA). A ligand-mimetic human monoclonal antibody AL-57 (activated LFA-1 clone 57) was identified by phage display to specifically recognize the affinity-upregulated I domain. Here, we describe the crystal structures of the Fab fragment of AL-57 in complex with IA, as well as in its unligated form. We discuss the structural features conferring AL-57's strong selectivity for the high affinity, open conformation of the I domain. The AL-57-binding site overlaps the ICAM-1 binding site on the I domain. Furthermore, an antibody Asp mimics an ICAM Glu by forming a coordination to the metal-ion dependent adhesion site (MIDAS). The structure also reveals better shape complementarity and a more hydrophobic interacting interface in AL-57 binding than in ICAM-1 binding. The results explain AL-57's antagonistic mimicry of LFA-1's natural ligands, the ICAM molecules.
C1 [Yang, Wei; Springer, Timothy; Shimaoka, Motomu] Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA.
[Springer, Timothy; Shimaoka, Motomu] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Zhang, Hongmin; Liu, Jin-huan; Wang, Jia-huai] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA.
[Zhang, Hongmin; Liu, Jin-huan; Wang, Jia-huai] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Yang, Wei; Springer, Timothy] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Shimaoka, Motomu] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA.
RP Springer, T (reprint author), Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA.
EM springer@idi.harvard.edu; jwang@red.dfci.harvard.edu
RI Zhang, Hongmin/C-4503-2009
OI Zhang, Hongmin/0000-0001-6357-4106
FU National Institutes of Health [HL48675, CA31798, AI063421]
FX This work has been supported by National Institutes of Health Grants
HL48675 (to J. H. W. and M. S.), CA31798 (to T. A. S.), and AI063421 (to
M. S.).
NR 26
TC 10
Z9 10
U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 27
PY 2009
VL 106
IS 43
BP 18345
EP 18350
DI 10.1073/pnas.0909301106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 512DB
UT WOS:000271222500055
PM 19805116
ER
PT J
AU Sos, ML
Fischer, S
Ullrich, R
Peifer, M
Heuckmann, JM
Koker, M
Heynck, S
Stuckrath, I
Weiss, J
Fischer, F
Michel, K
Goel, A
Regales, L
Politi, KA
Perera, S
Getlik, M
Heukamp, LC
Ansen, S
Zander, T
Beroukhim, R
Kashkar, H
Shokat, KM
Sellers, WR
Rauh, D
Orr, C
Hoeflich, KP
Friedman, L
Wong, KK
Pao, W
Thomas, RK
AF Sos, Martin L.
Fischer, Stefanie
Ullrich, Roland
Peifer, Martin
Heuckmann, Johannes M.
Koker, Mirjam
Heynck, Stefanie
Stueckrath, Isabel
Weiss, Jonathan
Fischer, Florian
Michel, Kathrin
Goel, Aviva
Regales, Lucia
Politi, Katerina A.
Perera, Samanthi
Getlik, Matthaeus
Heukamp, Lukas C.
Ansen, Sascha
Zander, Thomas
Beroukhim, Rameen
Kashkar, Hamid
Shokat, Kevan M.
Sellers, William R.
Rauh, Daniel
Orr, Christine
Hoeflich, Klaus P.
Friedman, Lori
Wong, Kwok-Kin
Pao, William
Thomas, Roman K.
TI Identifying genotype-dependent efficacy of single and combined PI3K-and
MAPK-pathway inhibition in cancer
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cancer genomics; combination therapy; high-throughput cell line
screening; oncogene dependency
ID CELL LUNG-CANCER; ACQUIRED-RESISTANCE; MEK INHIBITORS; BCR-ABL; IN-VIVO;
KINASE; MUTATIONS; GEFITINIB; ACTIVATION; RAPAMYCIN
AB In cancer, genetically activated proto-oncogenes often induce "upstream'' dependency on the activity of the mutant oncoprotein. Therapeutic inhibition of these activated oncoproteins can induce massive apoptosis of tumor cells, leading to sometimes dramatic tumor regressions in patients. The PI3K and MAPK signaling pathways are central regulators of oncogenic transformation and tumor maintenance. We hypothesized that upstream dependency engages either one of these pathways preferentially to induce "downstream'' dependency. Therefore, we analyzed whether downstream pathway dependency segregates by genetic aberrations upstream in lung cancer cell lines. Here, we show by systematically linking drug response to genomic aberrations in non-small-cell lung cancer, as well as in cell lines of other tumor types and in a series of in vivo cancer models, that tumors with genetically activated receptor tyrosine kinases depend on PI3K signaling, whereas tumors with mutations in the RAS/RAF axis depend on MAPK signaling. However, efficacy of downstream pathway inhibition was limited by release of negative feedback loops on the reciprocal pathway. By contrast, combined blockade of both pathways was able to overcome the reciprocal pathway activation induced by inhibitor-mediated release of negative feedback loops and resulted in a significant increase in apoptosis and tumor shrinkage. Thus, by using a systematic chemo-genomics approach, we identify genetic lesions connected to PI3K and MAPK pathway activation and provide a rationale for combined inhibition of both pathways. Our findings may have implications for patient stratification in clinical trials.
C1 [Sos, Martin L.; Fischer, Stefanie; Ullrich, Roland; Peifer, Martin; Heuckmann, Johannes M.; Koker, Mirjam; Heynck, Stefanie; Stueckrath, Isabel; Weiss, Jonathan; Fischer, Florian; Michel, Kathrin; Thomas, Roman K.] Univ Cologne, Max Planck Inst Neurol Res, D-50931 Cologne, Germany.
[Sos, Martin L.; Fischer, Stefanie; Ullrich, Roland; Peifer, Martin; Heuckmann, Johannes M.; Koker, Mirjam; Heynck, Stefanie; Stueckrath, Isabel; Weiss, Jonathan; Fischer, Florian; Michel, Kathrin; Thomas, Roman K.] Univ Cologne, Klaus Joachim Zulch Labs, Max Planck Soc, D-50931 Cologne, Germany.
[Sos, Martin L.; Fischer, Stefanie; Ullrich, Roland; Peifer, Martin; Heuckmann, Johannes M.; Koker, Mirjam; Heynck, Stefanie; Stueckrath, Isabel; Weiss, Jonathan; Fischer, Florian; Michel, Kathrin; Thomas, Roman K.] Univ Cologne, Fac Med, D-50931 Cologne, Germany.
[Goel, Aviva; Regales, Lucia; Politi, Katerina A.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA.
[Perera, Samanthi; Beroukhim, Rameen; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Getlik, Matthaeus; Rauh, Daniel; Thomas, Roman K.] Max Planck Soc, Chem Genom Ctr, D-44227 Dortmund, Germany.
[Heukamp, Lukas C.] Univ Hosp Bonn Med Sch, Dept Pathol, D-53127 Bonn, Germany.
[Ansen, Sascha; Zander, Thomas; Thomas, Roman K.] Univ Cologne, Fac Med, Dept Internal Med, D-50924 Cologne, Germany.
[Ansen, Sascha; Zander, Thomas; Thomas, Roman K.] Univ Cologne, Fac Med, Ctr Integrated Oncol Cologne Bonn, D-50924 Cologne, Germany.
[Kashkar, Hamid] Univ Cologne, Fac Med, Inst Med Microbiol Immunol & Hyg, D-50924 Cologne, Germany.
[Beroukhim, Rameen] Harvard & MIT, Broad Inst, Cambridge, MA 02141 USA.
[Shokat, Kevan M.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
[Shokat, Kevan M.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
[Shokat, Kevan M.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
[Sellers, William R.] Novartis Inst BioMed Res, Cambridge, MA 02139 USA.
[Orr, Christine; Hoeflich, Klaus P.; Friedman, Lori] Genentech Inc, Dept Canc Signaling & Translat Oncol, San Francisco, CA 94070 USA.
[Wong, Kwok-Kin] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Wong, Kwok-Kin] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Pao, William] Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA.
RP Thomas, RK (reprint author), Univ Cologne, Max Planck Inst Neurol Res, Gleueler Str 50, D-50931 Cologne, Germany.
EM nini@nf.mpg.de
RI Rauh, Daniel/G-1595-2013; Heukamp, Lukas/A-8338-2013;
OI Rauh, Daniel/0000-0002-1970-7642; wong, kwok kin/0000-0001-6323-235X
FU Deutsche Krebshilfe [107954]; Fritz-Thyssen-Stiftung [10.08.2.175];
German Ministry of Science and Education NGFNplus-program BMBF
[01GS08100]; Deutsche Forschungsgemeinschaft [SFB832]; National Cancer
Institute [R01 CA121210]; Cologne Fortune Program/Faculty of Medicine,
University of Cologne
FX This work was supported by Deutsche Krebshilfe Grant 107954,
Fritz-Thyssen-Stiftung Grant 10.08.2.175, and German Ministry of Science
and Education NGFNplus-program BMBF Grant 01GS08100 (to R. K. T.), by
the Deutsche Forschungsgemeinschaft through SFB832 (to R. K. T. and L.
C. H.), and National Cancer Institute Grant R01 CA121210 (to W. P.). S.
F. holds a scholarship of the Cologne Fortune Program/Faculty of
Medicine, University of Cologne.
NR 39
TC 156
Z9 156
U1 0
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 27
PY 2009
VL 106
IS 43
BP 18351
EP 18356
DI 10.1073/pnas.0907325106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 512DB
UT WOS:000271222500056
PM 19805051
ER
PT J
AU Bastani, S
Sherman, W
Schnickel, GT
Hsieh, GR
Bhatia, R
Fishbein, MC
Ardehali, A
AF Bastani, Sam
Sherman, William
Schnickel, Gabriel T.
Hsieh, George R.
Bhatia, Rubina
Fishbein, Michael C.
Ardehali, Abbas
TI Chemokine Receptor Blockade With a Synthetic Nonpeptide Compound
Attenuates Cardiac Allograft Vasculopathy
SO TRANSPLANTATION
LA English
DT Article
DE Chemokines; Transplantation; T-lymphocytes
ID CHRONIC REJECTION; SMALL-MOLECULE; IFN-GAMMA; INDUCIBLE PROTEIN-10;
CYTOKINE PRODUCTION; CCR5 ANTAGONIST; CARBON-MONOXIDE; TARGETING CCR5;
CXCR3; PATHOGENESIS
AB Background. Recruitment of recipient mononuclear cells to the donor heart is a central event in the development of cardiac allograft vasculopathy (CAV). The role of individual chemokine receptors in this process is incompletely defined. TAK-779 (N,N-dimethyl-N-[4-[[[2-(4-methylphen)-6,7-dihydro-5H-benzocyclohepten-8-yl]carbonyl]amino]benzyl]tetra-hydro-2H-pyran-4-aminium chloride) is a synthetic nonpeptide antagonist of CCR5 and CXCR3. The purpose of this study is to determine if combined CCR5 and CXCR3 blockade by TAK-779 would attenuate CAV in an experimental model.
Methods. We used a previously characterized murine model of CAV. Recipient mice were treated with TAK-779 or vehicle control. Donor hearts were harvested on day 24 posttransplantation and analyzed for intimal thickening and cellular infiltration. Recipient splenocytes were analyzed for proliferative response and interferon (IFN)-gamma production by enzyme-linked immunosorbent spot assay. The donor hearts were also examined for heme oxygenase-1 (HO-1) gene induction.
Results. CCR5 and CXCR3 blockade by TAK-779 reduced the severity of intimal lesions (53 +/- 10% vs. 16 +/- 2%; P<0.05) and decreased the number of graft infiltrating CCR5(+) and CXCR3(+) CD4 and CD8 lymphocytes. Moreover, treatment with TAK-779 (a) decreased alloantigen-specific T-lymphocyte proliferation and number of IFN-gamma producing cells and (b) increased HO-1 gene transcript level in the allografts.
Conclusions. Antagonism of CCR5 and CXCR3 by TAK-779 is effective in controlling CAV. The beneficial effects of TAK-779 maybe because of (a) reduction in CCR5(+) and CXCR3(+) T-lymphocyte subset infiltration into the graft, (b) attenuation of alloantigen-specific T-lymphocyte proliferative response and IFN-gamma production, and (c) induction of HO-1 gene. This compound may offer a novel approach in clinical management of CAV.
C1 [Ardehali, Abbas] Univ Calif Los Angeles, Med Ctr, Dept Surg, David Geffen Sch Med,Div Cardiothorac Surg, Los Angeles, CA 90024 USA.
[Bastani, Sam; Schnickel, Gabriel T.; Hsieh, George R.; Ardehali, Abbas] W Los Angeles VA Med Ctr, Los Angeles, CA USA.
[Fishbein, Michael C.] Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geffen Sch Med, Los Angeles, CA 90024 USA.
RP Ardehali, A (reprint author), Univ Calif Los Angeles, Med Ctr, Dept Surg, David Geffen Sch Med,Div Cardiothorac Surg, 62-186 CHS,10833 Le Conte Ave, Los Angeles, CA 90024 USA.
EM aardehali@mednet.ucla.edu
OI Schnickel, Gabriel/0000-0003-4392-2200
FU American Heart Association; Veterans Administration Research
FX This work was supported by the American Heart Association and Veterans
Administration Research services grants.
NR 35
TC 13
Z9 15
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD OCT 27
PY 2009
VL 88
IS 8
BP 995
EP 1001
DI 10.1097/TP.0b013e3181b9ccd5
PG 7
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 511MP
UT WOS:000271169700009
PM 19855245
ER
PT J
AU Balcioglu, A
AF Balcioglu, Ayguel
TI IDENTIFYING TARGETS FOR THE TREATMENT OF DYSTONIA AND PRECLINICALTESTING
OF THE LEAD COMPOUNDS
SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
LA English
DT Meeting Abstract
C1 [Balcioglu, Ayguel] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 7
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0928-0987
EI 1879-0720
J9 EUR J PHARM SCI
JI Eur. J. Pharm. Sci.
PD OCT 26
PY 2009
VL 38
IS 1
SU S
MA O32
BP 53
EP 54
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA V38LW
UT WOS:000209345900034
ER
PT J
AU Kalashnikov, M
Choi, W
Yu, CC
Sung, YJ
Dasari, RR
Badizadegan, K
Feld, MS
AF Kalashnikov, Maxim
Choi, Wonshik
Yu, Chung-Chieh
Sung, Yongjin
Dasari, Ramachandra R.
Badizadegan, Kamran
Feld, Michael S.
TI Assessing light scattering of intracellular organelles in single intact
living cells
SO OPTICS EXPRESS
LA English
DT Article
ID LOW-COHERENCE INTERFEROMETRY; SCANNING FLOW-CYTOMETRY; EPITHELIAL-CELLS;
IN-SITU; SPECTROSCOPY; MICROSCOPY
AB This report presents a model-independent method of assessing contributions to the light scattering from individual organelles in single intact cells. We first measure the 3D index map of a living cell, and then modify the map in such a way so as to eliminate contrast due to a particular intracellular organelle. By calculating and comparing the light scattering distributions calculated from the original and modified index maps using the Rytov approximation, we extract the light scattering contribution from the particular organelle of interest. The relative contributions of the nucleus and nucleolus to the scattering of the entire cell are thus determined, and the applicability of the homogeneous spherical model to non-spherical and heterogeneous organelles in forward scattering is evaluated. (C) 2008 Optical Society of America
C1 [Kalashnikov, Maxim; Choi, Wonshik; Yu, Chung-Chieh; Sung, Yongjin; Dasari, Ramachandra R.; Badizadegan, Kamran; Feld, Michael S.] MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA.
[Choi, Wonshik] Korea Univ, Dept Phys, Seoul 136701, South Korea.
[Badizadegan, Kamran] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Badizadegan, Kamran] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA.
RP Kalashnikov, M (reprint author), MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA.
EM wonshik@mit.edu
FU National Center for Research Resources of the National Institutes of
Health [P41-RR02594-18]; National Science Foundation [DBI-0754339];
Hamamatsu Corporation
FX This work was funded by the National Center for Research Resources of
the National Institutes of Health (P41-RR02594-18), the National Science
Foundation (DBI-0754339) and Hamamatsu Corporation.
NR 25
TC 16
Z9 16
U1 1
U2 10
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 1094-4087
J9 OPT EXPRESS
JI Opt. Express
PD OCT 26
PY 2009
VL 17
IS 22
BP 19674
EP 19681
DI 10.1364/OE.17.019674
PG 8
WC Optics
SC Optics
GA 517PS
UT WOS:000271629200035
PM 19997187
ER
PT J
AU Fang, QQ
Boas, DA
AF Fang, Qianqian
Boas, David A.
TI Monte Carlo Simulation of Photon Migration in 3D Turbid Media
Accelerated by Graphics Processing Units
SO OPTICS EXPRESS
LA English
DT Article
ID DOMAIN FLUORESCENCE TOMOGRAPHY; DIFFUSION-APPROXIMATION; HETEROGENEOUS
TISSUES; LIGHT TRANSPORT; HEAD MODELS; SCATTERING; ADULT; CODE;
SPECTROSCOPY; PROPAGATION
AB We report a parallel Monte Carlo algorithm accelerated by graphics processing units (GPU) for modeling time-resolved photon migration in arbitrary 3D turbid media. By taking advantage of the massively parallel threads and low-memory latency, this algorithm allows many photons to be simulated simultaneously in a GPU. To further improve the computational efficiency, we explored two parallel random number generators (RNG), including a floating-point-only RNG based on a chaotic lattice. An efficient scheme for boundary reflection was implemented, along with the functions for time-resolved imaging. For a homogeneous semi-infinite medium, good agreement was observed between the simulation output and the analytical solution from the diffusion theory. The code was implemented with CUDA programming language, and benchmarked under various parameters, such as thread number, selection of RNG and memory access pattern. With a low-cost graphics card, this algorithm has demonstrated an acceleration ratio above 300 when using 1792 parallel threads over conventional CPU computation. The acceleration ratio drops to 75 when using atomic operations. These results render the GPU-based Monte Carlo simulation a practical solution for data analysis in a wide range of diffuse optical imaging applications, such as human brain or small-animal imaging. (C) 2009 Optical Society of America
C1 [Fang, Qianqian; Boas, David A.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Fang, QQ (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA.
FU NIH [R01-EB006385]
FX The authors would like to acknowledge Eric Mills for developing and
sharing the shared-memory version of MT19976 random number generator. QF
would like to thank Stefan Carp and Anand Kumar for the discussions on
fluence normalization, and Jay Dubb for processing the brain MRI atlas.
We acknowledge funding support from NIH R01-EB006385 and the valuable
feedback from anonymous reviewers.
NR 35
TC 209
Z9 220
U1 7
U2 50
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 1094-4087
J9 OPT EXPRESS
JI Opt. Express
PD OCT 26
PY 2009
VL 17
IS 22
BP 20178
EP 20190
DI 10.1364/OE.17.020178
PG 13
WC Optics
SC Optics
GA 517PS
UT WOS:000271629200090
PM 19997242
ER
PT J
AU Moriarty, AT
Laucirica, R
Auger, M
Souers, RJ
Chmara, BA
Wilbur, DC
AF Moriarty, Ann T.
Laucirica, Rodolfo
Auger, Manon
Souers, Rhona J.
Chmara, Beth Anne
Wilbur, David C.
TI Granulomatous Inflammation: An Underestimated Cause of False Positive
Diagnoses in Lung Fine Needle Aspirates Observations from the College of
American Pathologists Non Gynecologic Cytopathology (NGC)
Interlaboratory Comparison Program
SO CANCER CYTOPATHOLOGY
LA English
DT Meeting Abstract
C1 [Moriarty, Ann T.] AmeriPath Indiana, Indianapolis, IN USA.
[Laucirica, Rodolfo] Baylor Coll Med, Houston, TX 77030 USA.
[Auger, Manon] McGill Univ, Montreal, PQ, Canada.
[Souers, Rhona J.; Chmara, Beth Anne] Coll Amer Pathologists, Northfield, IL USA.
[Wilbur, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1934-662X
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD OCT 25
PY 2009
VL 117
IS 5
BP 350
EP 350
PG 1
WC Oncology; Pathology
SC Oncology; Pathology
GA 510HM
UT WOS:000271078800004
ER
PT J
AU Ducatman, BS
Bentz, JS
Moriarty, AT
Souers, RJ
Fatheree, LA
Booth, CN
Wilbur, DC
AF Ducatman, Barbara S.
Bentz, Joel S.
Moriarty, Ann T.
Souers, Rhona J.
Fatheree, Lisa A.
Booth, Christine Noga
Wilbur, David C.
TI Performance in Gynecologic Cytology Proficiency Testing: What Have We
Learned?
SO CANCER CYTOPATHOLOGY
LA English
DT Meeting Abstract
C1 [Ducatman, Barbara S.] W Virginia Univ Hosp, Indianapolis, WV USA.
[Bentz, Joel S.] Univ Utah, Salt Lake City, UT USA.
[Moriarty, Ann T.] AmeriPath Indiana, Indianapolis, IN USA.
[Souers, Rhona J.; Fatheree, Lisa A.] Coll Amer Pathologists, Northfield, IL USA.
[Booth, Christine Noga] Cleveland Clin, Dept Anat Pathol, Cleveland, OH 44106 USA.
[Wilbur, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1934-662X
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD OCT 25
PY 2009
VL 117
IS 5
BP 352
EP 353
PG 2
WC Oncology; Pathology
SC Oncology; Pathology
GA 510HM
UT WOS:000271078800008
ER
PT J
AU Qayyum, S
Yagi, Y
Wilbur, DC
AF Qayyum, Sohail
Yagi, Yukako
Wilbur, David C.
TI Optimization of Whole Slide Imaging Parameters for Liquid-Based Cervical
Cytology Slides
SO CANCER CYTOPATHOLOGY
LA English
DT Meeting Abstract
C1 [Qayyum, Sohail; Yagi, Yukako; Wilbur, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1934-662X
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD OCT 25
PY 2009
VL 117
IS 5
BP 353
EP 354
PG 2
WC Oncology; Pathology
SC Oncology; Pathology
GA 510HM
UT WOS:000271078800010
ER
PT J
AU Sweeney, BJ
Wilbur, D
Arpin, RN
Nave, JO
Tambouret, R
AF Sweeney, Brenda J.
Wilbur, David
Arpin, Ronald N., III
Nave, Jolanta O.
Tambouret, Rosemary
TI Cell Cycle Markers in Urinary Cytology: Preliminary Studies Show Promise
for the Triage of Equivocal Specimens
SO CANCER CYTOPATHOLOGY
LA English
DT Meeting Abstract
C1 [Sweeney, Brenda J.; Wilbur, David; Arpin, Ronald N., III; Nave, Jolanta O.; Tambouret, Rosemary] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1934-662X
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD OCT 25
PY 2009
VL 117
IS 5
BP 371
EP 371
PG 1
WC Oncology; Pathology
SC Oncology; Pathology
GA 510HM
UT WOS:000271078800037
ER
PT J
AU Sweeney, BJ
Wilbur, D
Arpin, R
Tambouret, R
AF Sweeney, Brenda J.
Wilbur, David
Arpin, Ronald
Tambouret, Rosemary
TI Testing for High Risk Human Papillomavirus, p16 and ProEx (TM) C on
Cervico-vaginal Cytology
SO CANCER CYTOPATHOLOGY
LA English
DT Meeting Abstract
C1 [Sweeney, Brenda J.; Wilbur, David; Arpin, Ronald; Tambouret, Rosemary] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1934-662X
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD OCT 25
PY 2009
VL 117
IS 5
BP 386
EP 386
PG 1
WC Oncology; Pathology
SC Oncology; Pathology
GA 510HM
UT WOS:000271078800062
ER
PT J
AU Roh, MH
Jo, VY
Stelow, EB
Faquin, WC
Alexander, EK
Benson, CB
Frates, MC
Gawande, A
Larsen, PR
Marqusee, E
Moore, FD
Cibas, ES
AF Roh, Michael H.
Jo, Vickie Y.
Stelow, Edward B.
Faquin, William C.
Alexander, Erik K.
Benson, Carol B.
Frates, Mary C.
Gawande, Atul
Larsen, P. Reed
Marqusee, Ellen
Moore, Francis D., Jr.
Cibas, Edmund S.
TI The Predictive Value of the Fine Needle Aspiration Diagnosis "Suspicious
for a Hurthle Cell Neoplasm" in Patients with Hashimoto Thyroiditis
SO CANCER CYTOPATHOLOGY
LA English
DT Meeting Abstract
C1 [Alexander, Erik K.; Benson, Carol B.; Frates, Mary C.; Gawande, Atul; Larsen, P. Reed; Marqusee, Ellen; Moore, Francis D., Jr.; Cibas, Edmund S.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Jo, Vickie Y.; Stelow, Edward B.] Univ Virginia Hlth Syst, Charlottesville, VA USA.
[Faquin, William C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1934-662X
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD OCT 25
PY 2009
VL 117
IS 5
BP 434
EP 435
PG 2
WC Oncology; Pathology
SC Oncology; Pathology
GA 510HM
UT WOS:000271078800142
ER
PT J
AU Franciosi, S
Sosa, MAG
English, DF
Oler, E
Oung, T
Janssen, WGM
De Gasperi, R
Schmeidler, J
Dickstein, DL
Schmitz, C
Gandy, S
Hof, PR
Buxbaum, JD
Elder, GA
AF Franciosi, Sonia
Sosa, Miguel A. Gama
English, Daniel F.
Oler, Elizabeth
Oung, Twethida
Janssen, William G. M.
De Gasperi, Rita
Schmeidler, James
Dickstein, Dara L.
Schmitz, Christoph
Gandy, Sam
Hof, Patrick R.
Buxbaum, Joseph D.
Elder, Gregory A.
TI Novel cerebrovascular pathology in mice fed a high cholesterol diet
SO MOLECULAR NEURODEGENERATION
LA English
DT Article
ID DENSITY-LIPOPROTEIN RECEPTOR; ALZHEIMERS-DISEASE; MICROVASCULAR
RESPONSES; METABOLIC SYNDROME; APOLIPOPROTEIN-E; KNOCKOUT MICE;
RISK-FACTOR; LOW-FAT; HYPERCHOLESTEROLEMIA; ATHEROSCLEROSIS
AB Background: Hypercholesterolemia causes atherosclerosis in medium to large sized arteries. Cholesterol is less known for affecting the microvasculature and has not been previously reported to induce microvascular pathology in the central nervous system (CNS).
Results: Mice with a null mutation in the low-density lipoprotein receptor (LDLR) gene as well as C57BL/6J mice fed a high cholesterol diet developed a distinct microvascular pathology in the CNS that differs from cholesterol-induced atherosclerotic disease. Microvessel diameter was increased but microvascular density and length were not consistently affected. Degenerative changes and thickened vascular basement membranes were present ultrastructurally. The observed pathology shares features with the microvascular pathology of Alzheimer's disease (AD), including the presence of string-like vessels. Brain apolipoprotein E levels which have been previously found to be elevated in LDLR-/- mice were also increased in C57BL/6J mice fed a high cholesterol diet.
Conclusion: In addition to its effects as an inducer of atherosclerosis in medium to large sized arteries, hypercholesterolemia also induces a microvascular pathology in the CNS that shares features of the vascular pathology found in AD. These observations suggest that high cholesterol may induce microvascular disease in a range of CNS disorders including AD.
C1 [Franciosi, Sonia; Sosa, Miguel A. Gama; English, Daniel F.; De Gasperi, Rita; Schmeidler, James; Gandy, Sam; Buxbaum, Joseph D.; Elder, Gregory A.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
[Franciosi, Sonia; English, Daniel F.; Buxbaum, Joseph D.] Mt Sinai Sch Med, Lab Mol Neuropsychiat, New York, NY 10029 USA.
[Franciosi, Sonia; Sosa, Miguel A. Gama; De Gasperi, Rita] Vet Affairs Med Ctr, James J Peters Dept, Res & Dev Serv, Bronx, NY 10468 USA.
[Oler, Elizabeth; Oung, Twethida; Janssen, William G. M.; Dickstein, Dara L.; Schmitz, Christoph; Hof, Patrick R.; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA.
[Dickstein, Dara L.; Hof, Patrick R.] Mt Sinai Sch Med, Computat Neurobiol & Imaging Ctr, New York, NY 10029 USA.
[Gandy, Sam; Elder, Gregory A.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA.
[Gandy, Sam; Elder, Gregory A.] Vet Affairs Med Ctr, James J Peters Dept, Neurol Serv, Bronx, NY 10468 USA.
[Hof, Patrick R.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA.
[Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
RP Elder, GA (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl, New York, NY 10029 USA.
EM sfranciosi@cmmt.ubc.ca; miguel.gama-sosa@mssm.edu;
englishdaniel@gmail.com; lizoler@gmail.com; twethida.oung@mssm.edu;
bill.janssen@mssm.edu; rita.de-gasperi@mssm.edu;
james.schmeidler@mssm.edu; dara.dickstein@mssm.edu; cs.999@gmx.net;
samuel.gandy@mssm.edu; patrick.hof@mssm.edu; joseph.buxbaum@mssm.edu;
gregory.elder@mssm.edu
RI Dickstein, Dara/F-3036-2013;
OI Buxbaum, Joseph/0000-0001-8898-8313
FU NIH [AG02219, AG05138]
FX We thank Bridget Wicinski for expert technical assistance. This work was
supported by NIH grants AG02219 and AG05138.
NR 53
TC 11
Z9 11
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1750-1326
J9 MOL NEURODEGENER
JI Mol. Neurodegener.
PD OCT 24
PY 2009
VL 4
AR 42
DI 10.1186/1750-1326-4-42
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 517JG
UT WOS:000271608800001
PM 19852847
ER
PT J
AU Choi, AI
Shlipak, MG
Hunt, PW
Martin, JN
Deeks, SG
AF Choi, Andy I.
Shlipak, Michael G.
Hunt, Peter W.
Martin, Jeffrey N.
Deeks, Steven G.
TI HIV-infected persons continue to lose kidney function despite successful
antiretroviral therapy
SO AIDS
LA English
DT Article
DE antiretroviral therapy; glomerular filtration rate; HIV; kidney
diseases; viral load
ID IMPROVES RENAL-FUNCTION; RISK-FACTORS; SERUM CREATININE; DISEASE;
NEPHROPATHY; WOMEN; ASSOCIATION; FAILURE; RECOMMENDATIONS; PROTEINURIA
AB Objective: To identify risk factors associated with kidney function decline in a contemporary cohort of treated and untreated HIV-infected patients.
Methods: We followed individuals enrolled in the Study of the Consequences Of the Protease inhibitor Era cohort for longitudinal changes in kidney function, defined as glomerular filtration rate estimated from serum creatinine (eGFR). eGFR slope was calculated using linear mixed effects models adjusted for age, sex, race, and time-updated CD4 cell count, viral load, antiretroviral therapy (ART), and comorbid conditions.
Results: We followed 615 patients for a mean of 3.4 (+/- 2.5) years. In multivariable adjusted analyses, predictors of eGFR decline included female sex, diabetes, and hyperlipidemia; CD4 cell count and viral load were not associated with eGFR loss. Among patients who initiated treatment, antiretroviral exposure was associated with a +2.8 (95% confidence interval 0.8-4.7) ml/min per 1.73 m(2) per year effect on eGFR slope. Although these patients appeared to benefit from ART based on the slowing of their eGFR decline, they continued to lose kidney function at a rate of -1.9 (95% confidence interval -3.7 to -0.1) ml/min per 1.73 m(2) per year. In the subgroup of individuals receiving suppressive ART with viral loads maintained below 500 copies/ml, intermittent viremic episodes (blips) were strongly associated with more rapid rates of eGFR loss [-6.7 (95% confidence interval -11.1 to -2.4) ml/min per 1.73 m2 per year].
Conclusion: Although ART appears to help curb kidney function decline, patients who achieved durable viral suppression continue to manifest substantial loss of eGFR. Loss of kidney function may be attributable to treatment-related factors, intermittent viremia, and traditional risk factors for kidney disease. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
C1 [Choi, Andy I.; Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA.
[Choi, Andy I.; Shlipak, Michael G.; Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Hunt, Peter W.; Deeks, Steven G.] San Francisco Gen Hosp, Posit Hlth Program, San Francisco, CA 94110 USA.
[Martin, Jeffrey N.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA.
RP Choi, AI (reprint author), San Francisco VA Med Ctr, Dept Med, Box 111J,4150 Clement St, San Francisco, CA 94121 USA.
EM andy.choi@ucsf.edu
FU National Institutes of Health [K23DK080645-01A1, K23AI65244,
K24AI069994, R01 DK066488-01]; Centers for AIDS Research at UCSF
[A127763, MH59037]; UCSF Clinical and Translational Science Institute
[UL1 RR024131-01]; National Center for Research Resources [KL2
RR024130]; American Heart Association Early Investigator Award; American
Foundation for AIDS Research [106710-40-RGRL]
FX This study was supported by grants from the National Institutes of
Health (K23DK080645-01A1, K23AI65244, K24AI069994, and R01 DK066488-01),
the Centers for AIDS Research at UCSF (A127763 and MH59037), the UCSF
Clinical and Translational Science Institute (UL1 RR024131-01), the
National Center for Research Resources (KL2 RR024130), the American
Heart Association Early Investigator Award, and the American Foundation
for AIDS Research (106710-40-RGRL). These funding sources had no
involvement in the design or execution of this study.
NR 38
TC 53
Z9 54
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD OCT 23
PY 2009
VL 23
IS 16
BP 2143
EP 2149
DI 10.1097/QAD.0b013e3283313c91
PG 7
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 517FS
UT WOS:000271599200009
PM 19684507
ER
PT J
AU Snow, JW
Orkin, SH
AF Snow, Jonathan W.
Orkin, Stuart H.
TI Translational Isoforms of FOG1 Regulate GATA1-interacting Complexes
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TRANSCRIPTION FACTOR GATA-1; ZINC-FINGER PROTEIN; ERYTHROID-CELLS;
CO-REPRESSOR; NORMAL ERYTHROPOIESIS; MAMMALIAN-CELLS; BINDING-PROTEIN;
GENE-EXPRESSION; MESSENGER-RNA; ACTIVATION
AB Erythropoietic and megakaryocytic programs are directed by the transcription factor GATA1. Friend of GATA1 (FOG1), a protein interaction partner of GATA1, is critical for GATA1 function in multiple contexts. Previous work has shown that FOG1 recruits two multi-protein complexes, the nucleosome remodeling domain (NuRD) complex and a C-terminal binding protein (CTBP)-containing complex, into association with GATA1 to mediate activation and repression of target genes. To elucidate mechanisms that might differentially regulate the association of FOG1, as well as GATA1, with these two complexes, we characterized a previously unrecognized translational isoform of FOG1. We found that an N-terminally truncated version of FOG1 is produced from an internal ATG and that this isoform, designated FOG1S, lacks the nucleosome remodeling domain-binding domain, altering the complexes with which it interacts. Both isoforms interact with the C-terminal binding protein complex, which we show also contains lysine-specific demethylase 1 (LSD1). FOG1S is preferentially excluded from the nucleus by unknown mechanisms. These data reveal two novel mechanisms for the regulation of GATA1 interaction with FOG1-dependent protein complexes through the production of two translational isoforms with differential interaction profiles and independent nuclear localization controls.
C1 [Snow, Jonathan W.; Orkin, Stuart H.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Snow, Jonathan W.; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Snow, Jonathan W.; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Orkin, SH (reprint author), Childrens Hosp, Div Hematol, 300 Longwood Ave, Boston, MA 02115 USA.
EM stuart_orkin@dfci.harvard.edu
FU National Institutes of Health [HL32259, HL32262]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants HL32259 and HL32262 (to S. H. O.).
NR 52
TC 13
Z9 13
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 23
PY 2009
VL 284
IS 43
BP 29310
EP 29319
DI 10.1074/jbc.M109.043497
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 507ZW
UT WOS:000270896800010
PM 19654328
ER
PT J
AU Xu, HM
Eleswarapu, S
Geiger, H
Szczur, K
Daria, D
Zheng, Y
Settleman, J
Srour, EF
Williams, DA
Filippi, MD
AF Xu, Haiming
Eleswarapu, Satyam
Geiger, Hartmut
Szczur, Kathleen
Daria, Deidre
Zheng, Yi
Settleman, Jeffrey
Srour, Edward F.
Williams, David A.
Filippi, Marie-Dominique
TI Loss of the Rho GTPase activating protein p190-B enhances hematopoietic
stem cell engraftment potential
SO BLOOD
LA English
DT Article
ID SELF-RENEWAL; BONE-MARROW; FETAL LIVER; CYCLE TRANSIT; LIFE-SPAN;
PROLIFERATION; QUIESCENCE; MICE; NICHE; CDC42
AB Hematopoietic stem cell (HSC) engraftment is a multistep process involving HSC homing to bone marrow, self-renewal, proliferation, and differentiation to mature blood cells. Here, we show that loss of p190-B RhoGTPase activating protein, a negative regulator of Rho GTPases, results in enhanced long-term engraftment during serial transplantation. This effect is associated with maintenance of functional HSC-enriched cells. Furthermore, loss of p190-B led to marked improvement of HSC in vivo repopulation capacity during ex vivo culture without altering proliferation and multilineage differentiation of HSC and progeny. Transcriptional analysis revealed that p190-B deficiency represses the up-regulation of p16(Ink4a) in HSCs in primary and secondary transplantation recipients, providing a possible mechanism of p190-B-mediated HSC functions. Our study defines p190-B as a critical transducer element of HSC self-renewal activity and long-term engraftment, thus suggesting that p190-B is a target for HSC-based therapies requiring maintenance of engraftment phenotype. (Blood. 2009;114:3557-3566)
C1 [Xu, Haiming; Eleswarapu, Satyam; Geiger, Hartmut; Szczur, Kathleen; Daria, Deidre; Zheng, Yi; Williams, David A.; Filippi, Marie-Dominique] Cincinnati Childrens Res Fdn, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
[Xu, Haiming] Univ Cincinnati, Coll Med, Cell & Mol Biol Grad Program, Cincinnati, OH 45221 USA.
[Geiger, Hartmut] Univ Ulm, Dept Dermatol & Allerg Dis Aging Res, Ulm, Germany.
[Settleman, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Settleman, Jeffrey] Harvard Univ, Sch Med, Boston, MA USA.
[Srour, Edward F.] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA.
RP Filippi, MD (reprint author), Cincinnati Childrens Res Fdn, Div Expt Hematol & Canc Biol, S7-605, Cincinnati, OH 45229 USA.
EM DAWilliams@childrens.harvard.edu; Marie-Dominique.Filippi@cchmc.org
RI Xu, Haiming/A-2238-2014; Zheng, Yi/J-7235-2015
OI Zheng, Yi/0000-0001-7089-6074
FU Board of Trustee Cincinnati Children's Hospital Medical Center Award
(M.-D.F.); American Heart Association Scientific and Development;
National Institutes of Health [DK62757]
FX The work was supported in part by a Board of Trustee Cincinnati
Children's Hospital Medical Center Award (M.-D.F.), an American Heart
Association Scientific and Development Grant Award (M.-D.F.), and the
National Institutes of Health (DK62757) (D.A.W.).
NR 59
TC 13
Z9 13
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 22
PY 2009
VL 114
IS 17
BP 3557
EP 3566
DI 10.1182/blood-2009-02-205815
PG 10
WC Hematology
SC Hematology
GA 509NK
UT WOS:000271024500009
PM 19713466
ER
PT J
AU Pitsouli, C
Apidianakis, Y
Perrimon, N
AF Pitsouli, Chrysoula
Apidianakis, Yiorgos
Perrimon, Norbert
TI Homeostasis in Infected Epithelia: Stem Cells Take the Lead
SO CELL HOST & MICROBE
LA English
DT Review
ID UROPATHOGENIC ESCHERICHIA-COLI; DROSOPHILA MIDGUT; BACTERIAL-INFECTION;
URINARY-TRACT; HOST DEFENSES; SELF-RENEWAL; PROLIFERATION; REGENERATION;
ACTIVATION; INTESTINE
AB To maintain tissue homeostasis and avoid disease, epithelial cells damaged by pathogens need to be readily replenished, and this is mainly achieved by the activation of stem cells. In this Short Review, we discuss recent developments in the exciting field of host epithelia-pathogen interaction in Drosophila as well as in mammals.
C1 [Pitsouli, Chrysoula; Perrimon, Norbert] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Perrimon, Norbert] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Apidianakis, Yiorgos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Apidianakis, Yiorgos] Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA.
RP Perrimon, N (reprint author), Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM perrimon@receptor.med.harvard.edu
OI Apidianakis, Yiorgos/0000-0002-7465-3560
FU Howard Hughes Medical Institute
NR 32
TC 18
Z9 18
U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD OCT 22
PY 2009
VL 6
IS 4
BP 301
EP 307
DI 10.1016/j.chom.2009.10.001
PG 7
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 512EQ
UT WOS:000271227700006
PM 19837370
ER
PT J
AU Joubert, PE
Meiffren, G
Gregoire, IP
Pontini, G
Richetta, C
Flacher, M
Azocar, O
Vidalain, PO
Vidal, M
Lotteau, V
Codogno, P
Rabourdin-Combe, C
Faure, M
AF Joubert, Pierre-Emmanuel
Meiffren, Gregory
Gregoire, Isabel Pombo
Pontini, Guillemette
Richetta, Clemence
Flacher, Monique
Azocar, Olga
Vidalain, Pierre-Olivier
Vidal, Marc
Lotteau, Vincent
Codogno, Patrice
Rabourdin-Combe, Chantal
Faure, Mathias
TI Autophagy Induction by the Pathogen Receptor CD46
SO CELL HOST & MICROBE
LA English
DT Article
ID COFACTOR PROTEIN CD46; MEASLES-VIRUS; CELLULAR RECEPTOR; MONITORING
AUTOPHAGY; ADAPTIVE IMMUNITY; 3-KINASE COMPLEX; INNATE IMMUNITY;
HOST-CELL; RECOGNITION; BINDING
AB Autophagy is a highly regulated self-degradative mechanism required at a basal level for intracellular clearance and recycling of cytoplasmic contents. Upon intracellular pathogen invasion, autophagy can be induced as an innate immune mechanism to control infection. Nevertheless, pathogens have developed strategies to avoid or hijack autophagy for their own benefit. The molecular pathways inducing autophagy in response to infection remain poorly documented. We report here that the engagement of CD46, a ubiquitous human surface receptor able to bind several different pathogens, is sufficient to induce autophagy. CD46-Cyt-1, one of the two C-terminal splice variants of CD46, is linked to the autophagosome formation complex VPS34/Beclin1 via its interaction with the scaffold protein GOPC. Measles virus and group A Streptococcus, two CD46-binding pathogens, induce autophagy through a CD46-Cyt-1/GOPC pathway. Thus, upon microorganism recognition, a cell surface pathogen receptor can directly trigger autophagy, a critical step to control infection.
C1 [Joubert, Pierre-Emmanuel; Meiffren, Gregory; Gregoire, Isabel Pombo; Pontini, Guillemette; Richetta, Clemence; Flacher, Monique; Azocar, Olga; Lotteau, Vincent; Rabourdin-Combe, Chantal; Faure, Mathias] Univ Lyon, F-69003 Lyon, France.
[Joubert, Pierre-Emmanuel; Meiffren, Gregory; Gregoire, Isabel Pombo; Pontini, Guillemette; Richetta, Clemence; Flacher, Monique; Azocar, Olga; Lotteau, Vincent; Rabourdin-Combe, Chantal; Faure, Mathias] INSERM, U851, F-69007 Lyon, France.
[Joubert, Pierre-Emmanuel; Meiffren, Gregory; Gregoire, Isabel Pombo; Pontini, Guillemette; Richetta, Clemence; Flacher, Monique; Azocar, Olga; Lotteau, Vincent; Rabourdin-Combe, Chantal; Faure, Mathias] Univ Lyon 1, IFR128, F-69007 Lyon, France.
[Vidalain, Pierre-Olivier; Vidal, Marc] Harvard Univ, Sch Med, CCSB, Boston, MA 02115 USA.
[Vidalain, Pierre-Olivier; Vidal, Marc] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Vidalain, Pierre-Olivier; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Vidalain, Pierre-Olivier] Inst Pasteur, CNRS, URA 3015, F-75724 Paris 15, France.
[Codogno, Patrice] Univ Paris 11, Fac Pharm, F-92296 Chatenay Malabry, France.
[Codogno, Patrice] INSERM, U756, F-92296 Chatenay Malabry, France.
RP Faure, M (reprint author), Univ Lyon, F-69003 Lyon, France.
EM mathias.faure@inserm.fr
RI Codogno, Patrice/G-1384-2013; FAURE, Mathias/M-5627-2014; lotteau,
vincent/M-8143-2014
OI Codogno, Patrice/0000-0002-5492-3180;
FU INSER; UCBLyon-1; Institut National du Cancer- Canceropole; Ministere de
l'Enseignement Superieur et de la Recherche; [INCA ACI-63-04]; [ARC
3949]; [ANR-08-JCJC-0064-01]
FX We thank Dr. Gregoire Lauvau and Dr. Christophe Viret for critical
comments on the manuscript. We thank Drs. C. Delprat and L. Genestier
for discussion and M. Le Breton and A. Deloire for experimental help. We
thank, from the IFR128, A. Chaboud (protein production and analysis), F.
Simian-Lerme, C. Lionnet (Imaging PLATIM), and C. Bella (Flux
cytometry). We are grateful to Pr. C. Poyart, Dr. T. Yoshimori, Dr. B.
Loveland, and Dr. R. ucklan or providing us with materials. This work
was supported by INSER, UCBLyon-1, and Institut National du Cancer-
Canceropole, INCA ACI-63-04, ARC 3949, and ANR-08-JCJC-0064-01. G.M. and
P.-E.J. are recipients of a fellowship from the Ministere de
l'Enseignement Superieur et de la Recherche.
NR 57
TC 112
Z9 120
U1 0
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD OCT 22
PY 2009
VL 6
IS 4
BP 354
EP 366
DI 10.1016/j.chom.2009.09.006
PG 13
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 512EQ
UT WOS:000271227700011
PM 19837375
ER
PT J
AU Sidransky, E
Nalls, MA
Aasly, JO
Aharon-Peretz, J
Annesi, G
Barbosa, ER
Bar-Shira, A
Berg, D
Bras, J
Brice, A
Chen, CM
Clark, LN
Condroyer, C
De Marco, EV
Durr, A
Eblan, MJ
Fahn, S
Farrer, MJ
Fung, HC
Gan-Or, Z
Gasser, T
Gershoni-Baruch, R
Giladi, N
Griffith, A
Gurevich, T
Januario, C
Kropp, P
Lang, AE
Lee-Chen, GJ
Lesage, S
Marder, K
Mata, IF
Mirelman, A
Mitsui, J
Mizuta, I
Nicoletti, G
Oliveira, C
Ottman, R
Orr-Urtreger, A
Pereira, LV
Quattrone, A
Rogaeva, E
Rolfs, A
Rosenbaum, H
Rozenberg, R
Samii, A
Samaddar, T
Schulte, C
Sharma, M
Singleton, A
Spitz, M
Tan, EK
Tayebi, N
Toda, T
Troiano, AR
Tsuji, S
Wittstock, M
Wolfsberg, TG
Wu, YR
Zabetian, CP
Zhao, Y
Ziegler, SG
AF Sidransky, E.
Nalls, M. A.
Aasly, J. O.
Aharon-Peretz, J.
Annesi, G.
Barbosa, E. R.
Bar-Shira, A.
Berg, D.
Bras, J.
Brice, A.
Chen, C. -M.
Clark, L. N.
Condroyer, C.
De Marco, E. V.
Duerr, A.
Eblan, M. J.
Fahn, S.
Farrer, M. J.
Fung, H. -C.
Gan-Or, Z.
Gasser, T.
Gershoni-Baruch, R.
Giladi, N.
Griffith, A.
Gurevich, T.
Januario, C.
Kropp, P.
Lang, A. E.
Lee-Chen, G. -J.
Lesage, S.
Marder, K.
Mata, I. F.
Mirelman, A.
Mitsui, J.
Mizuta, I.
Nicoletti, G.
Oliveira, C.
Ottman, R.
Orr-Urtreger, A.
Pereira, L. V.
Quattrone, A.
Rogaeva, E.
Rolfs, A.
Rosenbaum, H.
Rozenberg, R.
Samii, A.
Samaddar, T.
Schulte, C.
Sharma, M.
Singleton, A.
Spitz, M.
Tan, E. -K.
Tayebi, N.
Toda, T.
Troiano, A. R.
Tsuji, S.
Wittstock, M.
Wolfsberg, T. G.
Wu, Y. -R.
Zabetian, C. P.
Zhao, Y.
Ziegler, S. G.
TI Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson's
Disease
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID LEWY BODY DISORDERS; GAUCHER-DISEASE; GENE-MUTATIONS; EARLY-ONSET;
RISK-FACTOR; GBA; SUSCEPTIBILITY; MANIFESTATIONS; POLYMORPHISM;
ASSOCIATION
AB Background
Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency of which causes Gaucher's disease, among patients with Parkinson's disease. We aimed to ascertain the frequency of GBA mutations in an ethnically diverse group of patients with Parkinson's disease.
Methods
Sixteen centers participated in our international, collaborative study: five from the Americas, six from Europe, two from Israel, and three from Asia. Each center genotyped a standard DNA panel to permit comparison of the genotyping results across centers. Genotypes and phenotypic data from a total of 5691 patients with Parkinson's disease (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews) were analyzed, with multivariate logistic-regression models and the Mantel-Haenszel procedure used to estimate odds ratios across centers.
Results
All 16 centers could detect two GBA mutations, L444P and N370S. Among Ashkenazi Jewish subjects, either mutation was found in 15% of patients and 3% of controls, and among non-Ashkenazi Jewish subjects, either mutation was found in 3% of patients and less than 1% of controls. GBA was fully sequenced for 1883 non-Ashkenazi Jewish patients, and mutations were identified in 7%, showing that limited mutation screening can miss half the mutant alleles. The odds ratio for any GBA mutation in patients versus controls was 5.43 across centers. As compared with patients who did not carry a GBA mutation, those with a GBA mutation presented earlier with the disease, were more likely to have affected relatives, and were more likely to have atypical clinical manifestations.
Conclusions
Data collected from 16 centers demonstrate that there is a strong association between GBA mutations and Parkinson's disease.
C1 [Sidransky, E.; Eblan, M. J.; Samaddar, T.; Tayebi, N.; Ziegler, S. G.] NHGRI, Sect Mol Neurogenet, Med Genet Branch, Bethesda, MD 20892 USA.
[Nalls, M. A.; Bras, J.; Samii, A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Wolfsberg, T. G.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Aasly, J. O.] St Olavs Hosp, Dept Neurol, Trondheim, Norway.
[Aasly, J. O.] Norwegian Univ Sci & Technol, Dept Neurosci, N-7034 Trondheim, Norway.
[Aharon-Peretz, J.] Technion Israel Inst Technol, Cognit Neurol & Movement Disorder Unit, Haifa, Israel.
[Gershoni-Baruch, R.] Technion Israel Inst Technol, Human Genet Rambam Med Ctr, Haifa, Israel.
[Gershoni-Baruch, R.] Technion Israel Inst Technol, Bruce Rappaport Fac Med, IL-31096 Haifa, Israel.
[Rosenbaum, H.] Technion Israel Inst Technol, Dept Hematol, IL-31096 Haifa, Israel.
[Rosenbaum, H.] Technion Israel Inst Technol, Dept Bone Marrow Transplant, IL-31096 Haifa, Israel.
[Nicoletti, G.; Quattrone, A.] Magna Graecia Univ Catanzaro, Dept Med Sci, Inst Neurol, Catanzaro, Italy.
[Annesi, G.; De Marco, E. V.; Nicoletti, G.; Quattrone, A.] CNR, Inst Neurol Sci, Cosenza, Italy.
[Barbosa, E. R.; Spitz, M.] Univ Sao Paulo, Sch Med, Dept Neurol, Movement Disorders Unit, Sao Paulo, Brazil.
[Pereira, L. V.; Rozenberg, R.] Univ Sao Paulo, Biosci Inst, Dept Genet & Evolutionary Biol, Mol Genet Lab, Sao Paulo, Brazil.
[Bar-Shira, A.; Gan-Or, Z.; Orr-Urtreger, A.] Tel Aviv Univ, Genet Inst, IL-69978 Tel Aviv, Israel.
[Giladi, N.; Gurevich, T.; Mirelman, A.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Neurol, Movement Disorders Unit,Parkinson Ctr, IL-69978 Tel Aviv, Israel.
[Gan-Or, Z.; Giladi, N.; Gurevich, T.; Orr-Urtreger, A.] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
[Berg, D.; Gasser, T.; Schulte, C.; Sharma, M.] Univ Tubingen, Dept Neurodegenerat Dis, Hertie Inst Clin Brain Res, Tubingen, Germany.
[Bras, J.; Oliveira, C.] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal.
[Januario, C.; Oliveira, C.] Univ Coimbra Hosp, Neurol Serv, Coimbra, Portugal.
[Brice, A.; Condroyer, C.; Duerr, A.; Lesage, S.] Univ Paris 06, INSERM, Ctr Rech,Inst Cerveau & Moelle Epiniere, Unite Mixte Rech S679, Paris, France.
[Brice, A.; Duerr, A.] Grp Hosp Pitie Salpetriere, AP HP, F-75634 Paris, France.
[Brice, A.; Duerr, A.] Grp Hosp Pitie Salpetriere, Dept Genet & Cytogenet, F-75634 Paris, France.
[Chen, C. -M.; Fung, H. -C.; Wu, Y. -R.] Chang Gung Univ, Coll Med, Chang Gung Mem Hosp, Dept Neurol, Taipei, Taiwan.
[Clark, L. N.; Marder, K.] Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA.
[Clark, L. N.] Columbia Univ Coll Phys & Surg, Ctr Human Genet, New York, NY 10032 USA.
[Clark, L. N.] Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA.
[Fahn, S.; Marder, K.; Ottman, R.] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA.
[Marder, K.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
[Marder, K.; Ottman, R.] Columbia Univ Coll Phys & Surg, Gertrude H Sergievsky Ctr, New York, NY 10032 USA.
[Ottman, R.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Ottman, R.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Farrer, M. J.] Mayo Clin, Coll Med, Dept Neurosci, Neurogenet Lab, Jacksonville, FL 32224 USA.
[Griffith, A.] Evergreen Hosp Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA.
[Kropp, P.] Univ Rostock, Inst Med Psychol, Rostock, Germany.
[Rolfs, A.] Univ Rostock, Albrecht Kossel Inst Neuroregenerat, Rostock, Germany.
[Wittstock, M.] Univ Rostock, Dept Neurol, Rostock, Germany.
[Lang, A. E.] Toronto Western Hosp, Movement Disorders Ctr, Div Neurol, Dept Med, Toronto, ON M5T 2S8, Canada.
[Rogaeva, E.] Univ Toronto, Ctr Res Neurodegenerat Dis, Toronto, ON, Canada.
[Lee-Chen, G. -J.] Natl Taiwan Normal Univ, Dept Life Sci, Taipei, Taiwan.
[Mata, I. F.; Samii, A.; Zabetian, C. P.] VA Puget Sound Hlth Care Syst, Parkinsons Dis & Geriatr Res Educ & Clin Ctr, Seattle, WA USA.
[Mata, I. F.; Samii, A.; Zabetian, C. P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Mitsui, J.; Tsuji, S.] Univ Tokyo, Grad Sch Med, Dept Neurol, Tokyo, Japan.
[Mizuta, I.; Toda, T.] Kobe Univ, Grad Sch Med, Div Neurol & Mol Brain Sci, Kobe, Hyogo 657, Japan.
[Tan, E. -K.] Singapore Gen Hosp, Natl Inst Neurosci, Singapore 0316, Singapore.
[Tan, E. -K.] Duke NUS Grada Med Sch, Singapore, Singapore.
RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, Rm 1A213,35 Convent Dr, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
RI Bras, Jose/D-3366-2009; Bras, Jose/A-1428-2011; Singleton,
Andrew/C-3010-2009; Mitsui, Jun/B-5455-2012; Pereira, Lygia/C-1049-2012;
Kropp, Peter/B-8132-2012; Barbosa, Egberto/G-7763-2012; Ottman,
Ruth/O-2371-2013; QUATTRONE, Aldo/A-6734-2016;
OI Gan-Or, Ziv/0000-0003-0332-234X; Zabetian, Cyrus/0000-0002-7739-4306;
Mitsui, Jun/0000-0001-7425-4765; Pereira, Lygia/0000-0002-0002-725X;
QUATTRONE, Aldo/0000-0003-2001-957X; Schulte,
Claudia/0000-0003-4006-1265; Oliveira, Catarina/0000-0001-6942-4328;
DEMARCO, ELVIRAVALERIA/0000-0002-4947-8481
FU National Institutes of Health [Z01AG000957-05]; National Institute of
Neurological Disorders and Stroke and the National Center for Research
Resources [NS050487, NS060113, NS40256]; Parkinson's Disease Foundation;
Department of Veterans Affairs, Seattle; German National Genome Network,
German Ministry for Education and Research [01GS08134]; French
Parkinson's Disease Genetics Study Group; Duke-National University of
Singapore (NUS) Graduate Medical School, National Medical Research
Council, Biomedical Research Council, Singapore Millennium Foundation;
SingHealth, Singapore General Hospital, National Neuroscience Institute;
Tel Aviv Sourasky Medical Center Grant of Excellence; Wolfson and Kahn
Foundations; Portuguese Fundacao para a Ciencia e a Tecnologia; National
Science Council, Executive Yuan, Taiwan [NSC-95-2314-B-182A-061];
Ministry of Education, Culture, Sports, Science and Technology of Japan
FX Supported in part by the Intramural Research Programs of NHGRI and the
National Institute on Aging (project Z01AG000957-05), National
Institutes of Health; grants from the National Institute of Neurological
Disorders and Stroke and the National Center for Research Resources
(NS050487, NS060113, and NS40256); grants from the Parkinson's Disease
Foundation; a Merit Review Award from the Department of Veterans
Affairs, Seattle; a grant from the German National Genome Network,
German Ministry for Education and Research (01GS08134); a grant from the
French Parkinson's Disease Genetics Study Group; a grant from the
Duke-National University of Singapore (NUS) Graduate Medical School,
National Medical Research Council, Biomedical Research Council,
Singapore Millennium Foundation; a grant from SingHealth, Singapore
General Hospital, National Neuroscience Institute; the Tel Aviv Sourasky
Medical Center Grant of Excellence; grants from the Wolfson and Kahn
Foundations; a grant from the Portuguese Fundacao para a Ciencia e a
Tecnologia; a grant from the National Science Council, Executive Yuan,
Taiwan (NSC-95-2314-B-182A-061); and a Grant-in-Aid for Scientific
Research on Priority Areas, Applied Genomics, and Scientific Research
from the Ministry of Education, Culture, Sports, Science and Technology
of Japan.
NR 44
TC 550
Z9 558
U1 4
U2 29
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 22
PY 2009
VL 361
IS 17
BP 1651
EP 1661
DI 10.1056/NEJMoa0901281
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 508YW
UT WOS:000270977400007
PM 19846850
ER
PT J
AU de Moya, MA
del Carmen, MG
Allain, RM
Hirschberg, RE
Shepard, JAO
Kradin, RL
AF de Moya, Marc A.
del Carmen, Marcela G.
Allain, Rae M.
Hirschberg, Ronald E.
Shepard, Jo-Anne O.
Kradin, Richard L.
TI A Woman with Fever, Abdominal Pain, and Hypotension after Cesarean
SectionCase 33-2009: A 35-Year-Old Woman with Fever, Abdominal Pain, and
Hypotension after Cesarean Section
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID TOXIC-SHOCK-SYNDROME; A STREPTOCOCCUS INFECTIONS; SOFT-TISSUE INFECTION;
TUMOR-NECROSIS-FACTOR; NECROTIZING FASCIITIS; SEPTIC SHOCK; SEVERE
SEPSIS; MANAGEMENT; PYOGENES; THERAPY
C1 [de Moya, Marc A.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
[del Carmen, Marcela G.] Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA.
[Allain, Rae M.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Hirschberg, Ronald E.] Massachusetts Gen Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA.
[Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Kradin, Richard L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Kradin, Richard L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Hirschberg, Ronald E.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA.
[de Moya, Marc A.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[del Carmen, Marcela G.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA.
[Allain, Rae M.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA.
[Hirschberg, Ronald E.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02115 USA.
[Shepard, Jo-Anne O.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Kradin, Richard L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Kradin, Richard L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP de Moya, MA (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
NR 24
TC 3
Z9 3
U1 1
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 22
PY 2009
VL 361
IS 17
BP 1689
EP 1697
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 508YW
UT WOS:000270977400013
PM 19846855
ER
PT J
AU Palevsky, PM
AF Palevsky, Paul M.
TI Renal Support in Acute Kidney Injury - How Much Is Enough?
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID CRITICALLY-ILL PATIENTS; CONTINUOUS VENOVENOUS HEMOFILTRATION;
RANDOMIZED-TRIAL; FAILURE; SURVIVAL; DIALYSIS; THERAPY
C1 [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA.
[Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA.
RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA.
OI Palevsky, Paul/0000-0002-7334-5400
NR 11
TC 8
Z9 16
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 22
PY 2009
VL 361
IS 17
BP 1699
EP 1701
DI 10.1056/NEJMe0907831
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 508YW
UT WOS:000270977400014
PM 19846856
ER
PT J
AU Albert, NM
Yancy, CW
Liang, L
Zhao, X
Hernandez, AF
Peterson, ED
Cannon, CP
Fonarow, GC
AF Albert, Nancy M.
Yancy, Clyde W.
Liang, Li
Zhao, Xin
Hernandez, Adrian F.
Peterson, Eric D.
Cannon, Christopher P.
Fonarow, Gregg C.
TI Use of Aldosterone Antagonists in Heart Failure
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID RENAL-INSUFFICIENCY; SPIRONOLACTONE; HYPERKALEMIA; GUIDELINES;
DYSFUNCTION; ASSOCIATION; MANAGEMENT; POTASSIUM; DIAGNOSIS; UPDATE
AB Context Aldosterone antagonists are recommended for patients with moderate to severe heart failure (HF) and systolic dysfunction. Prior studies suggest underuse of aldosterone antagonists in eligible patients as well as overuse in settings in which therapy may be harmful.
Objective To examine aldosterone antagonist prescription based on HF management guideline criteria, investigator-defined appropriateness criteria, and trends over time in patients hospitalized with heart failure.
Design, Setting, and Patients Observational analysis of 43 625 patients admitted with HF and discharged home from 241 hospitals participating in the Get With The Guidelines-HF quality improvement registry between January 2005 and December 2007.
Main Outcome Measures Prescription and predictors of use of aldosterone antagonists, based on guideline criteria.
Results Among 12 565 patients eligible for aldosterone antagonist therapy, 4087 (32.5%) received an aldosterone antagonist at discharge, and treatment increased modestly from 28% to 34% over the study period. There was also wide variation in aldosterone antagonist use among hospitals (0%-90.6%). Aldosterone antagonist use in eligible patients was associated with younger age (adjusted odds ratio [OR], 0.85; 95% confidence interval [CI], 0.82-0.88), African American race/ethnicity (adjusted OR, 1.17; 95% CI, 1.04-1.32), lower systolic blood pressure (adjusted OR, 0.94; 95% CI, 0.92-0.95), history of implantable cardioverter-defibrillator use (adjusted OR, 1.51; 95% CI, 1.34-1.69), depression (adjusted OR, 1.15; 95% CI, 1.01-1.30), alcohol use (adjusted OR, 1.23; 95% CI, 1.02-1.50), and pacemaker implantation (adjusted OR, 1.21; 95% CI, 1.06-1.38), and with having no history of renal insufficiency (adjusted OR, 0.85; 95% CI, 0.75-0.96). Applying serum creatinine and potassium appropriateness criteria, inappropriate and potentially inappropriate use of aldosterone antagonist therapy was low and did not change over the 3-year study period.
Conclusions Less than one-third of eligible patients hospitalized for HF and participating in a quality improvement registry received HF guideline-recommended aldosterone antagonist therapy. Use of aldosterone antagonist therapy among patients with documented contraindications was low. JAMA. 2009;302(15):1658-1665
C1 [Albert, Nancy M.] Cleveland Clin, Nursing Inst, Cleveland, OH 44106 USA.
[Albert, Nancy M.] Cleveland Clin, Kaufman Ctr Heart Failure, Cleveland, OH 44106 USA.
[Yancy, Clyde W.] Baylor Univ, Med Ctr, Baylor Heart & Vasc Inst, Dallas, TX USA.
[Liang, Li; Zhao, Xin; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA.
[Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA.
[Fonarow, Gregg C.] Univ Calif Los Angeles, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA.
RP Albert, NM (reprint author), 9500 Euclid Ave,Mail Code J3-4, Cleveland, OH 44195 USA.
EM albertn@ccf.org
RI Hernandez, Adrian F./A-7818-2016
OI Hernandez, Adrian F./0000-0003-3387-9616
FU American Heart Association; GlaxoSmithKline; Medtronic
FX The Get With The GuidelinesHeart Failure program is sponsored by the
American Heart Association and receives funding in part from
GlaxoSmithKline and Medtronic.
NR 25
TC 123
Z9 124
U1 0
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD OCT 21
PY 2009
VL 302
IS 15
BP 1658
EP 1665
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 508NX
UT WOS:000270941200020
PM 19843900
ER
PT J
AU Pedrini, S
Thomas, C
Brautigam, H
Schmeidler, J
Ho, L
Fraser, P
Westaway, D
Hyslop, PSG
Martins, RN
Buxbaum, JD
Pasinetti, GM
Dickstein, DL
Hof, PR
Ehrlich, ME
Gandy, S
AF Pedrini, Steve
Thomas, Carlos
Brautigam, Hannah
Schmeidler, James
Ho, Lap
Fraser, Paul
Westaway, David
Hyslop, Peter St George
Martins, Ralph N.
Buxbaum, Joseph D.
Pasinetti, Giulio M.
Dickstein, Dara L.
Hof, Patrick R.
Ehrlich, Michelle E.
Gandy, Sam
TI Dietary composition modulates brain mass and solubilizable A levels in a
mouse model of aggressive Alzheimer's amyloid pathology
SO MOLECULAR NEURODEGENERATION
LA English
DT Article
ID INSULIN-RESISTANCE; TRANSGENIC MICE; DISEASE; DEMENTIA; NEUROPATHOLOGY;
CHOLESTEROL; ACID; ACCUMULATION; DEFICITS
AB Objective: Alzheimer's disease (AD) is a progressive neurodegenerative disease of the central nervous system (CNS). Recently, an increased interest in the role diet plays in the pathology of AD has resulted in a focus on the detrimental effects of diets high in cholesterol and fat and the beneficial effects of caloric restriction. The current study examines how dietary composition modulates cerebral amyloidosis and neuronal integrity in the TgCRND8 mouse model of AD.
Methods: From 4 wks until 18 wks of age, male and female TgCRND8 mice were maintained on one of four diets: (1) reference (regular) commercial chow; (2) high fat/low carbohydrate custom chow (60 kcal% fat/30 kcal% protein/10 kcal% carbohydrate); (3) high protein/low carbohydrate custom chow (60 kcal% protein/30 kcal% fat/10 kcal% carbohydrate); or (4) high carbohydrate/low fat custom chow (60 kcal% carbohydrate/30 kcal% protein/10 kcal% fat). At age 18 wks, mice were sacrificed, and brains studied for (a) wet weight; (b) solubilizable A beta content by ELISA; (c) amyloid plaque burden; (d) stereologic analysis of selected hippocampal subregions.
Results: Animals receiving a high fat diet showed increased brain levels of solubilizable A beta, although we detected no effect on plaque burden. Unexpectedly, brains of mice fed a high protein/low carbohydrate diet were 5% lower in weight than brains from all other mice. In an effort to identify regions that might link loss of brain mass to cognitive function, we studied neuronal density and volume in hippocampal subregions. Neuronal density and volume in the hippocampal CA3 region of TgCRND8 mice tended to be lower in TgCRND8 mice receiving the high protein/low carbohydrate diet than in those receiving the regular chow. Neuronal density and volume were preserved in CA1 and in the dentate gyrus.
Interpretation: Dissociation of A beta changes from brain mass changes raises the possibility that diet plays a role not only in modulating amyloidosis but also in modulating neuronal vulnerability. However, in the absence of a study of the effects of a high protein/low carbohydrate diet on nontransgenic mice, one cannot be certain how much, if any, of the loss of brain mass exhibited by high protein/low carbohydrate diet-fed TgCRND8 mice was due to an interaction between cerebral amyloidosis and diet. Given the recent evidence that certain factors favor the maintenance of cognitive function in the face of substantial structural neuropathology, we propose that there might also exist factors that sensitize brain neurons to some forms of neurotoxicity, including, perhaps, amyloid neurotoxicity. Identification of these factors could help reconcile the poor clinicopathological correlation between cognitive status and structural neuropathology, including amyloid pathology.
C1 [Pedrini, Steve; Gandy, Sam] Thomas Jefferson Univ, Jefferson Med Coll, Farber Inst Neurosci, Philadelphia, PA 19107 USA.
[Thomas, Carlos; Brautigam, Hannah; Schmeidler, James; Ho, Lap; Buxbaum, Joseph D.; Pasinetti, Giulio M.; Dickstein, Dara L.; Hof, Patrick R.; Ehrlich, Michelle E.; Gandy, Sam] Mt Sinai Sch Med, Alzheimers Dis Res Ctr, New York, NY USA.
[Thomas, Carlos; Brautigam, Hannah; Schmeidler, James; Ho, Lap; Buxbaum, Joseph D.; Pasinetti, Giulio M.; Gandy, Sam] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
[Thomas, Carlos; Brautigam, Hannah; Ho, Lap; Pasinetti, Giulio M.; Ehrlich, Michelle E.; Gandy, Sam] Mt Sinai Sch Med, Dept Neurol, New York, NY USA.
[Thomas, Carlos; Brautigam, Hannah; Ho, Lap; Pasinetti, Giulio M.; Gandy, Sam] James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
[Fraser, Paul; Hyslop, Peter St George] Univ Toronto, Ctr Res Neurodegenerat Dis, Toronto, ON, Canada.
[Westaway, David] Univ Alberta, Ctr Prions & Prot Folding Dis, Edmonton, AB, Canada.
[Hyslop, Peter St George] Univ Cambridge, Cambridge, England.
[Martins, Ralph N.] Edith Cowan Univ, Joondalup, WA, Australia.
[Brautigam, Hannah; Dickstein, Dara L.; Hof, Patrick R.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA.
[Ehrlich, Michelle E.] Mt Sinai Sch Med, Dept Pediat, New York, NY USA.
RP Gandy, S (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Farber Inst Neurosci, Philadelphia, PA 19107 USA.
EM steve.pedrini@jefferson.edu; carlos.thomas@mssm.edu;
hannah.brautigam@mssm.edu; james.schmeidler@mssm.edu; lap.ho@mssm.edu;
paul.fraser@utoronto.ca; david.westaway@ualberta.ca;
p.hyslop@utoronto.ca; r.martins@ecu.edu.au; joseph.buxbaum@mssm.edu;
giulio.pasinetti@mssm.edu; dara.dickstein@mssm.edu;
patrick.hof@mssm.edu; michelle.ehrlich@mssm.edu; samuel.gandy@mssm.edu
RI Dickstein, Dara/F-3036-2013;
OI Buxbaum, Joseph/0000-0001-8898-8313
FU Dr. Robert C. and Veronica Atkins Foundation; NIH [P01 AG10491, P01
AG02219, P50 AG05138]
FX This work was supported by the Dr. Robert C. and Veronica Atkins
Foundation (S.G., S.P., C.T., G.M.P., L.H.) and NIH grants P01 AG10491
(S.G., S.P., C.T., H.B., J.D.B., R.N.M., M.E.E.; S. Gandy, Program
Director), P01 AG02219 (P.R.H., J.D.B., J.S., G.M.P., D.L.D.; H.
Haroutunian, Program Director), and P50 AG05138 (P.R.H., J.D.B., J.S.,
G.M.P., D.L.D.; M. Sano, Program Director).
NR 25
TC 16
Z9 18
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1750-1326
J9 MOL NEURODEGENER
JI Mol. Neurodegener.
PD OCT 21
PY 2009
VL 4
AR 40
DI 10.1186/1750-1326-4-40
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 517JD
UT WOS:000271608500001
PM 19845940
ER
PT J
AU Brenner, DJ
Elliston, CD
Hall, EJ
Paganetti, H
AF Brenner, David J.
Elliston, Carl D.
Hall, Eric J.
Paganetti, Harald
TI Reduction of the secondary neutron dose in passively scattered proton
radiotherapy, using an optimized pre-collimator/collimator
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID MODULATED RADIATION-THERAPY; MONTE-CARLO SIMULATIONS; BEAM
DELIVERY-SYSTEM; PROSTATE-CANCER; STRAY RADIATION; HUMAN-LYMPHOCYTES;
BOMB SURVIVORS; 2ND CANCERS; EQUIVALENT; COLLIMATOR
AB Proton radiotherapy represents a potential major advance in cancer therapy. Most current proton beams are spread out to cover the tumor using passive scattering and collimation, resulting in an extra whole-body high-energy neutron dose, primarily from proton interactions with the final collimator. There is considerable uncertainty as to the carcinogenic potential of low doses of high-energy neutrons, and thus we investigate whether this neutron dose can be significantly reduced without major modifications to passively scattered proton beam lines. Our goal is to optimize the design features of a patient-specific collimator or pre-collimator/collimator assembly. There are a number of often contradictory design features, in terms of geometry and material, involved in an optimal design. For example, plastic or hybrid plastic/metal collimators have a number of advantages. We quantify these design issues, and investigate the practical balances that can be achieved to significantly reduce the neutron dose without major alterations to the beamline design or function. Given that the majority of proton therapy treatments, at least for the next few years, will use passive scattering techniques, reducing the associated neutron-related risks by simple modifications of the collimator assembly design is a desirable goal.
C1 [Brenner, David J.; Elliston, Carl D.; Hall, Eric J.] Columbia Univ, Med Ctr, Ctr Radiol Res, New York, NY 10032 USA.
[Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA.
RP Brenner, DJ (reprint author), Columbia Univ, Med Ctr, Ctr Radiol Res, 630 W 168th St, New York, NY 10032 USA.
EM djb3@columbia.edu
FU NIH [P41-EB002033, PO1-CA49062, R01-CA088074]; DOE [DE-FG02-03ER63441,
DE-FG02-03ER63629]
FX This work was supported in part by NIH grants P41-EB002033, PO1-CA49062
and R01-CA088074, and DOE grants DE-FG02-03ER63441 and
DE-FG02-03ER63629.
NR 60
TC 19
Z9 19
U1 0
U2 5
PU IOP PUBLISHING LTD
PI BRISTOL
PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD OCT 21
PY 2009
VL 54
IS 20
BP 6065
EP 6078
DI 10.1088/0031-9155/54/20/003
PG 14
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 503TO
UT WOS:000270563300003
PM 19779218
ER
PT J
AU Raymond, SB
Kumar, ATN
Boas, DA
Bacskai, BJ
AF Raymond, S. B.
Kumar, A. T. N.
Boas, D. A.
Bacskai, B. J.
TI Optimal parameters for near infrared fluorescence imaging of amyloid
plaques in Alzheimer's disease mouse models
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID DIFFUSE OPTICAL TOMOGRAPHY; MULTIPHOTON MICROSCOPY; MOLECULAR
TOMOGRAPHY; BETA PLAQUES; HUMAN BRAIN; HUMAN HEAD; MICE; TISSUES;
TRANSPORT; RANGE
AB Amyloid-beta plaques are an Alzheimer's disease biomarker which present unique challenges for near-infrared fluorescence tomography because of size (< 50 mu m diameter) and distribution. We used high-resolution simulations of fluorescence in a digital Alzheimer's disease mouse model to investigate the optimal fluorophore and imaging parameters for near-infrared fluorescence tomography of amyloid plaques. Fluorescence was simulated for amyloid-targeted probes with emission at 630 and 800 nm, plaque-to-background ratios from 1-1000, amyloid burden from 0-10%, and for transmission and reflection measurement geometries. Fluorophores with high plaque-to-background contrast ratios and 800 nm emission performed significantly better than current amyloid imaging probes. We tested idealized fluorophores in transmission and full-angle tomographic measurement schemes (900 source-detector pairs), with and without anatomical priors. Transmission reconstructions demonstrated strong linear correlation with increasing amyloid burden, but underestimated fluorescence yield and suffered from localization artifacts. Full-angle measurements did not improve upon the transmission reconstruction qualitatively or in semi-quantitative measures of accuracy; anatomical and initial-value priors did improve reconstruction localization and accuracy for both transmission and full-angle schemes. Region-based reconstructions, in which the unknowns were reduced to a few distinct anatomical regions, produced highly accurate yield estimates for cortex, hippocampus and brain regions, even with a reduced number of measurements (144 source-detector pairs).
C1 [Raymond, S. B.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Raymond, S. B.; Bacskai, B. J.] Massachusetts Gen Hosp, Dept Neurol, Alzheimers Res Unit, Charlestown, MA 02129 USA.
[Kumar, A. T. N.; Boas, D. A.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Raymond, SB (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, 77 Mass Ave,E25-519, Cambridge, MA 02139 USA.
EM bbacskai@partners.org
OI Raymond, Scott/0000-0001-7008-8974
FU NIH [EB000768, P41-RR14075, AG026240, T32 EB001680]
FX This research was supported by NIH EB000768, P41-RR14075 and AG026240. S
B Raymond was supported by NIH T32 EB001680.
NR 41
TC 5
Z9 5
U1 0
U2 3
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
EI 1361-6560
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD OCT 21
PY 2009
VL 54
IS 20
BP 6201
EP 6216
DI 10.1088/0031-9155/54/20/011
PG 16
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 503TO
UT WOS:000270563300011
PM 19794239
ER
PT J
AU Mulley, AG
AF Mulley, Albert G.
TI Inconvenient truths about supplier induced demand and unwarranted
variation in medical practice
SO BRITISH MEDICAL JOURNAL
LA English
DT Editorial Material
ID REGIONAL-VARIATIONS; CONTROLLED-TRIAL; HEALTH OUTCOMES; DECISION AIDS;
PRIMARY-CARE; QUALITY; PROSTATECTOMY; INTENSITY; PROGRAM
C1 [Mulley, Albert G.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Mulley, Albert G.] Harvard Univ, Sch Med, Boston, MA USA.
RP Mulley, AG (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St, Boston, MA 02114 USA.
EM amulley@partners.org
NR 26
TC 25
Z9 25
U1 3
U2 7
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0959-535X
J9 BRIT MED J
JI Br. Med. J.
PD OCT 20
PY 2009
VL 339
AR b4073
DI 10.1136/bmj.b4073
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 510PJ
UT WOS:000271102100002
PM 19843566
ER
PT J
AU MacDonald, S
Taghian, AG
AF MacDonald, Shannon
Taghian, Alphonse G.
TI Prognostic Factors for Local Control After Breast Conservation: Does
Margin Status Still Matter?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID 20-YEAR FOLLOW-UP; CONSERVING THERAPY; RADIATION-THERAPY;
PROGESTERONE-RECEPTOR; ESTROGEN-RECEPTOR; RANDOMIZED-TRIAL; CANCER;
RECURRENCE; SURGERY; CARCINOMA
C1 [MacDonald, Shannon; Taghian, Alphonse G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA.
RP MacDonald, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA.
NR 19
TC 11
Z9 12
U1 0
U2 0
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 20
PY 2009
VL 27
IS 30
BP 4929
EP 4030
DI 10.1200/JCO.2009.23.6679
PG 2
WC Oncology
SC Oncology
GA 507SN
UT WOS:000270875100001
PM 19720895
ER
PT J
AU Zietman, A
AF Zietman, Anthony
TI Evidence-Based Medicine, Conscience-Based Medicine, and the Management
of Low-Risk Prostate Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID ACTIVE SURVEILLANCE; MORTALITY; TRIAL; MEN
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
RP Zietman, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
NR 13
TC 9
Z9 9
U1 0
U2 1
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 20
PY 2009
VL 27
IS 30
BP 4935
EP 4936
DI 10.1200/JCO.2009.24.4533
PG 2
WC Oncology
SC Oncology
GA 507SN
UT WOS:000270875100004
PM 19720880
ER
PT J
AU Brachtel, EF
Rusby, JE
Michaelson, JS
Chen, LL
Muzikansky, A
Smith, BL
Koerner, FC
AF Brachtel, Elena F.
Rusby, Jennifer E.
Michaelson, James S.
Chen, L. Leon
Muzikansky, Alona
Smith, Barbara L.
Koerner, Frederick C.
TI Occult Nipple Involvement in Breast Cancer: Clinicopathologic Findings
in 316 Consecutive Mastectomy Specimens
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID SKIN-SPARING MASTECTOMY; NEOPLASTIC INVOLVEMENT; AREOLA COMPLEX;
FOLLOW-UP; CARCINOMA; RECONSTRUCTION; SECTIONS; RISK
AB Purpose
Although breast-conserving surgery is a standard approach for patients with breast cancer, mastectomy often becomes necessary. Surgical options now include nipple-sparing mastectomy but its oncological safety is still controversial. This study evaluates frequency and patterns of occult nipple involvement in a large contemporary cohort of patients with the retroareolar margin as possible indicator of nipple involvement.
Patients and Methods
Three hundred sixteen consecutive mastectomy specimens (232 therapeutic, 84 prophylactic) with grossly unremarkable nipples were evaluated by coronal sections through the entire nipple and subareolar tissue. Extent and location of nipple involvement by carcinoma was assessed with the tissue deep to the skin as potential retroareolar en-face resection margin.
Results
Seventy-one percent of nipples from therapeutic mastectomies showed no pathologic abnormality, 21% had ductal carcinoma in situ (DCIS), invasive carcinoma (IC), or lymphovascular invasion (LVI), and 8% lobular neoplasia (lobular carcinoma in situ). Human epidermal growth factor receptor 2 amplification, tumor size, and tumor-nipple distance were associated with nipple involvement by multivariate analysis (P = .0047, .0126, and .0176); histologic grade of both DCIS (P = .002) and IC (P = .03), LVI (P = .03), and lymph node involvement (P = .02) by univariate analysis. Nipple involvement by IC or DCIS was identified in the retroareolar margin with a sensitivity of 0.8 and a negative predictive value of 0.96. None of the 84 prophylactic mastectomies showed nipple involvement by IC or DCIS.
Conclusion
Nipple-sparing mastectomy may be suitable for selected cases of breast carcinoma with low probability of nipple involvement by carcinoma and prophylactic procedures. A retroareolar en-face margin may be used to test for occult involvement in patients undergoing nipple-sparing mastectomy.
C1 [Brachtel, Elena F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Brachtel, EF (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN 2, Boston, MA 02114 USA.
EM ebrachtel@partners.org
NR 30
TC 69
Z9 78
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 20
PY 2009
VL 27
IS 30
BP 4948
EP 4954
DI 10.1200/JCO.2008.20.8785
PG 7
WC Oncology
SC Oncology
GA 507SN
UT WOS:000270875100007
PM 19720921
ER
PT J
AU Gray, R
Bhattacharya, S
Bowden, C
Miller, K
Comis, RL
AF Gray, Robert
Bhattacharya, Suman
Bowden, Christopher
Miller, Kathy
Comis, Robert L.
TI Independent Review of E2100: A Phase III Trial of Bevacizumab Plus
Paclitaxel Versus Paclitaxel in Women With Metastatic Breast Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CAPECITABINE
AB Purpose
E2100, an open-label, randomized, phase III trial conducted by the Eastern Cooperative Oncology Group (ECOG), demonstrated a significant improvement in progression-free survival (PFS) and overall response rate (ORR) with paclitaxel plus bevacizumab compared with paclitaxel alone as initial chemotherapy for patients with HER2-negative metastatic breast cancer.
Methods
An independent, blinded review of radiologic and clinical data was performed, assessing progression and response according to Response Evaluation Criteria in Solid Tumors. In addition, ECOG's investigator assessments were reanalyzed using the same methods applied to the independent review. The primary end point was PFS as assessed by an independent review facility (IRF).
Results
The addition of bevacizumab to paclitaxel resulted in a statistically significant improvement in PFS using both the IRF and investigator assessments. Hazard ratios for PFS (0.48, 95% CI, 0.385 to 0.607; P < .0001 for the IRF v 0.42,95% CI, 0.34 to 0.52; P < .0001 for ECOG investigators) and the improvement in median PFS (11.3 v 5.8 months for the IRF v 11.4 v 5.8 months for ECOG investigators) were similar. Among patients with measurable disease at baseline, the IRF-assessed ORR was significantly higher in patients treated with paclitaxel and bevacizumab (48.9% v 22.2%; P < .0001).
Conclusion
The risk of progression was reduced by more than half and the ORR more than doubled with the addition of bevacizumab to weekly paclitaxel in both analyses, confirming a substantial and robust bevacizumab treatment effect. The consistency between the IRF and ECOG analyses validates the original data previously reported by ECOG in this open-label trial.
C1 [Gray, Robert] Dana Farber Canc Inst, Boston, MA 02115 USA.
Genentech Inc, San Francisco, CA 94080 USA.
Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
Drexel Univ, Clin Trials Res Ctr, Philadelphia, PA 19104 USA.
RP Gray, R (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM gray@jimmy.harvard.edu
FU Genentech, South San Francisco, CA; United States Department of Health
and Human Services; National Institutes of Health [CA23318, CA66636,
CA21115]
FX Supported by Genentech, South San Francisco, CA; by the United States
Department of Health and Human Services; and by National Institutes of
Health Grants No. CA23318 (to the Eastern Cooperative Oncology Group
[ECOG] statistical center), CA66636 (to the ECOG data management
center), and CA21115 (to the ECOG coordinating center).
NR 4
TC 152
Z9 159
U1 1
U2 8
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 20
PY 2009
VL 27
IS 30
BP 4966
EP 4972
DI 10.1200/JCO.2008.21.6630
PG 7
WC Oncology
SC Oncology
GA 507SN
UT WOS:000270875100010
PM 19720913
ER
PT J
AU Saad, AG
Alyea, EP
Wen, PY
DeGirolami, U
Kesari, S
AF Saad, Ali G.
Alyea, Edwin P., III
Wen, Patrick Y.
DeGirolami, Umberto
Kesari, Santosh
TI Graft-Versus-Host Disease of the CNS After Allogeneic Bone Marrow
Transplantation
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; COMPLICATIONS; PATHOGENESIS; PATHOLOGY;
ANGIITIS; PATIENT
C1 [Saad, Ali G.] Arkansas Childrens Hosp, Dept Pathol, Little Rock, AR 72202 USA.
[Saad, Ali G.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[Alyea, Edwin P., III; Wen, Patrick Y.; Kesari, Santosh] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Alyea, Edwin P., III; Wen, Patrick Y.; DeGirolami, Umberto; Kesari, Santosh] Harvard Univ, Sch Med, Boston, MA USA.
[Wen, Patrick Y.; Kesari, Santosh] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA.
[DeGirolami, Umberto] Brigham & Womens Hosp, Dept Pathol, Div Neuropathol, Boston, MA 02115 USA.
RP Saad, AG (reprint author), Arkansas Childrens Hosp, Dept Pathol, 800 Marshall St, Little Rock, AR 72202 USA.
RI Kesari, Santosh/E-8461-2013
NR 21
TC 10
Z9 11
U1 0
U2 0
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 20
PY 2009
VL 27
IS 30
BP E147
EP E149
DI 10.1200/JCO.2009.21.7919
PG 3
WC Oncology
SC Oncology
GA 507SN
UT WOS:000270875100032
PM 19667266
ER
PT J
AU Gao, X
Simon, KC
Han, J
Schwarzschild, MA
Ascherio, A
AF Gao, X.
Simon, K. C.
Han, J.
Schwarzschild, M. A.
Ascherio, A.
TI Family history of melanoma and Parkinson disease risk
SO NEUROLOGY
LA English
DT Article
ID CUTANEOUS MALIGNANT-MELANOMA; CANCER-RISK; TOBACCO USE; LEVODOPA;
QUESTIONNAIRE; METAANALYSIS; CONSUMPTION; INHIBITION; APOPTOSIS; NEURONS
AB Background: Co-occurrence of Parkinson disease (PD) and melanoma has been reported in numerous studies. If this was due to common genetic mechanisms, a positive family history of melanoma would be associated with an excessive PD risk, independent of environmental risk factors for PD.
Methods: We prospectively examined associations between a family history of melanoma and PD among 157,036 men and women free of PD at baseline (1990 for men and 1982 for women) who participated in 2 ongoing US cohorts: the Health Professional Follow-up Study and the Nurses' Health Study. Information on family history of melanoma in parents or siblings was assessed via questionnaire. Relative risks and 95% confidence intervals were estimated using Cox proportional hazards models and pooled using a fixed-effects model.
Results: During 14-20 years follow-up, we identified 616 incident PD cases. A family history of melanoma in a first-degree relative was associated with a higher risk of PD (multivariate relative risk = 1.85; 95% confidence interval: 1.2, 2.8; p = 0.004), after adjusting for smoking, ethnicity, caffeine intake, and other covariates. In contrast, we did not observe significant associations between a family history of colorectal, lung, prostate, or breast cancer and PD risk. Interactions between melanoma family history and age, smoking, or caffeine intake were not significant and subgroup analyses according to these factors generated similar results.
Conclusions: Our findings support the notion that melanoma and Parkinson disease (PD) share common genetic components. The genetic determinants of melanoma could therefore be explored as susceptibility candidate genes for PD. Neurology (R) 2009;73:1286-1291
C1 Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Gao, X.; Han, J.; Ascherio, A.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
[Ascherio, A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Gao, X.; Simon, K. C.; Ascherio, A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Schwarzschild, M. A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Gao, X (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA.
EM xiang.gao@channing.harvard.edu
FU NIH/NINDS [R01 NS048517]; Parkinson Study Group; Parkinson's Disease
Foundation's Advancing Parkinson's Treatments Innovations Grant
FX The study was supported by NIH/NINDS grant R01 NS048517, and the
Parkinson Study Group and the Parkinson's Disease Foundation's Advancing
Parkinson's Treatments Innovations Grant.
NR 34
TC 51
Z9 51
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD OCT 20
PY 2009
VL 73
IS 16
BP 1286
EP 1291
DI 10.1212/WNL.0b013e3181bd13a1
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 508GU
UT WOS:000270918800007
PM 19841380
ER
PT J
AU Tamietto, M
Castelli, L
Vighetti, S
Perozzo, P
Geminiani, G
Weiskrantz, L
de Gelder, B
AF Tamietto, Marco
Castelli, Lorys
Vighetti, Sergio
Perozzo, Paola
Geminiani, Giuliano
Weiskrantz, Lawrence
de Gelder, Beatrice
TI Unseen facial and bodily expressions trigger fast emotional reactions
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE affective blindsight; electromyography; emotional body language; motor
resonance; emotional contagion; face
ID AFFECTIVE BLINDSIGHT; RIGHT AMYGDALA; BODY LANGUAGE; FACES; FEAR;
RECOGNITION; AWARENESS
AB The spontaneous tendency to synchronize our facial expressions with those of others is often termed emotional contagion. It is unclear, however, whether emotional contagion depends on visual awareness of the eliciting stimulus and which processes underlie the unfolding of expressive reactions in the observer. It has been suggested either that emotional contagion is driven by motor imitation (i.e., mimicry), or that it is one observable aspect of the emotional state arising when we see the corresponding emotion in others. Emotional contagion reactions to different classes of consciously seen and "unseen" stimuli were compared by presenting pictures of facial or bodily expressions either to the intact or blind visual field of two patients with unilateral destruction of the visual cortex and ensuing phenomenal blindness. Facial reactions were recorded using electromyography, and arousal responses were measured with pupil dilatation. Passive exposure to unseen expressions evoked faster facial reactions and higher arousal compared with seen stimuli, therefore indicating that emotional contagion occurs also when the triggering stimulus cannot be consciously perceived because of cortical blindness. Furthermore, stimuli that are very different in their visual characteristics, such as facial and bodily gestures, induced highly similar expressive responses. This shows that the patients did not simply imitate the motor pattern observed in the stimuli, but resonated to their affective meaning. Emotional contagion thus represents an instance of truly affective reactions that may be mediated by visual pathways of old evolutionary origin bypassing cortical vision while still providing a cornerstone for emotion communication and affect sharing.
C1 [Tamietto, Marco; de Gelder, Beatrice] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands.
[Vighetti, Sergio] Univ Torino, Dept Neurosci, I-10126 Turin, Italy.
[Tamietto, Marco] Inst Sci Interchange ISI Fdn, I-10133 Turin, Italy.
[Tamietto, Marco; Castelli, Lorys; Geminiani, Giuliano] Univ Torino, Dept Psychol, I-10123 Turin, Italy.
[Perozzo, Paola] Fdn Carlo Molo, Ctr Ric Neurosci, I-10123 Turin, Italy.
[Weiskrantz, Lawrence] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England.
[de Gelder, Beatrice] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Tamietto, M (reprint author), Tilburg Univ, Cognit & Affect Neurosci Lab, POB 90153, NL-5000 LE Tilburg, Netherlands.
EM m.tamietto@uvt.nl; larry.weiskrantz@psy.ox.ac.uk;
degelder@nmr.mgh.harvard.edu
RI Castelli, Lorys/G-9973-2012;
OI Castelli, Lorys/0000-0001-5009-2271; Tamietto, Marco/0000-0002-8815-8499
FU Netherlands Organization for Scientific Research [451-07-032];
Fondazione Carlo Molo; EU [FP6-2005-NEST-Path]; Italian Ministry for
University Education and Research [PRIN 2007]; McDonnell Oxford
Cognitive Neuroscience Centre
FX This study is dedicated to the precious memory of our dear friend and
colleague Luca Latini Corazzini, whose assistance during the testing
sessions was vital to this work. Wethank D. B. and G. Y. for their
patient collaboration and J. LeDoux and G. Berlucchi for valuable and
constructive comments. Thanks are also due to A. Avenanti, C.
Sinigaglia, and C. Urgesi for helpful discussions. M. T. was supported
by a Veni grant (451-07-032) from the Netherlands Organization for
Scientific Research, and partly by the Fondazione Carlo Molo. B. d. G.
was supported by a Communication with Emotional Body Language (COBOL)
grant from EU FP6-2005-NEST-Path, and by Netherlands Organization for
Scientific Research. G. G., L. C., and P. P. were supported by the PRIN
2007 from Italian Ministry for University Education and Research, and by
the Fondazione Carlo Molo. L. W. was supported by the McDonnell Oxford
Cognitive Neuroscience Centre.
NR 38
TC 115
Z9 121
U1 7
U2 40
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 20
PY 2009
VL 106
IS 42
BP 17661
EP 17666
DI 10.1073/pnas.0908994106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 508UR
UT WOS:000270963100013
PM 19805044
ER
PT J
AU Dar, MJ
Monel, B
Krishnan, L
Shun, MC
Di Nunzio, F
Helland, DE
Engelman, A
AF Dar, Mohd J.
Monel, Blandine
Krishnan, Lavanya
Shun, Ming-Chieh
Di Nunzio, Francesca
Helland, Dag E.
Engelman, Alan
TI Biochemical and virological analysis of the 18-residue C-terminal tail
of HIV-1 integrase
SO RETROVIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; DNA-BINDING DOMAIN; PHOTO-CROSS-LINKING;
PROTEIN IN-VITRO; PREINTEGRATION COMPLEXES; REVERSE-TRANSCRIPTASE;
RETROVIRAL INTEGRASE; NUCLEAR-LOCALIZATION; CRYSTAL-STRUCTURE; CATALYTIC
DOMAIN
AB Background: The 18 residue tail abutting the SH3 fold that comprises the heart of the C-terminal domain is the only part of HIV-1 integrase yet to be visualized by structural biology. To ascertain the role of the tail region in integrase function and HIV-1 replication, a set of deletion mutants that successively lacked three amino acids was constructed and analyzed in a variety of biochemical and virus infection assays. HIV-1/2 chimers, which harbored the analogous 23-mer HIV-2 tail in place of the HIV-1 sequence, were also studied. Because integrase mutations can affect steps in the replication cycle other than integration, defective mutant viruses were tested for integrase protein content and reverse transcription in addition to integration. The F185K core domain mutation, which increases integrase protein solubility, was furthermore analyzed in a subset of mutants.
Results: Purified proteins were assessed for in vitro levels of 3' processing and DNA strand transfer activities whereas HIV-1 infectivity was measured using luciferase reporter viruses. Deletions lacking up to 9 amino acids (1-285, 1-282, and 1-279) displayed near wild-type activities in vitro and during infection. Further deletion yielded two viruses, HIV-1(1-276) and HIV-1(1-273), that displayed approximately two and 5-fold infectivity defects, respectively, due to reduced integrase function. Deletion mutant HIV-1(1-270) and the HIV-1/2 chimera were non-infectious and displayed approximately 3 to 4-fold reverse transcription in addition to severe integration defects. Removal of four additional residues, which encompassed the C-terminal. strand of the SH3 fold, further compromised integrase incorporation into virions and reverse transcription.
Conclusion: HIV-1(1-270), HIV-1(1-266), and the HIV-1/2 chimera were typed as class II mutant viruses due to their pleiotropic replication defects. We speculate that residues 271-273 might play a role in mediating the known integrase-reverse transcriptase interaction, as their removal unveiled a reverse transcription defect. The F185K mutation reduced the in vitro activities of 1-279 and 1-276 integrases by about 25%. Mutant proteins 1-279/F185K and 1-276/F185K are therefore highlighted as potential structural biology candidates, whereas further deleted tail variants (1-273/F185K or 1-270/F185K) are less desirable due to marginal or undetectable levels of integrase function.
C1 [Dar, Mohd J.; Monel, Blandine; Krishnan, Lavanya; Shun, Ming-Chieh; Di Nunzio, Francesca; Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA.
[Dar, Mohd J.; Monel, Blandine; Krishnan, Lavanya; Shun, Ming-Chieh; Di Nunzio, Francesca; Engelman, Alan] Dana Farber Canc Inst, AIDS, Boston, MA 02115 USA.
[Helland, Dag E.] Univ Bergen, Inst Mol Biol, N-5020 Bergen, Norway.
RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol, 44 Binney St, Boston, MA 02115 USA.
EM mjd82+@pitt.edu; Blandine_Monel@dfci.harvard.edu;
lavanya_krishnan@dfci.harvard.edu; michelle_shun@dfci.harvard.edu;
Francesca_DiNunzio@dfci.harvard.edu; Helland@mbi.uib.no;
alan_engelman@dfci.harvard.edu
RI Di Nunzio, Francesca/A-6153-2014
OI Di Nunzio, Francesca/0000-0003-2879-3164
FU US NIH [AI039394, AI070042]; Harvard University Center for AIDS Research
(CFAR); NIH [P30AI060354]; NIAID; NCI; NIMH; NIDA; NICHD; NHLBI; NCCAM
FX The authors thank Nan Yan for valuable technical advice. This work was
supported by US NIH grants AI039394 and AI070042 ( to AE) and the
Harvard University Center for AIDS Research (CFAR), an NIH funded
program (P30AI060354) that is supported by the following NIH Institutes
and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NCCAM. The contents
of this manuscript do not necessarily reflect the views 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.
NR 67
TC 20
Z9 20
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD OCT 19
PY 2009
VL 6
AR 94
DI 10.1186/1742-4690-6-94
PG 13
WC Virology
SC Virology
GA 518FC
UT WOS:000271675000001
PM 19840380
ER
PT J
AU Feuerer, M
Shen, YL
Littman, DR
Benoist, C
Mathis, D
AF Feuerer, Markus
Shen, Yuelei
Littman, Dan R.
Benoist, Christophe
Mathis, Diane
TI How Punctual Ablation of Regulatory T Cells Unleashes an Autoimmune
Lesion within the Pancreatic Islets
SO IMMUNITY
LA English
DT Article
ID NONOBESE DIABETIC MICE; NATURAL-KILLER-CELLS; NOD MICE; IFN-GAMMA;
LYMPH-NODES; CROSS-TALK; ANTIGEN; FOXP3; COSTIMULATION; ENTEROPATHY
AB CD4(+)Foxp3(+) regulatory T cells (Treg cells) are known to control the progression of autoimmune diabetes, but when, where, and how they exert their influence in this context are questions still under vigorous debate. Exploiting a transgene encoding the human diphtheria toxin receptor, we punctually and specifically ablated Foxp3(+) cells in the BCD2.5/NOD mouse model of autoimmune diabetes. Strikingly, overt disease developed within 3 days. The earliest detectable event was the activation of natural killer (NK) cells directly within the insulitic lesion, particularly the induction of Ifng gene expression within 7 hours of Treg cell ablation. Interferon-gamma had a strong impact on the gene-expression program of the local CD4(+) T effector cell population, unleashing it to aggressively attack the islets, which was required for the development of diabetes. Thus, Treg cells regulate pancreatic autoimmunity in situ through control of a central innate immune system player, NK cells.
C1 [Feuerer, Markus; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Feuerer, Markus; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA.
[Mathis, Diane] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA.
[Shen, Yuelei; Littman, Dan R.] NYU, Sch Med, Kimmel Ctr Biol & Med, New York, NY 10016 USA.
[Shen, Yuelei; Littman, Dan R.] NYU, Sch Med, Skirball Inst, New York, NY 10016 USA.
[Shen, Yuelei; Littman, Dan R.] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA.
RP Benoist, C (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
EM cbdm@hms.harvard.edu; cbdm@hms.harvard.edu
RI Ain, Kenneth/A-5179-2012
OI Ain, Kenneth/0000-0002-2668-934X
FU Juvenile Diabetes Research Foundation [4-2007-1057]; NIH [R01 DK59658];
Asthma Research and the National Multiple Sclerosis Society;
NIDDK-funded Diabetes and Endocrinology Research Center; German Research
Foundation [FE 801/1-1]
FX We thank J. Stockton for producing the DTR transgenics; J. LaVecchio and
G. Buruzala for flow cytometry; J. Hill, J. Perez, and K. Leatherbee for
help with the microarray analyses; and H.-J. Wu for the IFN-gamma
signature. This work was supported by grants from the Juvenile Diabetes
Research Foundation (4-2007-1057) and the NIH (R01 DK59658) to D.M. and
C.B.; by grants from the Sandler Program in Asthma Research and the
National Multiple Sclerosis Society to D.R.L.; and by the core
facilities of Joslin Diabetes Center's NIDDK-funded Diabetes and
Endocrinology Research Center. M.F. was supported by postdoctoral
fellowships from the German Research Foundation (Emmy-Noether
Fellowship, FE 801/1-1) and the Charles A. King Trust.
NR 44
TC 117
Z9 119
U1 1
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD OCT 16
PY 2009
VL 31
IS 4
BP 654
EP 664
DI 10.1016/j.immuni.2009.08.023
PG 11
WC Immunology
SC Immunology
GA 514OI
UT WOS:000271403900016
PM 19818653
ER
PT J
AU Choi, Y
Seeliger, MA
Panjarian, SB
Kim, H
Deng, X
Sim, T
Couch, B
Koleske, AJ
Smithgall, TE
Gray, NS
AF Choi, Yongmun
Seeliger, Markus A.
Panjarian, Shoghag B.
Kim, Hakjoong
Deng, Xianming
Sim, Taebo
Couch, Brian
Koleske, Anthony J.
Smithgall, Thomas E.
Gray, Nathanael S.
TI N-Myristoylated c-Abl Tyrosine Kinase Localizes to the Endoplasmic
Reticulum upon Binding to an Allosteric Inhibitor
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BREAST-CANCER CELLS; BCR-ABL; GENE-PRODUCT; PROTEIN; ACTIN;
PROLIFERATION; TRANSLOCATION; ACTIVATION; EXPRESSION; LEUKEMIA
AB Allosteric kinase inhibitors hold promise for revealing unique features of kinases that may not be apparent using conventional ATP-competitive inhibitors. Here we explore the activity of a previously reported allosteric inhibitor of BCR-Abl kinase, GNF-2, against two cellular isoforms of Abl tyrosine kinase: one that carries a myristate in the N terminus and the other that is deficient in N-myristoylation. Our results show that GNF-2 inhibits the kinase activity of non-myristoylated c-Abl more potently than that of myristoylated c-Abl by binding to the myristate-binding pocket in the C-lobe of the kinase domain. Unexpectedly, indirect immunofluorescence reveals a translocation of myristoylated c-Abl to the endoplasmic reticulum in GNF-2-treated cells, whereas GNF-2 has no detectable effect on the localization of non-myristoylated c-Abl. These results indicate that GNF-2 competes with the NH(2)-terminal myristate for binding to the c-Abl kinase myristate-binding pocket and that the exposed myristoyl group accounts for the localization to the endoplasmic reticulum. We also demonstrate that GNF-2 can inhibit enzymatic and cellular kinase activity of Arg, a kinase highly homologous to c-Abl, which is also likely to be regulated through intramolecular binding of an NH(2)-terminal myristate lipid. These results suggest that non-ATP-competitive inhibitors, such as GNF-2, can serve as chemical tools that can discriminate between c-Abl isoform-specific behaviors.
C1 [Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Choi, Yongmun; Deng, Xianming; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Seeliger, Markus A.] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
[Seeliger, Markus A.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
[Panjarian, Shoghag B.; Smithgall, Thomas E.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15261 USA.
[Couch, Brian; Koleske, Anthony J.] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
RP Gray, NS (reprint author), AGM 628A,250 Longwood Ave, Boston, MA 02115 USA.
EM nathanael_gray@dfci.harvard.edu
RI Seeliger, Markus/D-6409-2013
FU National Institutes of Health [R01 CA130876-01A1, NS39475, MH77306, R01
CA101828]; Novartis Institute of Biomedical Research
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01 CA130876-01A1; NS39475 and MH77306 (to A. J. K.); and
R01 CA101828 (to T. E. S.). This work was also supported by the Novartis
Institute of Biomedical Research (to N. S. G.).
NR 31
TC 26
Z9 26
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 16
PY 2009
VL 284
IS 42
BP 29005
EP 29014
DI 10.1074/jbc.M109.026633
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 505GD
UT WOS:000270678900058
PM 19679652
ER
PT J
AU Domian, IJ
Chiravuri, M
van der Meer, P
Feinberg, AW
Shi, X
Shao, Y
Wu, SM
Parker, KK
Chien, KR
AF Domian, Ibrahim J.
Chiravuri, Murali
van der Meer, Peter
Feinberg, Adam W.
Shi, Xi
Shao, Ying
Wu, Sean M.
Parker, Kevin Kit
Chien, Kenneth R.
TI Generation of Functional Ventricular Heart Muscle from Mouse Ventricular
Progenitor Cells
SO SCIENCE
LA English
DT Article
ID MAMMALIAN HEART; SMOOTH-MUSCLE; ISL1; DIFFERENTIATION; TRANSCRIPTION;
EXPRESSION; LINEAGES; FIELD; MEF2C
AB The mammalian heart is formed from distinct sets of first and second heart field (FHF and SHF, respectively) progenitors. Although multipotent progenitors have previously been shown to give rise to cardiomyocytes, smooth muscle, and endothelial cells, the mechanism governing the generation of large numbers of differentiated progeny remains poorly understood. We have employed a two-colored fluorescent reporter system to isolate FHF and SHF progenitors from developing mouse embryos and embryonic stem cells. Genome-wide profiling of coding and noncoding transcripts revealed distinct molecular signatures of these progenitor populations. We further identify a committed ventricular progenitor cell in the Islet 1 lineage that is capable of limited in vitro expansion, differentiation, and assembly into functional ventricular muscle tissue, representing a combination of tissue engineering and stem cell biology.
C1 [Domian, Ibrahim J.; Chiravuri, Murali; van der Meer, Peter; Shi, Xi; Shao, Ying; Wu, Sean M.; Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Domian, Ibrahim J.; Wu, Sean M.; Parker, Kevin Kit; Chien, Kenneth R.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[van der Meer, Peter] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands.
[Feinberg, Adam W.; Parker, Kevin Kit] Harvard Univ, Sch Engn & Appl Sci, Dis Biophys Grp, Cambridge, MA 02138 USA.
[Parker, Kevin Kit] Harvard Univ, Wyss Inst Biologically Inspired Engn, Boston, MA 02115 USA.
[Chien, Kenneth R.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
RP Chien, KR (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charles River Plaza,CPZN 3200,185 Cambridge St, Boston, MA 02114 USA.
EM krchien@partners.org
RI Feinberg, Adam/A-7103-2009
OI Feinberg, Adam/0000-0003-3338-5456
FU NHLBI NIH HHS [K08 HL081086, K08 HL081086-01, K08 HL091209, R01
HL079126, R01 HL079126-01A1, T32 HL002807]
NR 21
TC 124
Z9 126
U1 1
U2 17
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD OCT 16
PY 2009
VL 326
IS 5951
BP 426
EP 429
DI 10.1126/science.1177350
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 506ZM
UT WOS:000270818600053
PM 19833966
ER
PT J
AU Sahin, NT
Pinker, S
Cash, SS
Schomer, D
Halgren, E
AF Sahin, Ned T.
Pinker, Steven
Cash, Sydney S.
Schomer, Donald
Halgren, Eric
TI Sequential Processing of Lexical, Grammatical, and Phonological
Information Within Broca's Area
SO SCIENCE
LA English
DT Article
ID WORD FORM AREA; BRAIN; LANGUAGE; MODEL; COMPREHENSION; FREQUENCY;
REGION; NOUNS; VERBS; FMRI
AB Words, grammar, and phonology are linguistically distinct, yet their neural substrates are difficult to distinguish in macroscopic brain regions. We investigated whether they can be separated in time and space at the circuit level using intracranial electrophysiology (ICE), namely by recording local field potentials from populations of neurons using electrodes implanted in language-related brain regions while people read words verbatim or grammatically inflected them (present/past or singular/plural). Neighboring probes within Broca's area revealed distinct neuronal activity for lexical (similar to 200 milliseconds), grammatical (similar to 320 milliseconds), and phonological (similar to 450 milliseconds) processing, identically for nouns and verbs, in a region activated in the same patients and task in functional magnetic resonance imaging. This suggests that a linguistic processing sequence predicted on computational grounds is implemented in the brain in fine-grained spatiotemporally patterned activity.
C1 [Sahin, Ned T.; Halgren, Eric] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92037 USA.
[Sahin, Ned T.; Pinker, Steven] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
[Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Schomer, Donald] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
RP Sahin, NT (reprint author), Univ Calif San Diego, Dept Radiol, La Jolla, CA 92037 USA.
EM sahin@post.harvard.edu
FU NIH [NS18741, NS44623, HD18381, T32-MH070328, NCRR P41-RR14075]; Mental
Illness and Neuroscience Discovery (MIND) Institute; Sackler Scholars
Programme in Psychobiology; Harvard Mind/Brain/Behavior Initiative
FX Supported by NIH grants NS18741 (E. H.), NS44623 (E. H.), HD18381 (S.
P.), T32-MH070328 (N. T. S.), NCRR P41-RR14075; and the Mental Illness
and Neuroscience Discovery (MIND) Institute (N. T. S.), Sackler Scholars
Programme in Psychobiology (N. T. S.), and Harvard Mind/Brain/Behavior
Initiative (N. T. S.). We heartily thank the patients. We also thank E.
Papavassiliou and J. Wu for access to their patients; S. Narayanan, N.
Dehghani, M. T. Wheeler, F. Kampmann, and L. Gruber for assistance with
intracranial electrophysiological data; R. Raizada for manuscript
suggestions; N. M. Sahin; and two anonymous reviewers whose suggestions
and encouragement greatly improved this paper.
NR 31
TC 167
Z9 168
U1 2
U2 43
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD OCT 16
PY 2009
VL 326
IS 5951
BP 445
EP 449
DI 10.1126/science.1174481
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 506ZM
UT WOS:000270818600059
PM 19833971
ER
PT J
AU Jneid, H
Cruz-Gonzalez, I
Sanchez-Ledesma, M
Maree, AO
Cubeddu, RJ
Leon, ML
Rengifo-Moreno, P
Otero, JP
Inglessis, I
Sanchez, PL
Palacios, IF
AF Jneid, Hani
Cruz-Gonzalez, Ignacio
Sanchez-Ledesma, Maria
Maree, Andrew O.
Cubeddu, Roberto J.
Leon, Milton L.
Rengifo-Moreno, Pablo
Otero, Juan Pal
Inglessis, Ignacio
Sanchez, Pedro L.
Palacios, Igor F.
TI Impact of Pre- and Postprocedural Mitral Regurgitation on Outcomes After
Percutaneous Mitral Valvuloplasty for Mitral Stenosis
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID BALLOON VALVOTOMY; PREDICTORS; VARIABLES
AB Percutaneous mitral valvuloplasty (PMV) is an effective therapy in patients with significant mitral stenosis. Few studies have examined the effect of mitral regurgitation (MR), a frequent periprocedural finding, on PMV outcomes. We examined the effects of pre- and postprocedural MR after PMV. Contrast left ventriculography was performed before and after PMV, and the MR severity was assessed using Sellers' classification. Clinical, hemodynamic, and morphologic variables were collected for all patients. Consecutive patients (n = 876) undergoing a first PMV procedure at a single tertiary center were evaluated. An increasing preprocedural MR severity was associated with reduced PMV success (no MR, 75%; 1+ MR, 65%; 2+ MR, 44%; p <0.0001), increased in-hospital mortality (0.6% vs 2.8% vs 4.9%, respectively; p = 0.007), and other complications. Increasing grades of pre- and postprocedural MR predicted, independently and in a grade-dependent manner, the composite outcome of mortality, mitral valve surgery, or redo PMV (preprocedural MR >= 1+, relative risk [RR] 1.4, 95% confidence interval [CI] 1.2 to 1.8; preprocedural MR >= 2+, RR 1.6, 95% CI 1.1 to 2.4; postprocedural MR >= 1+, RR 1.6,95% CI 1.2 to 2.0; postprocedural MR >= 2+, RR 2.2, 95% CI 1.7 to 2.7; and postprocedural MR >= 3+, RR 4.6, 95% CI 3.4 to 6.2, respectively). In conclusion, increasing pre- and postprocedural MR grades independently predicted the long-term clinical outcomes after PMV. Patients with moderate preprocedural MR, in particular, appeared to have suboptimal short- and long-term outcomes, necessitating careful monitoring and early referral for mitral valve surgery, when appropriate. Published by Elsevier Inc. (Am J Cardiol 2009;104:1122-1127)
C1 [Jneid, Hani] Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Cardiol Sect, Houston, TX USA.
[Jneid, Hani] Baylor Coll Med, Houston, TX 77030 USA.
[Cruz-Gonzalez, Ignacio; Sanchez-Ledesma, Maria; Maree, Andrew O.; Cubeddu, Roberto J.; Leon, Milton L.; Rengifo-Moreno, Pablo; Otero, Juan Pal; Inglessis, Ignacio; Palacios, Igor F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit, Boston, MA USA.
[Sanchez, Pedro L.] Gregorio Maranon Univ Hosp, Div Cardiol, Madrid, Spain.
RP Jneid, H (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Cardiol Sect, Houston, TX USA.
EM jneid@bcm.edu
RI 2009, Secribsal/A-1266-2012;
OI Sanchez, Pedro L/0000-0002-4288-345X
NR 13
TC 12
Z9 13
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD OCT 15
PY 2009
VL 104
IS 8
BP 1122
EP 1127
DI 10.1016/j.amjcard.2009.06.008
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 507OS
UT WOS:000270864600020
PM 19801035
ER
PT J
AU Joo, C
Ozkumur, E
Unlu, MS
de Boer, JF
AF Joo, Chulmin
Ozkumur, Emre
Unlu, M. Selim
de Boer, Johannes F.
TI Spectral-domain optical coherence phase microscopy for label-free
multiplexed protein microarray assay
SO BIOSENSORS & BIOELECTRONICS
LA English
DT Article
DE Optical interferometer; Optical coherence tomography; Label-free;
Microarray; Proteomics
ID INTERFEROMETRY; TOMOGRAPHY
AB Quantitative measurement of affinities and kinetics of various biomolecular interactions such as protein-protein, protein-DNA and receptor-ligand is central to our understanding of basic molecular and cellular functions and is useful for therapeutic evaluation. Here, we describe a laser-scanning quantitative imaging method, referred to as spectral-domain optical coherence phase microscopy, as an optical platform for label-free detection of biomolecular interactions. The instrument is based on a confocal interferometric microscope that enables depth-resolved quantitative phase measurements on sensor surface with high spatial resolution and phase stability. We demonstrate picogram per square millimeter surface mass sensitivity, and show its sensing capability by presenting static and dynamic detection of multiplexed protein microarray as immobilized antigens capture their corresponding antibodies. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Joo, Chulmin; de Boer, Johannes F.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Joo, Chulmin; de Boer, Johannes F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Joo, Chulmin] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
[Ozkumur, Emre; Unlu, M. Selim] Boston Univ, Dept Elect & Comp Engn, Boston, MA 02139 USA.
[de Boer, Johannes F.] Vrije Univ Amsterdam, Dept Phys & Astron, NL-1081 HV Amsterdam, Netherlands.
RP Joo, C (reprint author), GE Global Res, 1 Res Circle, Niskayuna, NY 12309 USA.
EM jooc@ge.com; jfdeboer@few.vu.nl
RI de Boer, Johannes/B-7590-2012; Unlu, Selim/B-4244-2013;
OI de Boer, Johannes/0000-0003-1253-4950; Joo, Chulmin/0000-0002-1812-2976
FU National Institute of Health [R01 RR19768, EY14975]; U.S. Department of
Defense [F4 9620-01-1-0014]; Army Research Laboratory
[W911NF-06-2-0040]; Center for Integration of Medicine and Innovative
Technology; Wellman Graduate Fellowship; MIT Department of Mechanical
Engineering
FX This work was supported by grants from National Institute of Health (R01
RR19768, EY14975 to J.F.dB), the U.S. Department of Defense (F4
9620-01-1-0014 to M.S.U.), Army Research Laboratory (W911NF-06-2-0040 to
M.S.U.), and the Center for Integration of Medicine and Innovative
Technology. The authors are grateful to Drs. Ki Hean Kim and Conor Evans
for their contributions to the system setup. C.J. would like to thank
the support through Wellman Graduate Fellowship and Hatsopoulous
Innovation Award from the MIT Department of Mechanical Engineering.
NR 30
TC 12
Z9 12
U1 0
U2 6
PU ELSEVIER ADVANCED TECHNOLOGY
PI OXFORD
PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON,
OXFORD OX5 1GB, OXON, ENGLAND
SN 0956-5663
J9 BIOSENS BIOELECTRON
JI Biosens. Bioelectron.
PD OCT 15
PY 2009
VL 25
IS 2
BP 275
EP 281
DI 10.1016/j.bios.2009.06.028
PG 7
WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical;
Electrochemistry; Nanoscience & Nanotechnology
SC Biophysics; Biotechnology & Applied Microbiology; Chemistry;
Electrochemistry; Science & Technology - Other Topics
GA 506GY
UT WOS:000270764300002
PM 19674885
ER
PT J
AU Bergman, J
Gore, JL
Saigal, CS
Kwan, L
Litwin, MS
AF Bergman, Jonathan
Gore, John L.
Saigal, Christopher S.
Kwan, Lorna
Litwin, Mark S.
TI Partnership and Outcomes in Men With Prostate Cancer
SO CANCER
LA English
DT Article
DE prostatic neoplasms; quality of life; marital relationship; outcome
assessment; neoplasms
ID QUALITY-OF-LIFE; BREAST-CANCER; PSYCHOLOGICAL DISTRESS; ERECTILE
DYSFUNCTION; COUPLES; HEALTH; SUPPORT; CARCINOMA; VALIDITY; WOMEN
AB BACKGROUND: Being in a supportive relationship may have improved the health-related quality of life (HRQOL) of men with prostate cancer, if the support was strong and positive. In the current study, the authors sought to examine the impact of partnership status on the mental health of men treated for localized prostate cancer. METHODS: Participants had clinically localized prostate cancer and chose treatment with radical prostatectomy (n=307), external-beam radiotherapy (n=78), or brachytherapy (n=91). The authors prospectively assessed subject characteristics and HRQOL outcomes and evaluated associations between partnership outcomes and HRQOL measures. Two multivariate linear regression models were then created, I for baseline HRQOL outcomes and 1 for change in HRQOL from baseline to 12 months, with partnership status as the main predictor and subject characteristics as covariates. RESULTS: Partnership status was not found to be associated with either baseline physical or mental health, but partnered participants had less bowel bother (P=.02) and a lower fear of recurrence (P=.03) at baseline than did unpartnered subjects. Men with fewer comorbid conditions scored better across almost all baseline HRQOL domains. Primary treatment type was significantly associated with changes in physical HRQOL, with men undergoing radical prostatectomy describing better changes in physical health than those treated with brachytherapy (P=.04) or those receiving external-beam radiotherapy (P <=.01). CONCLUSIONS: Physical and mental health was found to be comparable in the study cohort of partnered and unpartnered men treated for prostate cancer. The universally high socioeconomic status of the current study cohort may mitigate differences in HRQOL by partnership status. Cancer 2009;115:4688-94. (C) 2009 American Cancer Society.
C1 [Bergman, Jonathan; Gore, John L.] Univ Calif Los Angeles, Dept Urol, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90095 USA.
[Gore, John L.; Saigal, Christopher S.] Vet Adm Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA.
[Saigal, Christopher S.; Litwin, Mark S.] Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA 90095 USA.
[Saigal, Christopher S.; Kwan, Lorna; Litwin, Mark S.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
RP Bergman, J (reprint author), Univ Calif Los Angeles, Dept Urol, Robert Wood Johnson Clin Scholars Program, Box 951738, Los Angeles, CA 90095 USA.
EM jbergman@mednet.ucla.edu
OI Gore, John/0000-0002-2847-5062
NR 27
TC 11
Z9 12
U1 2
U2 8
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD OCT 15
PY 2009
VL 115
IS 20
BP 4688
EP 4694
DI 10.1002/cncr.24544
PG 7
WC Oncology
SC Oncology
GA 505ZJ
UT WOS:000270740900008
PM 19626653
ER
PT J
AU Firestein, R
Hahn, WC
AF Firestein, Ron
Hahn, William C.
TI Revving the Throttle on an Oncogene: CDK8 Takes the Driver Seat
SO CANCER RESEARCH
LA English
DT Review
ID BETA-CATENIN; MEDIATOR COMPLEX; GENE-EXPRESSION; TRANSCRIPTION;
ACTIVATION; PHOSPHORYLATION; SUBCOMPLEX; PYGOPUS; MED12
AB The Wnt/beta-catenin pathway plays an important role in initiation in most, if not all, colon cancers. Prior work has provided important insights into the regulation of beta-catenin stability in the cytoplasm; however, relatively little is known about the mechanism by which beta-catenin activates gene transcription in the nucleus. Using genetic approaches, studies in human colon cancers and Drosophila have identified CDK8 as a colon cancer oncogene that regidates beta-catenin transcriptional activity. These convergent observations provide new insights into the regulation of nuclear beta-catenin activity and identify a novel therapeutic target for beta-catenin-driven malignancies. [Cancer Res 2009;69(20):7899-901]
C1 [Firestein, Ron; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Firestein, Ron] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Hahn, William C.] Broad Inst Harvard & MIT, Cambridge, MA USA.
RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Dana 1538, Boston, MA 02115 USA.
EM william_hahn@dfci.harvard.edu
FU U.S. National Institutes of Health [R33 CA128625]
FX Grant support: U.S. National Institutes of Health (R33 CA128625).
NR 20
TC 23
Z9 25
U1 0
U2 2
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 15
PY 2009
VL 69
IS 20
BP 7899
EP 7901
DI 10.1158/0008-5472.CAN-09-1704
PG 3
WC Oncology
SC Oncology
GA 508MM
UT WOS:000270935500002
PM 19808961
ER
PT J
AU Xu, L
Duda, DG
di Tomaso, E
Ancukiewicz, M
Chung, DC
Lauwers, GY
Samuel, R
Shellito, P
Czito, BG
Lin, PC
Poleski, M
Bentley, R
Clark, JW
Willett, CG
Jain, RK
AF Xu, Lei
Duda, Dan G.
di Tomaso, Emmanuelle
Ancukiewicz, Marek
Chung, Daniel C.
Lauwers, Gregory Y.
Samuel, Rekha
Shellito, Paul
Czito, Brian G.
Lin, Pei-Chun
Poleski, Martin
Bentley, Rex
Clark, Jeffrey W.
Willett, Christopher G.
Jain, Rakesh K.
TI Direct Evidence that Bevacizumab, an Anti-VEGF Antibody, Up-regulates
SDF1 alpha, CXCR4, CXCL6, and Neuropilin 1 in Tumors from Patients with
Rectal Cancer
SO CANCER RESEARCH
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; ANTIANGIOGENIC THERAPY; CELL-MIGRATION;
COLORECTAL-CANCER; ANGIOGENESIS; VASCULATURE; METASTASIS; EXPRESSION
AB Clinical studies converge on the observation that circulating cytokines are elevated in most cancer patients by anti-vascular endothelial growth factor (VEGF) therapy. However, the source of these molecules and their relevance in tumor escape remain unknown. We examined the gene expression profiles of cancer cells and tumor-associated macrophages in tumor biopsies before and 12 days after monotherapy with the anti-VEGF antibody bevacizumab in patients with rectal carcinoma. Bevacizumab up-regulated stromal cell-derived factor 1 alpha. (SDF1 alpha), its receptor CXCR4, and CXCL6, and down-regulated PIGF, Ang1, and Ang2 in cancer cells. In addition, bevacizumab decreased Ang1 and induced neuropilin 1 (NRP1) expression in tumor-associated macrophages. Higher SDF1 alpha plasma levels during bevacizumab treatment significantly associated with distant metastasis at three years. These data show that VEGF blockade up-regulates inflammatory pathways and NRP1, which should be evaluated as potential targets for improving anti-VEGF therapy. [Cancer Res 2009;69(20):7905-10]
C1 [Jain, Rakesh K.] Massachusetts Gen Hosp, EL Steele Lab, Dept Radiat Oncol, Boston, MA 02114 USA.
[Chung, Daniel C.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Lauwers, Gregory Y.; Samuel, Rekha] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Shellito, Paul] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Clark, Jeffrey W.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Czito, Brian G.; Willett, Christopher G.] Duke Univ, Med Ctr, Div Radiat Oncol, Durham, NC 27710 USA.
[Poleski, Martin] Duke Univ, Med Ctr, Dept Gastroenterol, Durham, NC 27710 USA.
[Bentley, Rex] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
RP Jain, RK (reprint author), Massachusetts Gen Hosp, EL Steele Lab, Dept Radiat Oncol, 100 Blossom St,Cox 734, Boston, MA 02114 USA.
EM christopher.willett@duke.edu; jain@steele.mgh.harvard.edu
RI Lin, Pei-Chun/A-3200-2013
FU NIH [R21-CA99237, P01-CA80124, R01-CA115767, R01-CA85140, R01-CA126CA2];
Federal Share/National Cancer Institute Proton Beam Program Income;
National Foundation for Cancer Research
FX Grant support: NIH grants R21-CA99237, P01-CA80124, R01-CA115767,
R01-CA85140, and R01-CA126CA2; Federal Share/National Cancer Institute
Proton Beam Program Income grants; and by the National Foundation for
Cancer Research.
NR 20
TC 96
Z9 100
U1 1
U2 4
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 15
PY 2009
VL 69
IS 20
BP 7905
EP 7910
DI 10.1158/0008-5472.CAN-09-2099
PG 6
WC Oncology
SC Oncology
GA 508MM
UT WOS:000270935500003
PM 19826039
ER
PT J
AU Wang, X
Sansam, CG
Thom, CS
Metzger, D
Evans, JA
Nguyen, PTL
Roberts, CWM
AF Wang, Xi
Sansam, Courtney G.
Thom, Christopher S.
Metzger, Daniel
Evans, Julia A.
Nguyen, Phuong T. L.
Roberts, Charles W. M.
TI Oncogenesis Caused by Loss of the SNF5 Tumor Suppressor Is Dependent on
Activity of BRG1, the ATPase of the SWI/SNF Chromatin Remodeling Complex
SO CANCER RESEARCH
LA English
DT Article
ID CANCER CELL-LINES; ACUTE LYMPHOBLASTIC-LEUKEMIA; SOFT-TISSUE SARCOMAS;
RHABDOID TUMORS; PROTEIN EXPRESSION; GERMLINE MUTATION; INI1 EXPRESSION;
BREAST-CANCER; GENE; CYCLE
AB Alterations in chromatin play an important role in oncogenic transformation, although the underlying mechanisms are often poorly understood. The SWI/SNF complex contributes to epigenetic regulation by using the energy of ATP hydrolysis to remodel chromatin and thus regulate transcription of target genes. SNF5, a core subunit of the SWI/SNF complex, is a potent tumor suppressor that is specifically inactivated in several types of human cancer. However, the mechanism by which SNF5 mutation leads to cancer and the role of SNF5 within the SWI/SNF complex remain largely unknown. It has been hypothesized that oncogenesis in the absence of SNF5 occurs due to a loss of function of the SWI/SNF complex. Here, we show, however, distinct effects for inactivation of Snf5 and the ATPase subunit Brg1 in primary cells. Further, using both human cell lines and mouse models, we show that cancer formation in the absence of SNF5 does not result from SWI/SNF inactivation but rather that oncogenesis is dependent on continued presence of BRG1. Collectively, our results show that cancer formation in the absence of SNF5 is dependent on the activity of the residual BRG1-containing SWI/SNF complex. These findings suggest that, much like the concept of oncogene addiction, targeted inhibition of SWI/SNF ATPase activity may be an effective therapeutic approach for aggressive SNF5-deficient human tumors. [Cancer Res 2009; 69(20):8094-101]
C1 [Wang, Xi; Sansam, Courtney G.; Thom, Christopher S.; Evans, Julia A.; Nguyen, Phuong T. L.; Roberts, Charles W. M.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Wang, Xi; Sansam, Courtney G.; Thom, Christopher S.; Evans, Julia A.; Nguyen, Phuong T. L.; Roberts, Charles W. M.] Harvard Univ, Sch Med, Dept Pediat, Childrens Hosp Boston,Div Hematol Oncol, Boston, MA USA.
[Metzger, Daniel] Univ Strasbourg 1, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France.
RP Roberts, CWM (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Mayer 657,44 Binney St, Boston, MA 02115 USA.
EM charles_roberts@dfci.harvard.edu
FU Garrett B. Smith Foundation; Claudia Adams Barr Foundation; Sarcoma
Foundation of America; PHS award [R01CA113794, F32CA123776]; Flope
Street Kids Foundation
FX Grant support: Garrett B. Smith Foundation, the Claudia Adams Barr
Foundation, the Sarcoma Foundation of America, and PHS award R01CA113794
(C.W.M. Roberts) and PHS awards F32CA123776 and Flope Street Kids
Foundation (C.G. Sansam).
NR 50
TC 54
Z9 56
U1 1
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD OCT 15
PY 2009
VL 69
IS 20
BP 8094
EP 8101
DI 10.1158/0008-5472.CAN-09-0733
PG 8
WC Oncology
SC Oncology
GA 508MM
UT WOS:000270935500026
PM 19789351
ER
PT J
AU Kreeger, PK
Mandhana, R
Alford, SK
Haigis, KM
Lauffenburger, DA
AF Kreeger, Pamela K.
Mandhana, Roli
Alford, Shannon K.
Haigis, Kevin M.
Lauffenburger, Douglas A.
TI RAS Mutations Affect Tumor Necrosis Factor-Induced Apoptosis in Colon
Carcinoma Cells via ERK-Modulatory Negative and Positive Feedback
Circuits Along with Non-ERK Pathway Effects
SO CANCER RESEARCH
LA English
DT Article
ID INDUCIBLE AUTOCRINE CASCADE; LEAST-SQUARES REGRESSION; GROWTH-FACTOR
RECEPTOR; ONCOGENIC K-RAS; N-RAS; GENETIC ALTERATIONS;
ULCERATIVE-COLITIS; COLORECTAL-CANCER; EPITHELIAL-CELLS; SIGNAL
AB More than 40% of colon cancers have a mutation in K-RAS or N-RAS, GTPases that operate as central hubs for multiple key signaling pathways within the cell. Utilizing an isogenic panel of colon carcinoma cells with K-RAS or N-RAS variations, we observed differences in tumor necrosis factor-alpha (TNF alpha)-induced apoptosis. When the dynamics of phosphorylated ERK response to TNF alpha were examined, K-RAS mutant cells showed lower activation whereas N-RAS mutant cells exhibited prolonged duration. These divergent trends were partially explained by differential induction of two ERK-modulatory circuits: negative feedback mediated by dual-specificity phosphatase 5 and positive feedback by autocrine transforming growth factor-alpha. Moreover, in the various RAS mutant colon carcinoma lines, the transforming growth factor-alpha autocrine loop differentially elicited a further downstream chemokine (CXCL1/CXCL8) autocrine loop, with the two loops having opposite effects on apoptosis. Although the apoptotic responses of the RAS mutant panel to TNF alpha treatment showed significant dependence on the respective phosphorylated ERK dynamics, successful prediction across the various cell lines required contextual information concerning additional pathways including IKK and p38. A quantitative computational model based on weighted linear combinations of these pathway activities successfully predicted not only the spectrum of cell death responses but also the corresponding chemokine production responses. Our findings indicate that diverse RAS mutations yield differential cell behavioral responses to inflammatory cytokine exposure by means of (a) differential effects on ERK activity via multiple feedback circuit mechanisms, and (b) differential effects on other key signaling pathways contextually modulating ERK-related dependence. [Cancer Res 2009;69(20):8191-9]
C1 [Kreeger, Pamela K.; Mandhana, Roli; Alford, Shannon K.; Lauffenburger, Douglas A.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
[Lauffenburger, Douglas A.] MIT, Ctr Canc Res, Cambridge, MA 02139 USA.
[Haigis, Kevin M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Haigis, Kevin M.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA.
[Haigis, Kevin M.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA.
RP Lauffenburger, DA (reprint author), MIT, Dept Biol Engn, 77 Massachusetts Ave,16-343, Cambridge, MA 02139 USA.
EM kreeger@wisc.edu; lauffen@mit.edu
OI Hughes, Shannon/0000-0002-9778-140X; Kreeger, Pamela/0000-0001-8193-1007
FU NIH [U54-CA112967, P50-GM68762]; American Cancer Society
[PF-08-026-01-CCG]
FX Grant support: NIH grants U54-CA112967 and P50-GM68762, and by the
American Cancer Society, PF-08-026-01-CCG (P.K. Kreeger).
NR 40
TC 32
Z9 34
U1 1
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 15
PY 2009
VL 69
IS 20
BP 8191
EP 8199
DI 10.1158/0008-5472.CAN-09-1921
PG 9
WC Oncology
SC Oncology
GA 508MM
UT WOS:000270935500038
PM 19789336
ER
PT J
AU Zhao, JJ
Silver, DP
AF Zhao, Jean J.
Silver, Daniel P.
TI Estrogen Receptor-Negative Breast Cancer: New Insights into
Subclassification and Targeting
SO CLINICAL CANCER RESEARCH
LA English
DT Editorial Material
ID ADJUVANT CHEMOTHERAPY; TRASTUZUMAB; SUBTYPES
AB Classification schemes for disease states can help identify distinctions with useful implications for therapy and prognosis. Speers and colleagues provide a new subclassification scheme for estrogen receptor-negative breast cancer based upon kinome-wide gene expression profiling with interesting findings that are potentially relevant for both treatment and clinical outcome. (Clin Cancer Res 2009;15(20):6309-10)
C1 [Zhao, Jean J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Zhao, Jean J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Silver, Daniel P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Silver, Daniel P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
RP Silver, DP (reprint author), 1 Jimmy Fund Way, Boston, MA 02115 USA.
EM daniel_silver@dfci.harvard.edu
FU NCI NIH HHS [P50 CA089393, P50 CA089393-090010]
NR 13
TC 1
Z9 2
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD OCT 15
PY 2009
VL 15
IS 20
BP 6309
EP 6310
DI 10.1158/1078-0432.CCR-09-2010
PG 2
WC Oncology
SC Oncology
GA 509UI
UT WOS:000271043500001
PM 19825953
ER
PT J
AU Speers, C
Tsimelzon, A
Sexton, K
Herrick, AM
Gutierrez, C
Culhane, A
Quackenbush, J
Hilsenbeck, S
Chang, J
Brown, P
AF Speers, Corey
Tsimelzon, Anna
Sexton, Krystal
Herrick, Ashley M.
Gutierrez, Carolina
Culhane, Aedin
Quackenbush, John
Hilsenbeck, Susan
Chang, Jenny
Brown, Powel
TI Identification of Novel Kinase Targets for the Treatment of Estrogen
Receptor-Negative Breast Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GENE-EXPRESSION PATTERNS; AFRICAN-AMERICAN; CELL-LINES; PROGNOSIS;
SUBTYPES; SURVIVAL; TUMOR; SIGNATURE; CARCINOMA; DOCETAXEL
AB Purpose: Previous gene expression profiling studies of breast cancer have focused on the entire genome to identify genes differentially expressed between estrogen receptor (ER) a-positive and ER-a-negative cancers.
Experimental Design: Here, we used gene expression microarray profiling to identify a distinct kinase gene expression profile that identifies ER-negative breast tumors and subsets ER-negative breast tumors into four distinct subtypes.
Results: Based on the types of kinases expressed in these clusters, we identify a cell cycle regulatory subset, a S6 kinase pathway cluster, an immunomodulatory kinase-expressing cluster, and a mitogen-activated protein kinase pathway cluster. Furthermore, we show that this specific kinase profile is validated using independent sets of human tumors and is also seen in a panel of breast cancer cell lines. Kinase expression knockdown studies show that many of these kinases are essential for the growth of ER-negative, but not ER-positive, breast cancer cell lines. Finally, survival analysis of patients with breast cancer shows that the S6 kinase pathway signature subtype of ER-negative cancers confers an extremely poor prognosis, whereas patients whose tumors express high levels of immunomodulatory kinases have a significantly better prognosis.
Conclusions: This study identifies a list of kinases that are prognostic and may serve as druggable targets for the treatment of ER-negative breast cancer. (Clin Cancer Res 2009; 15(20):63 27-40)
C1 [Brown, Powel] Baylor Coll Med, Breast Ctr, Dept Med, Houston, TX 77030 USA.
[Speers, Corey; Herrick, Ashley M.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Tsimelzon, Anna; Sexton, Krystal; Gutierrez, Carolina; Hilsenbeck, Susan; Chang, Jenny; Brown, Powel] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.
[Culhane, Aedin; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA.
RP Brown, P (reprint author), Baylor Coll Med, Breast Ctr, Dept Med, 1 Baylor Plaza,BCM 600, Houston, TX 77030 USA.
EM pbrown@breastcenter.tmc.edu
FU NCI NIH HHS [P50 CA058183, P50 CA058183-090011, P50 CA 58183]
NR 46
TC 47
Z9 48
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD OCT 15
PY 2009
VL 15
IS 20
BP 6327
EP 6340
DI 10.1158/1078-0432.CCR-09-1107
PG 14
WC Oncology
SC Oncology
GA 509UI
UT WOS:000271043500005
PM 19808870
ER
PT J
AU Ogino, S
Nosho, K
Irahara, N
Meyerhardt, JA
Baba, Y
Shima, K
Glickman, JN
Ferrone, CR
Mino-Kenudson, M
Tanaka, N
Dranoff, G
Giovannucci, EL
Fuchs, CS
AF Ogino, Shuji
Nosho, Katsuhiko
Irahara, Natsumi
Meyerhardt, Jeffrey A.
Baba, Yoshifumi
Shima, Kaori
Glickman, Jonathan N.
Ferrone, Cristina R.
Mino-Kenudson, Mari
Tanaka, Noriko
Dranoff, Glenn
Giovannucci, Edward L.
Fuchs, Charles S.
TI Lymphocytic Reaction to Colorectal Cancer Is Associated with Longer
Survival, Independent of Lymph Node Count, Microsatellite Instability,
and CpG Island Methylator Phenotype
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID TUMOR-INFILTRATING LYMPHOCYTES; POPULATION-BASED SAMPLE; COLON-CANCER;
PROGNOSTIC-SIGNIFICANCE; LINE-1 HYPOMETHYLATION; MISMATCH REPAIR; BRAF
MUTATION; T-CELLS; CARCINOMA; NUMBER
AB Purpose: Host immune response to tumor may be an important prognostic factor for colon cancer patients. However, little is known on prognostic significance of histopathologic lymphoid reaction to tumor, independent of the number of lymph nodes examined and tumoral molecular alterations, including microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP), both of which are associated with lymphocytic reaction and clinical outcome.
Experimental Design: Using 843 colorectal cancer patients in two independent prospective cohorts, we examined patient prognosis in relation to four components of lymphocytic reaction (i.e., Crohn's-like reaction, peritumoral reaction, intratumoral periglandular reaction, and tumor-infiltrating lymphocytes) and overall lymphocytic score (0-12). CIMP was determined using eight markers including CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1. Cox proportional hazard models computed hazard ratio for mortality, adjusted for covariates including tumor stage, body mass index, lymph node count, KRAS, BRAF, p53, cyclooxygenase-2 (PTGS2), MSI, CIMP, and LINE-1 methylation.
Results: Increasing overall lymphocytic reaction score including tumor-infiltrating lymphocytes was associated with a significant improvement in colorectal cancer-specific and overall survival (log-rank P < 0.003). These findings remained significant (adjusted hazard ratio estimates, 0.49-0.71; P(trend) < 0.009) in multivariate models that adjusted for covariates, including body mass index, MSI, CIMP, LINE-1 hypomethylation, and cyclooxygenase-2. The beneficial effect of tumoral lymphocytic reaction was consistent across strata of clinical, pathologic, and molecular characteristics.
Conclusions: Lymphocytic reactions to tumor were associated with improved prognosis among colorectal cancer patients, independent of lymph node count and other clinical, pathologic, and molecular characteristics. (Clin Cancer Res 2009;15(20): 6412-20)
C1 [Ogino, Shuji] Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Pathol, Dana Farber Canc Inst,Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Ogino, Shuji; Nosho, Katsuhiko; Irahara, Natsumi; Meyerhardt, Jeffrey A.; Baba, Yoshifumi; Shima, Kaori; Ferrone, Cristina R.; Mino-Kenudson, Mari; Dranoff, Glenn; Giovannucci, Edward L.; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Giovannucci, Edward L.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Ogino, Shuji; Nosho, Katsuhiko; Irahara, Natsumi; Meyerhardt, Jeffrey A.; Baba, Yoshifumi; Shima, Kaori; Dranoff, Glenn; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA.
[Ferrone, Cristina R.; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ogino, Shuji; Tanaka, Noriko; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Pathol, Dana Farber Canc Inst,Ctr Mol Oncol Pathol, Room JF 215C,44 Binney St, Boston, MA 02115 USA.
EM shuji_ogino@dfci.harvard.edu
FU U.S. NIH [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA122826]; Bennett
Family Fund; Entertainment Industry Foundation National Colorectal
Cancer Research Alliance; Japan Society for Promotion of Science
FX U.S. NIH grants P01 CA87969 IS. Hankinson), P01 CA55075 (W. Willett),
P50 CA127003 (C.S. Fuchs), and K07 CA122826 IS. Ogino); the Bennett
Family Fund; the Entertainment Industry Foundation National Colorectal
Cancer Research Alliance; and a fellowship grant from the Japan Society
for Promotion of Science (K. Nosho). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of National Cancer Institute or NIH. Funding agencies did
not have any role in the design of the study; the collection, analysis,
or interpretation of the data; the decision to submit the manuscript for
publication; or the writing of the manuscript. The corresponding author
had full access to all of the data and takes full responsibility for the
veracity of the data and analysis. The costs of publication of this
article were defrayed in part by the payment of page charges. This
article must therefore be hereby marked advertisement in accordance with
18 U.S.C. Section 1734 solely to indicate this fact.
NR 50
TC 127
Z9 127
U1 1
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD OCT 15
PY 2009
VL 15
IS 20
BP 6412
EP 6420
DI 10.1158/1078-0432.CCR-09-1438
PG 9
WC Oncology
SC Oncology
GA 509UI
UT WOS:000271043500015
PM 19825961
ER
PT J
AU Snuderl, M
Eichler, AF
Ligon, KL
Vu, QU
Silver, M
Betensky, RA
Ligon, AH
Wen, PY
Louis, DN
Iafrate, AJ
AF Snuderl, Matija
Eichler, April F.
Ligon, Keith L.
Vu, Quynh U.
Silver, Michael
Betensky, Rebecca A.
Ligon, Azra H.
Wen, Patrick Y.
Louis, David N.
Iafrate, A. John
TI Polysomy for Chromosomes 1 and 19 Predicts Earlier Recurrence in
Anaplastic Oligodendrogliomas with Concurrent 1p/19q Loss
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID IN-SITU HYBRIDIZATION; TUMOR-SUPPRESSOR GENE; PROGNOSTIC VALUE;
TRANSCRIPT MAP; ALLELIC LOSSES; DELETIONS; SURVIVAL; GLIOMAS; KI-67;
OLIGOASTROCYTOMAS
AB Purpose: Loss of chromosome arms 1 p and 19q is a molecular feature of oligodendroglial tumors characterized by responsiveness to chemotherapy and a favorable prognosis. The purpose of this study was to evaluate the prognostic significance of polysomy of chromosomes 1 and 19 in the setting of lp/19q codeletion.
Experimental Design: We analyzed 64 anaplastic oligodendrogliomas with 1p/19q loss or maintenance diagnosed at Massachusetts General Hospital and Brigham and Women's Hospital from 1996 to 2005; fluorescence in situ hybridization for lp/19q and Ki-67 immunohistochemistry was done. Polysomy was defined as more than two 1q and 19p signals in >30% of the cells with concurrent 1p/19q deletion. Tumors were divided into groups based on their 1p/19q status and compared for progression-free survival, overall survival, and 5-year survival probabilities.
Results: Forty-six tumors (72%) in our cohort had lp/19q loss and 18 (28%) had lp/19q maintenance. Of those with loss, 19 (41%) had concurrent polysomy and 27 (59%) lacked polysomy. In agreement with previous studies, the group of anaplastic oligodendrogliomas with 1p/19q loss had significantly better progression-free survival and overall survival than anaplastic oligodendrogliomas with 1p/19q maintenance (P = 0.0009 and P < 0.0003, respectively). Among anaplastic oligodendrogliomas with lp/19q loss, those with polysomy showed shorter progression-free survival than those with 1p/19q loss without polysomy (P = 0.0048). Overall survival was similar in tumors with and without polysomy. The Ki-67 labeling index was not associated with polysomy and did not have prognostic significance.
Conclusion: The presence of polysomy in anaplastic oligodendrogliomas with deletion of 1p/19q is a marker of earlier recurrence. (Clin Cancer Res 2009;15(20):6430-7)
C1 [Snuderl, Matija; Vu, Quynh U.; Louis, David N.; Iafrate, A. John] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA.
[Eichler, April F.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA.
[Silver, Michael] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Ligon, Keith L.; Ligon, Azra H.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA.
[Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA.
RP Iafrate, AJ (reprint author), Massachusetts Gen Hosp, Pathol Serv, 55 Fruit St,Wrn 501, Boston, MA 02114 USA.
EM aiafrate@partners.org
OI Snuderl, Matija/0000-0003-0752-0917
FU NCI NIH HHS [R01 CA057683, R01 CA057683-16]
NR 32
TC 42
Z9 44
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD OCT 15
PY 2009
VL 15
IS 20
BP 6430
EP 6437
DI 10.1158/1078-0432.CCR-09-0867
PG 8
WC Oncology
SC Oncology
GA 509UI
UT WOS:000271043500017
PM 19808867
ER
PT J
AU Kim, M
Suh, J
Romano, D
Truong, MH
Mullin, K
Hooli, B
Norton, D
Tesco, G
Elliott, K
Wagner, SL
Moir, RD
Becker, KD
Tanzi, RE
AF Kim, Minji
Suh, Jaehong
Romano, Donna
Truong, Mimy H.
Mullin, Kristina
Hooli, Basavaraj
Norton, David
Tesco, Giuseppina
Elliott, Kathy
Wagner, Steven L.
Moir, Robert D.
Becker, K. David
Tanzi, Rudolph E.
TI Potential late-onset Alzheimer's disease-associated mutations in the
ADAM10 gene attenuate alpha-secretase activity
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID AMYLOID PRECURSOR PROTEIN; CONVERTING-ENZYME TACE; CYSTEINE SWITCH;
KINASE-C; DISINTEGRIN METALLOPROTEASE; BETA-SECRETASE; CLEAVAGE; FAMILY;
ACTIVATION; PRODOMAIN
AB ADAM10, a member of a disintegrin and metalloprotease family, is an alpha-secretase capable of anti-amyloidogenic proteolysis of the amyloid precursor protein. Here, we present evidence for genetic association of ADAM10 with Alzheimer's disease (AD) as well as two rare potentially disease-associated non-synonymous mutations, Q170H and R181G, in the ADAM10 prodomain. These mutations were found in 11 of 16 affected individuals (average onset age 69.5 years) from seven late-onset AD families. Each mutation was also found in one unaffected subject implying incomplete penetrance. Functionally, both mutations significantly attenuated alpha-secretase activity of ADAM10 (> 70% decrease), and elevated A beta levels (1.5-3.5-fold) in cell-based studies. In summary, we provide the first evidence of ADAM10 as a candidate AD susceptibility gene, and report two potentially pathogenic mutations with incomplete penetrance for late-onset familial AD.
C1 [Kim, Minji; Suh, Jaehong; Romano, Donna; Truong, Mimy H.; Mullin, Kristina; Hooli, Basavaraj; Norton, David; Tesco, Giuseppina; Moir, Robert D.; Tanzi, Rudolph E.] Massachusetts Gen Hosp, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA.
[Kim, Minji; Suh, Jaehong; Romano, Donna; Truong, Mimy H.; Mullin, Kristina; Hooli, Basavaraj; Norton, David; Tesco, Giuseppina; Moir, Robert D.; Tanzi, Rudolph E.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Elliott, Kathy; Wagner, Steven L.; Becker, K. David] TorreyPines Therapeut, La Jolla, CA 92037 USA.
RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, Bldg 114,16th St C3009, Charlestown, MA 02129 USA.
EM tanzi@helix.mgh.harvard.edu
FU Cure Alzheimer's Fund; National Institute of Mental Health [R37 MH60009]
FX This work was supported by the Cure Alzheimer's Fund and the National
Institute of Mental Health (R37 MH60009).
NR 48
TC 80
Z9 82
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD OCT 15
PY 2009
VL 18
IS 20
BP 3987
EP 3996
DI 10.1093/hmg/ddp323
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 499KF
UT WOS:000270218300018
PM 19608551
ER
PT J
AU Bertram, L
Tanzi, RE
AF Bertram, Lars
Tanzi, Rudolph E.
TI Genome-wide association studies in Alzheimer's disease
SO HUMAN MOLECULAR GENETICS
LA English
DT Review
ID SYSTEMATIC METAANALYSES; SUSCEPTIBILITY GENE; APOLIPOPROTEIN-E;
EXPRESSION; PROTEIN; BETA; APOE; POLYMORPHISMS; HYPOTHESIS; EPSILON-4
AB Genome-wide association studies (GWAS) have gained considerable momentum over the last couple of years for the identification of novel complex disease genes. In the field of Alzheimer's disease (AD), there are currently eight published and two provisionally reported GWAS, highlighting over two dozen novel potential susceptibility loci beyond the well-established APOE association. On the basis of the data available at the time of this writing, the most compelling novel GWAS signal has been observed in GAB2 (GRB2-associated binding protein 2), followed by less consistently replicated signals in galanin-like peptide (GALP), piggyBac transposable element derived 1 (PGBD1), tyrosine kinase, non-receptor 1 (TNK1). Furthermore, consistent replication has been recently announced for CLU (clusterin, also known as apolipoprotein J). Finally, there are at least three replicated loci in hitherto uncharacterized genomic intervals on chromosomes 14q32.13, 14q31.2 and 6q24.1 likely implicating the existence of novel AD genes in these regions. In this review, we will discuss the characteristics and potential relevance to pathogenesis of the outcomes of all currently available GWAS in AD. A particular emphasis will be laid on findings with independent data in favor of the original association.
C1 [Bertram, Lars] Max Planck Inst Mol Genet, Neuropsychiat Genet Grp, D-14195 Berlin, Germany.
[Tanzi, Rudolph E.] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Charlestown, MA USA.
RP Bertram, L (reprint author), Max Planck Inst Mol Genet, Neuropsychiat Genet Grp, Ihnestr 63,Room 204-1, D-14195 Berlin, Germany.
EM lbertram@molgen.mpg.de
RI Bertram, Lars/K-3889-2015
OI Bertram, Lars/0000-0002-0108-124X
FU Cure Alzheimer's Fund; NIMH; NIA; German Federal Ministry of Education
and Research (BMBF)
FX This work was made possible by support from the Cure Alzheimer's Fund,
NIMH, NIA, and the German Federal Ministry of Education and Research
(BMBF). The AlzGene database is funded by the Cure Alzheimer's Fund.
NR 40
TC 92
Z9 92
U1 1
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD OCT 15
PY 2009
VL 18
BP R137
EP R145
DI 10.1093/hmg/ddp406
PG 9
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 512QR
UT WOS:000271265600003
PM 19808789
ER
PT J
AU Janakiraman, A
Fixen, KR
Gray, AN
Niki, H
Goldberg, MB
AF Janakiraman, Anuradha
Fixen, Kathryn R.
Gray, Andrew N.
Niki, Hironori
Goldberg, Marcia B.
TI A Genome-Scale Proteomic Screen Identifies a Role for DnaK in
Chaperoning of Polar Autotransporters in Shigella
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID SURFACE PROTEIN ACTA; ESCHERICHIA-COLI; FLEXNERI 2A; UNIPOLAR
LOCALIZATION; FLUORESCENT PROTEIN; CRYSTAL-STRUCTURE; BACTERIAL-GROWTH;
GENE-EXPRESSION; VIRULENCE GENE; CELL-DIVISION
AB Autotransporters are outer membrane proteins that are widely distributed among gram-negative bacteria. Like other autotransporters, the Shigella autotransporter IcsA, which is required for actin assembly during infection, is secreted at the bacterial pole. In the bacterial cytoplasm, IcsA localizes to poles and potential cell division sites independent of the cell division protein FtsZ. To identify bacterial proteins involved in the targeting of IcsA to the pole in the bacterial cytoplasm, we screened a genome-scale library of Escherichia coli proteins tagged with green fluorescent protein (GFP) for those that displayed a localization pattern similar to that of IcsA-GFP in cells that lack functional FtsZ using a strain carrying a temperature-sensitive ftsZ allele. For each protein that mimicked the localization of IcsA-GFP, we tested whether IcsA localization was dependent on the presence of the protein. Although these approaches did not identify a polar receptor for IcsA, the cytoplasmic chaperone DnaK both mimicked IcsA localization at elevated temperatures as a GFP fusion and was required for the localization of IcsA to the pole in the cytoplasm of E. coli. DnaK was also required for IcsA secretion at the pole in Shigella flexneri. The localization of DnaK-GFP to poles and potential cell division sites was dependent on elevated growth temperature and independent of the presence of IcsA or functional FtsZ; native DnaK was found to be enhanced at midcell and the poles. A second Shigella autotransporter, SepA, also required DnaK for secretion, consistent with a role of DnaK more generally in the chaperoning of autotransporter proteins in the bacterial cytoplasm.
C1 [Janakiraman, Anuradha; Goldberg, Marcia B.] Massachusetts Gen Hosp, Div Infect Dis, Cambridge, MA 02139 USA.
[Janakiraman, Anuradha] CUNY City Coll, Dept Biol, New York, NY 10031 USA.
[Janakiraman, Anuradha] CUNY, Grad Ctr, New York, NY 10031 USA.
[Fixen, Kathryn R.; Gray, Andrew N.; Goldberg, Marcia B.] Harvard Univ, Dept Microbiol & Mol Genet, Sch Med, Boston, MA 02115 USA.
[Niki, Hironori] Natl Inst Genet, Radioisotope Ctr, Genet Strains Res Ctr, Shizuoka, Japan.
[Niki, Hironori] Natl Inst Genet, Microbial Genet Lab, Genet Strains Res Ctr, Shizuoka, Japan.
RP Goldberg, MB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 65 Landsdowne St, Cambridge, MA 02139 USA.
EM mgoldberg1@partners.org
FU American Heart Association [0425855T]; National Institute of General
Medical Sciences [GM082336]; Ministry of Education, Culture, Sports,
Science, and Technology of Japan; National Institutes of Allergy and
Infectious Diseases (NIH) [AI035817]
FX This research was supported by a fellowship from the American Heart
Association (0425855T) to A.J., a grant from the National Institute of
General Medical Sciences (GM082336) to A. J., a Grant-in-Aid for
Scientific Research on Priority Areas from the Ministry of Education,
Culture, Sports, Science, and Technology of Japan to H. N., and a grant
from the National Institutes of Allergy and Infectious Diseases (NIH
AI035817) to M. B. G.
NR 79
TC 15
Z9 16
U1 0
U2 4
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 15
PY 2009
VL 191
IS 20
BP 6300
EP 6311
DI 10.1128/JB.00833-09
PG 12
WC Microbiology
SC Microbiology
GA 499NG
UT WOS:000270227500012
PM 19684128
ER
PT J
AU Zalutskaya, AA
Cox, MK
Demay, MB
AF Zalutskaya, Alena A.
Cox, Megan K.
Demay, Marie B.
TI Phosphate Regulates Embryonic Endochondral Bone Development
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE PHOSPHATE; EMBRYONIC; BONE; DEVELOPMENT
ID GROWTH-FACTOR RECEPTOR-3; CHONDROCYTE PROLIFERATION;
PARATHYROID-HORMONE; APOPTOSIS; MICE; DIFFERENTIATION; CASPASES; PLATE;
STAT1; FGF
AB Phosphate is required for terminal differentiation of hypertrophic chondrocytes during postnatal growth plate maturation. in vitro models of chondrocyte differentiation demonstrate that 7 mM phosphate, a concentration analogous to that of the late gestational fetus, activates the mitochondrial apoptotic pathway in hypertrophic chondrocytes. This raises the question as to whether extracellular phosphate modulates chondrocyte differentiation and apoptosis during embryonic endochondral bone formation. To address this question, we performed investigations in the mouse metatarsal culture model that recapitulates in vivo bone development. Metatarsals were cultured for 4, 8, and 12 days with 1.25 and 7 mM phosphate. Metatarsals cultured with 7 mM phosphate showed a decrease in proliferation compared to those cultured in 1.25 mM phosphate. This decrease in proliferation was accompanied by an early enhancement in hypertrophic chondrocyte differentiation, associated with an increase in FGF18 expression. By 8 days in culture, an increase caspase-9 activation and apoptosis of hypertrophic chondrocytes was observed in the metatarsals cultured in 7 mM phosphate. Immunohistochemical analyses of embryonic bones demonstrated activation of caspase-9 in hypertrophic chondrocytes, associated with vascular invasion. Thus, these investigations demonstrate that phosphate promotes chondrocyte differentiation during embryonic development and implicate a physiological role for phosphate activation of the mitochondrial apoptotic pathway during embryonic endochondral bone formation. J. Cell. Biochem. 108: 668674, 2009. (C) 2009 Wiley-Liss, Inc.
C1 [Zalutskaya, Alena A.; Cox, Megan K.; Demay, Marie B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
RP Demay, MB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Thier 11, Boston, MA 02114 USA.
EM demay@helix.mgh.harvard.edu
FU NIH [R01DK46974, T32DK007028]
FX Grant sponsor: NIH; Grant numbers: R01DK46974, T32DK007028.
NR 24
TC 6
Z9 6
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0730-2312
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD OCT 15
PY 2009
VL 108
IS 3
BP 668
EP 674
DI 10.1002/jcb.22302
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 503UU
UT WOS:000270567100014
PM 19681042
ER
PT J
AU Smith, AC
Shah, SA
Hudson, AE
Purpura, KP
Victor, JD
Brown, EN
Schiff, ND
AF Smith, Anne C.
Shah, Sudhin A.
Hudson, Andrew E.
Purpura, Keith P.
Victor, Jonathan D.
Brown, Emery N.
Schiff, Nicholas D.
TI A Bayesian statistical analysis of behavioral facilitation associated
with deep brain stimulation
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE Deep brain stimulation; State-space models; Bayesian estimation;
Behavior; Model selection; Logistic regression
ID PARKINSONS-DISEASE; DYNAMIC-ANALYSIS; MONTE-CARLO; PERFORMANCE;
CONSCIOUSNESS; ENHANCEMENT; ALGORITHMS; DISORDERS; CAUDATE; NUCLEUS
AB Deep brain stimulation (DBS) is an established therapy for Parkinson's Disease and is being investigated as a treatment for chronic depression, obsessive compulsive disorder and for facilitating functional recovery of patients in minimally conscious states following brain injury. For all of these applications, quantitative assessments of the behavioral effects of DBS are crucial to determine whether the therapy is effective and, if so, how stimulation parameters can be optimized. Behavioral analyses for DBS are challenging because subject performance is typically assessed from only a small set of discrete measurements made on a discrete rating scale, the time course of DBS effects is unknown, and between-subject differences are often large. We demonstrate how Bayesian state-space methods can be used to characterize the relationship between DBS and behavior comparing our approach with logistic regression in two experiments: the effects of DBS on attention of a macaque monkey performing a reaction-time task, and the effects of DBS on motor behavior of a human patient in a minimally conscious state. The state-space analysis can assess the magnitude of DBS behavioral facilitation (positive or negative) at specific time points and has important implications for developing principled strategies to optimize DBS paradigms. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Smith, Anne C.] Univ Calif Davis, Dept Anesthesiol & Pain Med, Davis, CA 95616 USA.
[Shah, Sudhin A.] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10065 USA.
[Hudson, Andrew E.] Weill Cornell Med Coll, Dept Anesthesiol, New York, NY 10065 USA.
[Purpura, Keith P.; Victor, Jonathan D.; Schiff, Nicholas D.] Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY 10065 USA.
[Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA.
[Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Brown, Emery N.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Smith, AC (reprint author), Univ Calif Davis, Dept Anesthesiol & Pain Med, TB-170,1 Shields Ave, Davis, CA 95616 USA.
EM annesmith@ucdavis.edu
RI Victor, Jonathan/D-2931-2009; Hudson, Andrew/B-6152-2016
OI Hudson, Andrew/0000-0001-7292-5406
FU IntElect Medical; [R01 MH-071847]; [DP1 OD003646]; [NS02172]
FX This research was supported by R01 MH-071847 (ENB, ACS), DP1 OD003646
(ENB), NS02172 (NDS) and IntElect Medical (NDS, KPP, SAS).
NR 45
TC 21
Z9 22
U1 1
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0270
J9 J NEUROSCI METH
JI J. Neurosci. Methods
PD OCT 15
PY 2009
VL 183
IS 2
BP 267
EP 276
DI 10.1016/j.jneumeth.2009.06.028
PG 10
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 502SD
UT WOS:000270479500020
PM 19576932
ER
PT J
AU Diaz-Griffero, F
Qin, XR
Hayashi, F
Kigawa, T
Finzi, A
Sarnak, Z
Lienlaf, M
Yokoyama, S
Sodroski, J
AF Diaz-Griffero, Felipe
Qin, Xu-rong
Hayashi, Fumiaki
Kigawa, Takanori
Finzi, Andres
Sarnak, Zoe
Lienlaf, Maritza
Yokoyama, Shigeyuki
Sodroski, Joseph
TI A B-Box 2 Surface Patch Important for TRIM5 alpha Self-Association,
Capsid Binding Avidity, and Retrovirus Restriction
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MURINE LEUKEMIA-VIRUS; MONKEY TRIM5-ALPHA; NMR STRUCTURE; RING; DOMAIN;
PROTEIN; HIV-1; TRIMCYP; B-BOX-2; FAMILY
AB TRIM5 alpha is a tripartite motif (TRIM) protein that consists of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains. The TRIM5 alpha(rh) protein from rhesus monkeys recognizes the human immunodeficiency virus type 1 (HIV-1) capsid as it enters the host cell and blocks virus infection prior to reverse transcription. HIV-1-restricting ability can be eliminated by disruption of the B-box 2 domain. Changes in the TRIM5 alpha(rh) B-box 2 domain have been associated with alterations in TRIM5 alpha(rh) turnover, the formation of cytoplasmic bodies and higher-order oligomerization. We present here the nuclear magnetic resonance structure of the TRIM5 B-box 2 domain and identify an unusual hydrophobic patch (cluster 1) on the domain surface. Alteration of cluster 1 or the flanking arginine 121 resulted in various degrees of inactivation of HIV-1 restriction, in some cases depending on compensatory changes in other nearby charged residues. For this panel of TRIM5 alpha(rh) B-box 2 mutants, inhibition of HIV-1 infection was strongly correlated with higher-order self-association and binding affinity for capsid complexes but not with TRIM5 alpha(rh) half-life or the formation of cytoplasmic bodies. Thus, promoting cooperative TRIM5 alpha(rh) interactions with the HIV-1 capsid represents a major mechanism whereby the B-box 2 domain potentiates HIV-1 restriction.
C1 [Diaz-Griffero, Felipe; Finzi, Andres; Sarnak, Zoe; Lienlaf, Maritza; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Pathol,Div AIDS, Boston, MA 02115 USA.
[Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Qin, Xu-rong; Hayashi, Fumiaki; Kigawa, Takanori; Yokoyama, Shigeyuki] RIKEN, Yokohama Inst, Syst & Struct Biol Ctr, Yokohama, Kanagawa 2300445, Japan.
[Kigawa, Takanori] Tokyo Inst Technol, Interdisciplinary Grad Sch Sci & Engn, Dept Computat Intelligence & Syst Sci, Meguro Ku, Tokyo 1528550, Japan.
[Yokoyama, Shigeyuki] Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Bunko Ku, Tokyo 1130032, Japan.
RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Pathol,Div AIDS, 44 Binney St,CLSB 1010, Boston, MA 02115 USA.
EM joseph_sodroski@dfci.harvard.edu
RI Kigawa, Takanori/A-7679-2010; Yokoyama, Shigeyuki/N-6911-2015
OI Kigawa, Takanori/0000-0003-0146-9719; Yokoyama,
Shigeyuki/0000-0003-3133-7338
FU National Institutes of Health [1K99MH086162-01]; American Foundation for
AIDS Research Mathilde Krim [106987-43-RFHF]; Dana-Farber Cancer
Institute; Riken Structural Genomics/Proteomics Initiative of the
National Project on Protein Structural and Functional Analyses, Ministry
of Education, Culture, Sports, Science, and Technology of Japan;
[K99/R00]
FX We acknowledge the National Institutes of Health (grants AI063987 and
AI076094 and a Center for AIDS Research Award AI60354), the
International AIDS Vaccine Initiative, the Bristol-Myers Squibb
Foundation, and the late William F. McCarty-Cooper for research funding.
F. D.- G. is a recipient of a K99/R00 Pathway to Independence Award from
the National Institutes of Health (1K99MH086162-01), an American
Foundation for AIDS Research Mathilde Krim fellowship in basic
biomedical research (106987-43-RFHF), and a Claudia Adams Barr award
from the Dana-Farber Cancer Institute. The B-box 2 structure
determination was supported by the Riken Structural Genomics/Proteomics
Initiative of the National Project on Protein Structural and Functional
Analyses, Ministry of Education, Culture, Sports, Science, and
Technology of Japan.
NR 62
TC 83
Z9 88
U1 0
U2 15
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 15
PY 2009
VL 83
IS 20
BP 10737
EP 10751
DI 10.1128/JVI.01307-09
PG 15
WC Virology
SC Virology
GA 498FC
UT WOS:000270121600039
PM 19656869
ER
PT J
AU Pogoda, TK
Cramer, IE
Meterko, M
Lin, H
Hendricks, A
Holloway, RG
Chams, MP
AF Pogoda, Terri K.
Cramer, Irene E.
Meterko, Mark
Lin, Hai
Hendricks, Ann
Holloway, Robert G.
Chams, Martin P.
TI Patient and Organizational Factors Related to Education and Support Use
by Veterans with Parkinson's Disease
SO MOVEMENT DISORDERS
LA English
DT Article
DE Parkinson's disease; education; social support; multidisciplinary care;
specialty centers
ID QUALITY-OF-LIFE; MULTIDISCIPLINARY TREATMENT PROGRAM; HEALTH SURVEY
SF-36; SELF-MANAGEMENT; PRIMARY-CARE; CENTERED CARE; SOCIAL CARE;
INDIVIDUALS; PEOPLE; EFFICACY
AB Patient education and support services are recognized in the Department of Veterans Affairs (VA) as important to the patient-centered treatment of Parkinson's disease. Indeed, educating patients is one of the missions of the VA's six specialty Parkinson's Disease Research, Education and Clinical Centers (PADRECCs). We compared VA education/support services utilization by whether or not a patient's VA Medical Center (VAMC) contained a PADRECC. Our sample included Parkinson's disease patients from VAMCs with (n = 882) and without (n = 1,448) PADRECCs. Patients completed surveys that asked about demographic/individual characteristics, health status/function, and education/support utilization. Results showed that 15.8% (n = 354) of all patients utilized education/support services. Patients at PADRECC VAMCs were generally healthier and more educated than other VAMC patients. After statistically controlling for these differences, however, being a patient at a PADRECC VAMC site and using only VA providers (as compared to a combination of VA and non-VA providers) were significant predictors of education/support utilization. Further, proportionally more PADRECC VAMC site patients reported higher satisfaction and receiving a broad range of information from different modalities as compared to other VAMC patients. These findings suggest that PADRECC C 41 VAMCs are providing educational/support activities consistent with these specialty centers' goals. (C) 2009 Movement Disorder Society
C1 [Pogoda, Terri K.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Dept Vet Affairs, Boston, MA 02130 USA.
[Cramer, Irene E.; Meterko, Mark; Hendricks, Ann; Chams, Martin P.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Lin, Hai] Brown Univ, Women & Infants Hosp Rhode Isl, Brown Ctr Study Children Risk, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Hendricks, Ann] Dept Vet Affairs, Boston, MA USA.
[Holloway, Robert G.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA.
RP Pogoda, TK (reprint author), VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Dept Vet Affairs, 150 S Huntington Ave 152M, Boston, MA 02130 USA.
EM terri.pogoda@va.gov
OI Charns, Martin/0000-0002-7102-5331
NR 40
TC 2
Z9 2
U1 1
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD OCT 15
PY 2009
VL 24
IS 13
BP 1916
EP 1924
DI 10.1002/mds.22516
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 516PW
UT WOS:000271555700006
PM 19606487
ER
PT J
AU Salat, DH
Lee, SY
van der Kouwe, AJ
Greve, DN
Fischl, B
Rosas, HD
AF Salat, D. H.
Lee, S. Y.
van der Kouwe, A. J.
Greve, D. N.
Fischl, B.
Rosas, H. D.
TI Age-associated alterations in cortical gray and white matter signal
intensity and gray to white matter contrast
SO NEUROIMAGE
LA English
DT Article
DE Aging; Cerebral cortex; Cortical thickness; Gray matter; Cortical
surface; Tissue contrast
ID HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE IMAGES; SURFACE-BASED
ANALYSIS; ALZHEIMERS-DISEASE; OLDER-ADULTS; HUMAN BRAIN; IN-VIVO;
DIFFERENTIAL VULNERABILITY; GEOMETRICALLY ACCURATE; COGNITIVE
PERFORMANCE
AB Prior studies have focused on patterns of brain atrophy with aging and age-associated cognitive decline. It is possible that changes in neural tissue properties could provide an important marker of more subtle changes compared to gross morphometry. However, little is known about how MRI tissue parameters are altered in aging. We created cortical surface models of 148 individuals and mapped regional gray and white matter T1-weighted signal intensities from 3D MPRAGE images to examine patterns of age-associated signal alterations. Gray matter intensity was decreased with aging with strongest effects in medial frontal, anterior cingulate, and inferior temporal regions. White matter signal intensity decreased with aging in superior and medial frontal, cingulum, and medial and lateral temporal regions. The gray/white ratio (GWR) was altered throughout a large portion of the cortical mantle, with strong changes in superior and inferior frontal, lateral parietal, and superior temporal and precuneus regions demonstrating decreased overall contrast. Statistical effects of contrast changes were stronger than those of cortical thinning. These results demonstrate that there are strong regional changes in neural tissue properties with aging and tissue intensity measures may serve as an important biomarker of degeneration. Published by Elsevier Inc.
C1 [Salat, D. H.; Lee, S. Y.; van der Kouwe, A. J.; Greve, D. N.; Fischl, B.; Rosas, H. D.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Salat, D. H.; van der Kouwe, A. J.; Greve, D. N.; Fischl, B.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Salat, D. H.; van der Kouwe, A. J.; Greve, D. N.; Fischl, B.] Harvard Univ, Sch Med, Boston, MA USA.
[Lee, S. Y.; Rosas, H. D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Fischl, B.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
RP Salat, DH (reprint author), MGH MIT HMS, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Bldg 149,13th St,Mail Code 149 2301, Charlestown, MA 02129 USA.
EM salat@nmr.mgh.harvard.edu
FU National Institutes of Health [K01AG024898, R01NR010827, P41RR14075,
BIRN002, U24RR021382, R01EB001550, R01EB006758, R01NS052585,
U54EB005149]; Ellison Medical Foundation
FX This work was supported by the National Institutes of Health
[K01AG024898, R01NR010827, P41RR14075, BIRN002, U24RR021382,
R01EB001550, R01EB006758, R01NS052585, U54EB005149]; the Athinoula A.
Martinos Center for Biomedical Imaging, the Mental Illness and
Neuroscience Discovery (MIND) Institute, and The Autism & Dyslexia
Project funded by the Ellison Medical Foundation. We are grateful to
Christina Onorato for providing assistance with data analysis.
NR 66
TC 100
Z9 100
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD OCT 15
PY 2009
VL 48
IS 1
BP 21
EP 28
DI 10.1016/j.neuroimage.2009.06.074
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 488AO
UT WOS:000269321100006
PM 19580876
ER
PT J
AU Hinrichs, C
Singh, V
Mukherjee, L
Xu, GF
Chung, MK
Johnson, SC
AF Hinrichs, Chris
Singh, Vikas
Mukherjee, Lopamudra
Xu, Guofan
Chung, Moo K.
Johnson, Sterling C.
CA Alzheimer's Dis Neuroimaging Initi
TI Spatially augmented LPboosting for AD classification with evaluations on
the ADNI dataset
SO NEUROIMAGE
LA English
DT Article
ID DIMENSIONAL PATTERN-CLASSIFICATION; PRODROMAL ALZHEIMERS-DISEASE;
COGNITIVE DECLINE; FEATURE-SELECTION; BRAIN ATROPHY; MR-IMAGES;
DIAGNOSIS; ALGORITHM; DEMENTIA; PET
AB Structural and functional brain images are playing an important role in helping us understand the changes associated with neurological disorders such as Alzheimer's disease (AD). Recent efforts have now started investigating their utility for diagnosis purposes. This line of research has shown promising results where methods from machine learning (such as Support Vector Machines) have been used to identify AD-related patterns from images, for use in diagnosing new individual subjects. In this paper, we propose a new framework for AD classification which makes use of the Linear Program (LP) boosting with novel additional regularization based on spatial "smoothness" in 3D image coordinate spaces. The algorithm formalizes the expectation that since the examples for training the classifier are images, the voxels eventually selected for specifying the decision boundary must constitute spatially contiguous chunks, i.e., "regions" must be preferred over isolated voxels. This prior belief turns out to be useful for significantly reducing the space of possible classifiers and leads to substantial benefits in generalization. In our method, the requirement of spatial contiguity (of selected discriminating voxels) is incorporated within the optimization framework directly. Other methods have made use of similar biases as a pre- or post-processing step, however, our model incorporates this emphasis on spatial smoothness directly into the learning step. We report on extensive evaluations of our algorithm on MR and FDG-PET images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and discuss the relationship of the classification output with the clinical and cognitive biomarker data available within ADNI. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Hinrichs, Chris; Singh, Vikas] Univ Wisconsin, Dept Comp Sci, Madison, WI 53706 USA.
[Hinrichs, Chris; Singh, Vikas; Chung, Moo K.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53705 USA.
[Mukherjee, Lopamudra] Univ Wisconsin, Dept Math & Comp Sci, Whitewater, WI 53190 USA.
[Xu, Guofan; Johnson, Sterling C.] Univ Wisconsin, Dept Med, Madison, WI 53792 USA.
[Xu, Guofan; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53792 USA.
RP Hinrichs, C (reprint author), 7645 Med Sci Ctr, Madison, WI 53706 USA.
EM hinrichs@cs.wisc.edu
RI Scharre, Douglas/E-4030-2011;
OI Johnson, Sterling/0000-0002-8501-545X
FU Department of Biostatistics and Medical Informatics, University of
Wisconsin-Madison, UW ICTR through an NIH Clinical and Translational
Science Award (CTSA) [1UL1RR025011]; Department of Veterans Affairs;
Wisconsin Comprehensive Memory Program; NIH [AG021155, U01 AG024904];
Alzheimer's Disease Neuroimaging Initiative; National Institute on
Aging; National Institute of Biomedical Imaging and Bioengineering
(NIBIB); Pfizer Inc.; Wyeth Research; Bristol-Myers Squibb; Eli Lilly
and Company; GlaxoSmithKline; Merck Co. Inc.; AstraZeneca AB; Novartis
Pharmaceuticals Corporation; Alzheimer's Association; Eisai Global
Clinical Development; Elan Corporation plc; Forest Laboratories;
Institute for the Study of Aging
FX This research was supported in part by the Department of Biostatistics
and Medical Informatics, University of Wisconsin-Madison, UW ICTR
through an NIH Clinical and Translational Science Award (CTSA)
1UL1RR025011, a Merit Review Grant from the Department of Veterans
Affairs, the Wisconsin Comprehensive Memory Program, and an NIH grant
AG021155. The authors also acknowledge the facilities and resources at
the William S. Middleton Memorial Veterans Hospital.; Data collection
and sharing for this project was funded by the Alzheimer's Disease
Neuroimaging Initiative (ADNI; Principal Investigator: Michael Weiner;
NIH grant U01 AG024904). ADNI is funded by the National Institute on
Aging, the National Institute of Biomedical Imaging and Bioengineering
(NIBIB), and through generous contributions from the following: Pfizer
Inc., Wyeth Research, Bristol-Myers Squibb, Eli Lilly and Company,
GlaxoSmithKline, Merck & Co. Inc., AstraZeneca AB, Novartis
Pharmaceuticals Corporation, Alzheimer's Association, Eisai Global
Clinical Development, Elan Corporation plc, Forest Laboratories, and the
Institute for the Study of Aging, with participation from the U.S. Food
and Drug Administration. Industry partnerships are coordinated through
the Foundation for the National Institutes of Health. 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. ADNI data
are disseminated by the Laboratory of Neuro Imaging at the University of
California, Los Angeles.
NR 46
TC 72
Z9 72
U1 1
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD OCT 15
PY 2009
VL 48
IS 1
BP 138
EP 149
DI 10.1016/j.neuroimage.2009.05.056
PG 12
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 488AO
UT WOS:000269321100017
PM 19481161
ER
PT J
AU Mitchell, SL
Teno, JM
Kiely, DK
Shaffer, ML
Jones, RN
Prigerson, HG
Volicer, L
Givens, JL
Hamel, MB
AF Mitchell, Susan L.
Teno, Joan M.
Kiely, Dan K.
Shaffer, Michele L.
Jones, Richard N.
Prigerson, Holly G.
Volicer, Ladislav
Givens, Jane L.
Hamel, Mary Beth
TI The Clinical Course of Advanced Dementia
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID NURSING-HOME RESIDENTS; LONG-TERM-CARE; ADVANCED ALZHEIMERS-DISEASE;
MANAGEMENT; HOSPICE; PAIN; PATTERNS; SURVIVAL; FAILURE; HEALTH
AB BACKGROUND
Dementia is a leading cause of death in the United States but is underrecognized as a terminal illness. The clinical course of nursing home residents with advanced dementia has not been well described.
METHODS
We followed 323 nursing home residents with advanced dementia and their health care proxies for 18 months in 22 nursing homes. Data were collected to characterize the residents' survival, clinical complications, symptoms, and treatments and to determine the proxies' understanding of the residents' prognosis and the clinical complications expected in patients with advanced dementia.
CONCLUSIONS
Pneumonia, febrile episodes, and eating problems are frequent complications in patients with advanced dementia, and these complications are associated with high 6-month mortality rates. Distressing symptoms and burdensome interventions are also common among such patients. Patients with health care proxies who have an understanding of the prognosis and clinical course are likely to receive less aggressive care near the end of life.
C1 [Mitchell, Susan L.; Kiely, Dan K.; Jones, Richard N.; Givens, Jane L.] Hebrew SeniorLife Inst Aging Res, Boston, MA USA.
[Mitchell, Susan L.; Jones, Richard N.; Givens, Jane L.; Hamel, Mary Beth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychosocial Oncol & Palliat Care Res, Boston, MA 02115 USA.
[Teno, Joan M.] Brown Univ, Ctr Gerontol & Hlth Care Res, Dept Community Hlth, Alpert Med Sch, Providence, RI 02912 USA.
[Shaffer, Michele L.] Penn State Coll Med, Hershey, PA USA.
[Volicer, Ladislav] Univ S Florida, Sch Aging Studies, Tampa, FL USA.
RP Mitchell, SL (reprint author), Hebrew SeniorLife, 1200 Ctr St, Boston, MA 02131 USA.
EM smitchell@hrca.harvard.edu
OI Jones, Richard/0000-0002-1049-218X
FU National Institute on Aging [R01 AG024091, K24 AG033640]
FX Supported by a grant from the National Institute on Aging (R01 AG024091)
and by a Midcareer Award in Patient Oriented Research from the National
institute on Aging (K24 AG033640, to Dr. Mitchell).
NR 37
TC 461
Z9 469
U1 6
U2 41
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 15
PY 2009
VL 361
IS 16
BP 1529
EP 1538
DI 10.1056/NEJMoa0902234
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 506LT
UT WOS:000270777000006
PM 19828530
ER
PT J
AU Tamura, MK
Covinsky, KE
Chertow, GM
Yaffe, K
Landefeld, CS
McCulloch, CE
AF Tamura, Manjula Kurella
Covinsky, Kenneth E.
Chertow, Glenn M.
Yaffe, Kristine
Landefeld, C. Seth
McCulloch, Charles E.
TI Functional Status of Elderly Adults before and after Initiation of
Dialysis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID MINIMUM DATA SET; COMPREHENSIVE GERIATRIC ASSESSMENT; CHRONIC
KIDNEY-DISEASE; STAGE RENAL-DISEASE; CARDIAC REHABILITATION;
CORONARY-BYPASS; HEMODIALYSIS; SURVIVAL; OUTCOMES; HOSPITALIZATION
AB BACKGROUND
It is unclear whether functional status before dialysis is maintained after the initiation of this therapy in elderly patients with end-stage renal disease (ESRD).
METHODS
Using a national registry of patients undergoing dialysis, which was linked to a national registry of nursing home residents, we identified all 3702 nursing home residents in the United States who were starting treatment with dialysis between June 1998 and October 2000 and for whom at least one measurement of functional status was available before the initiation of dialysis. Functional status was measured by assessing the degree of dependence in seven activities of daily living (on the Minimum Data Set-Activities of Daily Living [MDS-ADL] scale of 0 to 28 points, with higher scores indication greater functional difficulty).
RESULTS
The median MDS-ADL score increased from 12 during the 3 months before the initiation of dialysis to 16 during the 3 months after the initiation of dialysis. Three months after the initiation of dialysis, functional status had been maintained in 39% of nursing home residents, but by 12 months after the initiation of dialysis, 58% had died and predialysis functional status had been maintained in only 13%. In a random-effects model, the initiation of dialysis was associated with a sharp declin in functional status, indicated by an increase of 2.8 points in the MDS-ADL score (95% confidence interval [CI], 2.5 to 3.0); this decline was independent of age, sex, race, and functional-status trajectory before the initiation of dialysis. The decline in functional status associated with the initiation of dialysis remained substantial (1.7 points; 95% CI, 1.4 to 2.1), even after adjustment for the presence or absence of an accelerated functional decline during the 3-month period before the initiation of dialysis.
CONCLUSIONS
Among nursing home residents with ESRD, the initiation of dialysis is associated with a substantial and sustained decline in functional status.
C1 [Tamura, Manjula Kurella; Chertow, Glenn M.] Stanford Univ, Sch Med, Div Nephrol, Dept Med, Palo Alto, CA 94304 USA.
[Covinsky, Kenneth E.; Landefeld, C. Seth] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat & Neurol, San Francisco, CA 94143 USA.
[Yaffe, Kristine; McCulloch, Charles E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Covinsky, Kenneth E.; Yaffe, Kristine; Landefeld, C. Seth] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Tamura, MK (reprint author), Stanford Univ, Sch Med, Div Nephrol, Dept Med, 780 Welch Rd,Suite 106, Palo Alto, CA 94304 USA.
EM mktamura@stanford.edu
RI Kurella Tamura, Manjula/C-8284-2014
OI Kurella Tamura, Manjula/0000-0001-5227-2479
FU National Institute of Aging [K23AG028952]; National Center for Research
Resources [KL2RR024130]; National Institute of Diabetes and Digestive
and Kidney Diseases [N01DK12450]
FX Supported by a Paul B. Beeson Career Development Award in Aging
(K23AG028952, to Dr. Kurella Tamura) from the National Institute of
Aging and grants from the National Center for Research Resources
(KL2RR024130) and the National Institute of Diabetes and Digestive and
Kidney Diseases (N01DK12450).
NR 26
TC 212
Z9 223
U1 2
U2 10
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 15
PY 2009
VL 361
IS 16
BP 1539
EP 1547
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 506LT
UT WOS:000270777000007
ER
PT J
AU Tager, AM
Sharma, A
Mark, EJ
AF Tager, Andrew M.
Sharma, Amita
Mark, Eugene J.
TI A Man with Progressive Dyspnea The Hermansky-Pudlak syndrome, with
interstitial pulmonary fibrosis and respiratory failure
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID LUNG-DISEASE; PNEUMONIA; MUTATIONS; MANIFESTATIONS; TYPE-2; FORM
C1 [Tager, Andrew M.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA.
[Tager, Andrew M.] Massachusetts Gen Hosp, Dept Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA.
[Sharma, Amita] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Tager, Andrew M.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA.
[Sharma, Amita] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA.
[Mark, Eugene J.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA.
RP Tager, AM (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA.
NR 30
TC 0
Z9 1
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 15
PY 2009
VL 361
IS 16
BP 1585
EP 1593
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 506LT
UT WOS:000270777000014
PM 19828536
ER
PT J
AU Srinivasan, VJ
Sakadzic, S
Gorczynska, I
Ruvinskaya, S
Wu, WC
Fujimoto, JG
Boas, DA
AF Srinivasan, Vivek J.
Sakadzic, Sava
Gorczynska, Iwona
Ruvinskaya, Svetlana
Wu, Weicheng
Fujimoto, James G.
Boas, David A.
TI Depth-resolved microscopy of cortical hemodynamics with optical
coherence tomography
SO OPTICS LETTERS
LA English
DT Article
ID IN-VIVO; NEURONAL-ACTIVITY; VISUALIZATION; CORTEX
AB We describe depth-resolved microscopy of cortical hemodynamics with high-speed spectral/Fourier domain optical coherence tomography (OCT). Stimulus-evoked changes in blood vessel diameter, flow, and total hemoglobin were measured in the rat somatosensory cortex. The results show OCT measurements of hemodynamic changes during functional activation and represent an important step toward understanding functional hyperemia at the microscopic level. (C) 2009 Optical Society of America
C1 [Srinivasan, Vivek J.; Sakadzic, Sava; Ruvinskaya, Svetlana; Wu, Weicheng; Boas, David A.] Harvard Univ, Massachusetts Gen Hosp, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Sch Med,Photon Migrat Imaging Lab, Charlestown, MA 02129 USA.
[Gorczynska, Iwona; Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
[Gorczynska, Iwona; Fujimoto, James G.] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
RP Boas, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Sch Med,Photon Migrat Imaging Lab, Charlestown, MA 02129 USA.
EM dboas@nmr.mgh.harvard.edu
RI Gorczynska, Iwona/P-9367-2015
OI Gorczynska, Iwona/0000-0002-6120-8791
FU National Institutes of Health (NIH) [R01-NS057476, P01NS055104,
P50NS010828, K99NS067050, R01-CA07528912]; Air Force Office of
Scientific Research (AFOSR) [FA9550-07-1-0014]; Medical Free-Electron
Laser Program [FA9550-07-1-0101]
FX We acknowledge support by the National Institutes of Health (NIH)
(R01-NS057476, P01NS055104, P50NS010828, K99NS067050, and
R01-CA07528912) the Air Force Office of Scientific Research (AFOSR)
FA9550-07-1-0014 and the Medical Free-Electron Laser Program
FA9550-07-1-0101.
NR 15
TC 21
Z9 21
U1 0
U2 1
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 0146-9592
J9 OPT LETT
JI Opt. Lett.
PD OCT 15
PY 2009
VL 34
IS 20
BP 3086
EP 3088
PG 3
WC Optics
SC Optics
GA 514DM
UT WOS:000271374500014
PM 19838234
ER
PT J
AU Costa, AN
Castellvi, JMSI
Spagnolo, AG
Comoretto, N
Lafitte, J
Gabel, H
Delmonico, FL
Muehlbacher, F
Schaupp, W
Glazier, AK
Garcia, VD
Abbud, M
Medina-Pestana, JO
Grainer, MG
Donadio, PP
Guermani, A
Bosco, R
Giordano, F
de Arroyabe, BML
Brunetti, M
Manyalich, M
Paez, G
Valero, R
Matesanz, R
Coll, E
Dominguez-Gil, B
Mahillo, B
Escobar, EM
Garrido, G
Cantarovich, F
AF Costa, Alessandro Nanni
Simon i Castellvi, J. M.
Spagnolo, Antonio G.
Comoretto, Nunziata
Lafitte, Jean
Gabel, Hakan
Delmonico, Francis L.
Muehlbacher, Ferdinand
Schaupp, Walter
Glazier, Alexandra K.
Garcia, Valter D.
Abbud-Filho, Mario
Medina-Pestana, Jose O.
Grainer, Mariangela Gritta
Donadio, Pier Paolo
Guermani, Anna
Bosco, Riccardo
Giordano, Francesco
de Arroyabe, Blanca Martinez Lopez
Brunetti, Marco
Manyalich, Marti
Paez, Gloria
Valero, Ricardo
Matesanz, Rafael
Coll, Elisabeth
Dominguez-Gil, Beatriz
Mahillo, Beatriz
Escobar, Eduardo Martin
Garrido, Gregorio
Cantarovich, Felix
TI A Colloquium on the Congress "A Gift for Life. Considerations on Organ
Donation"
SO TRANSPLANTATION
LA English
DT Review
ID TRAUMATIC BRAIN-INJURY; DEAD DONOR RULE; QUALITY-OF-LIFE; PRESUMED
CONSENT; INFORMED-CONSENT; TRANSPLANTATION TOLERANCE;
LIVER-TRANSPLANTATION; HEART-TRANSPLANTATION; DEVELOPING-COUNTRIES;
MEDICAL-STUDENTS
C1 [Costa, Alessandro Nanni] Italian Natl Transplant Ctr, I-00161 Rome, Italy.
[Abbud-Filho, Mario] Fac Med, BR-15015200 Sao Jose Do Rio Preto, SP, Brazil.
[Abbud-Filho, Mario] Inst Urol Sao Jose Rio Preto, BR-15015200 Sao Jose Do Rio Preto, SP, Brazil.
[Brunetti, Marco] Off Pastoral Care Hlth, Archdiocese Of Turin, Italy.
[Cantarovich, Felix] Catholic Univ, Buenos Aires, DF, Argentina.
[Cantarovich, Felix] Hop Necker Enfants Malad, Serv Transplantat Adultes, F-75016 Paris, France.
[Spagnolo, Antonio G.; Comoretto, Nunziata] Univ Cattolica Sacro Cuore, Ctr Bioeth, I-00168 Rome, Italy.
[Delmonico, Francis L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA.
[Donadio, Pier Paolo] Univ Molinette San Giovanni Battista Torino, Piedmont Reg Organ Procurement Org Responsible, Azienda Osped, I-10126 Turin, Italy.
[Glazier, Alexandra K.] New England Organ Bank Inc, Gateway Ctr 1, Newton, MA 02458 USA.
[Manyalich, Marti] Univ Barcelona, Transplant Procurement Management IL3, Barcelona 08018, Spain.
[de Arroyabe, Blanca Martinez Lopez] Santa Maria Misericordia Univ Hosp, Dept Anesthesiol & Intens Care Med, I-33100 Udine, Italy.
[Matesanz, Rafael] ONT, Madrid 28029, Spain.
[Medina-Pestana, Jose O.] Univ Fed Sao Paulo, Hosp Rim e Hipertensao, BR-04038002 Sao Paulo, Brazil.
[Muehlbacher, Ferdinand] Med Univ Vienna, Dept Surg, Transplantat Unit, Gen Hosp Vienna, A-1090 Vienna, Austria.
[Schaupp, Walter] Karl Franzens Univ Graz, Fac Cathol Theol, A-8010 Graz, Austria.
[Spagnolo, Antonio G.] Univ Macerata, Dpt Educ Sci, Rome, Italy.
RP Costa, AN (reprint author), Italian Natl Transplant Ctr, Viale Regina Elena 299, I-00161 Rome, Italy.
EM cnt@iss.it; metges@federaciocristians.org; agSpagnolo@unimc.it;
nunziata.comoretto@rm.unicatt.it; jlafitte@acdlife.va; hakan@Gabel.se;
francis_delmonico@neob.org; ferdinand.muehlbacher@meduniwien.ac.at;
walter.Schaupp@uni-graz.at; alexandra_glazier@neob.org;
medina@hrim.com.br; mgrainer@interplanet.it;
pdonadio@molinette.piemonte.it; aguermani@molinette.piemonte.it;
rbosco@molinette.piemonte.it; blancamartinez@libero.it;
salute@diocesi.torino.it; tpmproject@il3.ub.edu; rmatesanz@mps.es;
felix.cantarovich@orange.fr
RI Valero, Ricard/G-1770-2015
OI Valero, Ricard/0000-0001-7875-9496
NR 220
TC 5
Z9 5
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0041-1337
EI 1534-6080
J9 TRANSPLANTATION
JI Transplantation
PD OCT 15
PY 2009
VL 88
IS 7
SU S
BP S108
EP S158
PG 51
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 507HK
UT WOS:000270842600004
PM 19823162
ER
PT J
AU Hu, JC
Gu, XM
Lipsitz, SR
Barry, MJ
D'Amico, AV
Weinberg, AC
Keating, NL
AF Hu, Jim C.
Gu, Xiangmei
Lipsitz, Stuart R.
Barry, Michael J.
D'Amico, Anthony V.
Weinberg, Aaron C.
Keating, Nancy L.
TI Comparative Effectiveness of Minimally Invasive vs Open Radical
Prostatectomy
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID ASSISTED LAPAROSCOPIC PROSTATECTOMY; RETROPUBIC PROSTATECTOMY;
SINGLE-INSTITUTION; LEARNING-CURVE; CLAIMS DATA; CANCER; OUTCOMES;
ROBOT; COMPLICATIONS; EXPERIENCE
AB Context Minimally invasive radical prostatectomy (MIRP) has diffused rapidly despite limited data on outcomes and greater costs compared with open retropubic radical prostatectomy (RRP).
Objective To determine the comparative effectiveness of MIRP vs RRP.
Design, Setting, and Patients Population-based observational cohort study using US Surveillance, Epidemiology, and End Results Medicare linked data from 2003 through 2007. We identified men with prostate cancer who underwent MIRP (n=1938) vs RRP (n=6899).
Main Outcome Measures We compared postoperative 30-day complications, anastomotic stricture 31 to 365 days postoperatively, long-term incontinence and erectile dysfunction more than 18 months postoperatively, and postoperative use of additional cancer therapies, a surrogate for cancer control.
Results Among men undergoing prostatectomy, use of MIRP increased from 9.2% (95% confidence interval [CI], 8.1%-10.5%) in 2003 to 43.2% (95% CI, 39.6%-46.9%) in 2006-2007. Men undergoing MIRP vs RRP were more likely to be recorded as Asian (6.1% vs 3.2%), less likely to be recorded as black (6.2% vs 7.8%) or Hispanic (5.6% vs 7.9%), and more likely to live in areas with at least 90% high school graduation rates (50.2% vs 41.0%) and with median incomes of at least $60 000 (35.8% vs 21.5%) (all P<.001). In propensity score-adjusted analyses, MIRP vs RRP was associated with shorter length of stay (median, 2.0 vs 3.0 days; P<.001) and lower rates of blood transfusions (2.7% vs 20.8%; P<.001), postoperative respiratory complications (4.3% vs 6.6%; P=.004), miscellaneous surgical complications (4.3% vs 5.6%; P=.03), and anastomotic stricture (5.8% vs 14.0%; P<.001). However, MIRP vs RRP was associated with an increased risk of genitourinary complications (4.7% vs 2.1%; P=.001) and diagnoses of incontinence (15.9 vs 12.2 per 100 person-years; P=.02) and erectile dysfunction (26.8 vs 19.2 per 100 person-years; P=.009). Rates of use of additional cancer therapies did not differ by surgical procedure (8.2 vs 6.9 per 100 person-years; P=.35).
Conclusion Men undergoing MIRP vs RRP experienced shorter length of stay, fewer respiratory and miscellaneous surgical complications and strictures, and similar postoperative use of additional cancer therapies but experienced more genitourinary complications, incontinence, and erectile dysfunction. JAMA. 2009; 302(14): 1557-1564
C1 [Hu, Jim C.] Brigham & Womens Hosp, Div Neurol, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA.
[Hu, Jim C.; Weinberg, Aaron C.] Div Urol Surg, Boston, MA USA.
[Hu, Jim C.; Gu, Xiangmei; Lipsitz, Stuart R.; Weinberg, Aaron C.] Ctr Surg & Publ Hlth, Boston, MA USA.
[D'Amico, Anthony V.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Keating, Nancy L.] Div Gen Internal Med, Boston, MA USA.
[Barry, Michael J.] Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA.
[Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
RP Hu, JC (reprint author), Brigham & Womens Hosp, Div Neurol, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 45 Francis St,ASBII 3, Boston, MA 02115 USA.
EM jhu2@partners.org
FU Department of Defense Prostate Cancer Physician Training Award
FX This research was funded by a Department of Defense Prostate Cancer
Physician Training Award to Dr Hu.
NR 54
TC 429
Z9 436
U1 5
U2 27
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD OCT 14
PY 2009
VL 302
IS 14
BP 1557
EP 1564
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 505UA
UT WOS:000270721800024
PM 19826025
ER
PT J
AU Young, AB
AF Young, Anne B.
TI Four Decades of Neurodegenerative Disease Research: How Far We Have
Come!
SO JOURNAL OF NEUROSCIENCE
LA English
DT Review
ID POSITRON-EMISSION-TOMOGRAPHY; SUBTHALAMIC NUCLEUS STIMULATION;
GAMMA-AMINOBUTYRIC-ACID; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE;
HUNTINGTONS-DISEASE; BASAL GANGLIA; KAINIC ACID;
1-METHYL-4-PHENYLPYRIDINIUM ION; POSTEROVENTRAL PALLIDOTOMY
C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA.
RP Young, AB (reprint author), Massachusetts Gen Hosp, Neurol Serv, ACC 720, Boston, MA 02114 USA.
EM abyoung@partners.org
FU NIA NIH HHS [R37 AG013617-07, P01 AG011337-040001, P01 AG011337-05, P01
AG011337-050001, R01 AG013617, R01 AG013617-05, R37 AG013617, R37
AG013617-06, R37 AG013617-08, R37 AG013617-09, R37 AG013617-10, R37
AG013617-11, R37 AG013617-12, R37 AG013617-13, R37 AG013617-14, R37
AG013617-15]; NINDS NIH HHS [P50 NS038372, P50 NS038372-02, P50
NS038372-03, P50 NS038372-04, P50 NS038372-04S1, P50 NS038372-05, P50
NS038372-05S1, P50 NS038372-05S2, P50 NS038372-06A1, P50
NS038372-06A19003, P50 NS038372-06A1S1, P50 NS038372-07, P50
NS038372-08, P50 NS038372-09, P50 NS038372-10, P50 NS038372-10S1, P50
NS038372-10S2]
NR 110
TC 15
Z9 15
U1 0
U2 4
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD OCT 14
PY 2009
VL 29
IS 41
BP 12722
EP 12728
DI 10.1523/JNEUROSCI.3767-09.2009
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 507IF
UT WOS:000270845000003
PM 19828782
ER
PT J
AU Morfini, GA
Burns, M
Binder, LI
Kanaan, NM
LaPointe, N
Bosco, DA
Brown, RH
Brown, H
Tiwari, A
Hayward, L
Edgar, J
Nave, KA
Garberrn, J
Atagi, Y
Song, YY
Pigino, G
Brady, ST
AF Morfini, Gerardo A.
Burns, Matthew
Binder, Lester I.
Kanaan, Nicholas M.
LaPointe, Nichole
Bosco, Daryl A.
Brown, Robert H., Jr.
Brown, Hannah
Tiwari, Ashutosh
Hayward, Lawrence
Edgar, Julia
Nave, Klaus-Armin
Garberrn, James
Atagi, Yuka
Song, Yuyu
Pigino, Gustavo
Brady, Scott T.
TI Axonal Transport Defects in Neurodegenerative Diseases
SO JOURNAL OF NEUROSCIENCE
LA English
DT Review
ID AMYOTROPHIC-LATERAL-SCLEROSIS; HEREDITARY SPASTIC PARAPLEGIA;
MOTOR-NEURON DEGENERATION; CENTRAL-NERVOUS-SYSTEM; KINESIN HEAVY-CHAIN;
PELIZAEUS-MERZBACHER-DISEASE; ACTIVATED PROTEIN-KINASE; LINKED SOD1
MUTANTS; ALZHEIMERS-DISEASE; HUNTINGTONS-DISEASE
AB Adult-onset neurodegenerative diseases (AONDs) comprise a heterogeneous group of neurological disorders characterized by a progressive, age-dependent decline in neuronal function and loss of selected neuronal populations. Alterations in synaptic function and axonal connectivity represent early and critical pathogenic events in AONDs, but molecular mechanisms underlying these defects remain elusive. The large size and complex subcellular architecture of neurons render them uniquely vulnerable to alterations in axonal transport (AT). Accordingly, deficits in AT have been documented in most AONDs, suggesting a common defect acquired through different pathogenic pathways. These observations suggest that many AONDs can be categorized as dysferopathies, diseases in which alterations in AT represent a critical component in pathogenesis. Topics here address various molecular mechanisms underlying alterations in AT in several AONDs. Illumination of such mechanisms provides a framework for the development of novel therapeutic strategies aimed to prevent axonal and synaptic dysfunction in several major AONDs.
C1 [Morfini, Gerardo A.; Burns, Matthew; Atagi, Yuka; Song, Yuyu; Pigino, Gustavo; Brady, Scott T.] Univ Illinois, Dept Anat & Cell Biol, Chicago, IL 60612 USA.
[Binder, Lester I.; Kanaan, Nicholas M.; LaPointe, Nichole] Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA.
[Bosco, Daryl A.; Brown, Robert H., Jr.; Hayward, Lawrence] Univ Massachusetts, Med Ctr, Dept Neurol, Worcester, MA 01655 USA.
[Brown, Hannah] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Tiwari, Ashutosh] Michigan Technol Univ, Dept Chem, Houghton, MI 49931 USA.
[Edgar, Julia] Univ Glasgow, Inst Comparat Med, Div Cell Sci, Appl Neurobiol Grp, Glasgow G61 1QH, Lanark, Scotland.
[Nave, Klaus-Armin] Max Planck Inst Expt Med, Dept Neurogenet, D-37075 Gottingen, Germany.
[Garberrn, James] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA.
[Garberrn, James] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
RP Morfini, GA (reprint author), Univ Illinois, Dept Anat & Cell Biol, MC512,909 S Wolcott St,COMRB Room 6051, Chicago, IL 60612 USA.
EM gmorfini@uic.edu
RI Nave, Klaus-Armin/C-8883-2011; Tiwari, Ashutosh/A-7458-2008;
OI Tiwari, Ashutosh/0000-0001-7373-349X; Song, Yuyu/0000-0002-9196-1610;
Kanaan, Nicholas/0000-0002-4362-2593
FU National Institutes of Health (NIH) [AG09466, T32 AG020506-07, NS23868,
NS23320, NS41170]; ALS Association (ALSA); ALS Therapy Alliance; ALSA,
Muscular Dystrophy Association; Multiple Sclerosis Society (Scotland);
Huntington's Disease Society of America; American Parkinson Disease
Association
FX This work was supported by National Institutes of Health (NIH) Grants
AG09466 to L. I. B. and T32 AG020506-07 to N. M. K.; ALS Association
(ALSA) and ALS Therapy Alliance grants to D. A. B.; ALSA, Muscular
Dystrophy Association, and NIH (NS23868, NS23320, NS41170) grants to S.
T. B.; a Multiple Sclerosis Society (Scotland) grant to J. E.; and
Huntington's Disease Society of America and American Parkinson Disease
Association grants to G. M.
NR 125
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U1 2
U2 29
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD OCT 14
PY 2009
VL 29
IS 41
BP 12776
EP 12786
DI 10.1523/JNEUROSCI.3463-09.2009
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 507IF
UT WOS:000270845000010
PM 19828789
ER
PT J
AU Vassar, R
Kovacs, DM
Yan, RQ
Wong, PC
AF Vassar, Robert
Kovacs, Dora M.
Yan, Riqiang
Wong, Philip C.
TI The beta-Secretase Enzyme BACE in Health and Alzheimer's Disease:
Regulation, Cell Biology, Function, and Therapeutic Potential
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID AMYLOID PRECURSOR PROTEIN; GATED SODIUM-CHANNELS; APP TRANSGENIC MICE;
A-BETA; CLEAVING ENZYME; GAMMA-SECRETASE; KNOCKOUT MICE; GGA PROTEINS;
LIPID RAFTS; ASPARTYL PROTEASE
AB The beta-amyloid (A beta) peptide is the major constituent of amyloid plaques in Alzheimer's disease (AD) brain and is likely to play a central role in the pathogenesis of this devastating neurodegenerative disorder. The beta-secretase, beta-site amyloid precursor protein cleaving enzyme (BACE1; also called Asp2, memapsin 2), is the enzyme responsible for initiating A beta generation. Thus, BACE is a prime drug target for the therapeutic inhibition of A beta production in AD. Since its discovery 10 years ago, much has been learned about BACE. This review summarizes BACE properties, describes BACE translation dysregulation in AD, and discusses BACE physiological functions in sodium current, synaptic transmission, myelination, and schizophrenia. The therapeutic potential of BACE will also be considered. This is a summary of topics covered at a symposium held at the 39th annual meeting of the Society for Neuroscience and is not meant to be a comprehensive review of BACE.
C1 [Vassar, Robert] Northwestern Univ, Dept Cell & Mol Biol, Chicago, IL 60611 USA.
[Kovacs, Dora M.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA.
[Kovacs, Dora M.] Harvard Univ, Sch Med, Dept Neurol, Charlestown, MA 02129 USA.
[Yan, Riqiang] Cleveland Clin, Lerner Res Inst, Dept Neurosci, Cleveland, OH 44195 USA.
[Wong, Philip C.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA.
RP Vassar, R (reprint author), Northwestern Univ, Dept Cell & Mol Biol, Chicago, IL 60611 USA.
EM r-vassar@northwestern.edu
FU NIA NIH HHS [R01 AG022560-07, R01 AG022560]
NR 100
TC 247
Z9 258
U1 3
U2 34
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD OCT 14
PY 2009
VL 29
IS 41
BP 12787
EP 12794
DI 10.1523/JNEUROSCI.3657-09.2009
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 507IF
UT WOS:000270845000011
PM 19828790
ER
PT J
AU Schrum, JP
Ricardo, A
Krishnamurthy, M
Blain, JC
Szostak, JW
AF Schrum, Jason P.
Ricardo, Alonso
Krishnamurthy, Mathangi
Blain, J. Craig
Szostak, Jack W.
TI Efficient and Rapid Template-Directed Nucleic Acid Copying Using 2
'-Amino-2 ',3 '-dideoxyribonucleoside-5 '-Phosphorimidazolide Monomers
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID CHEMICAL PRIMER EXTENSION; SELF-REPLICATION; MODEL PROTOCELL; DNA; RNA;
RIBOZYME; OLIGOMERIZATION; POLYMERIZATION; EMERGENCE; ANALOGS
AB The development of a sequence-general nucleic acid copying system is an essential step in the assembly of a synthetic protocell, an autonomously replicating spatially localized chemical system capable of spontaneous Darwinian evolution. Previously described nonenzymatic template-copying experiments have validated the concept of nonenzymatic replication, but have not yet achieved robust, sequence-general polynucleotide replication. The 5'-phosphorimidazolides of the 2'-amino-2',3'-dideoxyribonucleotides are attractive as potential monomers for such a system because they polymerize by forming 2'-> 5' linkages, which are favored in nonenzymatic polymerization reactions using similarly activated ribonucleotides on RNA templates. Furthermore, the 5'-activated 2'-amino nucleotides do not cyclize. We recently described the rapid and efficient nonenzymatic copying of a DNA homopolymer template (dC(15)) encapsulated within fatty acid vesicles using 2'-amino-2',3'-dideoxyguanosine-5'-phosphorimidazolide as the activated monomer. However, to realize a true Darwinian system, the template-copying chemistry must be able to copy most sequences and their complements to allow for the transmission of information from generation to generation. Here, we describe the copying of a series of nucleic acid templates using 2'-amino-2',3'-dideoxynucleotide-5'-phosphorimidazolides. Polymerization reactions proceed rapidly to completion on short homopolymer RNA and LNA templates, which favor an A-type duplex geometry. We show that more efficiently copied sequences are generated by replacing the adenine nucleobase with diaminopurine, and uracil with C5-(1-propynyl)uracil. Finally, we explore the copying of longer, mixed-sequence RNA templates to assets the sequence-general copying ability of2'-amino-2',3'-dideoxynucleoside-5'-phosphorimidazolides. Our results are a significant step forward in the realization of a self-replicating genetic polymer compatible with protocell template copying and suggest that N2'-> P5'-phosphoramidate DNA may have the potential to function as a self-replicating system.
C1 [Szostak, Jack W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
RP Szostak, JW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA 02114 USA.
EM szostak@molbio.mgh.harvard.edu
FU NSF [CHE 0434507]
FX We are grateful to Jesse J. Chen, Yollete V. Guillen-Schlippe, Ben
Heuberger, Sylvia Tobe, Doug Treco, Tina Yuan, and Shenglong Zhang for
helpful discussions. A.R. is a Research Associate and J.W.S. is an
Investigator of the Howard Hughes Medical Institute. This work was
supported in part by NSF Grant CHE 0434507 to JW.S.
NR 52
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U1 2
U2 26
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD OCT 14
PY 2009
VL 131
IS 40
BP 14560
EP 14570
DI 10.1021/ja906557v
PG 11
WC Chemistry, Multidisciplinary
SC Chemistry
GA 512SS
UT WOS:000271271500097
PM 19757789
ER
PT J
AU Baldys, A
Raymond, JR
AF Baldys, Aleksander
Raymond, John R., Sr.
TI Critical Role of ESCRT Machinery in EGFR Recycling
SO BIOCHEMISTRY
LA English
DT Article
ID ENDOCYTIC MEMBRANE TRAFFICKING
AB The molecular mechanisms of EGFR vesicular trafficking to lysosomes have recently received considerable attention. It is now clear that endosomal sorting complexes required for transport (ESCRTs) are critical for EGFR degradation. Although an increasing number of membrane receptors also undergo recycling via specific pathways, little information is available regarding regulated recycling of EGFR. In this study, we investigated the roles of ESCRTs in EGFR recycling after stimulation with amphiregulin (AR). We used ESCRT small interfering RNA (siRNA) duplexes to demonstrate that AR-induced EGFR intracellular processing involves active sorting to the recycling pathway through specific members of the ESCRT family.
C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA.
Ralph H Johnson Vet Affairs Med Ctr, Med Serv, Charleston, SC 29425 USA.
Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29425 USA.
RP Raymond, JR (reprint author), Room 213,Colcock Hall,179 Ashley Ave, Charleston, SC 29425 USA.
EM raymondj@musc.edu
FU Department of Veterans Affairs Merit; Research Enhancement Award
Program; National Institutes of Health [DK052448, GM063909]; American
Heart Association; Medical University of South Carolina Division of
Nephrology and Dialysis Clinics, Inc.
FX This work was supported by Department of Veterans Affairs Merit and
Research Enhancement Award Program grants (to J.R.R.), by National
Institutes of Health Grants DK052448 and GM063909 (J.R.R.), by an
American Heart Association (Mid-Atlantic) fellowship (to A.B.), and by a
laboratory endowment jointly supported by the Medical University of
South Carolina Division of Nephrology and Dialysis Clinics, Inc. (to
J.R.R.).
NR 10
TC 21
Z9 21
U1 0
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD OCT 13
PY 2009
VL 48
IS 40
BP 9321
EP 9323
DI 10.1021/bi900865u
PG 3
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 502KU
UT WOS:000270459100001
PM 19673488
ER
PT J
AU Rahilly-Tierney, CR
Lawler, EV
Scranton, RE
Gaziano, JM
AF Rahilly-Tierney, Catherine R.
Lawler, Elizabeth V.
Scranton, Richard E.
Gaziano, J. Michael
TI Cardiovascular Benefit of Magnitude of Low-Density Lipoprotein
Cholesterol Reduction A Comparison of Subgroups by Age
SO CIRCULATION
LA English
DT Article
DE aging; lipids; lipoproteins; epidemiology; prevention
ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED
CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; LIPID-LOWERING THERAPY;
OLDER PATIENTS; HYPERTENSIVE PATIENTS; PRIMARY PREVENTION; CARDIAC
OUTCOMES; ELDERLY-PATIENTS
AB Background-We examined the effect of the magnitude of low-density lipoprotein cholesterol (LDL-C) reduction across subjects of various ages in a retrospective cohort study.
Methods and Results-We selected 20 132 male veterans at high risk for an acute cardiovascular event and who had 2 or more LDL-C measurements before their first documented acute myocardial infarction, revascularization, death, or censoring date. LDL-C reduction was categorized as no reduction (<10 mg/dL; reference), small reduction (between 10 and 40 mg/dL), moderate reduction (between 40 and 70 mg/dL), or large reduction (>= 70 mg/dL). The primary outcome was combined acute myocardial infarction or revascularization. The first and last LDL-C levels in the databases were used to calculate the LDL-C reduction in patients who experienced no outcome or who died. Within each age quartile and in a subgroup of patients >= 80 years of age, a Cox proportional hazards model was used to determine hazard ratios for each category of LDL-C reduction compared with the reference category, with adjustment for age, body mass index, current smoking status, medications, and comorbidities. In all age groups, the magnitude of LDL-C reduction was proportional to the magnitude of cardiovascular risk reduction. Risk reduction for the combined outcome in patients who achieved a large LDL-C reduction was similar in all age quartiles, with multivariate-adjusted hazard ratios of approximately 0.30.
Conclusions-In a cohort of veterans at high risk for cardiovascular events, patients of all ages, including those 80 years or older, benefitted the most from large reductions in LDL-C. (Circulation. 2009;120:1491-1497.)
C1 [Rahilly-Tierney, Catherine R.; Lawler, Elizabeth V.; Scranton, Richard E.; Gaziano, J. Michael] Boston VA Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr, Boston, MA USA.
[Rahilly-Tierney, Catherine R.; Lawler, Elizabeth V.; Scranton, Richard E.; Gaziano, J. Michael] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
[Rahilly-Tierney, Catherine R.; Lawler, Elizabeth V.; Scranton, Richard E.; Gaziano, J. Michael] Brigham & Womens Hosp, Div Cardiol & Preventat Med, Boston, MA 02115 USA.
[Scranton, Richard E.] VeroScience LLC, Tiverton, RI USA.
RP Rahilly-Tierney, CR (reprint author), 150 S Huntington Ave,MAVERIC 13th Floor, Jamaica Plain, MA 02130 USA.
EM Catherine.Rahilly@va.gov
FU Epidemiology and Research Information Center of the Veterans Affairs
Cooperative Studies Program.
FX This research has been funded by the Epidemiology and Research
Information Center of the Veterans Affairs Cooperative Studies Program.
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U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD OCT 13
PY 2009
VL 120
IS 15
BP 1491
EP 1497
DI 10.1161/CIRCULATIONAHA.108.846931
PG 7
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 505PM
UT WOS:000270706500006
PM 19786636
ER
PT J
AU Steinhart, B
Thorpe, KE
Bayoumi, AM
Moe, G
Januzzi, JL
Mazer, CD
AF Steinhart, Brian
Thorpe, Kevin E.
Bayoumi, Ahmed M.
Moe, Gordon
Januzzi, James L., Jr.
Mazer, C. David
TI Improving the Diagnosis of Acute Heart Failure Using a Validated
Prediction Model
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE acute heart failure; diagnosis; natriuretic peptide; prediction model;
Bayesian theorem
ID EMERGENCY-DEPARTMENT PRIDE; PULMONARY-EMBOLISM; NATRIURETIC PEPTIDE;
MEDICAL LITERATURE; BIOCHEMICAL SCORE; USERS GUIDES; DYSPNEA; BNP;
MANAGEMENT; RECLASSIFICATION
AB Objectives We sought to derive and validate a prediction model by using N-terminal pro-B-type natriuretic peptide (NT-proBNP) and clinical variables to improve the diagnosis of acute heart failure (AHF).
Background The optimal way of using natriuretic peptides to enhance the diagnosis of AHF remains uncertain.
Methods Physician estimates of probability of AHF in 500 patients treated in the emergency department from the multicenter IMPROVE CHF (Improved Management of Patients With Congestive Heart Failure) trial recruited between December 2004 and December 2005 were classified into low (0% to 20%), intermediate (21% to 79%), or high (80% to 100%) probability for AHF and then compared with the blinded adjudicated AHF diagnosis. Likelihood ratios were calculated and multiple logistic regression incorporated covariates into an AHF prediction model that was validated internally by the use of bootstrapping and externally by applying the model to another 573 patients from the separate PRIDE (N-Terminal Pro-BNP Investigation of Dyspnea in the Emergency Department) study of the use of NT-proBNP in patients with dyspnea.
Results Likelihood ratios for AHF with NT-proBNP were 0.11 (95% confidence interval [CI]: 0.06 to 0.19) for cut- point values < 300 pg/ml; increasing to 3.43 (95% CI: 2.34 to 5.03) for values 2,700 to 8,099 pg/ml, and 12.80 (95% CI: 5.21 to 31.45) for values >= 8,100 pg/ml. Variables used to predict AHF were age, pre-test probability, and log NT-proBNP. When applied to the external data by use of its adjudicated final diagnosis as the gold standard, the model appropriately reclassified 44% of patients by intermediate clinical probability to either low or high probability of AHF with negligible (< 2%) inappropriate redirection.
Conclusions A diagnostic prediction model for AHF that incorporates both clinical assessment and NT-proBNP has been derived and validated and has excellent diagnostic accuracy, especially in cases with indeterminate likelihood for AHF. (J Am Coll Cardiol 2009; 54: 1515-21) (C) 2009 by the American College of Cardiology Foundation
C1 [Steinhart, Brian; Bayoumi, Ahmed M.; Moe, Gordon] St Michaels Hosp, Dept Med, Toronto, ON M5B 1W8, Canada.
[Mazer, C. David] St Michaels Hosp, Dept Anesthesia & Crit Care Med, Toronto, ON M5B 1W8, Canada.
[Thorpe, Kevin E.; Bayoumi, Ahmed M.; Moe, Gordon; Mazer, C. David] St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada.
[Steinhart, Brian] Univ Toronto, Dept Med, Div Emergency Med, Toronto, ON, Canada.
[Bayoumi, Ahmed M.] Univ Toronto, Div Gen Med, Toronto, ON, Canada.
[Moe, Gordon] Univ Toronto, Div Cardiol, Toronto, ON, Canada.
[Mazer, C. David] Univ Toronto, Fac Med, Dept Anesthesia, Toronto, ON, Canada.
[Mazer, C. David] Univ Toronto, Fac Med, Dept Physiol, Toronto, ON, Canada.
[Thorpe, Kevin E.] Univ Toronto, Fac Med, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Bayoumi, Ahmed M.] Univ Toronto, Fac Med, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada.
[Januzzi, James L., Jr.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Januzzi, James L., Jr.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Steinhart, B (reprint author), 1-008C Shuter Wing,30 Bond St, Toronto, ON M5B 1W8, Canada.
EM steinhartb@smh.toronto.on.ca
NR 40
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U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD OCT 13
PY 2009
VL 54
IS 16
BP 1515
EP 1521
DI 10.1016/j.jacc.2009.05.065
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 503EC
UT WOS:000270514400004
PM 19815122
ER
PT J
AU Giugliano, RP
Braunwald, E
AF Giugliano, Robert P.
Braunwald, Eugene
TI The Year in Non-ST-Segment Elevation Acute Coronary Syndrome
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Review
DE year in; non-ST-segment; coronary syndrome
ID OPTICAL COHERENCE TOMOGRAPHY; GLYCOPROTEIN IIB/IIIA INHIBITORS; RESIDUAL
PLATELET REACTIVITY; P2Y(12) RECEPTOR ANTAGONIST; INTENSIVE STATIN
THERAPY; LOW-DENSITY-LIPOPROTEIN; TRIAGE STRATEGY TRIAL; ACUTE
CHEST-PAIN; MYOCARDIAL-INFARCTION; UNFRACTIONATED HEPARIN
C1 [Giugliano, Robert P.; Braunwald, Eugene] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med,Dept Med,TIMI Study Grp, Boston, MA 02115 USA.
RP Braunwald, E (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med,Dept Med,TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA.
EM ebraunwald@partners.org
NR 115
TC 3
Z9 3
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD OCT 13
PY 2009
VL 54
IS 16
BP 1544
EP 1555
DI 10.1016/j.jacc.2009.06.025
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 503EC
UT WOS:000270514400009
PM 19815127
ER
PT J
AU Ticozzi, N
Silani, V
LeClerc, AL
Keagle, P
Gellera, C
Ratti, A
Taroni, F
Kwiatkowski, TJ
McKenna-Yasek, DM
Sapp, PC
Brown, RH
Landers, JE
AF Ticozzi, N.
Silani, V.
LeClerc, A. L.
Keagle, P.
Gellera, C.
Ratti, A.
Taroni, F.
Kwiatkowski, T. J., Jr.
McKenna-Yasek, D. M.
Sapp, P. C.
Brown, R. H., Jr.
Landers, J. E.
TI Analysis of FUS gene mutation in familial amyotrophic lateral sclerosis
within an Italian cohort
SO NEUROLOGY
LA English
DT Article
ID SUPEROXIDE-DISMUTASE GENE; EXONIC SPLICING ENHANCERS; RNA-BINDING
PROTEIN; TARDBP MUTATIONS; ALS; IDENTIFICATION; TDP-43; TLS;
ONCOPROTEIN; TOOL
AB Objective: Mutations in the FUS gene on chromosome 16 have been recently discovered as a cause of familial amyotrophic lateral sclerosis (FALS). This study determined the frequency and identities of FUS gene mutations in a cohort of Italian patients with FALS.
Methods: We screened all 15 coding exons of FUS for mutations in 94 Italian patients with FALS.
Results: We identified 4 distinct missense mutations in 5 patients; 2 were novel. The mutations were not present in 376 healthy Italian controls and thus are likely to be pathogenic.
Conclusions: Our results demonstrate that FUS mutations cause similar to 4% of familial amyotrophic lateral sclerosis cases in the Italian population. Neurology (R) 2009; 73: 1180-1185
C1 [Ticozzi, N.; LeClerc, A. L.; Keagle, P.; McKenna-Yasek, D. M.; Sapp, P. C.; Brown, R. H., Jr.; Landers, J. E.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA.
[Ticozzi, N.; Silani, V.; Ratti, A.] Univ Milan, Dept Neurol & Lab Neurosci, Ctr Dino Ferrari, IRCCS Ist Auxol Italiano, Milan, Italy.
[Gellera, C.; Taroni, F.] Ist Neurol Carlo Besta, Fdn IRCCS, Unit Genet Neurodegenerat & Metab Dis, Milan, Italy.
[Kwiatkowski, T. J., Jr.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Sapp, P. C.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
[Sapp, P. C.] MIT, Dept Biol, Cambridge, MA 02139 USA.
RP Landers, JE (reprint author), LRB604,364 Plantat St, Worcester, MA 01605 USA.
EM john.landers@umassmed.edu
RI Ticozzi, Nicola/K-8094-2016; GELLERA, CINZIA/J-7887-2016;
OI Ticozzi, Nicola/0000-0001-5963-7426; GELLERA,
CINZIA/0000-0002-3582-665X; Silani, Vincenzo/0000-0002-7698-3854
FU ALS Therapy Alliance; Project ALS; Angel Fund; Pierre L. de Bourgknecht
ALS Research Foundation; Al-Athel ALS Research Foundation; ALS Family
Charitable Foundation; National Institute of Neurological Disorders and
Stroke [NS050557, NS050641]; Italian Ministry of Health [n.533F/N1,
RF2007/INN644440]; Howard Hughes Medical Institute (HHMI); Fondazione
Telethon
FX Supported by the ALS Therapy Alliance, Project ALS, the Angel Fund, the
Pierre L. de Bourgknecht ALS Research Foundation, the Al-Athel ALS
Research Foundation, the ALS Family Charitable Foundation, and the
National Institute of Neurological Disorders and Stroke (NS050557 and
NS050641). N.T., V.S., and A.R. were supported by the Italian Ministry
of Health (Malattie Neurodegenerative, ex Art. 56, n.533F/N1). F. T. and
C. G. were supported by the Italian Ministry of Health grant
RF2007/INN644440. P.S. was supported by the Howard Hughes Medical
Institute (HHMI) through the auspices of Prof. H. Robert Horvitz, an
Investigator in the HHMI. R. H. B. is a cofounder of AviTx, which
targets development of therapies.
NR 39
TC 91
Z9 93
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD OCT 13
PY 2009
VL 73
IS 15
BP 1180
EP 1185
DI 10.1212/WNL.0b013e3181bbff05
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 505OQ
UT WOS:000270704000004
PM 19741215
ER
PT J
AU Lee, YN
Alt, FW
Reyes, J
Gleason, M
Zarrin, AA
Jung, D
AF Lee, Yu Nee
Alt, Frederick W.
Reyes, Julia
Gleason, Megan
Zarrin, Ali A.
Jung, David
TI Differential utilization of T cell receptor TCR alpha/TCR delta locus
variable region gene segments is mediated by accessibility
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE epigenetic regulation; T cell development; VDJ recombination
ID V(D)J RECOMBINATION; ALPHA/DELTA-LOCUS; SIGNAL SEQUENCES; LYMPHOCYTES-T;
CHAIN; BETA; REARRANGEMENTS; EXPRESSION; THYMOCYTES; ENHANCER
AB T cell receptor (TCR) variable region exons are assembled from germline V, (D), and J gene segments, each of which is flanked by recombination signal (RS) sequences that are composed of a conserved heptamer, a spacer of 12 or 23 bp, and a characteristic nonamer. V(D) J recombination only occurs between V, D, and J segments flanked by RS sequences that contain, respectively, 12(12-RS)- and 23(23-RS)-bp spacers (12/23 rule). Additional mechanisms can restrict joining of 12/23 RS matched segments beyond the 12/23 rule (B12/23). The TCR delta locus is contained within the TCR alpha locus; TCR alpha variable region exons are encoded by TRAV and TRAJ segments and those of TCR delta by TRDV, TRDD, and TRDJ segments. On the basis of the 12/23 rule, both TRAV and TRDV gene segments are compatible to rearrange with TRDD gene segments; however, TRAV-to-TRDD joins are not observed in vivo. Absence of TRAV-to-TRDD rearrangement might be explained either by B12/23 restriction or by differential accessibility of the TRDV versus TRAV gene segments for rearrangement to TRDD. We used in vitro substrate analysis to reveal that both TRAV and TRDV 23-RSs mediate rearrangements to the 5'TRDD1 12-RS, demonstrating that B12/23 restriction does not explain these rearrangement biases. However, targeted replacement of TRDD1 and its 12-RSs with TRAJ38 and its 12-RS showed that TRDV gene segments rearrange with the ectopic TRAJ38, whereas TRAV segments do not. Our results demonstrate that sorting of TRAV and TRDV gene segments is determined by differential locus accessibility during T cell development.
C1 [Lee, Yu Nee; Alt, Frederick W.; Reyes, Julia; Gleason, Megan; Zarrin, Ali A.; Jung, David] Harvard Univ, Sch Med, Childrens Hosp Boston, Howard Hughes Med Inst,Immune Dis Inst, Boston, MA 02115 USA.
RP Alt, FW (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Howard Hughes Med Inst,Immune Dis Inst, Boston, MA 02115 USA.
EM alt@enders.tch.harvard.edu
FU Human Frontiers Science Program; Medical Scientist Training Program;
Harvard Medical School; National Institutes of Health [AI-20047]
FX We thank Michael Krangel and Barry Sleckman for critical review of this
manuscript. Y. N. L. was supported by the Human Frontiers Science
Program. D. J. received support from the Medical Scientist Training
Program, Harvard Medical School. F. W. A. is an investigator of the
Howard Hughes Medical Institute and is supported by National Institutes
of Health Grant AI-20047.
NR 33
TC 8
Z9 8
U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 13
PY 2009
VL 106
IS 41
BP 17487
EP 17492
DI 10.1073/pnas.0909723106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 506DS
UT WOS:000270754400049
PM 19805067
ER
PT J
AU Duan, ZF
Choy, E
Hornicek, FJ
AF Duan, Zhenfeng
Choy, Edwin
Hornicek, Francis J.
TI NSC23925, Identified in a High-Throughput Cell-Based Screen, Reverses
Multidrug Resistance
SO PLOS ONE
LA English
DT Article
AB Background: Multidrug resistance (MDR) is a major factor which contributes to the failure of cancer chemotherapy, and numerous efforts have been attempted to overcome MDR. To date, none of these attempts have yielded a tolerable and effective therapy to reverse MDR; thus, identification of new agents would be useful both clinically and scientifically.
Methodology/Principal Findings: To identify small molecule compounds that can reverse chemoresistance, we developed a 96-well plate high-throughput cell-based screening assay in a paclitaxel resistant ovarian cancer cell line. Coincubating cells with a sublethal concentration of paclitaxel in combination with each of 2,000 small molecule compounds from the National Cancer Institute Diversity Set Library, we identified a previously uncharacterized molecule, NSC23925, that inhibits Pgp1 and reverses MDR1 (Pgp1) but does not inhibit MRP or BCRP-mediated MDR. The cytotoxic activity of NSC23925 was further evaluated using a panel of cancer cell lines expressing Pgp1, MRP, and BCRP. We found that at a concentration of >10 mu M NSC23925 moderately inhibits the proliferation of both sensitive and resistant cell lines with almost equal activity, but its inhibitory effect was not altered by co-incubation with the Pgp1 inhibitor, verapamil, suggesting that NSC23925 itself is not a substrate of Pgp1. Additionally, NSC23925 increases the intracellular accumulation of Pgp1 substrates: calcein AM, Rhodamine-123, paclitaxel, mitoxantrone, and doxorubicin. Interestingly, we further observed that, although NSC23925 directly inhibits the function of Pgp1 in a dose-dependent manner without altering the total expression level of Pgp1, NSC23925 actually stimulates ATPase activity of Pgp, a phenomenon seen in other Pgp inhibitors.
Conclusions/Significance: The ability of NSC23925 to restore sensitivity to the cytotoxic effects of chemotherapy or to prevent resistance could significantly benefit cancer patients.
RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, Boston, MA 02114 USA.
EM zduan@partners.org
OI Duan, Zhenfeng/0000-0002-8543-083X; Choy, Edwin/0000-0001-9896-8084
FU NCI NIH HHS [R01-CA119617, R01 CA119617]
NR 45
TC 30
Z9 31
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 12
PY 2009
VL 4
IS 10
AR e7415
DI 10.1371/journal.pone.0007415
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 505VX
UT WOS:000270728500014
PM 19823672
ER
PT J
AU Mahimainathan, L
Ghosh-Choudhury, N
Venkatesan, B
Das, F
Mandal, CC
Dey, N
Habib, SL
Kasinath, BS
Abboud, HE
Choudhury, GG
AF Mahimainathan, Lenin
Ghosh-Choudhury, Nandini
Venkatesan, Balachandar
Das, Falguni
Mandal, Chandi C.
Dey, Nirmalya
Habib, Samy L.
Kasinath, Balakuntalam S.
Abboud, Hanna E.
Choudhury, Goutam Ghosh
TI TSC2 Deficiency Increases PTEN via H1F1 alpha
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TUBEROUS SCLEROSIS COMPLEX; TUMOR-SUPPRESSOR GENE; INDUCIBLE FACTOR-I;
CELL-SURVIVAL; RENAL ANGIOMYOLIPOMAS; 3-KINASE/AKT PATHWAY; SIGNALING
PATHWAY; MESANGIAL CELLS; DOWN-REGULATION; S6 KINASE
AB Substantial evidence suggests roles of TSC2 and PTEN in the development of cancer predisposition syndromes. Loss of TSC2 results in benign tumors, neurological disorders, and angiomyolipomas. We found that PTEN mRNA and protein levels are elevated in Tsc2(-/-) mouse embryo fibroblasts with concomitant reduction in Akt phosphorylation. Reconstitution of TSC2 in Tsc2(-/-) mouse embryo fibroblasts decreases PTEN levels. Interestingly, increased HIF1 alpha activity present in Tsc2 null cells is required for PTEN transcription and protein expression. We identified a canonical hypoxia-responsive element in the PTEN promoter, which regulates the transcription of this tumor suppressor protein in a TSC2-dependent manner. Finally, we demonstrate a positive correlation between expression of HIF1 alpha and PTEN in renal angiomyolipomas from TSC patients. Our results reveal a unique function of HIF1 alpha in up-regulation of PTEN and provide a new mechanism of reduced Akt phosphorylation in Tsc2 null cells. These data suggest that PTEN may safeguard against developing malignant tumors in patients with TSC deficiency.
C1 [Mahimainathan, Lenin; Venkatesan, Balachandar; Das, Falguni; Dey, Nirmalya; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Ghosh-Choudhury, Nandini; Mandal, Chandi C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA.
[Ghosh-Choudhury, Nandini; Habib, Samy L.; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, Vet Affairs Res, San Antonio, TX 78229 USA.
[Habib, Samy L.; Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA.
RP Choudhury, GG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM choudhuryg@uthscsa.edu
FU National Institutes of Health [RC1 DIK50190]; Juvenile Diabetes Research
Foundation; Veterans Affairs Research Service Merit Review Grants
FX This work was supported, in whole or in part, by National Institutes of
Health Grant RC1 DIK50190. This work was also supported by the Juvenile
Diabetes Research Foundation and Veterans Affairs Research Service Merit
Review Grants (to G. G. C.).
NR 60
TC 15
Z9 15
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 9
PY 2009
VL 284
IS 41
BP 27790
EP 27798
DI 10.1074/jbc.M109.028860
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 505FP
UT WOS:000270676300005
PM 19648120
ER
PT J
AU Pioszak, AA
Parker, NR
Gardella, TJ
Xu, HE
AF Pioszak, Augen A.
Parker, Naomi R.
Gardella, Thomas J.
Xu, H. Eric
TI Structural Basis for Parathyroid Hormone-related Protein Binding to the
Parathyroid Hormone Receptor and Design of Conformation-selective
Peptides
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID COUPLED-RECEPTOR; MOLECULAR RECOGNITION; EXTRACELLULAR DOMAIN; PTH/PTHRP
RECEPTOR; CRYSTAL-STRUCTURE; LIGAND-BINDING; PTH; OSTEOPOROSIS;
REFINEMENT; FRAGMENT
AB Parathyroid hormone (PTH) and PTH-related protein (PTHrP) are two related peptides that control calcium/phosphate homeostasis and bone development, respectively, through activation of the PTH/PTHrP receptor (PTH1R), a class B G protein-coupled receptor. Both peptides hold clinical interest for their capacities to stimulate bone formation. PTH and PTHrP display different selectivity for two distinct PTH1R conformations, but how their binding to the receptor differs is unclear. The high resolution crystal structure of PTHrP bound to the extracellular domain (ECD) of PTH1R reveals that PTHrP binds as an amphipathic a-helix to the same hydrophobic groove in the ECD as occupied by PTH, but in contrast to a straight, continuous PTH helix, the PTHrP helix is gently curved and C-terminally "unwound." The receptor accommodates the altered binding modes by shifting the side chain conformations of two residues within the binding groove: Leu-41 and Ile-115, the former acting as a rotamer toggle switch to accommodate PTH/PTHrP sequence divergence, and the latter adapting to the PTHrP curvature. Binding studies performed with PTH/PTHrP hybrid ligands having reciprocal exchanges of residues involved in different contacts confirmed functional consequences for the altered interactions and enabled the design of altered PTH and PTHrP peptides that adopt the ECD-binding mode of the opposite peptide. Hybrid peptides that bound the ECD poorly were selective for the G protein-coupled PTH1R conformation. These results establish a molecular model for better understanding of how two biologically distinct ligands can act through a single receptor and provide a template for designing better PTH/PTHrP therapeutics.
C1 [Pioszak, Augen A.; Parker, Naomi R.; Xu, H. Eric] Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA.
[Gardella, Thomas J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02144 USA.
RP Pioszak, AA (reprint author), Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA.
EM augie.pioszak@vai.org; eric.xu@vai.org
FU National Institutes of Health [DK071662, DK066202, HL089301, DK-11794];
Jay and Betty Van Andel Foundation
FX This work was supported, in whole or in part, by National Institutes of
Health Grants DK071662, DK066202, and HL089301 (to H. E. X.), and
DK-11794 (toT. J. G.).This work was also supported by the Jay and Betty
Van Andel Foundation.
NR 44
TC 55
Z9 57
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 9
PY 2009
VL 284
IS 41
BP 28382
EP 28391
DI 10.1074/jbc.M109.022905
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 505FP
UT WOS:000270676300063
PM 19674967
ER
PT J
AU Yan, QS
Dutt, S
Xu, R
Graves, K
Juszczynski, P
Manis, JP
Shipp, MA
AF Yan, Qingsheng
Dutt, Shilpee
Xu, Rong
Graves, Katherine
Juszczynski, Przemyslaw
Manis, John P.
Shipp, Margaret A.
TI BBAP Monoubiquitylates Histone H4 at Lysine 91 and Selectively Modulates
the DNA Damage Response
SO MOLECULAR CELL
LA English
DT Article
ID DOUBLE-STRAND BREAKS; B-CELL LYMPHOMAS; H2B UBIQUITYLATION; REPAIR
PROTEINS; H3 METHYLATION; UBIQUITINATION; CHROMATIN; GENE;
METHYLTRANSFERASE; TRANSCRIPTION
AB Although the BBAP E3 ligase and its binding partner BAL are overexpressed in chemotherapy-resistant lymphomas, the role of these proteins in DNA damage responses remains undefined. Because BAL proteins modulate promoter-coupled transcription and contain structural motifs associated with chromatin remodeling and DNA repair, we reasoned that the BBAP E3 ligase might target nucleosomal proteins. Herein, we demonstrate that BBAP selectively monoubiquitylates histone H4 lysine 91 and protects cells exposed to DNA-damaging agents. Disruption of BBAP-mediated monoubiquitylation of histone H4K91 is associated with the loss of chromatin-associated H4K20 methylase, mono- and dimethyl H4K20, and a delay in the kinetics of 53BP1 foci formation at sites of DNA damage. Because 53BP1 localizes to DNA damage sites, in part, via an interaction with dimethyl H4K20, these data directly implicate BBAP in the monoubiquitylation and additional posttranslational modification of histone H4 and an associated DNA damage response.
C1 [Yan, Qingsheng; Xu, Rong; Juszczynski, Przemyslaw; Shipp, Margaret A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Dutt, Shilpee; Graves, Katherine; Manis, John P.] Harvard Univ, Childrens Hosp Boston, Sch Med, Boston, MA 02115 USA.
[Dutt, Shilpee; Graves, Katherine; Manis, John P.] Harvard Univ, Joint Program Transfus Med, Sch Med, Boston, MA 02115 USA.
RP Shipp, MA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM margaret_shipp@dfci.harvard.edu
FU NCI NIH HHS [P01 CA092625, P01 CA092625-08, P01 CA092625-09]
NR 52
TC 60
Z9 65
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD OCT 9
PY 2009
VL 36
IS 1
BP 110
EP 120
DI 10.1016/j.molcel.2009.08.019
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 510AN
UT WOS:000271060500011
PM 19818714
ER
PT J
AU Amit, I
Garber, M
Chevrier, N
Leite, AP
Donner, Y
Eisenhaure, T
Guttman, M
Grenier, JK
Li, WB
Zuk, O
Schubert, LA
Birditt, B
Shay, T
Goren, A
Zhang, XL
Smith, Z
Deering, R
McDonald, RC
Cabili, M
Bernstein, BE
Rinn, JL
Meissner, A
Root, DE
Hacohen, N
Regev, A
AF Amit, Ido
Garber, Manuel
Chevrier, Nicolas
Leite, Ana Paula
Donner, Yoni
Eisenhaure, Thomas
Guttman, Mitchell
Grenier, Jennifer K.
Li, Weibo
Zuk, Or
Schubert, Lisa A.
Birditt, Brian
Shay, Tal
Goren, Alon
Zhang, Xiaolan
Smith, Zachary
Deering, Raquel
McDonald, Rebecca C.
Cabili, Moran
Bernstein, Bradley E.
Rinn, John L.
Meissner, Alex
Root, David E.
Hacohen, Nir
Regev, Aviv
TI Unbiased Reconstruction of a Mammalian Transcriptional Network Mediating
Pathogen Responses
SO SCIENCE
LA English
DT Article
ID GENE-EXPRESSION; REGULATORS; INDUCTION; MODULE; RNA
AB Models of mammalian regulatory networks controlling gene expression have been inferred from genomic data but have largely not been validated. We present an unbiased strategy to systematically perturb candidate regulators and monitor cellular transcriptional responses. We applied this approach to derive regulatory networks that control the transcriptional response of mouse primary dendritic cells to pathogens. Our approach revealed the regulatory functions of 125 transcription factors, chromatin modifiers, and RNA binding proteins, which enabled the construction of a network model consisting of 24 core regulators and 76 fine-tuners that help to explain how pathogen-sensing pathways achieve specificity. This study establishes a broadly applicable, comprehensive, and unbiased approach to reveal the wiring and functions of a regulatory network controlling a major transcriptional response in primary mammalian cells.
C1 [Amit, Ido; Garber, Manuel; Leite, Ana Paula; Donner, Yoni; Guttman, Mitchell; Grenier, Jennifer K.; Zuk, Or; Shay, Tal; Goren, Alon; Zhang, Xiaolan; Smith, Zachary; Cabili, Moran; Bernstein, Bradley E.; Rinn, John L.; Meissner, Alex; Root, David E.; Hacohen, Nir; Regev, Aviv] MIT, Broad Inst, Cambridge, MA 02142 USA.
[Amit, Ido; Garber, Manuel; Leite, Ana Paula; Donner, Yoni; Guttman, Mitchell; Grenier, Jennifer K.; Zuk, Or; Shay, Tal; Goren, Alon; Zhang, Xiaolan; Smith, Zachary; Cabili, Moran; Bernstein, Bradley E.; Rinn, John L.; Meissner, Alex; Root, David E.; Hacohen, Nir; Regev, Aviv] Harvard Univ, Cambridge, MA 02142 USA.
[Amit, Ido; Chevrier, Nicolas; Eisenhaure, Thomas; Li, Weibo; Deering, Raquel; McDonald, Rebecca C.; Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA.
[Amit, Ido; Chevrier, Nicolas; Eisenhaure, Thomas; Li, Weibo; Deering, Raquel; McDonald, Rebecca C.; Bernstein, Bradley E.; Hacohen, Nir] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Amit, Ido; Guttman, Mitchell; Regev, Aviv] MIT, Dept Biol, Cambridge, MA 02142 USA.
[Leite, Ana Paula] MIT, Cambridge, MA 02139 USA.
[Schubert, Lisa A.; Birditt, Brian] NanoString Technol, Seattle, WA 98109 USA.
[Goren, Alon; Bernstein, Bradley E.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA.
[Goren, Alon; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA.
[Regev, Aviv] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Hacohen, N (reprint author), MIT, Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02142 USA.
EM nhacohen@partners.org
RI Shay, Tal/J-4028-2016;
OI Shay, Tal/0000-0003-0755-1350; Leite, Ana Paula/0000-0001-5773-3211
FU American Physicians Fellowship for Medicine in Israel; NIH [R21
AI71060]; Burroughs Wellcome Fund; Sloan Foundation
FX We thank E. Lander, I. Wapinski, D. Pe'er, N. Friedman, J. Kagan, A.
Luster, V. Kuchroo, and A. Citri for discussions and comments; L.
Gaffney for assistance with artwork; S. Gupta and the Broad Genetic
Analysis Platform for microarray processing; and T. Mikkelsen and the
Broad Sequencing Platform for help with the ChIP-seq experiments.
Supported by the Human Frontier Science Program Organization and a
Claire and Emanuel G. Rosenblatt Award from the American Physicians
Fellowship for Medicine in Israel (I. A.); NIH grant R21 AI71060 and the
NIH New Innovator Award (N. H.); and a Career Award at the Scientific
Interface from the Burroughs Wellcome Fund, an NIH Pioneer Award, and
the Sloan Foundation (A. R.). A. R. is an Early Career Scientist of the
Howard Hughes Medical Institute and an investigator of the Merkin
Foundation for Stem Cell Research at the Broad Institute. Complete
microarray data sets are available at the Gene Expression Omnibus
(accession no. GSE17721).
NR 28
TC 281
Z9 283
U1 1
U2 19
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD OCT 9
PY 2009
VL 326
IS 5950
BP 257
EP 263
DI 10.1126/science.1179050
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 504EX
UT WOS:000270599500035
PM 19729616
ER
PT J
AU Walker, LM
Phogat, SK
Chan-Hui, PY
Wagner, D
Phung, P
Goss, JL
Wrin, T
Simek, MD
Fling, S
Mitcham, JL
Lehrman, JK
Priddy, FH
Olsen, OA
Frey, SM
Hammond, PW
Kaminsky, S
Zamb, T
Moyle, M
Koff, WC
Poignard, P
Burton, DR
AF Walker, Laura M.
Phogat, Sanjay K.
Chan-Hui, Po-Ying
Wagner, Denise
Phung, Pham
Goss, Julie L.
Wrin, Terri
Simek, Melissa D.
Fling, Steven
Mitcham, Jennifer L.
Lehrman, Jennifer K.
Priddy, Frances H.
Olsen, Ole A.
Frey, Steven M.
Hammond, Phillip W.
Kaminsky, Stephen
Zamb, Timothy
Moyle, Matthew
Koff, Wayne C.
Poignard, Pascal
Burton, Dennis R.
CA Protocol G Principal Investigators
TI Broad and Potent Neutralizing Antibodies from an African Donor Reveal a
New HIV-1 Vaccine Target
SO SCIENCE
LA English
DT Article
ID SIMIAN/HUMAN IMMUNODEFICIENCY VIRUS; MONOCLONAL-ANTIBODIES; PASSIVE
TRANSFER; V2 DOMAIN; GP120; ENVELOPE; PROTECTION; MACAQUES; EPITOPE;
DESIGN
AB Broadly neutralizing antibodies (bNAbs), which develop over time in some HIV-1-infected individuals, define critical epitopes for HIV vaccine design. Using a systematic approach, we have examined neutralization breadth in the sera of about 1800 HIV-1-infected individuals, primarily infected with non-clade B viruses, and have selected donors for monoclonal antibody (mAb) generation. We then used a high-throughput neutralization screen of antibody-containing culture supernatants from about 30,000 activated memory B cells from a clade A-infected African donor to isolate two potent mAbs that target a broadly neutralizing epitope. This epitope is preferentially expressed on trimeric Envelope protein and spans conserved regions of variable loops of the gp120 subunit. The results provide a framework for the design of new vaccine candidates for the elicitation of bNAb responses.
C1 [Phogat, Sanjay K.; Wagner, Denise; Kaminsky, Stephen; Zamb, Timothy] Int AIDS Vaccine Initiat, AIDS Vaccine Design & Dev Lab, New York, NY 11220 USA.
[Walker, Laura M.; Fling, Steven; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Walker, Laura M.; Fling, Steven; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
[Chan-Hui, Po-Ying; Mitcham, Jennifer L.; Olsen, Ole A.; Frey, Steven M.; Hammond, Phillip W.; Moyle, Matthew] Theraclone Sci, Seattle, WA 98104 USA.
[Phung, Pham; Goss, Julie L.; Wrin, Terri] Monogram Biosci Inc, San Francisco, CA 94080 USA.
[Simek, Melissa D.; Lehrman, Jennifer K.; Priddy, Frances H.; Koff, Wayne C.] Int AIDS Vaccine Initiat, New York, NY 10038 USA.
[Burton, Dennis R.] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA.
[Burton, Dennis R.] Harvard Univ, Boston, MA 02114 USA.
RP Phogat, SK (reprint author), Int AIDS Vaccine Initiat, AIDS Vaccine Design & Dev Lab, New York, NY 11220 USA.
EM SPhogat@iavi.org; burton@scripps.edu
RI poignard, pascal/N-6678-2013; Kaminsky, Stephen/J-5141-2016
OI Kaminsky, Stephen/0000-0003-1869-834X
FU International AIDS Vaccine Initiative (IAVI); U. S. Agency for
International Development (USAID); National Institute of Allergy and
Infectious Diseases; NIH [AI33292]
FX We thank R. Aguilar-Sino for technical assistance at The Scripps
Research Institute; C. Ward, W. Cieplak, and M. Branum for technical
assistance at Theraclone Sciences; R. Pejchal for assistance in
structural modeling; S. M. Eagol and C. Williams for assistance with
figures; E. Anton from Monogram R & D and the Monogram Clinical
Reference Laboratory staff; all the study participants and research
staff at each of the Protocol G clinical centers; and Protocol G project
team members for all of the support that they have provided for this
study (individuals and affiliations are listed in the supporting online
material text as notes). We also thank A. Pinter for supplying the
antibodies 10/76b and c108 g, W. Olson and J. Moore for providing the
KNH1144 SOSIP trimer, and R. Wyatt for providing the YU2gp140foldon
trimer. This work was supported by the International AIDS Vaccine
Initiative (IAVI) through the contributions of a number of government
and private donors who are listed on the Web site www. iavi. org, as
well as IAVI's Innovation Fund (which is cofunded by the Bill & Melinda
Gates Foundation); the U. S. Agency for International Development
(USAID); and the National Institute of Allergy and Infectious Diseases,
NIH, AI33292 (D. R. B.). The contents are the responsibility of the
authors and do not necessarily reflect the views of USAID or the U. S.
government. The authors declare competing financial interests. Protocol
G Principal Investigators: G. Miiro, J. Serwanga, A. Pozniak, D. McPhee,
O. Manigart, L. Mwananyanda, E. Karita, A. Inwoley, W. Jaoko, J.
DeHovitz, L. G. Bekker, P. Pitisuttithum, R. Paris, and S. Allen.
NR 23
TC 919
Z9 938
U1 7
U2 87
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD OCT 9
PY 2009
VL 326
IS 5950
BP 285
EP 289
DI 10.1126/science.1178746
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 504EX
UT WOS:000270599500042
PM 19729618
ER
PT J
AU Gandhi, RT
O'Neill, D
Bosch, RJ
Chan, ES
Bucy, RP
Shopis, J
Baglyos, L
Adams, E
Fox, L
Purdue, L
Marshak, A
Flynn, T
Masih, R
Schock, B
Mildvan, D
Schlesinger, SJ
Marovich, MA
Bhardwaj, N
Jacobson, JM
AF Gandhi, Rajesh T.
O'Neill, David
Bosch, Ronald J.
Chan, Ellen S.
Bucy, R. Pat
Shopis, Janet
Baglyos, Lynn
Adams, Elizabeth
Fox, Lawrence
Purdue, Lynette
Marshak, Ann
Flynn, Theresa
Masih, Reena
Schock, Barbara
Mildvan, Donna
Schlesinger, Sarah J.
Marovich, Mary A.
Bhardwaj, Nina
Jacobson, Jeffrey M.
CA AIDS Clinical Trials Grp A5130 Tea
TI A randomized therapeutic vaccine trial of canarypox-HIV-pulsed dendritic
cells vs. canarypox-HIV alone in HIV-1-infected patients on
antiretroviral therapy
SO VACCINE
LA English
DT Article
DE HIV-1; Dendritic cells; Canarypox; Therapeutic vaccine; Clinical trial
ID CD8(+) T-CELL; VIRUS TYPE-1 HIV-1; LYMPHOCYTE RESPONSES; RECOMBINANT
GP160; IMMUNIZATION; INFECTION; CD4(+); VCP1452; PROTEIN; IMMUNOGENICITY
AB Targeting canarypox (CP)-HIV vaccine to dendritic cells (DCs) elicits anti-HIV-1 immune responses in vitro. We conducted a phase I/II clinical trial to evaluate whether adding DC to a CP-HIV vaccine improved virologic control during analytic treatment interruption (ATI) in HIV-1-infected subjects. Twenty-nine subjects on suppressive antiretroviral therapy were randomized to vaccination with autologous DCs infected with CP-HIV + keyhole limpet hemocyanin (KLH) (arm A, n = 14) or CP-HIV + KLH alone (arm B, n = 15). The mean viral load (VL) setpoint during ATI did not differ between subjects in arms A and B. A higher percentage of subjects in the DC group had a VL setpoint <5000 c/mL during ATI (4/13 or 31% in arm A compared with 0/13 in arm B, p = 0.096), but virologic control was transient. Subjects in arm A had a greater increase in KLH lymphoproliferative response than subjects in arm B; however. summed ELISPOT responses to HIV-1 antigens did not differ by treatment arm. We conclude that a DC-CP-HIV vaccine is well-tolerated in HIV-1-infected patients, but does not lower VL setpoint during ATI compared with CP-HIV alone. New methods to enhance the immunogenicity and antiviral efficacy of DC-based vaccines for HIV-1 infection are needed. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Gandhi, Rajesh T.; Shopis, Janet; Flynn, Theresa] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[O'Neill, David; Bhardwaj, Nina] NYU, Sch Med, New York, NY 10003 USA.
[Bosch, Ronald J.; Chan, Ellen S.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA.
[Bucy, R. Pat] Univ Alabama, Birmingham, AL USA.
[Adams, Elizabeth; Fox, Lawrence; Purdue, Lynette; Masih, Reena] NIH, Bethesda, MD 20892 USA.
[Marshak, Ann; Mildvan, Donna] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA.
[Schlesinger, Sarah J.] Rockefeller Univ, New York, NY USA.
[Marovich, Mary A.] Walter Reed Army Inst, Silver Spring, MD 20910 USA.
[Jacobson, Jeffrey M.] Drexel Univ, Coll Med, Philadelphia, PA USA.
RP Gandhi, RT (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRJ 504, Boston, MA 02114 USA.
EM rgandhi@partners.org
FU NIAID NIH HHS [AI38855, AI38858, AI68634, AI68636, R01 AI066992, R01
AI066992-04, R37 AI044628, R37 AI044628-08, U01 AI038855, U01 AI038858,
U01 AI068634, U01 AI068634-01, U01 AI068636, U01 AI068636-01, U01
AI069472, U01 AI069472-01, UM1 AI068634, UM1 AI068636]; PHS HHS
[A146370, AIO69472]
NR 34
TC 48
Z9 52
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD OCT 9
PY 2009
VL 27
IS 43
BP 6088
EP 6094
DI 10.1016/j.vaccine.2009.05.016
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 511MW
UT WOS:000271170500023
PM 19450647
ER
PT J
AU Blotta, S
Tassone, P
Prabhala, RH
Tagliaferri, P
Cervi, D
Amin, S
Jakubikova, J
Tai, YT
Podar, K
Mitsiades, CS
Zullo, A
Franco, B
Anderson, KC
Munshi, NC
AF Blotta, Simona
Tassone, Pierfrancesco
Prabhala, Rao H.
Tagliaferri, Piersandro
Cervi, David
Amin, Samir
Jakubikova, Jana
Tai, Yu-Tzu
Podar, Klaus
Mitsiades, Constantine S.
Zullo, Alessandro
Franco, Brunella
Anderson, Kenneth C.
Munshi, Nikhil C.
TI Identification of novel antigens with induced immune response in
monoclonal gammopathy of undetermined significance
SO BLOOD
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; MULTIPLE-MYELOMA CELLS; CLONAL PLASMA-CELLS;
PRIMARY CILIA; BONE-MARROW; LONG-TERM; EXPRESSION; CANCER; PROGNOSIS;
PROTEIN
AB The transformation from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) is thought to be associated with changes in immune processes. We have therefore used serologic analysis of recombinant cDNA expression library to screen the sera of MGUS patients to identify tumor-associated antigens. A total of 10 antigens were identified, with specific antibody responses in MGUS. Responses appeared to be directed against intracellular proteins involved in cellular functions, such as apoptosis (SON, IFT57/HIPPI), DNA and RNA binding (ZNF292, GPATCH4), signal transduction regulators (AKAP11), transcriptional corepressor (IRF2BP2), developmental proteins (OFD1), and proteins of the ubiquitin-proteasome pathway (PSMC1). Importantly, the gene responsible for the oral-facial-digital type I syndrome (OFD1) had response in 6 of 29 (20.6%) MGUS patients but 0 of 11 newly diagnosed MM patients. Interestingly, 3 of 11 (27.2%) MM patients after autologous stem cell transplantations showed responses to OFD1. We have confirmed T-cell responses against OFD1 in MGUS and observed down-regulation of GLI1/PTCH1 and p-beta-catenin after OFD1 knock-down with specific siRNA, suggesting its functional role in the regulation of Hh and Wnt pathways. These findings demonstrate OFD1 as an important immune target and highlight its possible role in signal transduction and tumorigenesis in MGUS and MM. (Blood. 2009; 114: 3276-3284)
C1 [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA.
[Blotta, Simona; Prabhala, Rao H.; Cervi, David; Amin, Samir; Jakubikova, Jana; Tai, Yu-Tzu; Podar, Klaus; Mitsiades, Constantine S.; Anderson, Kenneth C.; Munshi, Nikhil C.] Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA.
[Blotta, Simona; Prabhala, Rao H.; Amin, Samir; Munshi, Nikhil C.] Harvard Univ, Sch Med, Vet Adm Boston Healthcare Syst, Boston, MA 02115 USA.
[Blotta, Simona; Tassone, Pierfrancesco; Tagliaferri, Piersandro] Univ Magna Graecia & Canc Ctr, Catanzaro, Italy.
[Zullo, Alessandro; Franco, Brunella] Telethon Inst Genet & Med, Naples, Italy.
[Franco, Brunella] Univ Naples Federico 2, Med Genet Dept Pediat, Naples, Italy.
RP Munshi, NC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St,M1B28, Boston, MA 02115 USA.
EM Nikhil_Munshi@dfci.harvard.edu
OI FRANCO, Brunella/0000-0001-5588-4569; Amin, Samir/0000-0002-3207-9505
FU Specialized Program of Research Excellence; National Institutes of
Health (NIH) [P50CA-100707, RO1-129494, PO1-78378]; Career Development
Award; Italian Telethon Foundation; Italian Association for Cancer
Research, Milan, Italy; Department of Veterans Affairs; Leukemia &
Lymphoma Society Scholar; Lebow Fund to Cure Myeloma
FX This work was supported by the Specialized Program of Research
Excellence in Myeloma, National Institutes of Health (NIH; grant
P50CA-100707), a Career Development Award (S. B.), the Italian Telethon
Foundation (B. F.), the Italian Association for Cancer Research, Milan,
Italy (P. Tassone), the Department of Veterans Affairs merit review
award, and Leukemia & Lymphoma Society Scholar in Translational Research
Award and NIH (grant RO1-129494; N.C.M.), NIH grants P50CA-100707 and
PO1-78378 (N.C.M., K. C. A.), and the Lebow Fund to Cure Myeloma (K. C.
A.).
NR 51
TC 20
Z9 21
U1 0
U2 5
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 8
PY 2009
VL 114
IS 15
BP 3276
EP 3284
DI 10.1182/blood-2009-04-219436
PG 9
WC Hematology
SC Hematology
GA 504DW
UT WOS:000270595700020
PM 19587378
ER
PT J
AU Zhao, BQ
Chauhan, AK
Canault, M
Patten, IS
Yang, JJ
Dockal, M
Scheiflinger, F
Wagner, DD
AF Zhao, Bing-Qiao
Chauhan, Anil K.
Canault, Matthias
Patten, Ian S.
Yang, Janie J.
Dockal, Michael
Scheiflinger, Friedrich
Wagner, Denisa D.
TI vonWillebrand factor-cleaving protease ADAMTS13 reduces ischemic brain
injury in experimental stroke
SO BLOOD
LA English
DT Article
ID VON-WILLEBRAND-FACTOR; THROMBOTIC THROMBOCYTOPENIC PURPURA; MOUSE MODEL;
P-SELECTIN; INFLAMMATION; DISEASE; MICE; HEMOSTASIS; HEMORRHAGE;
FIBRINOGEN
AB Stroke is a leading cause of death and disability. The only therapy available is recombinant tissue plasminogen activator, but side effects limit its use. Platelets play a crucial role during stroke, and the inflammatory reaction promotes neurodegeneration. von Willebrand factor (VWF), an adhesion molecule for platelets, is elevated in patients with acute stroke. The activity of VWF is modulated by ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type I repeats-13) that cleaves VWF to smaller less-active forms. We recently documented that ADAMTS13 negatively regulates both thrombosis and inflammation. We report that deficiency or reduction of VWF reduces infarct volume up to 2-fold after focal cerebral ischemia in mice, thus showing the importance of VWF in stroke injury. In contrast, ADAMTS13 deficiency results in larger infarctions, but only in mice that have VWF. Importantly, infusion of a high dose of recombinant human ADAMTS13 into a wild-type mouse immediately before reperfusion reduces infarct volume and improves functional outcome without producing cerebral hemorrhage. Furthermore, recombinant ADAMTS13 did not enhance bleeding in a hemorrhagic stroke model. Our findings show the importance of VWF in regulating infarction and suggest that recombinant ADAMTS13 could be considered as a new therapeutic agent for prevention and/or treatment of stroke. (Blood. 2009; 114: 3329-3334)
C1 [Zhao, Bing-Qiao; Chauhan, Anil K.; Canault, Matthias; Patten, Ian S.; Yang, Janie J.; Wagner, Denisa D.] Immune Dis Inst, Boston, MA 02115 USA.
[Zhao, Bing-Qiao; Chauhan, Anil K.; Canault, Matthias; Patten, Ian S.; Yang, Janie J.; Wagner, Denisa D.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Zhao, Bing-Qiao; Chauhan, Anil K.; Canault, Matthias; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Dockal, Michael; Scheiflinger, Friedrich] Baxter Biosci, Vienna, Austria.
RP Wagner, DD (reprint author), Immune Dis Inst, 3 Blackfan Cir, Boston, MA 02115 USA.
EM wagner@idi.harvard.edu
RI Canault, Matthias/H-5128-2013
OI Canault, Matthias/0000-0002-7880-5250
FU NHLBI NIH HHS [R01 HL041002, R37 HL041002]
NR 34
TC 110
Z9 115
U1 2
U2 7
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 8
PY 2009
VL 114
IS 15
BP 3329
EP 3334
DI 10.1182/blood-2009-03-213264
PG 6
WC Hematology
SC Hematology
GA 504DW
UT WOS:000270595700027
PM 19687510
ER
PT J
AU Montagut, C
Settleman, J
AF Montagut, Clara
Settleman, Jeff
TI Targeting the RAF-MEK-ERK pathway in cancer therapy
SO CANCER LETTERS
LA English
DT Review
DE RAF kinase; MEK kinase; Selective kinase inhibitors; Cancer
ID SIGNAL-REGULATED KINASE; REFRACTORY SOLID TUMORS; ENDOTHELIAL
GROWTH-FACTOR; RENAL-CELL CARCINOMA; RANDOMIZED DISCONTINUATION TRIAL;
INHIBITOR AZD6244 ARRY-142886; FACTOR RECEPTOR INHIBITOR; DAYS ON/7
DAYS; B-RAF; PHASE-I
AB The clinical success of selective kinase inhibitors, such as imatinib and erlotinib, as therapeutic agents for several human cancers has prompted substantial interest in the further development and clinical testing of such inhibitors for a wide variety of malignancies. While much of this effort has been focused on the receptor tyrosine kinases, including EGFR, HER2, PDGF receptor, c-KIT, and MET, inhibitors of serine/threonine kinases are also beginning to emerge within discovery pipelines. Among these kinases, the RAF and MEK kinases have received substantial attention, owing largely to the relatively high frequency of activating mutations of RAS (similar to 20% of all human cancers), an upstream activator of the well established RAF-MEK-ERK signaling cascade, as well as frequent activating mutations in the BRAF kinase (similar to 7% of all human cancers). Here, we summarize the current state of development of kinase inhibitors directed at this signaling pathway, a few of which have already demonstrating favorable toxicity profiles as well as promising activity in early phase clinical studies. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Settleman, Jeff] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Settleman, Jeff] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Montagut, Clara] Hosp Mar IMIM, Dept Med Oncol, Barcelona 08003, Spain.
[Montagut, Clara] Hosp Mar IMIM, Canc Res Program, Barcelona 08003, Spain.
RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA.
EM settleman@helix.mgh.harvard.edu
FU RTICC [06/0020/0109]
FX C.M. has been supported by RTICC 06/0020/0109 and Fundacio Cellex
(Barcelona).
NR 75
TC 221
Z9 233
U1 5
U2 33
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD OCT 8
PY 2009
VL 283
IS 2
BP 125
EP 134
DI 10.1016/j.canlet.2009.01.022
PG 10
WC Oncology
SC Oncology
GA 498QR
UT WOS:000270157800002
PM 19217204
ER
PT J
AU Thomas, DL
Thio, CL
Martin, MP
Qi, Y
Ge, D
O'hUigin, C
Kidd, J
Kidd, K
Khakoo, SI
Alexander, G
Goedert, JJ
Kirk, GD
Donfield, SM
Rosen, HR
Tobler, LH
Busch, MP
McHutchison, JG
Goldstein, DB
Carrington, M
AF Thomas, David L.
Thio, Chloe L.
Martin, Maureen P.
Qi, Ying
Ge, Dongliang
O'hUigin, Colm
Kidd, Judith
Kidd, Kenneth
Khakoo, Salim I.
Alexander, Graeme
Goedert, James J.
Kirk, Gregory D.
Donfield, Sharyne M.
Rosen, Hugo R.
Tobler, Leslie H.
Busch, Michael P.
McHutchison, John G.
Goldstein, David B.
Carrington, Mary
TI Genetic variation in IL28B and spontaneous clearance of hepatitis C
virus
SO NATURE
LA English
DT Article
ID NATURAL-HISTORY; INFECTION; HEMOPHILIA; ALPHA-2A; FAMILY; HOST
AB Hepatitis C virus (HCV) infection is the most common bloodborne infection in the United States, with estimates of 4 million HCV-infected individuals in the United States and 170 million worldwide(1). Most (70-80%) HCV infections persist and about 30% of individuals with persistent infection develop chronic liver disease, including cirrhosis and hepatocellular carcinoma(2). Epidemiological, viral and host factors have been associated with the differences in HCV clearance or persistence, and studies have demonstrated that a strong host immune response against HCV favours viral clearance(3,4). Thus, variation in genes involved in the immune response may contribute to the ability to clear the virus. In a recent genome-wide association study, a single nucleotide polymorphism (rs12979860) 3 kilobases upstream of the IL28B gene, which encodes the type III interferon IFN-lambda 3, was shown to associate strongly with more than a twofold difference in response to HCV drug treatment(5). To determine the potential effect of rs12979860 variation on outcome to HCV infection in a natural history setting, we genotyped this variant in HCV cohorts comprised of individuals who spontaneously cleared the virus (n = 388) or had persistent infection (n = 620). We show that the C/C genotype strongly enhances resolution of HCV infection among individuals of both European and African ancestry. To our knowledge, this is the strongest and most significant genetic effect associated with natural clearance of HCV, and these results implicate a primary role for IL28B in resolution of HCV infection.
C1 [Martin, Maureen P.; Qi, Ying; O'hUigin, Colm; Carrington, Mary] NCI Frederick, SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Thomas, David L.; Thio, Chloe L.] Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21205 USA.
[Martin, Maureen P.; Qi, Ying; O'hUigin, Colm; Carrington, Mary] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA.
[Martin, Maureen P.; Qi, Ying; O'hUigin, Colm; Carrington, Mary] Harvard Univ, Boston, MA 02114 USA.
[Ge, Dongliang; Goldstein, David B.] Duke Univ, Inst Genome Sci & Policy, Ctr Human Genome Variat, Durham, NC 27708 USA.
[Kidd, Judith; Kidd, Kenneth] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA.
[Alexander, Graeme] Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England.
[Khakoo, Salim I.] Univ London Imperial Coll Sci Technol & Med, Div Med, London W2 1NY, England.
[Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Kirk, Gregory D.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Donfield, Sharyne M.] Rho Inc, Chapel Hill, NC 27517 USA.
[Rosen, Hugo R.] Univ Colorado, Hlth Sci Ctr, Div Gastroenterol & Hepatol, Aurora, CO 80045 USA.
[Tobler, Leslie H.] Blood Syst Res Inst, San Francisco, CA 94118 USA.
[Busch, Michael P.] Duke Univ, Duke Clin Res Inst, Durham, NC 27705 USA.
[McHutchison, John G.] Duke Univ, Sch Med, Div Gastroenterol, Durham, NC 27705 USA.
RP Carrington, M (reprint author), NCI Frederick, SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA.
EM carringm@mail.nih.gov
RI Ge, Dongliang/A-2073-2010;
OI Khakoo, Salim/0000-0002-4057-9091
FU National Cancer Institute; National Institutes of Health
[HHSN261200800001E, R01DA013324, R01DA004334, R01HL076902, R01DK60590,
R01HD41224]; Wellcome Trust Senior Clinical Fellow
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract number 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. This
Research was supported in part by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. This
research was supported by NIH grants R01DA013324 ( D. L. T.),
R01DA004334 ( G. D. K.), R01HL076902 ( M. P. B.), R01DK60590 ( H. R. R.)
and R01HD41224 ( S. M. D.). S. I. K. is a Wellcome Trust Senior Clinical
Fellow.
NR 24
TC 1275
Z9 1331
U1 4
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 8
PY 2009
VL 461
IS 7265
BP 798
EP U52
DI 10.1038/nature08463
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 503OR
UT WOS:000270547500037
PM 19759533
ER
PT J
AU Weiss, LA
Arking, DE
AF Weiss, Lauren A.
Arking, Dan E.
CA Johns Hopkins & Autism Consortium
TI A genome-wide linkage and association scan reveals novel loci for autism
SO NATURE
LA English
DT Article
ID SPECTRUM DISORDERS; WILLIAMS-SYNDROME; GENETIC VARIANT; COMMON DISEASES;
EXPRESSION; GTF2IRD1; DEFICITS; MARKERS; CNTNAP2; CORTEX
AB Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success(1). Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families ( 1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 ( between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 x 10(-7)). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants.
C1 [Weiss, Lauren A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Weiss, Lauren A.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Weiss, Lauren A.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Arking, Dan E.] Johns Hopkins Univ, Ctr Complex Dis Genom, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
RP Weiss, LA (reprint author), Univ Calif San Francisco, Dept Psychiat, Inst Human Genet, Ctr Neurobiol & Psychiat, San Francisco, CA 94143 USA.
RI Vicente, Astrid/F-8692-2014; Monaco, Anthony/A-4495-2010; Altshuler,
David/A-4476-2009; Haines, Jonathan/C-3374-2012; Howe,
Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013; Pickles,
Andrew/A-9625-2011; MOTTRON, Laurent/H-2020-2013; Sutcliffe,
James/C-1348-2012; Bolton, Patrick/E-8501-2010; Bailey,
Anthony/J-2860-2014; Tansey, Katherine/B-1033-2013; Paterson,
Andrew/A-4088-2011;
OI Oliveira, Guiomar Goncalves/0000-0003-4031-3880; West,
Andrew/0000-0002-3034-4061; Buxbaum, Joseph/0000-0001-8898-8313; Anney,
Richard/0000-0002-6083-407X; Oliveira, Guiomar/0000-0002-7049-1277;
Betancur, Catalina/0000-0002-3327-4804; Fombonne,
Eric/0000-0002-8605-3538; McNeil, Kirsty/0000-0003-0437-3608; Correia,
Catarina/0000-0001-5481-2010; Vicente, Astrid/0000-0001-7134-8037;
Gallagher, Louise/0000-0001-9462-2836; Green,
Jonathan/0000-0002-0143-181X; Wijsman, Ellen/0000-0002-2725-6669;
Nurnberger, John/0000-0002-7674-1767; Gill, Michael/0000-0003-0206-5337;
Monaco, Anthony/0000-0001-7480-3197; Altshuler,
David/0000-0002-7250-4107; Scherer, Stephen /0000-0002-8326-1999;
Pickles, Andrew/0000-0003-1283-0346; Sutcliffe,
James/0000-0001-5200-6007; Bolton, Patrick/0000-0002-5270-6262; Bailey,
Anthony/0000-0003-4257-972X; Tansey, Katherine/0000-0002-9663-3376;
Paterson, Andrew/0000-0002-9169-118X; R Magalhaes,
Tiago/0000-0002-5528-2119
FU National Center for Research Resources [U54 RR020278]; National
Institutes of Mental Health [MH60007, MH081754]; Simons Foundation;
Autism Consortium of Boston; NIMH [1R01 MH083565, 1K23MH080954]; Nancy
Lurie Marks ( NLM) Family Foundation; National Institute of Health
[MH52708, MH39437, MH00219, MH00980, MH6454, MH61009, MH55135, MH55284,
HD055782, NS042165]; National Health Medical Research Council [0034328];
Scottish Rite; Spunk Fund, Inc.; Rebecca and Solomon Baker Fund; APEX
Foundation; National Alliance for Research in Schizophrenia and
Affective Disorders ( NARSAD),; Nancy Pritzker Laboratory; Cure Autism
Now Foundation; Fundacao Calouste Gulbenkian; INSERM, Fondation de
France, Fondation Orange; Fondation pour la Recherche Medicale; Swedish
Science Council; The Seaver Foundation; The Children's Medical &
Research Foundation; Our Lady's Children's Hospital, Crumlin, Ireland;
The Medical Research Council ( MRC)
FX The Autism Genome Project ( AGP) work was supported by the following
grants: ( 1) The Hilibrand Foundation ( Principal Investigaor Joachim F.
Hallmayer); ( 2) Autism Speaks ( for the AGP); ( 3) grants from the
National Institutes of Health (NIH) MH61009 ( James S. Sutcliffe),
MH55135 ( Susan E. Folstein), MH55284 ( Joseph Piven), HD055782 ( Ellen
M. Wijsman), NS042165 (Joachim F. Hallmayer); ( 4) Fundacao para a
Ciencia e Tecnologia (POCTI/39636/ESP/2001) Fundacao Calouste Gulbenkian
( Astrid Vincente); ( 5) INSERM, Fondation de France, Fondation Orange,
Fondation pour la Recherche Medicale ( Catalina Betancur, Marion
Leboyer), and the Swedish Science Council ( Christopher Gillberg); ( 6)
The Seaver Foundation ( Joseph D. Buxbaum); ( 7) The Children's Medical
& Research Foundation ( CMRF), Our Lady's Children's Hospital, Crumlin,
Ireland (Sean Ennis); ( 8) The Medical Research Council ( MRC) ( Anthony
P. Monaco, Anthony J. Bailey). Fresh-frozen brain tissue samples were
obtained through the Autism Tissue Program and the Harvard Brain Bank.
NR 42
TC 323
Z9 335
U1 1
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 8
PY 2009
VL 461
IS 7265
BP 802
EP U62
DI 10.1038/nature08490
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 503OR
UT WOS:000270547500038
PM 19812673
ER
PT J
AU Okike, K
Kocher, MS
Wei, EX
Mehlman, CT
Bhandari, M
AF Okike, Kanu
Kocher, Mininder S.
Wei, Erin X.
Mehlman, Charles T.
Bhandari, Mohit
TI Accuracy of Conflict-of-Interest Disclosures Reported by Physicians
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID CLINICAL-TRIALS; FUNDING SOURCE; PHARMACEUTICAL-INDUSTRY; ORTHOPEDIC
RESEARCH; DRUG TRIALS; ASSOCIATION; SPONSORSHIP; OUTCOMES; CONCLUSIONS;
IMPACT
AB Background
The recent public reporting of payments made to physicians by manufacturers of orthopedic devices provides an opportunity to assess the accuracy of physicians' conflict-of-interest disclosures.
Methods
We analyzed the reports of payments made to physicians by five manufacturers of total hip and knee prostheses in 2007. For each payment recipient who was an author of a presentation or served as a committee member or board member at the 2008 annual meeting of the American Academy of Orthopaedic Surgeons, the disclosure statement was reviewed to determine whether the payment had been disclosed. To ascertain the reasons for nondisclosure, a survey was administered to physicians who had received payments that were not disclosed.
Results
The overall rate of disclosure was 71.2% (245 of 344 payments). For payments that were directly related to the topic of the presentation at the meeting, the rate was 79.3% (165 of 208); for payments that were indirectly related, the rate was 50.0% (16 of 32); and for payments that were unrelated, the rate was 49.2% (29 of 59) (P = 0.008). In the multivariate analysis, payments were also more likely to have been disclosed if they exceeded $10,000 (P<0.001), were directed toward an individual physician rather than a company or organization (P=0.04), or included an in-kind component (P=0.002). Among the 36 physicians who responded to the survey regarding reasons for nondisclosure (response rate, 39.6%), the reasons most commonly given for nondisclosure were that the payment was unrelated to the topic of presentation at the annual meeting (38.9% of respondents) and that the physician had misunderstood the disclosure requirements (13.9%); 11.1% reported that the payment had been disclosed but was mistakenly omitted from the program.
Conclusions
In this study of self-reported conflict-of-interest disclosure by physicians at a large annual meeting, the rate of disclosure was 79.3% for directly related payments and 50.0% for indirectly related payments.
C1 [Okike, Kanu] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA.
[Okike, Kanu] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA.
[Kocher, Mininder S.] Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA.
[Kocher, Mininder S.; Wei, Erin X.] Harvard Univ, Sch Med, Boston, MA USA.
[Mehlman, Charles T.] Univ Cincinnati, Med Ctr, Coll Med,Cincinnati Childrens Hosp, Div Pediat Orthoped Surg, Cincinnati, OH 45267 USA.
[Bhandari, Mohit] McMaster Univ, Hamilton Gen Hosp, Dept Orthopaed Surg, Hamilton, ON, Canada.
RP Okike, K (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, 55 Fruit St, Boston, MA 02114 USA.
EM okike@post.harvard.edu
OI Okike, Kanu/0000-0001-9310-9969
FU ConMed Linvatec; DePuy; Smith and Nephew; Stryker; Zimmer
FX Dr. Kocher reports receiving grant support from ConMed Linvatec and
serving as a consultant for ConMed Linvatec, Covidien, EBI ( a
subsidiary of Biomet), and Smith and Nephew; Dr. Mehlman, receiving
grant support from Abbott Spine ( now part of Zimmer), DePuy Spine,
Globus Medical, Medtronic, and Synthes; and Dr. Bhandari, receiving
grant support from DePuy, Smith and Nephew, Stryker, and Zimmer and
serving as a consultant for Amgen, Osteogenix, Pfizer, and Zelos
Therapeutics. No other potential conflict of interest relevant to this
article was reported.
NR 40
TC 78
Z9 79
U1 0
U2 3
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 8
PY 2009
VL 361
IS 15
BP 1466
EP 1474
DI 10.1056/NEJMsa0807160
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 503MU
UT WOS:000270540000008
PM 19812403
ER
PT J
AU Alam, HB
Fricchione, GL
Guimaraes, ASR
Zukerberg, LR
AF Alam, Hasan B.
Fricchione, Gregory L.
Guimaraes, Alexander S. R.
Zukerberg, Lawrence R.
TI A Man with Abdominal Distention and Shock Acute megacolon (Ogilvie's
syndrome), with extensive mucosal ischemic necrosis, due to
clozapine-induced gastrointestinal hypomotility.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID SEPTIC SHOCK; INTRAABDOMINAL HYPERTENSION; EARLY COAGULOPATHY; TOXIC
MEGACOLON; CRITICALLY-ILL; DAMAGE-CONTROL; SEVERE SEPSIS;
CHLORPROMAZINE; MANAGEMENT; THERAPY
C1 [Alam, Hasan B.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Fricchione, Gregory L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Guimaraes, Alexander S. R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Alam, Hasan B.] Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA.
[Fricchione, Gregory L.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA.
[Guimaraes, Alexander S. R.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA.
[Zukerberg, Lawrence R.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA.
RP Alam, HB (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
NR 30
TC 7
Z9 7
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 8
PY 2009
VL 361
IS 15
BP 1487
EP 1496
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 503MU
UT WOS:000270540000013
PM 19812406
ER
PT J
AU Lieberman, J
AF Lieberman, Judy
TI Micromanaging Cancer
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID LIVER-CANCER; MICRORNAS
C1 [Lieberman, Judy] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA.
[Lieberman, Judy] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP Lieberman, J (reprint author), Childrens Hosp, Immune Dis Inst, 300 Longwood Ave, Boston, MA 02115 USA.
RI Lieberman, Judy/A-2717-2015
NR 11
TC 7
Z9 7
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 8
PY 2009
VL 361
IS 15
BP 1500
EP 1501
DI 10.1056/NEJMe0906321
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 503MU
UT WOS:000270540000015
PM 19812408
ER
PT J
AU Chan, SY
Zhang, YY
Hemann, C
Mahoney, CE
Zweier, JL
Loscalzo, J
AF Chan, Stephen Y.
Zhang, Ying-Yi
Hemann, Craig
Mahoney, Christopher E.
Zweier, Jay L.
Loscalzo, Joseph
TI MicroRNA-210 Controls Mitochondrial Metabolism during Hypoxia by
Repressing the Iron-Sulfur Cluster Assembly Proteins ISCU1/2
SO CELL METABOLISM
LA English
DT Article
ID GENE-EXPRESSION; CELLS; OXYGEN; HIF-1; INACTIVATION; RESPIRATION;
BIOGENESIS; MECHANISMS; FRATAXIN; KINASE
AB Repression of mitochondrial respiration represents an evolutionarily ancient cellular adaptation to hypoxia and profoundly influences cell survival and function; however, the underlying molecular mechanisms are incompletely understood. Primarily utilizing pulmonary arterial endothelial Cells as a representative hypoxic cell type, we identify the iron-sulfur cluster assembly proteins (ISCU1/2) as direct targets for repression by the hypoxia-induced microRNA-210 (miR-210). ISCU1/2 facilitate the assembly of iron-sulfur clusters, prosthetic groups that are critical for electron transport and mitochondrial oxidation-reduction reactions. Under in vivo conditions of upregulating miR-210 and repressing ISCU1/2, the integrity of iron-sulfur clusters is disrupted. In turn, by repressing ISCU1/2 during hypoxia, miR-210 decreases the activity of prototypical iron-sulfur proteins controlling mitochondrial metabolism, including Complex I and aconitase. Consequently, miR-210 represses mitochondrial respiration and associated downstream functions. These results identify important mechanistic connections among microRNA, iron-sulfur cluster biology, hypoxia, and mitochondrial function, with broad implications for cellular metabolism and adaptation to cellular stress.
C1 [Zhang, Ying-Yi; Mahoney, Christopher E.; Loscalzo, Joseph] Brigham & Womens Hosp, Div Cardiovasc Med, Dept Med, Boston, MA 02115 USA.
[Chan, Stephen Y.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Chan, Stephen Y.; Zhang, Ying-Yi; Mahoney, Christopher E.; Loscalzo, Joseph] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Hemann, Craig; Zweier, Jay L.] Ohio State Univ, Dept Med, Columbus, OH 43210 USA.
RP Loscalzo, J (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, Dept Med, Boston, MA 02115 USA.
EM jloscalzo@partners.org
OI Hemann, Craig/0000-0002-7380-4072
FU MGH Cardiology NIH-T32; AHA [0825906D]; National Institutes of Health
(NIH) [HL 61795, NO1 HV 28178, PO1 81587, U54 HL 70819]
FX This work was supported by MGH Cardiology NIH-T32 grant (S.Y.C.), AHA
grant 0825906D (S.Y.C.), and National Institutes of Health (NIH) grants
HL 61795, NO1 HV 28178, PO1 81587, and U54 HL 70819 (J.L. and Y.-Y.Z.).
We thank the Loscalzo laboratory and R. Liao for fruitful discussions;
N. Kelly (bioinformatics); W. Kaelin, J. Moslehi, and Y. Minamishima
(VHL WT and VHL-/- murine tissue); H. Ardehali (miR-210
expression vector); T. Rouault (ISCU expression vectors); V. Mootha
(technical aid in measuring oxygen consumption); S.K. Chan and J.W. Snow
(critical reading of the manuscript); and S. Tribuna (administrative
assistance).
NR 36
TC 234
Z9 249
U1 1
U2 24
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD OCT 7
PY 2009
VL 10
IS 4
BP 273
EP 284
DI 10.1016/j.cmet.2009.08.015
PG 12
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 510KE
UT WOS:000271086600007
PM 19808020
ER
PT J
AU Granot, Z
Swisa, A
Magenheim, J
Stolovich-Rain, M
Fujimoto, W
Manduchi, E
Miki, T
Lennerz, JK
Stoeckert, CJ
Meyuhas, O
Seino, S
Permutt, MA
Piwnica-Worms, H
Bardeesy, N
Dor, Y
AF Granot, Zvi
Swisa, Avital
Magenheim, Judith
Stolovich-Rain, Miri
Fujimoto, Wakako
Manduchi, Elisabetta
Miki, Takashi
Lennerz, Jochen K.
Stoeckert, Christian J., Jr.
Meyuhas, Oded
Seino, Susumu
Permutt, M. Alan
Piwnica-Worms, Helen
Bardeesy, Nabeel
Dor, Yuval
TI LKB1 Regulates Pancreatic beta Cell Size, Polarity, and Function
SO CELL METABOLISM
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; STIMULATED INSULIN-SECRETION; GENE-EXPRESSION;
GLUCOSE-HOMEOSTASIS; ENDOCRINE PANCREAS; LUMEN POLARITY; IN-VIVO; ISLET;
PATHWAY; ENERGY
AB Pancreatic beta cells, organized in the islets of Langerhans, sense glucose and secrete appropriate amounts of insulin. We have studied the roles of LKB1, a conserved kinase implicated in the control of cell polarity and energy metabolism, in adult beta cells. LKB1-deficient beta cells show a dramatic increase in insulin secretion in vivo. Histologically, LKB1-deficient beta cells have striking alterations in the localization of the nucleus and cilia relative to blood vessels, suggesting a shift from hepatocyte-like to columnar polarity. Additionally, LKB1 deficiency causes a 65% increase in beta cell volume. We show that distinct targets of LKB1 mediate these effects. LKB1 controls beta cell size, but not polarity, via the mTOR pathway. Conversely, the precise position of the beta cell nucleus, but not cell size, is controlled by the LKB1 target Par1b. Insulin secretion and content are restricted by LKB1, at least in part, via AMPK. These results expose a molecular mechanism, orchestrated by LKB1, for the coordinated maintenance of beta cell size, form, and function.
C1 [Granot, Zvi; Swisa, Avital; Magenheim, Judith; Stolovich-Rain, Miri; Dor, Yuval] Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel.
[Meyuhas, Oded] Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Biochem & Mol Biol, IL-91120 Jerusalem, Israel.
[Fujimoto, Wakako; Miki, Takashi; Seino, Susumu] Kobe Univ, Div Cellular & Mol Med, Grad Sch Med, Kobe, Hyogo 6500017, Japan.
[Manduchi, Elisabetta; Stoeckert, Christian J., Jr.] Univ Penn, Sch Med, Ctr Bioinformat, Philadelphia, PA 19104 USA.
[Manduchi, Elisabetta; Stoeckert, Christian J., Jr.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
[Lennerz, Jochen K.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Permutt, M. Alan] Washington Univ, Sch Med, Div Endocrinol Metab & Lipid Res, St Louis, MO 63110 USA.
[Piwnica-Worms, Helen] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA.
[Piwnica-Worms, Helen] Washington Univ, Sch Med, Dept Cell Biol & Physiol & Med, St Louis, MO 63110 USA.
[Bardeesy, Nabeel] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Dept Med, Boston, MA 02114 USA.
RP Dor, Y (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel.
EM yuvald@ekmd.huji.ac.il
RI Dor, Yuval/C-2405-2011; Piwnica-Worms, Helen/C-5214-2012
FU JDRF; NIH (BCBC); ISF; ICRF (Barbara Goodman PC-RCDA); European Union;
NIH [R37 DK16746]; Core Research for Evolutional Science and Technology
(CREST)
FX We are grateful to Rachel Hertz and Jacob Bar-Tana for providing advice
and generously sharing unpublished reagents. We thank Cris Welling for
technical assistance; Morris Birnbaum for providing RIP-AKT mice;
Bangyan Stiles for providing slides of PTEN mutant mice; Ittai
Ben-Porath, Hadas Masuri, and Rotem Karni for assistance with viral
infections; and Chris Wright for the gift of anti pdx1 antibodies. Y.
Dor was supported by grants from JDRF, NIH (BCBC), ISF, ICRF (Barbara
Goodman PC-RCDA), the Sixth Framework Programme of the European Union,
and the JDRF Center for beta Cell Therapy in Diabetes. This work was
supported in part by an NIH grant (R37 DK16746, to M.A. Permutt) and the
Core Research for Evolutional Science and Technology (CREST) to S.
Seino. The Washington University DRTC (NIH P60 DK20579) is acknowledged
for assistance from the Immunoassay Core. C. Stoeckert and E. Manduchi
were supported by JDRF and NIH (BCBC).
NR 57
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Z9 81
U1 1
U2 15
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD OCT 7
PY 2009
VL 10
IS 4
BP 296
EP 308
DI 10.1016/j.cmet.2009.08.010
PG 13
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 510KE
UT WOS:000271086600009
PM 19808022
ER
PT J
AU Lau, NC
Ohsumi, T
Borowsky, M
Kingston, RE
Blower, MD
AF Lau, Nelson C.
Ohsumi, Toshiro
Borowsky, Mark
Kingston, Robert E.
Blower, Michael D.
TI Systematic and single cell analysis of Xenopus Piwi-interacting RNAs and
Xiwi
SO EMBO JOURNAL
LA English
DT Article
DE piRNA; Piwi; Xenopus
ID SMALL INTERFERING RNAS; DROSOPHILA-MELANOGASTER; EGG EXTRACTS;
ENDOGENOUS SIRNAS; MITOTIC SPINDLE; DNA METHYLATION; PIRNA COMPLEX;
MOUSE OOCYTES; C-ELEGANS; GERMLINE
AB Piwi proteins and Piwi-interacting RNAs (piRNAs) are essential for germ cell development, but analysis of the molecular mechanisms of these ribonucleoproteins remains challenging in most animal germ cells. To address this challenge, we systematically characterized Xiwi, a Xenopus Piwi homologue, and piRNAs from Xenopus eggs and oocytes. We used the large size of Xenopus eggs to analyze small RNAs at the single cell level, and find abundant piRNAs and large piRNA clusters in the Xenopus tropicalis genome, some of which resemble the Drosophila piRNA-generating flamenco locus. Although most piRNA clusters are expressed simultaneously in an egg, individual frogs show distinct profiles of cluster expression. Xiwi is associated with microtubules and the meiotic spindle, and is localized to the germ plasm-a cytoplasmic determinant of germ cell formation. Xiwi associates with translational regulators in an RNA-dependent manner, but Xenopus tudor interacts with Xiwi independently of RNA. Our study adds insight to piRNA transcription regulation by showing that individual animals can have differential piRNA expression profiles. We suggest that in addition to regulating transposable elements, Xiwi may function in specifying RNA localization in vertebrate oocytes. The EMBO Journal (2009) 28, 2945-2958. doi: 10.1038/emboj.2009.237; Published online 27 August 2009
C1 [Lau, Nelson C.; Ohsumi, Toshiro; Borowsky, Mark; Kingston, Robert E.; Blower, Michael D.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02163 USA.
[Lau, Nelson C.; Ohsumi, Toshiro; Borowsky, Mark; Kingston, Robert E.; Blower, Michael D.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
RP Blower, MD (reprint author), Harvard Univ, Sch Med, Dept Genet, 185 Cambridge St,CPZN 7250, Boston, MA 02163 USA.
EM blower@molbio.mgh.harvard.edu
FU Whitney foundation fellowship; NIH
FX Author Contributions: NCL and MDB designed and carried out the
experiments, TO and MB provided informatics and sequencing analysis, and
NCL, MDB, and REK wrote the paper. The small RNA sequencing data from
this paper are deposited in the Gene Expression Omnibus under the series
accession number GSE15556.
NR 57
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Z9 53
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD OCT 7
PY 2009
VL 28
IS 19
BP 2945
EP 2958
DI 10.1038/emboj.2009.237
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 503DY
UT WOS:000270514000009
PM 19713941
ER
PT J
AU Meyer-Luehmann, M
Mielke, M
Spires-Jones, TL
Stoothoff, W
Jones, P
Bacskai, BJ
Hyman, BT
AF Meyer-Luehmann, Melanie
Mielke, Matthew
Spires-Jones, Tara L.
Stoothoff, Will
Jones, Phill
Bacskai, Brian J.
Hyman, Bradley T.
TI A Reporter of Local Dendritic Translocation Shows Plaque-Related Loss of
Neural System Function in APP-Transgenic Mice
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID AMYLOID-BETA PLAQUES; ALZHEIMERS-DISEASE; PROTEIN-SYNTHESIS; MOUSE
MODEL; IN-VIVO; HIPPOCAMPAL-NEURONS; DISRUPTION; ABNORMALITIES; MEMORY;
EXPRESSION
AB Although neuronal communication is thought to be summated within local dendritic segments, no technique is currently available to monitor activity in vivo at this level of resolution. To overcome this challenge, we developed an optical reporter of neuronal activity using the coding sequence of Venus, flanked by short stretches of the 5'- and 3'-untranslated regions from calcium/calmodulin-dependent kinase II alpha (CAMKII alpha). This reporter takes advantage of the fact that CAMKII alpha mRNA is transported to the dendrite and locally translated in an activity-dependent manner. Using adeno-associated virus, we used this reporter to study neuronal activity in adult mice. Exposure of the mice to an enriched environment led to enhancement of Venus expression in dendritic segments of somatosensory cortex, demonstrating in vivo that dendritic mRNA translocation and local translation occur in response to physiologically relevant stimuli. We then used this system to examine the impact of Alzheimer-related local amyloid-beta deposits on neural system function to test the hypothesis that plaques are toxic. In APPswe/PS1dE9 (APP/PS1) mice, neurons close to plaques, and dendritic segments close to plaques, both showed diminished fluorescent intensity and therefore neuronal activity. In contrast to wild-type mice, fluorescent intensity in neurons near plaques in transgenic mice did not increase after environmental enrichment. These data indicate that neuronal activity in dendritic segments and neurons in the vicinity of a plaque is decreased compared with wild-type mice, supporting the idea that plaques are a focal lesion leading to impaired neural system function.
C1 [Meyer-Luehmann, Melanie; Mielke, Matthew; Spires-Jones, Tara L.; Stoothoff, Will; Jones, Phill; Bacskai, Brian J.; Hyman, Bradley T.] Harvard Univ, Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Dept Neurol,Med Sch,MassGen Inst Neurodegenerat D, Charlestown, MA 02129 USA.
[Meyer-Luehmann, Melanie] Univ Munich, Deutsch Zentrum Neurodegenerat Erkrankungen, D-80336 Munich, Germany.
[Meyer-Luehmann, Melanie] Univ Munich, Adolf Butenandt Inst Biochem, D-80336 Munich, Germany.
RP Hyman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Dept Neurol,Med Sch,MassGen Inst Neurodegenerat D, 114 16th St,Room 2009, Charlestown, MA 02129 USA.
EM bhyman@partners.org
OI Meyer-Luehmann, Melanie/0000-0003-3661-2220
FU National Institutes of Health [AG08487, EB000768]
FX This work was supported by National Institutes of Health Grants AG08487
(to B. T. H.) and EB000768 (to B. J. B.). Wethank Kathryn Bercury,
Hisatomo Kowa, Mirjam Koker, and Anne Thomas for technical help and Erin
Schuman for the gift of the CAMKII alpha GFP construct.
NR 23
TC 30
Z9 30
U1 0
U2 7
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD OCT 7
PY 2009
VL 29
IS 40
BP 12636
EP 12640
DI 10.1523/JNEUROSCI.1948-09.2009
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 503UX
UT WOS:000270567400028
PM 19812338
ER
PT J
AU Hedden, T
Van Dijk, KRA
Becker, JA
Mehta, A
Sperling, RA
Johnson, KA
Buckner, RL
AF Hedden, Trey
Van Dijk, Koene R. A.
Becker, J. Alex
Mehta, Angel
Sperling, Reisa A.
Johnson, Keith A.
Buckner, Randy L.
TI Disruption of Functional Connectivity in Clinically Normal Older Adults
Harboring Amyloid Burden
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; PITTSBURGH-COMPOUND-B; DEFAULT-MODE NETWORK;
PRECLINICAL ALZHEIMERS-DISEASE; RESTING-STATE NETWORKS; HUMAN BRAIN;
NONDEMENTED INDIVIDUALS; SENSORY STIMULATION; CINGULATE CORTEX; PET
AB Amyloid deposition is present in 20-50% of nondemented older adults yet the functional consequences remain unclear. The current study found that amyloid accumulation is correlated with functional disruption of the default network as measured by intrinsic activity correlations. Clinically normal participants (n = 38, aged 60-88 years) were characterized using (11)C-labeled Pittsburgh Compound B positron emission tomography imaging to estimate fibrillar amyloid burden and, separately, underwent functional magnetic resonance imaging (fMRI). The integrity of the default network was estimated by correlating rest-state fMRI time courses extracted from a priori regions including the posterior cingulate, lateral parietal, and medial prefrontal cortices. Clinically normal participants with high amyloid burden displayed significantly reduced functional correlations within the default network relative to participants with low amyloid burden. These reductions were also observed when amyloid burden was treated as a continuous, rather than a dichotomous, measure and when controlling for age and structural atrophy. Whole-brain analyses initiated by seeding the posterior cingulate cortex, a region of high amyloid burden in Alzheimer's disease, revealed significant disruption in the default network including functional disconnection of the hippocampal formation.
C1 [Hedden, Trey; Van Dijk, Koene R. A.; Mehta, Angel; Sperling, Reisa A.; Buckner, Randy L.] Massachusetts Gen Hosp East, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Hedden, Trey; Becker, J. Alex; Johnson, Keith A.; Buckner, Randy L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA.
[Sperling, Reisa A.; Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA.
[Buckner, Randy L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA.
[Hedden, Trey; Van Dijk, Koene R. A.; Mehta, Angel] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
[Hedden, Trey; Van Dijk, Koene R. A.; Mehta, Angel] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
[Buckner, Randy L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
[Sperling, Reisa A.; Johnson, Keith A.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Hedden, T (reprint author), Massachusetts Gen Hosp East, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA.
EM hedden@nmr.mgh.harvard.edu
RI Van Dijk, Koene/G-3317-2012
OI Van Dijk, Koene/0000-0001-6137-4282
FU National Institutes on Aging [AG-021910, AG-027435-S1]; Alzheimer
Disease Research Center [P50AG005134]; Howard Hughes Medical Institute;
Alzheimer's Association; Netherlands Organization for Scientific
Research
FX This research was supported by National Institutes on Aging Grants
AG-021910 and AG-027435-S1, Alzheimer Disease Research Center, Grant
P50AG005134, the Howard Hughes Medical Institute, and the Alzheimer's
Association. K. R. A. V. D. was supported by the Netherlands
Organization for Scientific Research. We thank Renee Poulin, Jeremy
Caramasin, and Meghan Frey for assistance during data collection, and
Tanveer Talukdar and Itamar Kahn for technical advice. The Athinoula A.
Martinos Center MRI Core provided assistance with MRI imaging, and the
Massachusetts General Hospital Molecular Imaging PET Core provided
assistance with amyloid imaging. Bill Klunk and Chet Mathis provided
assistance with PiB. Dorene Rentz and the Massachusetts Alzheimer's
Disease Research Center provided assistance with clinical and
neuropsychological characterization of the participants.
NR 78
TC 276
Z9 283
U1 2
U2 23
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD OCT 7
PY 2009
VL 29
IS 40
BP 12686
EP 12694
DI 10.1523/JNEUROSCI.3189-09.2009
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 503UX
UT WOS:000270567400033
PM 19812343
ER
PT J
AU Yamada, H
Penney, KL
Takahashi, H
Katoh, T
Yamano, Y
Yamakado, M
Kimura, T
Kuruma, H
Kamata, Y
Egawa, S
Freedman, ML
AF Yamada, Hiroki
Penney, Kathryn L.
Takahashi, Hiroyuki
Katoh, Takahiko
Yamano, Yuko
Yamakado, Minoru
Kimura, Takahiro
Kuruma, Hidetoshi
Kamata, Yuko
Egawa, Shin
Freedman, Matthew L.
TI Replication of Prostate Cancer Risk Loci in a Japanese Case-Control
Association Study
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; 8Q24; VARIANTS; SUSCEPTIBILITY; POPULATION
AB Two prostate cancer genome-wide scans in populations of European ancestry identified several genetic variants that are strongly associated with prostate cancer risk. The effect of these risk variants and their cumulative effect in other populations are unknown.
We evaluated the association of 23 risk single-nucleotide polymorphisms (SNPs) with prostate cancer risk and clinical covariates (Gleason score, tumor aggressiveness, and age at diagnosis) in men of Japanese ancestry (311 case subjects and 1035 control subjects) using unconditional logistic regression. We also used logistic regression to test the association between increasing numbers of independently associated risk alleles and the risk of prostate cancer, prostate cancer aggressiveness, and age at diagnosis. All statistical tests were two-sided.
Seven of the 23 SNPs (five independent loci) were associated with prostate cancer risk (P values ranged from .0084 to 2.3 x 10(-8) and effect sizes [estimated as odds ratios, ORs] ranged from 1.35 to 1.82). None of the seven SNPs was associated with Gleason score or aggressive disease. rs6983561 and rs4430796 were associated with age at diagnosis (Ps = .0188 and .0339, respectively). Men with six or more risk alleles (27% of case patients and 11% of control subjects) had a higher risk of prostate cancer than men with two or fewer risk alleles (7% of case patients and 20% of control subjects) (OR = 6.22, P = 1.5 x 10(-12)).
These results highlight the critical importance of considering ancestry in understanding how risk alleles influence disease and suggest that risk estimates and variants differ across populations. It is important to perform studies in multiple ancestral populations so that the composite genetic architecture of prostate cancer can be rigorously addressed.
C1 [Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Yamada, Hiroki; Kimura, Takahiro; Kuruma, Hidetoshi; Kamata, Yuko; Egawa, Shin] Jikei Univ, Sch Med, Dept Urol, Tokyo, Japan.
[Penney, Kathryn L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Takahashi, Hiroyuki] Jikei Univ, Dept Pathol, Sch Med, Tokyo 105, Japan.
[Katoh, Takahiko] Kumamoto Univ, Grad Sch Med Sci, Dept Publ Hlth, Kumamoto, Japan.
[Yamano, Yuko] Showa Univ, Sch Med, Dept Hyg & Prevent Med, Tokyo 142, Japan.
[Yamakado, Minoru] Mitsui Mem Hosp, Ctr Multiphas Hlth Testing & Serv, Dept Hlth Care, Tokyo 101, Japan.
RP Freedman, ML (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM s-egpro@jikei.ac.jp; freedman@broad.mit.edu
NR 14
TC 47
Z9 52
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 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD OCT 7
PY 2009
VL 101
IS 19
BP 1330
EP 1336
DI 10.1093/jnci/djp287
PG 7
WC Oncology
SC Oncology
GA 505QR
UT WOS:000270709900011
PM 19726753
ER
PT J
AU Riboldi, M
Sharp, GC
Baroni, G
Chen, GTY
AF Riboldi, M.
Sharp, G. C.
Baroni, G.
Chen, G. T. Y.
TI Four-dimensional targeting error analysis in image-guided radiotherapy
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID POINT-BASED REGISTRATION; INDUCED TUMOR MOTION; RADIATION-THERAPY;
LUNG-CANCER; COMPUTED-TOMOGRAPHY; IMRT OPTIMIZATION; ORGAN MOTION;
TRACKING; SYSTEM; ACCURACY
AB Image-guided therapy (IGT) involves acquisition and processing of biomedical images to actively guide medical interventions. The proliferation of IGT technologies has been particularly significant in image-guided radiotherapy (IGRT), as a way to increase the tumor targeting accuracy. When IGRT is applied to moving tumors, image guidance becomes challenging, as motion leads to increased uncertainty. Different strategies may be applied to mitigate the effects of motion: each technique is related to a different technological effort and complexity in treatment planning and delivery. The objective comparison of different motion mitigation strategies can be achieved by quantifying the residual uncertainties in tumor targeting, to be detected by means of IGRT technologies. Such quantification requires an extension of targeting error theory to a 4D space, where the 3D tumor trajectory as a function of time measured (4D Targeting Error, 4DTE). Accurate 4DTE analysis can be represented by a motion probability density function, describing the statistical fluctuations of tumor trajectory. We illustrate the application of 4DTE analysis through examples, including weekly variations in tumor trajectory as detected by 4DCT, respiratory gating via external surrogates and real-time tumor tracking.
C1 [Riboldi, M.; Baroni, G.] Politecn Milan Univ, Dept Bioengn, TBMLab, I-20133 Milan, Italy.
[Sharp, G. C.; Chen, G. T. Y.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Sharp, G. C.; Chen, G. T. Y.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Riboldi, M (reprint author), Politecn Milan Univ, Dept Bioengn, TBMLab, I-20133 Milan, Italy.
EM marco.riboldi@polimi.it
RI Baroni, Guido/D-3012-2011; Riboldi, Marco/I-2980-2014
OI Riboldi, Marco/0000-0002-2431-4966
FU Progetto Rocca Foundation
FX The authors acknowledge Lei Dong (MD Anderson Cancer Center) and Sonja
Dieterich (Stanford School of Medicine) for providing data for the
analysis. The work was partly supported by a post-doc grant provided by
the Progetto Rocca Foundation.
NR 37
TC 18
Z9 19
U1 1
U2 5
PU IOP PUBLISHING LTD
PI BRISTOL
PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD OCT 7
PY 2009
VL 54
IS 19
BP 5995
EP 6008
DI 10.1088/0031-9155/54/19/022
PG 14
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 497IE
UT WOS:000270051600023
PM 19773606
ER
PT J
AU Crowley, WF
Gusella, JF
AF Crowley, William F., Jr.
Gusella, James F.
TI Changing Models of Biomedical Research
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID POLYMORPHIC DNA MARKER; AMYOTROPHIC-LATERAL-SCLEROSIS; CLINICAL-RESEARCH
ENTERPRISE; CYSTIC-FIBROSIS LOCUS; HUNTINGTONS-DISEASE; GENE; LINKAGE;
NEUROFIBROMATOSIS; REGION; MAPS
AB Thanks to the revolutions in information technology, human "-omics" research, and intricate medical device development, academic health centers (AHCs) now have an unparalleled potential to become translational engines that both generate basic science advances and then translate them into human studies and, ultimately, into improved health care. However, AHC infrastructures have traditionally been optimized to foster basic research. Now modifications must be made to meet these expanded roles of AHCs, from providing fundamental biomedical insights to first-in-human interventions and, if warranted, to larger randomized clinical trials. Eventually, AHCs must integrate these improved treatments into patient care. Challenges to this process have been defined by the Institute of Medicine. Building the appropriate infrastructures for human investigation and stabilizing the careers of young physicians essential to these translational events have become critical needs that will require systemic investments if AHCs are to respond to these biological revolutions and fulfill their promise.
C1 [Crowley, William F., Jr.] Harvard Univ, Massachusetts Gen Hosp, Dept Genet, Harvard Reprod Endocrine Sci Ctr,Dept Med,Sch Med, Boston, MA 02114 USA.
[Gusella, James F.] Harvard Univ, Massachusetts Gen Hosp, Dept Genet, Ctr Human Genet Res,Sch Med, Boston, MA 02114 USA.
RP Crowley, WF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Genet, Harvard Reprod Endocrine Sci Ctr,Dept Med,Sch Med, Boston, MA 02114 USA.
EM wcrowley@partners.org
NR 30
TC 4
Z9 4
U1 1
U2 6
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD OCT 7
PY 2009
VL 1
IS 1
AR 1cm1
DI 10.1126/scitranslmed.3000124
PG 6
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 589KY
UT WOS:000277147500001
PM 20368150
ER
PT J
AU Davies, JK
Nadler, LM
Guinan, EC
AF Davies, Jeffrey K.
Nadler, Lee M.
Guinan, Eva C.
TI Expansion of Allospecific Regulatory T Cells After Anergized, Mismatched
Bone Marrow Transplantation
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID VERSUS-HOST-DISEASE; COSTIMULATORY BLOCKADE; ACUTE-LEUKEMIA;
DONOR-PROGRAM; HLA; ALLOANTIGEN; INDUCTION; LYMPHOCYTES; ACTIVATION;
DEPLETION
AB Transplantation of hematopoietic stem cells from healthy donors can cure patients with many diseases. Donor T cells can protect against recurrence of infection and disease, but some of these (alloreactive) T cells recognize patient tissues as foreign, causing graft-versus-host disease. Removing T cells from donor grafts before transplantation reduces graft-versus-host disease but increases infection and disease recurrence. Inactivation of alloreactive T cells by inducing tolerance to patient cells (anergization) before transplantation preserves beneficial donor T cell effects while reducing graft-versus-host disease. We show that this approach also results in expansion of regulatory T cells that specifically suppress alloreactive donor T cell responses in the recipient. In addition to reducing graft-versus-host disease, antigen-specific regulatory T cells generated with this strategy could suppress unwanted T cell responses that cause rejection of solid organ transplants and tissue damage in autoimmune disorders.
C1 [Davies, Jeffrey K.; Nadler, Lee M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Davies, Jeffrey K.; Nadler, Lee M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Guinan, Eva C.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Guinan, Eva C.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
RP Davies, JK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM jeff_davies@dfci.harvard.edu
FU NCI NIH HHS [R21 CA137645, R21 CA137645-01A1, R21 CA137645-02, U19
CA100265, U19 CA100265-03, U19 CA100265-04, U19 CA100265-05]
NR 45
TC 9
Z9 9
U1 1
U2 3
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD OCT 7
PY 2009
VL 1
IS 1
AR 1ra3
DI 10.1126/scitranslmed.3000153
PG 9
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 589KY
UT WOS:000277147500002
PM 20368155
ER
PT J
AU Gesty-Palmer, D
Flannery, P
Yuan, L
Corsino, L
Spurney, R
Lefkowitz, RJ
Luttrell, LM
AF Gesty-Palmer, Diane
Flannery, Pat
Yuan, Ling
Corsino, Leonor
Spurney, Robert
Lefkowitz, Robert J.
Luttrell, Louis M.
TI A beta-Arrestin-Biased Agonist of the Parathyroid Hormone Receptor
(PTH1R) Promotes Bone Formation Independent of G Protein Activation
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID OSTEOBLASTIC CELLS; KIDNEY-CELLS; KINASE; MICE; BETA-ARRESTIN2;
ENDOCYTOSIS; SELECTIVITY; COMPLEXES; PATHWAYS; SIGNALS
AB About 40% of the therapeutic agents in use today exert their effects through seven-transmembrane receptors (7TMRs). When activated by ligands, these receptors trigger two pathways that independently transduce signals to the cell: one through heterotrimeric GTP-binding proteins (G proteins) and one through beta-arrestins; so-called biased agonists can selectively activate these distinct pathways. Here, we investigate selective activation of these pathways through the use of a biased agonist for the type 1 parathyroid hormone (PTH)-PTH-related protein receptor (PTH1R), (D-Trp(12), Tyr(34))-PTH(7-34) (PTH-beta arr), which activates beta-arrestin but not classic G protein signaling. In mice, PTH-beta arr induces anabolic bone formation, as does the nonselective agonist PTH (1-34), which activates both mechanisms. In beta-arrestin2-null mice, the increase in bone mineral density evoked by PTH(1-34) is attenuated and that stimulated by PTH-beta arr is ablated. The beta-arrestin2-dependent pathway contributes primarily to trabecular bone formation and does not stimulate bone resorption. These results show that a biased agonist selective for the beta-arrestin pathway can elicit a response in vivo distinct from that elicited by nonselective agonists. Ligands with these properties may form the basis for improved 7TMR-directed pharmacologic agents with enhanced therapeutic specificity.
C1 [Gesty-Palmer, Diane; Flannery, Pat; Yuan, Ling; Corsino, Leonor; Spurney, Robert; Lefkowitz, Robert J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Gesty-Palmer, Diane] Durham Vet Affairs Med Ctr, Durham, NC 27705 USA.
[Lefkowitz, Robert J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
[Lefkowitz, Robert J.] Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA.
[Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Luttrell, Louis M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA.
[Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA.
RP Lefkowitz, RJ (reprint author), Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
EM lefko001@receptor-biol.duke.edu
FU Howard Hughes Medical Institute; NHLBI NIH HHS [HL70631, R01 HL070631,
HL16037, R01 HL016037, R01 HL016037-37]; NICHD NIH HHS [HD043446, K12
HD043446]; NIDDK NIH HHS [DK55524, DK64353, R01 DK055524, T32 DK007012,
R01 DK064353, R56 DK055524]
NR 42
TC 70
Z9 70
U1 0
U2 5
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD OCT 7
PY 2009
VL 1
IS 1
AR 1ra1
DI 10.1126/scitranslmed.3000071
PG 9
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 589KY
UT WOS:000277147500004
PM 20368153
ER
PT J
AU Ward, CP
McCoy, JG
McKenna, JT
Connolly, NP
McCarley, RW
Strecker, RE
AF Ward, Christopher P.
McCoy, John G.
McKenna, James T.
Connolly, Nina P.
McCarley, Robert W.
Strecker, Robert E.
TI Spatial learning and memory deficits following exposure to 24 h of sleep
fragmentation or intermittent hypoxia in a rat model of obstructive
sleep apnea
SO BRAIN RESEARCH
LA English
DT Article
DE Sleep apnea; Sleep fragmentation; Intermittent hypoxia; Water maze;
Spatial memory
ID MORRIS WATER MAZE; NITRIC-OXIDE SYNTHASE; WORKING-MEMORY; PARADOXICAL
SLEEP; OXIDATIVE STRESS; SYNAPTIC PLASTICITY; HIPPOCAMPAL-NEURONS;
DEPENDENT CHANGES; CA3 REGIONS; REM-SLEEP
AB Obstructive sleep apnea is primarily characterized by hypoxemia due to frequent apneic episodes and fragmentation of sleep due to the brief arousals that terminate the apneic episodes. Though neurobehavioral deficits frequently accompany sleep apnea, the relative roles of hypoxia versus sleep fragmentation are difficult to separate in apneic patients. Here, we assessed cognitive function as measured by water maze in the Fischer/Brown Norway (FBN) rat, comparing 24 h of sleep interruption (SI) to 24 h of intermittent hypoxia (IH), in order to dissociate their relative contributions to cognitive impairment. For SI, automated treadmills were used to induce brief ambulation in rats every 2 min, either prior to, or after, initial water maze acquisition training. IH was simulated by cycling environmental oxygen levels between 6% and 19% every 2 min, again either prior to, or after, acquisition. Twenty-four hours of IH exposure had no significant effect on either acquisition or retention, irrespective of whether IH occur-red prior to, or after, acquisition. To replicate previous work, another group of rats, exposed to 3 days of IH (10 h/day) prior to acquisition, had impaired performance during acquisition. A comparison of the 24 h IH and 3 day IH findings suggests that a minimum amount of IH exposure is necessary to produce detectable spatial memory impairments. Although SI before acquisition had no effect on acquisition or later retention of the hidden platform location, SI after acquisition robustly impaired retention, indicating that spatial memory consolidation is more susceptible to the effects of sleep disruption than is the acquisition (learning) of spatial information. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Ward, Christopher P.] Univ Houston Clear Lake City, Dept Psychol, Houston, TX 77058 USA.
[Ward, Christopher P.; McCoy, John G.; McKenna, James T.; Connolly, Nina P.; McCarley, Robert W.; Strecker, Robert E.] VA Boston Healthcare Syst, Brockton, MA USA.
[Ward, Christopher P.; McCoy, John G.; McKenna, James T.; Connolly, Nina P.; McCarley, Robert W.; Strecker, Robert E.] Harvard Univ, Sch Med, Neurosci Lab, Brockton, MA 02301 USA.
[McCoy, John G.] Stonehill Coll, Dept Psychol, Easton, MA 02357 USA.
[Connolly, Nina P.] Wheaton Coll, Dept Psychol, Norton, MA 02766 USA.
RP Ward, CP (reprint author), Univ Houston Clear Lake City, Dept Psychol, 2700 Bay Area Blvd, Houston, TX 77058 USA.
EM wardchris@uhcl.edu; jmccoy1@stonehill.edu;
robert_strecker@hms.harvard.edu
RI McCarley, Robert/N-5562-2014;
OI McCarley, Robert/0000-0001-5705-7495; Ward,
Christopher/0000-0001-9932-3894
FU Department of Veterans Affairs [NIH HL060292, NIH T32 HL07901, NIH F32
MH070156]
FX This research was supported by the Department of Veterans Affairs (RES
and RWM), NIH HL060292 (RWM and RES), NIH T32 HL07901 (JTM), and NIH F32
MH070156 (JTM).
NR 57
TC 32
Z9 34
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD OCT 6
PY 2009
VL 1294
BP 128
EP 137
DI 10.1016/j.brainres.2009.07.064
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 504ZZ
UT WOS:000270658500013
PM 19643093
ER
PT J
AU Settleman, J
AF Settleman, Jeff
TI A Therapeutic Opportunity in Melanoma: ErbB4 Makes a Mark on Skin
SO CANCER CELL
LA English
DT Editorial Material
ID SOMATIC MUTATIONS; CANCER
AB Malignant melanomas are aggressive tumors that are largely refractory to conventional drug therapies. A recent study reported in Nature Genetics identified mutationally activated ErbB4 alleles in 20% of cases. These tumor cells exhibit ErbB4 dependency, suggesting that ErbB4 kinase inhibition may constitute an effective therapeutic strategy in this setting.
C1 [Settleman, Jeff] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Settleman, Jeff] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
EM settleman@helix.mgh.harvard.edu
NR 10
TC 5
Z9 5
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD OCT 6
PY 2009
VL 16
IS 4
BP 278
EP 279
DI 10.1016/j.ccr.2009.09.013
PG 2
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 506JF
UT WOS:000270770400006
PM 19800573
ER
PT J
AU Hahn, CK
Berchuck, JE
Ross, KN
Kakoza, RM
Clauser, K
Schinzel, AC
Ross, L
Galinsky, I
Davis, TN
Silver, SJ
Root, DE
Stone, RM
DeAngelo, DJ
Carroll, M
Hahn, WC
Carr, SA
Golub, TR
Kung, AL
Stegmaier, K
AF Hahn, Cynthia K.
Berchuck, Jacob E.
Ross, Kenneth N.
Kakoza, Rose M.
Clauser, Karl
Schinzel, Anna C.
Ross, Linda
Galinsky, Ilene
Davis, Tina N.
Silver, Serena J.
Root, David E.
Stone, Richard M.
DeAngelo, Daniel J.
Carroll, Martin
Hahn, William C.
Carr, Steven A.
Golub, Todd R.
Kung, Andrew L.
Stegmaier, Kimberly
TI Proteomic and Genetic Approaches Identify Syk as an AML Target
SO CANCER CELL
LA English
DT Article
ID ACUTE MYELOGENOUS LEUKEMIA; ACUTE MYELOID-LEUKEMIA; TYROSINE KINASE SYK;
RENAL-CELL CARCINOMA; MYELODYSPLASTIC SYNDROME; THERAPEUTIC TARGET;
CYTOTOXIC ACTIVITY; SMALL MOLECULES; LUNG-CANCER; EXPRESSION
AB Cell-based screening can facilitate the rapid identification of compounds inducing complex cellular phenotypes. Advancing a compound toward the clinic, however, generally requires the identification of precise mechanisms of action. We previously found that epidermal growth factor receptor (EGFR) inhibitors induce acute myeloid leukemia (AML) differentiation via a non-EGFR mechanism. In this report, we integrated proteomic and RNAi-based strategies to identify their off-target, anti-AML mechanism. These orthogonal approaches identified Syk as a target in AML. Genetic and pharmacological inactivation of Syk with a drug in clinical trial for other indications promoted differentiation of AML cells and attenuated leukemia growth in vivo. These results demonstrate the power of integrating diverse chemical, proteomic, and genomic screening approaches to identify therapeutic strategies for cancer.
C1 [Hahn, Cynthia K.; Berchuck, Jacob E.; Kakoza, Rose M.; Ross, Linda; Davis, Tina N.; Golub, Todd R.; Kung, Andrew L.; Stegmaier, Kimberly] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Hahn, Cynthia K.; Berchuck, Jacob E.; Kakoza, Rose M.; Ross, Linda; Davis, Tina N.; Golub, Todd R.; Kung, Andrew L.; Stegmaier, Kimberly] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA.
[Ross, Kenneth N.; Clauser, Karl; Schinzel, Anna C.; Silver, Serena J.; Root, David E.; Hahn, William C.; Carr, Steven A.; Golub, Todd R.; Stegmaier, Kimberly] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA.
[Ross, Kenneth N.; Clauser, Karl; Schinzel, Anna C.; Silver, Serena J.; Root, David E.; Hahn, William C.; Carr, Steven A.; Golub, Todd R.; Stegmaier, Kimberly] MIT, Cambridge, MA 02142 USA.
[Schinzel, Anna C.; Galinsky, Ilene; Stone, Richard M.; DeAngelo, Daniel J.; Hahn, William C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Carroll, Martin] Univ Penn, Div Hematol Oncol, Philadelphia, PA 19104 USA.
[Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
RP Stegmaier, K (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
EM kimberly_stegmaier@dfci.harvard.edu
OI Kung, Andrew/0000-0002-9091-488X
FU National Cancer Institute [5K08 CA098444]; Howard Hughes Medical
Institute; Sidney Kimmel Cancer Foundation; Claudia Adams Barr
Foundation; Gloria Spivak Support Fund
FX We thank Rigel Pharmaceuticals, particularly Elliott Grossbard and Polly
Pine, for supplying R406 and R788 chow. We also thank Jeri Grenier for
RNAi screening guidance; John Daley, Jill Angelosanto, and Kathleen
Brosnahan for FACS assistance; Jinyan Du and Shao-En Ong for insight
regarding the proteomics experiment; Susan Buchanan for primary sample
collection; Jeff Kutock for pathology slide review; Anu Narla and
Benjamin Ebert for facilitating testing of normal myeloid progenitor
cells; Giovanni Roti, Dorhyun Johng, and Robin Perry for technical
assistance; and Curtis Glavin for graphical design. We thank all
patients and clinicians who contributed invaluable primary AML samples.
This work was supported by the National Cancer Institute (NCI; 5K08
CA098444), the Howard Hughes Medical Institute, the Sidney Kimmel Cancer
Foundation, the Claudia Adams Barr Foundation, and the Gloria Spivak
Support Fund (K.S.).
NR 41
TC 89
Z9 91
U1 1
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD OCT 6
PY 2009
VL 16
IS 4
BP 281
EP 294
DI 10.1016/j.ccr.2009.08.018
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 506JF
UT WOS:000270770400007
PM 19800574
ER
PT J
AU Chauhan, D
Singh, AV
Brahmandam, M
Carrasco, R
Bandi, M
Hideshima, T
Bianchi, G
Podar, K
Tai, YT
Mitsiades, C
Raje, N
Jaye, DL
Kumar, SK
Richardson, P
Munshi, N
Anderson, KC
AF Chauhan, Dharminder
Singh, Ajita V.
Brahmandam, Mohan
Carrasco, Ruben
Bandi, Madhavi
Hideshima, Teru
Bianchi, Giada
Podar, Klaus
Tai, Yu-Tzu
Mitsiades, Constantine
Raje, Noopur
Jaye, David L.
Kumar, Shaji K.
Richardson, Paul
Munshi, Nikhil
Anderson, Kenneth C.
TI Functional Interaction of Plasmacytoid Dendritic Cells with Multiple
Myeloma Cells: A Therapeutic Target
SO CANCER CELL
LA English
DT Article
ID INTERFERON-PRODUCING CELLS; REGULATORY T-CELLS; BONE-MARROW;
NUCLEIC-ACIDS; HUMAN BLOOD; EXPRESSION; SURVIVAL; INDUCE;
DIFFERENTIATION; INTERLEUKIN-6
AB Multiple myeloma (MM) remains incurable despite novel therapies, suggesting the need for further identification of factors mediating tumorigenesis and drug resistance. Using both in vitro and in vivo MM xenograft models, we show that plasmacytoid dendritic cells (pDCs) in the bone marrow (BM) microenvironment both mediate immune deficiency characteristic of MM and promote MM cell growth, survival, and drug resistance. Microarray, cell signaling, cytokine profile, and immunohistochemical analysis delineate the mechanisms mediating these sequelae. Although pDCs are resistant to novel therapies, targeting Toll-like receptors with CpG oligodeoxynucleotides both restores pDC immune function and abrogates pDC-induced MM cell growth. Our study therefore validates targeting pDC-MM interactions as a therapeutic strategy to overcome drug resistance in MM.
C1 [Chauhan, Dharminder; Singh, Ajita V.; Brahmandam, Mohan; Carrasco, Ruben; Bandi, Madhavi; Hideshima, Teru; Bianchi, Giada; Podar, Klaus; Tai, Yu-Tzu; Mitsiades, Constantine; Raje, Noopur; Richardson, Paul; Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA.
[Chauhan, Dharminder; Singh, Ajita V.; Brahmandam, Mohan; Carrasco, Ruben; Bandi, Madhavi; Hideshima, Teru; Bianchi, Giada; Podar, Klaus; Tai, Yu-Tzu; Mitsiades, Constantine; Raje, Noopur; Richardson, Paul; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Myeloma Res,Dept Med Oncol, Boston, MA 02115 USA.
[Jaye, David L.] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Kumar, Shaji K.] Mayo Clin, Dept Hematol, Rochester, MN 55905 USA.
[Munshi, Nikhil] Harvard Univ, Sch Med, Vet Adm Boston Healthcare Syst, Boston, MA 02115 USA.
RP Chauhan, D (reprint author), Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA.
EM dharminder_chauhan@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu
RI Kumar, Shaji/A-9853-2008
OI Kumar, Shaji/0000-0001-5392-9284
FU NIH [SPORE-P50100707, PO1-CA078378, RO1CA050947]; Myeloma Research
Foundation
FX This investigation was supported by NIH grants SPORE-P50100707,
PO1-CA078378, and RO1CA050947, and by Myeloma Research Foundation. D.C.
designed research, analyzed data, and wrote the manuscript; A.S.
designed, interpreted, and performed most experiments; M.B. performed
growth/survival assays; G.B. isolated normal plasma cells; R.C. and D.J.
helped with IHC; T.H., S.H., P.R., Y.T., N.R., C.M., and N.M. provided
clinical samples; and K.A. analyzed data and wrote the manuscript. We
also thank Robert Schlossman, Bryan Ciccarelli, and Sagar Lonial for
providing blood samples. We are thankful to Lay-Hong Ang for confocal
microscopy, John F. Daley for FACS, and Sangeetha Battar, Gaurav Chetri,
and David Vasir for technical help and insightful discussions.
NR 49
TC 91
Z9 93
U1 0
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD OCT 6
PY 2009
VL 16
IS 4
BP 309
EP 323
DI 10.1016/j.ccr.2009.08.019
PG 15
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 506JF
UT WOS:000270770400009
PM 19800576
ER
PT J
AU Morley, JF
Duda, JE
AF Morley, James F.
Duda, John E.
TI Autopsy investigation of neurodegenerative disease transplant patients
Hindsight is 20/20
SO NEUROLOGY
LA English
DT Editorial Material
ID PARKINSONS-DISEASE; PATHOLOGY; NEURONS
C1 [Duda, John E.] Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA.
[Morley, James F.] Penn Hosp, Parkinsons Dis & Movement Disorders Ctr, Philadelphia, PA 19107 USA.
Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
RP Duda, JE (reprint author), Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, MS 127,3900 Woodland Ave, Philadelphia, PA 19104 USA.
EM john.duda@va.gov
NR 10
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD OCT 6
PY 2009
VL 73
IS 14
BP 1086
EP 1087
DI 10.1212/WNL.0b013e3181bc6758
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 502QG
UT WOS:000270474500002
PM 19726748
ER
PT J
AU Novak, CE
Keuthen, NJ
Stewart, SE
Pauls, DL
AF Novak, Carol E.
Keuthen, Nancy J.
Stewart, S. Evelyn
Pauls, David L.
TI A Twin Concordance Study of Trichotillomania
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE trichotillomania; hair pulling; twin; genetic; etiology; heritability
ID OBSESSIVE-COMPULSIVE DISORDER; PATHOLOGICAL SKIN PICKING; MGH
HAIRPULLING SCALE; FAMILIAL TRICHOTILLOMANIA; ZYGOSITY; COMORBIDITY;
POPULATION; PREVALENCE; REGISTRY
AB Trichotillomania (TTM) is a disorder with putative genetic underpinnings. Family studies report higher than expected rates of TTM among relatives of affected individuals, but no twin concordance studies have been completed to estimate heritability rates. Same-sex twin pairs with hair pulling in at least one co-twin were included. Subjects were recruited following phone screens and questionnaire completion for zygosity and hair pulling variables. Three sets of criteria were used to define hair pulling and TTM. Two other sets of criteria were widened to include skin picking and bothersome hair manipulation. Fisher exact tests assessed pairwise concordance rates for monozygotic and dizygotic twin pairs and heritability estimates were calculated where significant differences existed. Among 34 identified twin pairs, 24 were monozygotic (MZ) and 10 were dizygotic (DZ). Respective concordance rates for MZ and DZ twin pairs were significantly different at 38.1% and 0% for DSM-IV TTM criteria, 39.1% and 0% using modified DSM criteria, and 58.3% and 20% for noticeable non-cosmetic hair pulling (heritability estimates 76.2%). MZ and DZ concordance rates were not significantly different when broadening hair pulling criteria to include skin picking or when including bothersome hair manipulation. Concordance rates from this study suggest that genetic factors play a significant role in the etiology of TTM. Given the reported discordance rates among the MZ twins, further research is required to fully understand contributory non-genetic factors. (C) 2009 Wiley-Liss, Inc.
C1 [Stewart, S. Evelyn; Pauls, David L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Keuthen, Nancy J.; Stewart, S. Evelyn] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Trichotillomania Clin, Boston, MA 02114 USA.
[Novak, Carol E.] Hlth Partners, St Paul, MN USA.
RP Pauls, DL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, 185 Cambridge St,6th Floor, Boston, MA 02114 USA.
EM pauls@pngu.mgh.harvard.edu
RI Citations, TLC SAB/C-4006-2011; Stewart, Evelyn/K-6961-2014;
OI Stewart, S. Evelyn/0000-0002-0994-6383
FU HealthPartners Research Foundation, Minneapolis, MN
FX Grant sponsor: HealthPartners Research Foundation, Minneapolis, MN.
NR 33
TC 27
Z9 28
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD OCT 5
PY 2009
VL 150B
IS 7
BP 944
EP 949
DI 10.1002/ajmg.b.30922
PG 6
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 502FN
UT WOS:000270441100007
PM 19199280
ER
PT J
AU Duchrow, T
Shtatland, T
Guettler, D
Pivovarov, M
Kramer, S
Weissleder, R
AF Duchrow, Timo
Shtatland, Timur
Guettler, Daniel
Pivovarov, Misha
Kramer, Stefan
Weissleder, Ralph
TI Enhancing navigation in biomedical databases by community voting and
database-driven text classification
SO BMC BIOINFORMATICS
LA English
DT Article
ID DOCUMENT CLASSIFICATION; INFORMATION; ANNOTATION; PERSPECTIVE;
ALGORITHMS; EXTRACTION; SEQUENCES; KNOWLEDGE; BIOLOGY; CANCER
AB Background: The breadth of biological databases and their information content continues to increase exponentially. Unfortunately, our ability to query such sources is still often suboptimal. Here, we introduce and apply community voting, database-driven text classification, and visual aids as a means to incorporate distributed expert knowledge, to automatically classify database entries and to efficiently retrieve them.
Results: Using a previously developed peptide database as an example, we compared several machine learning algorithms in their ability to classify abstracts of published literature results into categories relevant to peptide research, such as related or not related to cancer, angiogenesis, molecular imaging, etc. Ensembles of bagged decision trees met the requirements of our application best. No other algorithm consistently performed better in comparative testing. Moreover, we show that the algorithm produces meaningful class probability estimates, which can be used to visualize the confidence of automatic classification during the retrieval process. To allow viewing long lists of search results enriched by automatic classifications, we added a dynamic heat map to the web interface. We take advantage of community knowledge by enabling users to cast votes in Web 2.0 style in order to correct automated classification errors, which triggers reclassification of all entries. We used a novel framework in which the database "drives" the entire vote aggregation and reclassification process to increase speed while conserving computational resources and keeping the method scalable. In our experiments, we simulate community voting by adding various levels of noise to nearly perfectly labelled instances, and show that, under such conditions, classification can be improved significantly.
Conclusion: Using PepBank as a model database, we show how to build a classification-aided retrieval system that gathers training data from the community, is completely controlled by the database, scales well with concurrent change events, and can be adapted to add text classification capability to other biomedical databases.
C1 [Pivovarov, Misha; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol,Dept Syst Biol, Boston, MA USA.
[Duchrow, Timo; Shtatland, Timur; Guettler, Daniel; Pivovarov, Misha; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA USA.
Tech Univ Munich, Inst Informat I12, D-8046 Garching, Germany.
RP Shtatland, T (reprint author), Beckman Coulter Genom Inc, Cummings Ctr 500, Suite 2450, Beverly, MA USA.
EM timo.duchrow@dfki.de; tshtatland@beckman.com; dguettler@mgh.harvard.edu;
mpivovarov@mgh.harvard.edu; kramer@in.tum.de;
rweissleder@mgh.harvard.edu
FU NIH [P50-CA86355]
FX We thank Jerry Xu and Dennis Gurgul of the Enterprise Research IS group
at Partners Healthcare for their excellent support and use of the HPC
facilities. We also thank Vladimir Morozov and Gabriel Berriz for
helpful discussions. We thank the anonymous reviewers for their
comments, and the PepBank user community for support and valuable
feedback. This work was supported in part by NIH grant P50-CA86355 (RW).
NR 85
TC 13
Z9 13
U1 1
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD OCT 3
PY 2009
VL 10
AR 317
DI 10.1186/1471-2105-10-317
PG 15
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 519IP
UT WOS:000271759800001
PM 19799796
ER
PT J
AU Hansson, EM
Lindsay, ME
Chien, KR
AF Hansson, Emil M.
Lindsay, Mark E.
Chien, Kenneth R.
TI Regeneration Next: Toward Heart Stem Cell Therapeutics
SO CELL STEM CELL
LA English
DT Review
ID ACUTE MYOCARDIAL-INFARCTION; BONE-MARROW-CELLS; SKELETAL MYOBLAST
TRANSPLANTATION; RANDOMIZED CONTROLLED-TRIAL; IMPROVES CARDIAC-FUNCTION;
HUMAN SOMATIC-CELLS; PROGENITOR CELLS; DEFINED FACTORS;
ISCHEMIC-MYOCARDIUM; ADULT MYOCARDIUM
AB Stem cell biology holds great promise for a new era of cell-based therapy, sparking considerable interest among scientists, clinicians, and their patients. However, the translational arm of stem cell science is in a relatively primitive state. Although a number of clinical studies have been initiated, the early returns point to several inherent problems. In this regard, the clinical potential of stem cells can only be fully realized by the identification of the key barriers to clinical implementation. Here, we examine experimental paradigms to address the critical steps in the transition from stem cell biology to regenerative medicine, utilizing cardiovascular disease as a case study.
C1 [Hansson, Emil M.; Lindsay, Mark E.; Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Chien, Kenneth R.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Lindsay, Mark E.] Johns Hopkins Univ Hosp, Dept Pediat, Div Pediat Cardiol, Baltimore, MD 21205 USA.
RP Chien, KR (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charles River Plaza,CPZN 3200,185 Cambridge St, Boston, MA 02114 USA.
EM krchien@partners.org
FU NIH; LeDucq Foundation; Harvard Stem Cell Institute
FX We apologize to our colleagues whose work could not be cited due to
space constraints. We thank Goran K. Hansson and B. Alexander Yi for
helpful comments on the manuscript and Mattias Karlen for help with the
artwork. E.M.H. is a Wenner-Gren Foundations fellow. M.E.L. is supported
by a HHMI postdoctoral fellowship in the laboratory of H.C. Dietz.
K.R.C. is supported by NIH, the LeDucq Foundation, and the Harvard Stem
Cell Institute.
NR 110
TC 107
Z9 112
U1 2
U2 15
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD OCT 2
PY 2009
VL 5
IS 4
BP 364
EP 377
DI 10.1016/j.stem.2009.09.004
PG 14
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 514NP
UT WOS:000271401900009
PM 19796617
ER
PT J
AU Trowbridge, JJ
Snow, JW
Kim, J
Orkin, SH
AF Trowbridge, Jennifer J.
Snow, Jonathan W.
Kim, Jonghwan
Orkin, Stuart H.
TI DNA Methyltransferase 1 Is Essential for and Uniquely Regulates
Hematopoietic Stem and Progenitor Cells
SO CELL STEM CELL
LA English
DT Article
ID SELF-RENEWAL; METHYLATION; DIFFERENTIATION; MAINTENANCE; SURVIVAL;
DNMT3B
AB DNA methylation is essential for development and in diverse biological processes. The DNA methyltransferase Dnmt1 maintains parental cell methylation patterns on daughter DNA strands in mitotic cells; however, the precise role of Dnmt1 in regulation of quiescent adult stem cells is not known. To examine the role of Dnmt1 in adult hematopoietic stem cells (HSCs), we conditionally disrupted Dnmt1 in the hematopoietic system. Defects were observed in Dnmt1 deficient HSC self-renewal, niche retention, and in the ability of Dnmt1-deficient HSCs to give rise to multilineage hematopoiesis. Loss of Dnmt1 also had specific impact on myeloid progenitor cells, causing enhanced cell cycling and inappropriate expression of mature lineage genes. Dnmt1 regulates distinct patterns of methylation and expression of discrete gene families in long-term HSCs and multipotent and lineage-restricted progenitors, suggesting that Dnmt1 differentially controls these populations. These findings establish a unique and critical role for Dnmt1 in the primitive hematopoietic compartment.
C1 [Trowbridge, Jennifer J.; Snow, Jonathan W.; Kim, Jonghwan; Orkin, Stuart H.] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kim, Jonghwan; Orkin, Stuart H.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Trowbridge, Jennifer J.; Snow, Jonathan W.; Kim, Jonghwan; Orkin, Stuart H.] Harvard Univ, Sch Med, Childrens Hosp Boston,Div Hematol Oncol, Harvard Stem Cell Inst,Dept Pediat Oncol, Boston, MA 02115 USA.
[Kim, Jonghwan; Orkin, Stuart H.] Harvard Univ, Sch Med, Childrens Hosp Boston,Div Hematol Oncol, Harvard Stem Cell Inst,Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
EM orkin@bloodgroup.tch.harvard.edu
FU Fellows of the Leukemia & Lymphoma Society; HHMI Research Associate
FX We thank Drs. C.R. Walkley, L.E. Purton, J. Xu, D.A. Williams, G.C.
Yuan, and M.D. Kiers for helpful discussion and critical comments; J.
Chong for technical assistance; Children's Hospital Animal Facility
Staff for care of experimental animals; and J. Daley and S.
Lazo-Kallanian of the DFCI HemNeo Flow Facility for cell sorting. J.J.T.
and J.W.S. are Fellows of the Leukemia & Lymphoma Society, J.K. is a
HHMI Research Associate, and S.H.O. is an Investigator of the HHMI.
NR 16
TC 170
Z9 173
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD OCT 2
PY 2009
VL 5
IS 4
BP 442
EP 449
DI 10.1016/j.stem.2009.08.016
PG 8
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 514NP
UT WOS:000271401900015
PM 19796624
ER
PT J
AU Chan, ST
Tang, SW
Lee, WK
Tang, KW
Lo, SS
Kwong, KK
AF Chan, Suk-Tak
Tang, Sze-Wing
Lee, Wing-Kit
Tang, Kwok-Wing
Lo, Shing-Shun
Kwong, Kenneth K.
TI Can Cantonese rhymes be used in the assessment of hemispheric dominance
for language?
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Language; Cantonese; Rhyme; Hemispheric dominance
ID EVENT-RELATED FMRI; AUDITORY-CORTEX; FUNCTIONAL MRI; CHINESE CHARACTERS;
SPEECH-PERCEPTION; HUMAN BRAIN; VOWELS; LATERALIZATION; ORGANIZATION;
ACTIVATION
AB English vowels had been proposed in previous studies to be used as a simple tool for the brain mapping of language. A proper fMRI study of Cantonese rhymes, each of which being a required and fundamental unit of a Cantonese syllable, remains to be carried out. Using an auditory task with Cantonese rhymes which carry no semantic meaning, we observed a minimal amount of positive BOLD signal at the caudate nucleus when Cantonese rhymes were contrasted with their corresponding filtered sounds. Typical language activating regions of the prefrontal cortex, the medial prefrontal cortex and the lateral temporal cortex on both left and right sides were not activated by Cantonese rhymes. Based on the absence of brain activation at the typical language areas in the contrast of Cantonese rhymes relative to filtered sounds, the auditory task with Cantonese rhymes may not be a robust tool for the individual clinical assessment of hemispheric dominance for language. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Chan, Suk-Tak; Lee, Wing-Kit] Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Hong Kong, Hong Kong, Peoples R China.
[Tang, Sze-Wing] Hong Kong Polytech Univ, Dept Chinese & Bilingual Studies, Hong Kong, Hong Kong, Peoples R China.
[Tang, Kwok-Wing] Queen Elizabeth Hosp, Dept Diagnost Radiol & Imaging, Hong Kong, Hong Kong, Peoples R China.
[Lo, Shing-Shun] United Christian Hosp, Dept Radiol & Organ Imaging, Hong Kong, Hong Kong, Peoples R China.
[Kwong, Kenneth K.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
RP Chan, ST (reprint author), Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Hong Kong, Hong Kong, Peoples R China.
EM htphoebe@inet.polyu.edu.hk
RI Chan, Suk-tak/G-5846-2015
FU Hong Kong Research Grants Council [PolyU 5403/04M]
FX This research was supported by the Hong Kong Research Grants Council
(PolyU 5403/04M) and The Hong Kong Polytechnic University. We thank the
radiographers at the United Christian Hospital and the Queen Elizabeth
Hospital for assistance in data collection.
NR 38
TC 1
Z9 1
U1 2
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD OCT 2
PY 2009
VL 463
IS 2
BP 103
EP 107
DI 10.1016/j.neulet.2009.07.057
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 494JK
UT WOS:000269808700001
PM 19631717
ER
PT J
AU Stearns, CR
Gonzales, R
Camargo, CA
Maselli, J
Metlay, JP
AF Stearns, Cordelia R.
Gonzales, Ralph
Camargo, Carlos A., Jr.
Maselli, Judith
Metlay, Joshua P.
TI Antibiotic Prescriptions Are Associated with Increased Patient
Satisfaction With Emergency Department Visits for Acute Respiratory
Tract Infections
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article
DE patient satisfaction; respiratory tract infections; antibacterial agents
ID EXPECTATIONS; QUALITY; ACUITY
AB Objectives:
Health care providers cite patient satisfaction as a common reason for prescribing antibiotics for viral acute upper respiratory infections (URIs), even though quality performance measures emphasize nonantibiotic treatment for these conditions. In a secondary analysis of a cluster-randomized trial to test a combined patient and physician educational intervention to reduce antibiotic prescribing for URIs, the authors examined whether satisfaction is greater among patients diagnosed with URIs who are prescribed antibiotics in emergency department (ED) settings.
Methods:
This was a follow-up telephone survey of 959 patients who received care for acute respiratory infections at any of eight Veterans Administration (VA) hospital EDs or eight location-matched non-VA hospital EDs around the United States. Patients reported their satisfaction with the amount of time spent in the ED, the explanation of treatment, the provider treatment, and overall satisfaction on a five-point Likert scale. The primary measure of effect was the association between antibiotic prescription and visit satisfaction, adjusted for patient and visit characteristics.
Results:
Antibiotic treatment was significantly associated with increased overall visit satisfaction in non-VA EDs (adjusted odds ratio [OR] = 1.97, 95% confidence interval [CI] = 1.23 to 3.17), but not VA EDs (adjusted OR = 1.13, 95% CI = 0.81 to 1.58). Patients managed in non-VA EDs who received antibiotics were also significantly more likely to be satisfied with the explanation of treatment and the manner in which they were treated by the provider.
Conclusions:
Antibiotic prescriptions are associated with increased overall patient satisfaction in non-VA, but not VA, ED visits for URIs. Continued efforts to reduce unnecessary prescriptions in these settings must address ways to maintain patient satisfaction and still reduce antibiotic prescriptions.
C1 [Stearns, Cordelia R.; Metlay, Joshua P.] Univ Penn, Sch Med, VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA.
[Stearns, Cordelia R.; Metlay, Joshua P.] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA USA.
[Stearns, Cordelia R.; Metlay, Joshua P.] Univ Penn, Sch Med, Ctr Educ & Res Therapeut, Philadelphia, PA USA.
[Gonzales, Ralph; Maselli, Judith] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Gonzales, Ralph; Maselli, Judith] Univ Calif San Francisco, Div Gen Internal Med, Dept Med, San Francisco, CA 94143 USA.
[Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA.
RP Metlay, JP (reprint author), Univ Penn, Sch Med, VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA.
EM jmetlay@mail.med.upenn.edu
FU joint Agency for Healthcare Research and Quality [1 R01 HS013915];
Veteran's Administration (VA) Health Services Research and Development
Service [AVA-03-239]
FX This study was conducted as part of a joint Agency for Healthcare
Research and Quality (1 R01 HS013915) and Veteran's Administration (VA)
Health Services Research and Development Service Award (AVA-03-239) to
compare the translation of research into practice across VA and non-VA
settings.
NR 22
TC 20
Z9 20
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1069-6563
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD OCT
PY 2009
VL 16
IS 10
BP 934
EP 941
DI 10.1111/j.1553-2712.2009.00522.x
PG 8
WC Emergency Medicine
SC Emergency Medicine
GA 501QP
UT WOS:000270396700003
PM 19799568
ER
PT J
AU Newman-Toker, DE
Camargo, CA
Hsieh, YH
Pelletier, AJ
Edlow, JA
AF Newman-Toker, David E.
Camargo, Carlos A., Jr.
Hsieh, Yu-Hsiang
Pelletier, Andrea J.
Edlow, Jonathan A.
TI Disconnect Between Charted Vestibular Diagnoses and Emergency Department
Management Decisions: A Cross-sectional Analysis From a Nationally
Representative Sample
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article; Proceedings Paper
CT 25th Barany-Society Meeting
CY APR, 2008
CL Kyoto, JAPAN
SP Barany Soc
DE dizziness; vertigo; vestibular diseases; diagnosis; medical error;
cross-sectional studies
ID PAROXYSMAL POSITIONAL VERTIGO; RANDOMIZED CLINICAL-TRIAL; CEREBELLAR
INFARCTION; SYMPTOM QUALITY; DIZZY PATIENTS; OLDER-ADULTS; NEURITIS;
DIZZINESS; PHYSICIANS; PATIENT
AB Objectives:
The most common vestibular disorders seen in the emergency department (ED) are benign paroxysmal positional vertigo (BPPV) and acute peripheral vestibulopathy (APV; i.e., vestibular neuritis or labyrinthitis). BPPV and APV are two very distinct disorders that have different clinical presentations that require different diagnostic and treatment strategies. BPPV can be diagnosed without imaging and is treated with canalith-repositioning maneuvers. APV sometimes requires neuroimaging by magnetic resonance imaging (MRI) to exclude posterior fossa stroke mimics and should be treated with vestibular sedatives and corticosteroids. We sought to determine if emergency physicians (EPs) apply best practices to diagnose and treat these common vestibular disorders.
Methods:
This was a cross-sectional study of ED visits from the National Hospital Ambulatory Medical Care Survey (NHAMCS). A weighted sample of U.S. ED visits (1993-2005) was used. Patients at least 16 years of age who were given a final ED diagnosis of BPPV (International Classification of Diseases, 9th Revision [ICD-9], 386.11) or APV (ICD-9 386.12 or 386.3x) comprised the study population. The frequency of imaging and drug therapy in those diagnosed as BPPV or APV versus controls was the main outcome measure.
Results:
A total of 9,472 dizzy patient visits were sampled over 13 years (weighted estimate 33.6 million U.S. ED visits over that period). A weighted estimate of 2.5 million patients (7.4%) were given a vestibular diagnosis, mostly BPPV (weighted 0.2 million) or APV (weighted 1.9 million). Patients given BPPV (19%) and APV (19%) diagnoses were more likely to undergo imaging (all by computed tomography [CT]) than controls (7%; p < 0.001). Patients given BPPV (58%) and APV (70%) diagnoses were more likely to receive meclizine than controls (0.1%; p < 0.001). Corticosteroid administration was rarely documented (2% BPPV, 1% APV).
Conclusions:
Patients given a vestibular diagnosis in the ED may not be managed optimally. Patients given BPPV and APV diagnoses undergo imaging (predominantly CT) with equal frequency, suggesting overuse of CT (BPPV) and probably underuse of MRI (APV). Most patients diagnosed with BPPV are given meclizine, which is not indicated. Specific therapy for APV (corticosteroids) is probably underutilized. Educational initiatives and clinical guidelines merit consideration.
ACADEMIC EMERGENCY MEDICINE 2009; 16:970-977 <(C)> 2009 by the Society for Academic Emergency Medicine.
C1 [Newman-Toker, David E.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Newman-Toker, David E.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol, Baltimore, MD 21205 USA.
[Hsieh, Yu-Hsiang] Johns Hopkins Univ, Sch Med, Dept Emergency Med, Baltimore, MD 21205 USA.
[Camargo, Carlos A., Jr.; Pelletier, Andrea J.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Edlow, Jonathan A.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA USA.
RP Newman-Toker, DE (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
EM toker@jhu.edu
NR 68
TC 38
Z9 39
U1 0
U2 6
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1069-6563
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD OCT
PY 2009
VL 16
IS 10
BP 970
EP 977
DI 10.1111/j.1553-2712.2009.00523.x
PG 8
WC Emergency Medicine
SC Emergency Medicine
GA 501QP
UT WOS:000270396700008
PM 19799573
ER
PT J
AU Courtney, DM
Neumar, RW
Venkatesh, AK
Kaji, AH
Cairns, CB
Lavonas, E
Richardson, LD
AF Courtney, D. Mark
Neumar, Robert W.
Venkatesh, Arjun K.
Kaji, Amy H.
Cairns, Charles B.
Lavonas, Eric
Richardson, Lynne D.
TI Unique Characteristics of Emergency Care Research: Scope, Populations,
and Infrastructure
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article
DE emergency care research networks
ID INFORMED-CONSENT; ETHICS; FOOD
AB The National Institutes of Health (NIH) Clinical and Translational Science Awards (CTSA) program and the 2006 Institute of Medicine (IOM) Report on the future of emergency care highlight the need for coordinated emergency care research (ECR) to improve the outcomes of acutely ill or injured patients. In response, the Society for Academic Emergency Medicine (SAEM) and the American College of Emergency Physicians (ACEP) sponsored the Emergency Care Research Network (ECRN) Conference in Washington, DC, on May 28, 2008. The conference objectives were to identify the unique nature of ECR and the infrastructure needed to support ECR networks and to understand the optimal role of emergency medicine (EM) and other acute care specialties in research networks. Prior to the conference, participants responded to questions addressing the relevant issues that would form the basis of breakout session discussions; two of these breakout questions are summarized in this report: 1) what makes EM research unique? and 2) what are the critical components needed to establish and maintain networked ECR? Emergency care research was defined as "the systematic examination of patient care that is expected to be continuously available to diverse populations presenting with undifferentiated symptoms of acute illness, or acutely decompensated chronic illness, and whose outcomes depend on timely diagnosis and treatment." The chain of ECR may extend beyond the physical emergency department (ED) in both place and time and integrate prehospital care, as well as short- and long-term outcome determination. ECR may extend beyond individual patients and have as the focus of investigation the actual system of emergency care delivery itself and its effects on the community with respect to access to care, use of resources, and cost. Infrastructure determinants of research network success identified by conference participants included multidisciplinary collaboration, accurate long-term outcome determination, novel information technology, intellectual infrastructure, and wider network relationships that extend beyond the ED.
ACADEMIC EMERGENCY MEDICINE 2009; 16:990-994 (C) 2009 by the Society for Academic Emergency Medicine.
C1 [Courtney, D. Mark] Northwestern Univ, Feinberg Sch Med, Dept Emergency Med, Chicago, IL 60611 USA.
[Neumar, Robert W.] Univ Penn, Sch Med, Hosp Univ Penn, Philadelphia, PA 19104 USA.
[Venkatesh, Arjun K.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA.
[Kaji, Amy H.] Univ Calif Los Angeles, Harbor UCLA Med Ctr, Dept Emergency Med, David Geffen Sch Med, Torrance, CA USA.
[Cairns, Charles B.] Univ N Carolina, Dept Emergency Med, Chapel Hill, NC USA.
[Lavonas, Eric] Rocky Mt Poison & Drug Ctr, Denver, CO USA.
[Lavonas, Eric] Univ Colorado, Sch Med, Dept Surg Emergency Med, Aurora, CO USA.
[Richardson, Lynne D.] Mt Sinai Sch Med, Dept Emergency Med, New York, NY USA.
RP Courtney, DM (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Emergency Med, Chicago, IL 60611 USA.
EM mcourtney@nmff.org
NR 16
TC 10
Z9 10
U1 2
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1069-6563
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD OCT
PY 2009
VL 16
IS 10
BP 990
EP 994
DI 10.1111/j.1553-2712.2009.00530.x
PG 5
WC Emergency Medicine
SC Emergency Medicine
GA 501QP
UT WOS:000270396700014
PM 19799578
ER
PT J
AU Papa, L
Kuppermann, N
Lamond, K
Barsan, WG
Camargo, CA
Ornato, JP
Stiell, IG
Talan, DA
AF Papa, Linda
Kuppermann, Nathan
Lamond, Katherine
Barsan, William G.
Camargo, Carlos A., Jr.
Ornato, Joseph P.
Stiell, Ian G.
Talan, David A.
TI Structure and Function of Emergency Care Research Networks: Strengths,
Weaknesses, and Challenges
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article
DE research networks; emergency care; emergency research; multicenter
research; collaboration; research funding
ID RESUSCITATION OUTCOMES CONSORTIUM; ANIMAL EXPOSURES; MULTICENTER;
MEDICINE; PROTOCOL; TRIAL; BRONCHIOLITIS; EPIDEMIOLOGY; INFECTIONS;
RATIONALE
AB The ability of emergency care research (ECR) to produce meaningful improvements in the outcomes of acutely ill or injured patients depends on the optimal configuration, infrastructure, organization, and support of emergency care research networks (ECRNs). Through the experiences of existing ECRNs, we can learn how to best accomplish this. A meeting was organized in Washington, DC, on May 28, 2008, to discuss the present state and future directions of clinical research networks as they relate to emergency care. Prior to the conference, at the time of online registration, participants responded to a series of preconference questions addressing the relevant issues that would form the basis of the breakout session discussions. During the conference, representatives from a number of existing ECRNs participated in discussions with the attendees and provided a description of their respective networks, infrastructure, and challenges. Breakout sessions provided the opportunity to further discuss the strengths and weaknesses of these networks and patterns of success with respect to their formation, management, funding, best practices, and pitfalls. Discussions centered on identifying characteristics that promote or inhibit successful networks and their interactivity, productivity, and expansion. Here the authors describe the current state of ECRNs and identify the strengths, weaknesses, and potential pitfalls of research networks. The most commonly cited strengths of population- or disease-based research networks identified in the preconference survey were access to larger numbers of patients; involvement of physician experts in the field, contributing to high-level study content; and the collaboration among investigators. The most commonly cited weaknesses were studies with too narrow a focus and restrictive inclusion criteria, a vast organizational structure with a risk of either too much or too little central organization or control, and heterogeneity of institutional policies and procedures among sites. Through the survey and structured discussion process involving multiple stakeholders, the authors have identified strengths and weaknesses that are consistent across a number of existing ECRNs. By leveraging the strengths and addressing the weaknesses, strategies can be adopted to enhance the scientific value and productivity of these networks and give direction to future ECRNs.
ACADEMIC EMERGENCY MEDICINE 2009; 16:995-1004 (C) 2009 by the Society for Academic Emergency Medicine.
C1 [Papa, Linda] Orlando Reg Med Ctr Inc, Dept Emergency Med, Orlando, FL USA.
[Kuppermann, Nathan] UC Davis Hlth Syst, Dept Emergency Med, Sacramento, CA USA.
[Kuppermann, Nathan] UC Davis Hlth Syst, Dept Pediat, Sacramento, CA USA.
[Lamond, Katherine] Univ Penn, Sch Med, Dept Emergency Med, Philadelphia, PA 19104 USA.
[Barsan, William G.] Univ Michigan, Dept Emergency Med, Ann Arbor, MI 48109 USA.
[Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Boston, MA USA.
[Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Ornato, Joseph P.] Virginia Commonwealth Univ Hlth Syst, Dept Emergency Med, Richmond, VA USA.
[Stiell, Ian G.] Univ Ottawa, Dept Emergency Med, Ottawa, ON, Canada.
[Stiell, Ian G.] Ottawa Hlth Res Inst, Ottawa, ON, Canada.
[Talan, David A.] Olive View UCLA, Dept Emergency Med, Los Angeles, CA USA.
RP Papa, L (reprint author), Orlando Reg Med Ctr Inc, Dept Emergency Med, Orlando, FL USA.
EM lpstat@aol.com
OI Stiell, Ian/0000-0002-2583-6408
NR 26
TC 7
Z9 7
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1069-6563
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD OCT
PY 2009
VL 16
IS 10
BP 995
EP 1004
DI 10.1111/j.1553-2712.2009.00531.x
PG 10
WC Emergency Medicine
SC Emergency Medicine
GA 501QP
UT WOS:000270396700015
PM 19799579
ER
PT J
AU Sullivan, AF
Ginde, AA
Espinola, JA
Camargo, CA
AF Sullivan, Ashley F.
Ginde, Adit A.
Espinola, Janice A.
Camargo, Carlos A., Jr.
TI Supply and Demand of Board-certified Emergency Physicians by US State,
2005
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article
DE emergency physicians; board certification; workforce; rural; staffing
ID MEDICINE; WORKFORCE; DEPARTMENTS; COVERAGE; LOCATION
AB Objectives:
The objective was to estimate the emergency medicine (EM) board-certified emergency physician (EP) workforce supply and demand by U.S. state.
Methods:
The 2005 National Emergency Department Inventories-USA provided annual visit volumes for U.S. emergency departments (EDs). We estimated full-time equivalent (FTE) EP demand at each ED by dividing the actual number of visits by the estimated average EP visit volume (3,548 visits/year) and then summing FTEs by state. Our model assumed that at least one EP should be present 24/7 in each ED. The number of EM board-certified EPs per state was provided by the American Board of Medical Specialties (American Board of Emergency Medicine, American Board of Pediatrics) and the American Osteopathic Board of Emergency Medicine. We used U.S. Census Bureau civilian population estimates to calculate EP population density by state.
Results:
The supply of EM board-certified EPs was 58% of required FTEs to staff all EDs nationally and ranged from 10% in South Dakota to 104% in Hawai'i (i.e., there were more EPs than the estimated need). Texas and Florida had the largest absolute shortages of EM board-certified EPs (2,069 and 1,146, respectively). The number of EM board-certified EPs per 100,000 U.S. civilian population ranged from 3.6 in South Dakota to 13.8 in Washington, DC. States with a higher population density of EM board-certified EPs had higher percent high school graduates and a lower percent rural population and whites.
Conclusions:
The supply and demand of EM board-certified EPs varies by state. Only one state had an adequate supply of EM board-certified EPs to fully staff its EDs.
C1 [Sullivan, Ashley F.; Espinola, Janice A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Ginde, Adit A.] Univ Colorado, Denver Sch Med, Dept Emergency Med, Aurora, CO USA.
RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
EM ccamargo@partners.org
RI Siry, Bonnie/D-7189-2017
NR 26
TC 8
Z9 8
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1069-6563
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD OCT
PY 2009
VL 16
IS 10
BP 1014
EP 1018
DI 10.1111/j.1553-2712.2009.00509.x
PG 5
WC Emergency Medicine
SC Emergency Medicine
GA 501QP
UT WOS:000270396700018
PM 19719820
ER
PT J
AU Isaac, C
Lee, B
Carnes, M
AF Isaac, Carol
Lee, Barbara
Carnes, Molly
TI Interventions That Affect Gender Bias in Hiring: A Systematic Review
SO ACADEMIC MEDICINE
LA English
DT Article
AB Purpose
To systematically review experimental evidence for interventions mitigating gender bias in employment. Unconscious endorsement of gender stereotypes can undermine academic medicine's commitment to gender equity.
Method
The authors performed electronic and hand searches for randomized controlled studies since 1973 of interventions that affect gender differences in evaluation of job applicants. Twenty-seven studies met all inclusion criteria. Interventions fell into three categories: application information, applicant features, and rating conditions.
Results
The studies identified gender bias as the difference in ratings or perceptions of men and women with identical qualifications. Studies reaffirmed negative bias against women being evaluated for positions traditionally or predominantly held by men (male sex-typed jobs). The assessments of male and female raters rarely differed. Interventions that provided raters with clear evidence of job-relevant competencies were effective. However, clearly competent women were rated lower than equivalent men for male sex-typed jobs unless evidence of communal qualities was also provided. A commitment to the value of credentials before review of applicants and women's presence at above 25% of the applicant pool eliminated bias against women. Two studies found unconscious resistance to "antibias" training, which could be overcome with distraction or an intervening task. Explicit employment equity policies and an attractive appearance benefited men more than women, whereas repeated employment gaps were more detrimental to men. Masculine-scented perfume favored the hiring of both sexes. Negative bias occurred against women who expressed anger or who were perceived as self-promoting.
Conclusions
High-level evidence exists for strategies to mitigate gender bias in hiring. Acad Med. 2009; 84: 1440-1446.
C1 [Isaac, Carol; Carnes, Molly] Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53715 USA.
[Carnes, Molly] Meriter Hosp, Madison, WI USA.
[Carnes, Molly] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53715 USA.
[Carnes, Molly] Univ Wisconsin, Dept Psychiat, Sch Med & Publ Hlth, Madison, WI 53715 USA.
[Carnes, Molly] Univ Wisconsin, Dept Ind & Syst Engn, Madison, WI 53715 USA.
[Carnes, Molly] Univ Wisconsin, WISELI, Coll Engn, Madison, WI 53715 USA.
[Carnes, Molly] William S Middleton Mem Vet Adm Med Ctr, Women Vet Hlth Program, Madison, WI USA.
[Isaac, Carol] Univ Wisconsin, Dept Orthoped & Rehabil, Madison, WI 53715 USA.
RP Carnes, M (reprint author), Univ Wisconsin, Ctr Womens Hlth Res, 700 Regent St,Suite 301, Madison, WI 53715 USA.
EM mlcarnes@wisc.edu
FU University of Wisconsin School of Medicine and Public Health; Meriter
Hospital; National Institute on Aging [T32 AG00265]
FX This research was funded by the University of Wisconsin School of
Medicine and Public Health and Meriter Hospital. Dr. Isaac was supported
by grant no. T32 AG00265 from the National Institute on Aging. Dr.
Carnes is employed part time by the William S. Middleton Veterans
Hospital. This report is GRECC manuscript no. 2000-30.
NR 62
TC 44
Z9 44
U1 3
U2 38
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-2446
J9 ACAD MED
JI Acad. Med.
PD OCT
PY 2009
VL 84
IS 10
BP 1440
EP 1446
DI 10.1097/ACM.0b013e3181b6ba00
PG 7
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA V15EU
UT WOS:000207786100032
PM 19881440
ER
PT J
AU Rudolph, JW
Morrison, JB
Carroll, JS
AF Rudolph, Jenny W.
Morrison, J. Bradley
Carroll, John S.
TI THE DYNAMICS OF ACTION-ORIENTED PROBLEM SOLVING: LINKING INTERPRETATION
AND CHOICE
SO ACADEMY OF MANAGEMENT REVIEW
LA English
DT Article
ID DECISION-MAKING; CLINICAL JUDGMENT; ORGANIZATIONS; EXPLANATION;
PERSPECTIVE; SENSEMAKING; HEURISTICS; PSYCHOLOGY; COLLAPSE; DISASTER
AB We offer a theory of action-oriented problem solving that links interpretation and choice, processes usually separated in the sensemaking literature and decision-making literature. Through an iterative, simulation-based process we developed a formal model. Three insights emerged: (1) action-oriented problem solving includes acting. interpreting, and cultivating diagnoses; (2) feedback among these processes opens and closes windows of adaptive problem solving; and (3) reinforcing feedback and confirmation bias, usually considered dysfunctional, are helpful for adaptive problem solving.
C1 [Rudolph, Jenny W.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Rudolph, Jenny W.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Morrison, J. Bradley] Brandeis Univ, Brandeis Int Business Sch, Waltham, MA 02254 USA.
[Carroll, John S.] MIT, Alfred P Sloan Sch Management, Cambridge, MA 02139 USA.
RP Rudolph, JW (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
EM jwrudolph@partners.org; bmorriso@brandeis.edu; jcarroll@mit.edu
NR 84
TC 51
Z9 52
U1 7
U2 68
PU ACAD MANAGEMENT
PI BRIARCLIFF MANOR
PA PACE UNIV, PO BOX 3020, 235 ELM RD, BRIARCLIFF MANOR, NY 10510-8020 USA
SN 0363-7425
J9 ACAD MANAGE REV
JI Acad. Manage. Rev.
PD OCT
PY 2009
VL 34
IS 4
BP 733
EP 756
PG 24
WC Business; Management
SC Business & Economics
GA 505ZB
UT WOS:000270739900009
ER
PT J
AU Roche-Labarbe, N
Surova, A
Carp, S
Patel, M
Boas, DA
Grant, PE
Franceschini, MA
AF Roche-Labarbe, N.
Surova, A.
Carp, S.
Patel, M.
Boas, D. A.
Grant, P. E.
Franceschini, M. A.
TI NON-INVASIVE OPTICAL MEASURES OF CBV, STO2, CBF INDEX, AND RCMRO2 IN
PREMATURE BRAINS DURING THE FIRST 6 WEEKS OF LIFE
SO ACTA PAEDIATRICA
LA English
DT Meeting Abstract
C1 [Roche-Labarbe, N.; Surova, A.; Carp, S.; Patel, M.; Boas, D. A.; Franceschini, M. A.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Grant, P. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI Roche-Labarbe, Nadege/N-9101-2015
OI Roche-Labarbe, Nadege/0000-0002-5010-0400
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0803-5253
J9 ACTA PAEDIATR
JI Acta Paediatr.
PD OCT
PY 2009
VL 98
SU 460
BP 48
EP 48
PG 1
WC Pediatrics
SC Pediatrics
GA 495AR
UT WOS:000269862100120
ER
PT J
AU Mueser, KT
Glynn, SM
Cather, C
Zarate, R
Fox, L
Feldman, J
Wolfe, R
Clark, RE
AF Mueser, Kim T.
Glynn, Shirley M.
Cather, Corinne
Zarate, Roberto
Fox, Lindy
Feldman, James
Wolfe, Rosemarie
Clark, Robin E.
TI Family intervention for co-occurring substance use and severe
psychiatric disorders: Participant characteristics and correlates of
initial engagement and more extended exposure in a randomized controlled
trial
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Comorbidity; Co-occurring disorders; Dual disorders; Family therapy;
Family psychoeducation; Severe mental illness; Schizophrenia
ID MENTAL-HEALTH-SERVICES; GENDER DIFFERENCES; EXPRESSED EMOTION; ATTITUDE
SCALE; DRUG-ABUSE; SCHIZOPHRENIA; ILLNESS; RELAPSE; PEOPLE; ALCOHOL
AB Clients with severe mental illness and Substance use disorder (i.e., dual disorders) frequently have contact with family members, who may provide valuable emotional and material support, but have limited skills and knowledge to promote recovery. Furthermore, high levels of family conflict and stress are related to higher rates of relapse. The present study was a two-site randomized controlled trial comparing a comprehensive, behaviorally-based family intervention for dual disorders program (FIDD) to a shorter-term family psychoeducational program (FPE). The modal family was a single male son in his early 30s diagnosed with both alcohol and drug problems and a schizophrenia-spectrum disorder participating with his middle-aged mother, with whom he lived. Initial engagement rates following consent to participate in the study and the family intervention programs were moderately high for both programs (88% and 84%, respectively), but rates of longer term retention and exposure to the core elements of each treatment model were lower (61% and 55%, respectively). Characteristics of the relatives were the strongest predictors Of Successful initial engagement in the family programs with the most important predictor being relatives who reported higher levels of benefit related to the relationship with the client. Subsequent successful exposure to the family treatment models was more strongly associated with client factors, including less severity of drug abuse and male client gender. The results suggest that attention to issues of motivating relatives to participate in family intervention, and more focused efforts to address the disruptive effects of drug abuse on the family could improve rates of engagement and retention in family programs for dual disorders. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Mueser, Kim T.; Fox, Lindy; Wolfe, Rosemarie] Dartmouth Psychiat Res Ctr, Concord, NH 03301 USA.
[Mueser, Kim T.; Fox, Lindy; Wolfe, Rosemarie] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Psychiat, Hanover, NH 03756 USA.
[Mueser, Kim T.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA.
[Glynn, Shirley M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Glynn, Shirley M.; Zarate, Roberto] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
[Cather, Corinne] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA.
[Cather, Corinne; Feldman, James] Harvard Univ, Sch Med, Boston, MA USA.
[Zarate, Roberto] Pacific Clin, Los Angeles, CA USA.
[Feldman, James] Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA.
[Clark, Robin E.] Univ Massachusetts, Sch Med, Ctr Hlth Policy & Res, Amherst, MA 01003 USA.
RP Mueser, KT (reprint author), Dartmouth Psychiat Res Ctr, Main Bldg,105 Pleasant St, Concord, NH 03301 USA.
EM kim.t.Mueser@dartmouth.edu
RI Clark, Robin/I-7224-2012
FU National Institute of Mental Health [MH62629]; National Institute on
Drug Abuse
FX This research was supported by grant #MH62629 from the National
Institute of Mental Health and the National Institute on Drug Abuse.
This paper is subject to the National Institutes of Health Public Access
Policy. An earlier version of this paper was presented at the 40th
Annual Convention of the Association for Behavioral and Cognitive
Therapies in Chicago, Illinois, November, 2006.; The authors appreciate
the following persons for their contributions to this study: Dan Beck,
Bruce Bird, Elsa Busch, Kimberly Carr, Margaret Guyer Deason, Robert E.
Drake, Barbara Echevarria, Joan Friebly, Michelle Friedman-Yakoobian,
Rona Gershovsky, Jennifer D. Gottlieb, Gretchen Grappone, Daniel
E.Jimenez, Abigaiijudge, Lynette King, Alex Kopelowicz, Linda LaRose,
Glenda Madden, Gregory McHugo, Krystal A. Murray, Noosha Niv, Thomas
Quinlan, Joan Packard, Kenneth Park, Mary Parker, Jean Russo, Diane
Schiavo, Melissa Stern, Shannon R. Weston, and James Wheeler.
NR 62
TC 17
Z9 17
U1 1
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
EI 1873-6327
J9 ADDICT BEHAV
JI Addict. Behav.
PD OCT
PY 2009
VL 34
IS 10
SI SI
BP 867
EP 877
DI 10.1016/j.addbeh.2009.03.025
PG 11
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 486BL
UT WOS:000269170300012
PM 19375870
ER
PT J
AU Pasquale, LR
Walt, JG
Stern, LS
Wiederkehr, D
Malangone, E
Dolgitser, M
AF Pasquale, Louis R.
Walt, John G.
Stern, Lee S.
Wiederkehr, Daniel
Malangone, Elisabetta
Dolgitser, Margarita
TI Healthcare charges in patients who transition from ocular hypertension
to primary open-angle glaucoma based on ophthalmic coding data
SO ADVANCES IN THERAPY
LA English
DT Article
DE healthcare economics; ocular hypertension; open-angle glaucoma;
ophthalmology
ID BEAVER-DAM EYE; INTRAOCULAR-PRESSURE; UNITED-STATES; ECONOMIC BURDEN;
BARBADOS EYE; DIRECT COSTS; CLAIMS DATA; PREVALENCE; POPULATION;
MANAGEMENT
AB The purpose of this research was to assess the impact of transition from ocular hypertension (OHT) to primary open-angle glaucoma (POAG) on healthcare charges.
A case-control group was identified using PharMetrics claims database (1998-2005). Cases (n=1055) had a transition from OHT to POAG based on International Classification of Disease, Ninth Edition coding (ICD-9=365.11). Controls (n=2110) retained an ICD-9 code for OHT (ICD-9=365.04) and were matched to cases (2:1) on gender, age, diagnosis year, and follow-up time post-diagnosis. The index date marked the transition for cases and a date of similar duration after OHT diagnosis for controls. Conditional logistic regression and multiple linear regression models determined the impact of transitioning on healthcare charges.
Cases had significantly higher increases in ophthalmology-related charges ($797 vs. -$385, P < 0.0001) but similar total healthcare charges ($1689 vs. $1386, P=0.8277) from the year pre- to year post-index date when compared with controls. After adjusting for key covariates, cases were 1.56 times (95% CI: 1.33-1.82) more likely to have increased total charges and 5.26 times (95% CI: 4.27-6.47) more likely to have increased ophthalmology-related charges compared with controls. In multiple linear regression analyses, cases experienced $48 (55%) higher increases in ophthalmology-related charges from the year pre- to year post-index date compared with controls ($85 vs. $37, respectively; P < 0.0001).
Patients with a transition from OHT to POAG based on ICD-9 coding had higher ophthalmology-related charges the year after transition compared with patients who retained a code for OHT. Prevention of this transition could result in healthcare resource savings.
C1 [Stern, Lee S.; Wiederkehr, Daniel; Malangone, Elisabetta; Dolgitser, Margarita] Analyt Int, New York, NY 10018 USA.
[Pasquale, Louis R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Glaucoma Serv, Boston, MA USA.
[Walt, John G.] Allergan Pharmaceut Inc, Irvine, CA 92715 USA.
RP Stern, LS (reprint author), Analyt Int, 24 W 40th St,8th Floor, New York, NY 10018 USA.
EM lstern@analyticaintl.com
FU Allergan, Inc., Irvine, California, USA
FX Editorial assistance in the preparation of this manuscript was provided
by Jacob M. Willet, MPH, of Analytica International. Support for this
assistance was funded by Allergan, Inc., Irvine, California, USA.
NR 31
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0741-238X
J9 ADV THER
JI Adv. Ther.
PD OCT
PY 2009
VL 26
IS 10
BP 947
EP 958
DI 10.1007/s12325-009-0073-y
PG 12
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 528PP
UT WOS:000272459100005
PM 19907929
ER
PT J
AU Oliveira, RP
Abate, JP
Dilks, K
Landis, J
Ashraf, J
Murphy, CT
Blackwell, TK
AF Oliveira, Riva P.
Abate, Jess Porter
Dilks, Kieran
Landis, Jessica
Ashraf, Jasmine
Murphy, Coleen T.
Blackwell, T. Keith
TI Condition-adapted stress and longevity gene regulation by Caenorhabditis
elegans SKN-1/Nrf
SO AGING CELL
LA English
DT Article
DE aging; Caenorhabditis elegans; detoxification; insulin signaling;
oxidative stress; SKN-1
ID TRANSCRIPTION FACTOR SKN-1; C-ELEGANS; OXIDATIVE-STRESS; LIFE-SPAN;
MULTIDRUG-RESISTANCE; BINDING DOMAIN; DAF-16 TARGETS; INSULIN;
MECHANISMS; EXPRESSION
AB P>Studies in model organisms have identified regulatory processes that profoundly influence aging, many of which modulate resistance against environmental or metabolic stresses. In Caenorhabditis elegans, the transcription regulator SKN-1 is important for oxidative stress resistance and acts in multiple longevity pathways. SKN-1 is the ortholog of mammalian Nrf proteins, which induce Phase 2 detoxification genes in response to stress. Phase 2 enzymes defend against oxygen radicals and conjugate electrophiles that are produced by Phase 1 detoxification enzymes, which metabolize lipophilic compounds. Here, we have used expression profiling to identify genes and processes that are regulated by SKN-1 under normal and stress-response conditions. Under nonstressed conditions SKN-1 upregulates numerous genes involved in detoxification, cellular repair, and other functions, and downregulates a set of genes that reduce stress resistance and lifespan. Many of these genes appear to be direct SKN-1 targets, based upon presence of predicted SKN-binding sites in their promoters. The metalloid sodium arsenite induces skn-1-dependent activation of certain detoxification gene groups, including some that were not SKN-1-upregulated under normal conditions. An organic peroxide also triggers induction of a discrete Phase 2 gene set, but additionally stimulates a broad SKN-1-independent response. We conclude that under normal conditions SKN-1 has a wide range of functions in detoxification and other processes, including modulating mechanisms that reduce lifespan. In response to stress, SKN-1 and other regulators tailor transcription programs to meet the challenge at hand. Our findings reveal striking complexity in SKN-1 functions and the regulation of systemic detoxification defenses.
C1 [Oliveira, Riva P.; Abate, Jess Porter; Blackwell, T. Keith] Harvard Univ, Sch Med, Harvard Stem Cell Inst,Dept Pathol, Joslin Diabet Ctr,Sect Dev & Stem Cell Biol, Boston, MA 02215 USA.
[Dilks, Kieran; Landis, Jessica; Ashraf, Jasmine; Murphy, Coleen T.] Princeton Univ, Lewis Sigler Inst Integrat Genom, Dept Mol Biol, Princeton, NJ 08544 USA.
RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, Harvard Stem Cell Inst,Dept Pathol, Joslin Diabet Ctr,Sect Dev & Stem Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA.
EM ctmurphy@princeton.edu; keith.blackwell@joslin.harvard.edu
RI Oliveira, Riva/J-8408-2013
OI Oliveira, Riva/0000-0002-4917-7646
FU Kirchstein fellowship [GM70088, DK07260]; NIH [GM62891]; NSF; NIH
National Center for Research Resources (NCRR)
FX We thank Elizabeth Veal and Blackwell lab members for critically reading
this manuscript, and Joe Baker and Aileen Zhen for early contributions
to the study. Supported by a Kirchstein fellowship to RO (GM70088),
training grant funding to RO and JPA (DK07260), NIH grant GM62891 to
TKB, Pew Biomedical Scholar and Sloan Fellow funding to CTM, and an NSF
Predoctoral fellowship to JL. Some nematode strains used in this work
were provided by the Caenorhabditis Genetics Center, which is funded by
the NIH National Center for Research Resources (NCRR).
NR 65
TC 126
Z9 130
U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
EI 1474-9726
J9 AGING CELL
JI Aging Cell
PD OCT
PY 2009
VL 8
IS 5
BP 524
EP 541
DI 10.1111/j.1474-9726.2009.00501.x
PG 18
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 498FU
UT WOS:000270123400003
PM 19575768
ER
PT J
AU Schwer, B
Eckersdorff, M
Li, Y
Silva, JC
Fermin, D
Kurtev, MV
Giallourakis, C
Comb, MJ
Alt, FW
Lombard, DB
AF Schwer, Bjoern
Eckersdorff, Mark
Li, Yu
Silva, Jeffrey C.
Fermin, Damian
Kurtev, Martin V.
Giallourakis, Cosmas
Comb, Michael J.
Alt, Frederick W.
Lombard, David B.
TI Calorie restriction alters mitochondrial protein acetylation
SO AGING CELL
LA English
DT Editorial Material
DE calorie restriction; longevity; mass spectrometry; metabolism;
mitochondria; sirtuins
ID LYSINE ACETYLATION; CELLS; LIVER
AB P>Calorie restriction (CR) increases lifespan in organisms ranging from budding yeast through mammals. Mitochondrial adaptation represents a key component of the response to CR. Molecular mechanisms underlying this adaptation are largely unknown. Here we show that lysine acetylation of mitochondrial proteins is altered during CR in a tissue-specific fashion. Via large-scale mass spectrometry screening, we identify 72 candidate proteins involved in a variety of metabolic pathways with altered acetylation during CR. Mitochondrial acetylation changes may play an important role in the pro-longevity CR response.
C1 [Schwer, Bjoern; Giallourakis, Cosmas; Alt, Frederick W.; Lombard, David B.] Childrens Hosp, Howard Hughes Med Inst, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Schwer, Bjoern; Giallourakis, Cosmas; Alt, Frederick W.; Lombard, David B.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Eckersdorff, Mark; Fermin, Damian; Lombard, David B.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Lombard, David B.] Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA.
[Li, Yu; Silva, Jeffrey C.; Comb, Michael J.] Cell Signaling Technol, Danvers, MA 01923 USA.
[Kurtev, Martin V.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, Program Cellular & Mol Med, Boston, MA 02115 USA.
EM alt@enders.tch.harvard.edu; davidlom@umich.edu
FU Howard Hughes Medical Institute; NIA NIH HHS [K08 AG022325-06, AG022325,
K08 AG022325]; NIGMS NIH HHS [T32 GM007753]
NR 16
TC 139
Z9 145
U1 2
U2 20
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1474-9718
J9 AGING CELL
JI Aging Cell
PD OCT
PY 2009
VL 8
IS 5
BP 604
EP 606
DI 10.1111/j.1474-9726.2009.00503.x
PG 3
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 498FU
UT WOS:000270123400010
PM 19594485
ER
PT J
AU Weiser, SD
Bangsberg, DR
Kegeles, S
Ragland, K
Kushel, MB
Frongillo, EA
AF Weiser, Sheri D.
Bangsberg, David R.
Kegeles, Susan
Ragland, Kathleen
Kushel, Margot B.
Frongillo, Edward A.
TI Food Insecurity Among Homeless and Marginally Housed Individuals Living
with HIV/AIDS in San Francisco
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Food insecurity; HIV/AIDS; San Francisco; Homeless
ID ACTIVE ANTIRETROVIRAL THERAPY; BODY-MASS INDEX; DISEASE PROGRESSION;
HIV-INFECTION; MENTAL-HEALTH; WELFARE RECIPIENTS; PATIENT POPULATION;
NUTRITIONAL-STATUS; WEIGHT-LOSS; SURVIVAL
AB Food insecurity is a risk factor for both HIV transmission and worse HIV clinical outcomes. We examined the prevalence of and factors associated with food insecurity among homeless and marginally housed HIV-infected individuals in San Francisco recruited from the Research on Access to Care in the Homeless Cohort. We used multiple logistic regression to determine socio-demographic and behavioral factors associated with food insecurity, which was measured using the Household Food Insecurity Access Scale. Among 250 participants, over half (53.6%) were food insecure. Higher odds of food insecurity was associated with being white, low CD4 counts, recent crack use, lack of health insurance, and worse physical and mental health. Food insecurity is highly prevalent among HIV-infected marginally housed individuals in San Francisco, and is associated with poor physical and mental health and poor social functioning. Screening for and addressing food insecurity should be a critical component of HIV prevention and treatment programs.
C1 [Weiser, Sheri D.] Univ Calif San Francisco, Posit Hlth Program, San Francisco Gen Hosp, San Francisco, CA 94143 USA.
[Weiser, Sheri D.; Kegeles, Susan] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA.
[Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Initiat Global Hlth, Boston, MA USA.
[Ragland, Kathleen; Kushel, Margot B.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco Gen Hosp, San Francisco, CA 94143 USA.
[Frongillo, Edward A.] Univ S Carolina, Dept Hlth Promot Educ & Behav, Arnold Sch Publ Hlth, Columbia, SC 29208 USA.
RP Weiser, SD (reprint author), Univ Calif San Francisco, Posit Hlth Program, San Francisco Gen Hosp, POB 0874, San Francisco, CA 94143 USA.
EM Sheri.Weiser@ucsf.edu
FU NCRR NIH HHS [UL1 RR024131]; NIAAA NIH HHS [K24 AA015287, K024
AA015287]; NIMH NIH HHS [K23 MH079713, K24 MH087227, R01 MH054907, K23
MH079713-01]; PHS HHS [R01 #54907]
NR 54
TC 68
Z9 68
U1 1
U2 5
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS behav.
PD OCT
PY 2009
VL 13
IS 5
BP 841
EP 848
DI 10.1007/s10461-009-9597-z
PG 8
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 502AI
UT WOS:000270425800002
PM 19644748
ER
PT J
AU Mimiaga, MJ
Reisner, SL
Bland, S
Skeer, M
Cranston, K
Isenberg, D
Vega, BA
Mayer, KH
AF Mimiaga, Matthew J.
Reisner, Sari L.
Bland, Sean
Skeer, Margie
Cranston, Kevin
Isenberg, Deborah
Vega, Benny A.
Mayer, Kenneth H.
TI Health System and Personal Barriers Resulting in Decreased Utilization
of HIV and STD Testing Services among At-Risk Black Men Who Have Sex
with Men in Massachusetts
SO AIDS PATIENT CARE AND STDS
LA English
DT Article
ID NEW-YORK-CITY; BEHAVIORAL SURVEILLANCE SYSTEM;
SEXUALLY-TRANSMITTED-DISEASES; AFRICAN-AMERICAN MEN; PACIFIC ISLANDER
MEN; YOUNG MEN; CAGE QUESTIONNAIRE; PARTNER CHARACTERISTICS;
PSYCHOMETRIC EVALUATION; UNITED-STATES
AB Testing for HIV and other sexually transmitted diseases (STD) remains a cornerstone of public health prevention interventions. This analysis was designed to explore the frequency of testing, as well as health system and personal barriers to testing, among a community-recruited sample of Black men who have sex with men (MSM) at risk for HIV and STDs. Black MSM (n = 197) recruited via modified respondent-driven sampling between January and July 2008 completed an interviewer-administered assessment, with optional voluntary HIV counseling and testing. Logistic regression procedures examined factors associated with not having tested in the 2 years prior to study enrollment for: (1) HIV (among HIV-uninfected participants, n 145) and (2) STDs (among the entire mixed serostatus sample, n = 197). The odds ratios and their 95% confidence intervals obtained from this analysis were converted to relative risks. (1) HIV: Overall, 33% of HIV-uninfected Black MSM had not been tested for HIV in the 2 years prior to study enrollment. Factors uniquely associated with not having a recent HIV test included: being less educated; engaging in serodiscordant unprotected sex; and never having been HIV tested at a community health clinic, STD clinic, or jail. (2) STDs: Sixty percent had not been tested for STDs in the 2 years prior to study enrollment, and 24% of the sample had never been tested for STDs. Factors uniquely associated with not having a recent STD test included: older age; having had a prior STD; and never having been tested at an emergency department or urgent care clinic. Overlapping factors associated with both not having had a recent HIV or STD test included: substance use during sex; feeling that using a condom during sex is "very difficult''; less frequent contact with other MSM; not visiting a health care provider (HCP) in the past 12 months; having a HCP not recommend HIV or STD testing at their last visit; not having a primary care provider (PCP); current PCP never recommending they get tested for HIV or STDs. In multivariable models adjusting for relevant demographic and behavioral factors, Black MSM who reported that a HCP recommended getting an HIV test (adjusted relative risk [ARR] = 0.26; p = 0.01) or STD test (ARR = 0.11; p = 0.0004) at their last visit in the past 12 months were significantly less likely to have not been tested for HIV or STDs in the past 2 years. Many sexually active Black MSM do not regularly test for HIV or STDs. HCPs play a pivotal role in encouraging testing for Black MSM. Additional provider training is warranted to educate HCPs about the specific health care needs of Black MSM, in order to facilitate access to timely, culturally competent HIV and STD testing and treatment services for this population.
C1 [Mimiaga, Matthew J.; Reisner, Sari L.; Bland, Sean; Skeer, Margie; Vega, Benny A.; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA.
[Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Mimiaga, Matthew J.; Reisner, Sari L.; Skeer, Margie] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Cranston, Kevin; Isenberg, Deborah] Massachusetts Dept Publ Hlth, Boston, MA USA.
[Mayer, Kenneth H.] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA.
RP Mimiaga, MJ (reprint author), Fenway Community Hlth, Fenway Inst, Prudential Tower,4th Floor,800 Boylston St, Boston, MA 02119 USA.
EM mmimiaga@fenwayhealth.org
FU Office of HIV/AIDS, Massachusetts Department of Public Health; National
Institute on Drug Abuse (PI: M. Mimiaga) [R03DA023393]
FX This work was funded by the Office of HIV/AIDS, Massachusetts Department
of Public Health. Some of the investigator time on this project was
supported by grant number R03DA023393 from the National Institute on
Drug Abuse (PI: M. Mimiaga). The content is solely the responsibility of
the authors and does not necessarily represent the official views of the
National Institutes of Health.
NR 70
TC 53
Z9 56
U1 3
U2 11
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1087-2914
J9 AIDS PATIENT CARE ST
JI Aids Patient Care STDS
PD OCT
PY 2009
VL 23
IS 10
BP 825
EP 835
DI 10.1089/apc.2009.0086
PG 11
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 505VM
UT WOS:000270727200005
PM 19803696
ER
PT J
AU Maccioni, P
Carai, MAM
Kaupmann, K
Guery, S
Froestl, W
Leite-Morris, KA
Gessa, GL
Colombo, G
AF Maccioni, Paola
Carai, Mauro A. M.
Kaupmann, Klemens
Guery, Sebastien
Froestl, Wolfgang
Leite-Morris, Kimberly A.
Gessa, Gian Luigi
Colombo, Giancarlo
TI Reduction of Alcohol's Reinforcing and Motivational Properties by the
Positive Allosteric Modulator of the GABA(B) Receptor, BHF177, in
Alcohol-Preferring Rats
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE GABA(B) Receptor; Positive Allosteric Modulators of the GABA(B)
Receptor; BHF177; Alcohol Self-Administration; Fixed Ratio (FR) and
Progressive Ratio (PR) Schedules of Reinforcement; Alcohol's Reinforcing
and Motivational Properties; Sardinian Alcohol-Preferring (sP) Rats
ID MIDBRAIN DOPAMINE NEURONS; AGONIST BACLOFEN; PRESYNAPTIC INHIBITION;
ETHANOL SEEKING; ANIMAL-MODELS; B RECEPTORS; GS39783; SUCROSE; COCAINE;
CGP7930
AB Background:
The positive allosteric modulators of the GABA(B) receptor, CGP7930 and GS39783, have been found to reduce alcohol self-administration in alcohol-preferring rats. The present study was designed to assess the effect of the newly synthesized positive allosteric modulator of the GABA(B) receptor, BHF177, on alcohol's reinforcing and motivational properties in selectively bred Sardinian alcohol-preferring (sP) rats.
Methods:
sP rats were initially trained to respond on a lever [on a fixed ratio 4 (FR4) schedule of reinforcement] to orally self-administer alcohol (15%, v/v) or sucrose (1 to 3%, w/v) in daily 30-minute sessions. Once responding reached stable levels, rats were allocated to 2 different experiments: in the first experiment, rats were exposed to sessions with the FR4 schedule of reinforcement; in the second experiment, rats were exposed to sessions with a conventional progressive ratio (PR) schedule of reinforcement. In both experiments, the effect of BHF177 (0, 12.5, 25, and 50 mg/kg; i.g.) on responding for alcohol and sucrose (FR experiment: 1%, w/v; PR experiment: 3%, w/v) was determined.
Results:
In the FR experiment, pretreatment with 25 and 50 mg/kg BHF177 produced a 30 and 45% reduction, respectively, in responding for alcohol. In the PR experiment, pretreatment with 50 mg/kg BHF177 resulted in a 35% reduction in breakpoint for alcohol (defined as the lowest response requirement not achieved by each rat and used as index of the motivational strength of alcohol). In both experiments, the effect of BHF177 on alcohol self-administration was specific, since responding for sucrose was unaltered by BHF177 pretreatment.
Conclusions:
The present results extend to BHF177 the capacity of the 2 previously tested positive allosteric modulators of the GABA(B) receptor, CGP7930 and GS39783, to specifically suppress alcohol's reinforcing and motivational properties in alcohol-preferring rats.
C1 [Maccioni, Paola; Carai, Mauro A. M.; Gessa, Gian Luigi; Colombo, Giancarlo] CNR, Inst Neurosci, I-09126 Cagliari, CA, Italy.
[Kaupmann, Klemens] Novartis Inst BioMed Res, Basel, Switzerland.
[Guery, Sebastien] IMD Int, Lausanne, Switzerland.
[Froestl, Wolfgang] AC Immune SA, Lausanne, Switzerland.
[Leite-Morris, Kimberly A.] Boston Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Div Psychiat, Boston, MA 02118 USA.
[Leite-Morris, Kimberly A.] Boston VA Healthcare Syst, Res Serv, Boston, MA USA.
RP Colombo, G (reprint author), CNR, Inst Neurosci, Viale Diaz 182, I-09126 Cagliari, CA, Italy.
EM colomb@unica.it
OI Leite-Morris, Kimberly/0000-0003-3407-7375
NR 37
TC 30
Z9 30
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD OCT
PY 2009
VL 33
IS 10
BP 1749
EP 1756
DI 10.1111/j.1530-0277.2009.01012.x
PG 8
WC Substance Abuse
SC Substance Abuse
GA 497OD
UT WOS:000270068400011
PM 19572981
ER
PT J
AU Laine, L
Connors, L
Griffin, MR
Curtis, SP
Kaur, A
Cannon, CP
AF Laine, L.
Connors, L.
Griffin, M. R.
Curtis, S. P.
Kaur, A.
Cannon, C. P.
TI Prescription rates of protective co-therapy for NSAID users at high GI
risk and results of attempts to improve adherence to guidelines
SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INHIBITORS; AGENTS;
GASTROPROTECTION; OSTEOARTHRITIS; POPULATION; MANAGEMENT; COSTS
AB P>Background
Protective co-therapy is recommended in NSAID users with GI risk factors, but adherence is poor.
Aim
To assess the proportion of NSAID users receiving co-therapy and strategies to improve adherence.
Methods
Arthritis patients >= 50 years of age received etoricoxib or diclofenac in a double-blind randomized trial. Reminders that high-risk patients (age >= 65; previous ulcer/haemorrhage; corticosteroid, anticoagulant, aspirin use) should receive co-therapy were given at study initiation. Free PPI was provided. An intervention midway through the study included a written reminder and required written response regarding co-therapy.
Results
16 244/23 504 (69%) patients had GI risk factors. Pre-intervention, co-therapy was most common with previous ulcer/haemorrhage [706/1107 (64%)] and 3-4 risk factors [331/519 (64%)]. In the 10 026 patients enrolled pre-intervention and remaining in the study >= 6 months after, co-therapy in high-risk patients increased from 2958/6843 (43%) to 4177/6843 (61%) (difference = 18%; 95% CI 16%,19%). The increase was greater outside the US (22%; 19%,24%) than in the US (15%; 13%,17%).
Conclusions
Less than 50% of NSAID users with GI risk factors are given protective co-therapy - even if prescribers are given reminders and cost is not an issue. Direct communication requiring written response significantly increased adherence to guidelines, but achieving higher levels of adherence will require additional strategies.
C1 [Laine, L.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA.
[Connors, L.; Curtis, S. P.; Kaur, A.] Merck Res Labs, Rahway, NJ USA.
[Griffin, M. R.] Vanderbilt Univ, Med Ctr, Dept Prevent Med, Nashville, TN USA.
[Cannon, C. P.] Harvard Univ, Brigham & Womens Hosp, Thrombolysis Myocardial Infarct TIMI Study Grp, Cardiovasc Div,Dept Med,Med Sch, Boston, MA 02115 USA.
RP Laine, L (reprint author), Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, 2025 Zonal Ave, Los Angeles, CA 90033 USA.
EM llaine@usc.edu
OI Connors, Lawreen/0000-0002-4672-4296
FU TAP; Glaxo SmithKline; Merck; Pfizer; Accumetrics; AstraZeneca;
Bristol-Myers Squibb/Sanofi; Merck/Schering Plough; Merck Co., Inc.;
Whitehouse Station, NJ
FX Declaration of personal interests: L. Laine has served as a consultant
for Merck, AstraZeneca, Horizon, Santarus, Eisai, and Pozen; has
received research funding from TAP and Glaxo SmithKline; and has served
on a data safety and monitoring board for Pfizer and Bayer. L. Connors,
S. Curtis, A. Kaur are employees of Merck and own stock and/or stock
options. M. Griffin has served on a data safety and monitoring board for
Merck and received research funding from Merck and Pfizer. C. Cannon has
served as a consultant to Audiomedics; has received research funding
from Accumetrics, AstraZeneca, Bristol-Myers Squibb/Sanofi partnership,
Glaxo Smith Kline, and Merck/Schering Plough partnership; and has equity
in Audiomedics Medical Systems. Declaration of funding interests: This
study was funded by Merck & Co., Inc., Whitehouse Station, NJ. The
authors performed the analyses and wrote the manuscript without outside
assistance or support.
NR 21
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U1 3
U2 3
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-2813
J9 ALIMENT PHARM THER
JI Aliment. Pharmacol. Ther.
PD OCT 1
PY 2009
VL 30
IS 7
BP 767
EP 774
DI 10.1111/j.1365-2036.2009.04090.x
PG 8
WC Gastroenterology & Hepatology; Pharmacology & Pharmacy
SC Gastroenterology & Hepatology; Pharmacology & Pharmacy
GA 490WE
UT WOS:000269538000010
PM 19594486
ER
PT J
AU Bradford, A
Kunik, ME
Schulz, P
Williams, SP
Singh, H
AF Bradford, Andrea
Kunik, Mark E.
Schulz, Paul
Williams, Susan P.
Singh, Hardeep
TI Missed and Delayed Diagnosis of Dementia in Primary Care Prevalence and
Contributing Factors
SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS
LA English
DT Review
DE dementia; diagnostic errors; primary care
ID GENERAL-PRACTITIONERS; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT;
HEALTH-CARE; ELDERLY PATIENTS; UNITED-STATES; MENTAL-STATE; PHYSICIANS;
ATTITUDES; PERSPECTIVES
AB Dementia is a growing public health problem for which early detection may be beneficial. Currently, the diagnosis of dementia in primary care is dependent mostly on clinical suspicion on the basis of patient symptoms or caregivers' concerns and is prone to be missed or delayed. We conducted a systematic review of the literature to ascertain the prevalence and contributing factors for missed and delayed dementia diagnoses in primary care. Prevalence of missed and delayed diagnosis was estimated by abstracting quantitative data from studies of diagnostic sensitivity among primary care providers. Possible predictors and contribution factory factors were determined from the text of quantitative and qualitative Studies of patient, caregiver, provider, and system-related barriers. Overall estimates of diagnostic sensitivity varied among studies and seemed to be in part a function of dementia severity, degree of patient impairment, dementia subtype, and frequency of patient-provider contact. Major contributory factors included problems with attitudes and patient-provider communication, educational deficits. and system resource constraints. The true prevalence of missed and delayed diagnoses of dementia is unknown but seems to be high. Until the case for dementia screening becomes more compelling, efforts to promote timely detection should focus on removing barriers to diagnosis.
C1 [Bradford, Andrea] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
[Kunik, Mark E.] Baylor Coll Med, Houston VA HSR&D Ctr Excellence, Hlth Serv Delivery & Org Program, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
[Kunik, Mark E.; Singh, Hardeep] Baylor Coll Med, Sect Hlth Serv Res, Dept Med, Houston, TX 77030 USA.
[Schulz, Paul] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA.
[Williams, Susan P.] Baylor Coll Med, Dept Med, Sect Geriatr, Houston, TX 77030 USA.
[Singh, Hardeep] Baylor Coll Med, Hlth Policy & Qual Program, Houston VA HSR&D Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
[Singh, Hardeep] Baylor Coll Med, Ctr Inquiry Improve Outpatient Safety Effect Elec, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
RP Bradford, A (reprint author), Baylor Coll Med, Dept Psychiat & Behav Sci, VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM abradfor@bcm.tmc.edu
OI Bradford, Andrea/0000-0002-8390-8844
FU NIH K23 career development award [K23CA125585]; Houston VA HSR&D Center
of Excellence [HFP90-020]
FX The study was supported by an NIH K23 career development award
(K23CA125585) to Dr Singh, and in part by the Houston VA HSR&D Center of
Excellence (HFP90-020).
NR 76
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U1 4
U2 21
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0893-0341
J9 ALZ DIS ASSOC DIS
JI Alzheimer Dis. Assoc. Dis.
PD OCT-DEC
PY 2009
VL 23
IS 4
BP 306
EP 314
PG 9
WC Clinical Neurology; Pathology
SC Neurosciences & Neurology; Pathology
GA 527XE
UT WOS:000272403700002
PM 19568149
ER
PT J
AU Krueger, KR
Wilson, RS
Bennett, DA
Aggarwal, NT
AF Krueger, Kristin R.
Wilson, Robert S.
Bennett, David A.
Aggarwal, Neelum T.
TI A Battery of Tests for Assessing Cognitive Function in Older Latino
Persons
SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS
LA English
DT Article
DE Spanish language tests; cognitive domains; cognitive function;
longitudinal studies
ID ALZHEIMERS-DISEASE; NEUROPSYCHOLOGICAL BATTERY; INDIVIDUAL-DIFFERENCES;
SPANISH-SPEAKING; COMMUNITY; ENGLISH; PERFORMANCE; IMPAIRMENT; SYSTEMS;
AGE
AB With the proportion of older Latinos in the United States rapidly growing, dementia is expected to be an increasing public health problem in this segment of the population. Yet relatively few cognitive test batteries have been developed for evaluating older Spanish-speaking- persons. We selected a batter), of cognitive tests used in cognitive aging studies of English speakers, adapted it for Spanish speakers, and administered it to 66 older Latinos (mean age = 71.1, SD = 8.1). The results of a factor analysis supported grouping the tests into the same 5 functional domains identified for English speakers. Composite measures of performance in each domain were positively related to education and. with some exceptions, inversely related to age. The results suggest that this battery may be useful in epidemiologic research on cognition in older Latinos.
C1 [Krueger, Kristin R.; Wilson, Robert S.; Bennett, David A.; Aggarwal, Neelum T.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
[Krueger, Kristin R.; Wilson, Robert S.] Rush Univ, Med Ctr, Dept Behav Sci, Chicago, IL 60612 USA.
[Wilson, Robert S.; Bennett, David A.; Aggarwal, Neelum T.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.
RP Krueger, KR (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA.
EM Kristin.Krueger@va.gov
FU National Institute on Aging [P30 AG10161]
FX Supported by grant P30 AG10161 from the National Institute on Aging.
NR 30
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U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0893-0341
J9 ALZ DIS ASSOC DIS
JI Alzheimer Dis. Assoc. Dis.
PD OCT-DEC
PY 2009
VL 23
IS 4
BP 384
EP 388
PG 5
WC Clinical Neurology; Pathology
SC Neurosciences & Neurology; Pathology
GA 527XE
UT WOS:000272403700014
PM 19561439
ER
PT J
AU Cannon, CP
Dansky, HM
Davidson, M
Gotto, AM
Brinton, EA
Gould, AL
Stepanavage, M
Liu, SX
Shah, S
Rubino, J
Gibbons, P
Hermanowski-Vosatka, A
Binkowitz, B
Mitchel, Y
Barter, P
AF Cannon, Christopher P.
Dansky, Hayes M.
Davidson, Michael
Gotto, Antonio M., Jr.
Brinton, Eliot A.
Gould, A. Lawrence
Stepanavage, Michael
Liu, Sherry Xueyu
Shah, Sukrut
Rubino, Joseph
Gibbons, Patrice
Hermanowski-Vosatka, Anne
Binkowitz, Bruce
Mitchel, Yale
Barter, Philip
CA DEFINE Investigators
TI Design of the DEFINE trial: Determining the EFficacy and Tolerability of
CETP INhibition with AnacEtrapib
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID HIGH-DENSITY-LIPOPROTEIN; ESTER TRANSFER PROTEIN; CHOLESTEROL LEVELS;
THERAPEUTIC TARGET; HDL CHOLESTEROL; TORCETRAPIB; ATHEROSCLEROSIS;
ATORVASTATIN; STATINS; SAFETY
AB Background Residual cardiovascular (CV) risk often remains high despite statin therapy to lower low-density lipoprotein cholesterol (LDL-C). New therapies to raise high-density lipoprotein cholesterol (HDL-C) are currently being investigated. Anacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor that raises HDL-C and reduces LDL-C when administered alone or with a statin. Adverse effects on blood pressure, electrolytes, and aldosterone levels, seen with another drug in this class, have not been noted in studies of anacetrapib to date.
Methods Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib (DEFINE) is a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety profile of anacetrapib in patients with coronary heart disease (CHD) or CHID risk equivalents (clinical trials.gov NCT00685776). Eligible patients at National Cholesterol Education Program-Adult Treatment Panel III LDL-C treatment goal on a statin, with or without other lipid-modifying medications, are treated with anacetrapib, 100 mg, or placebo for 18 months, followed by a 3-month, poststudy follow-up. The primary end points are percent change from baseline in LDL-C and the safety and tolerability of anacetrapib. Comprehensive preplanned interim safety analyses will be performed at the 6- and 12-month time points to examine treatment effects on key safety end points, including blood pressure and electrolytes. A preplanned Bayesian analysis will be performed to interpret the CV event distribution, given the limited number of events expected in this study.
Results A total of 2,757 patients were screened at 153 centers in 20 countries, and 1,623 patients were randomized into the trial. Lipid results, clinical CV events, and safety outcomes from this trial are anticipated in 2010. (Am Heart J 2009; 158:513-9.)
C1 [Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA.
[Dansky, Hayes M.; Stepanavage, Michael; Liu, Sherry Xueyu; Shah, Sukrut; Gibbons, Patrice; Hermanowski-Vosatka, Anne; Binkowitz, Bruce; Mitchel, Yale] Merck Res Labs, Rahway, NJ USA.
[Davidson, Michael; Brinton, Eliot A.] Radiant Res, Chicago, IL USA.
[Gotto, Antonio M., Jr.] Weill Cornell Med Coll, New York, NY USA.
Univ Utah, Sch Med, Salt Lake City, UT USA.
[Gould, A. Lawrence; Rubino, Joseph] Merck Res Labs, Upper Gwynedd, PA USA.
[Barter, Philip] Heart Res Inst, Sydney, NSW, Australia.
RP Cannon, CP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA.
EM cpcannon@partners.org
FU Accumetrics, San Diego, CA; AstraZeneca, Wilmington, DE; Bristol-Myers
Squibb, Princeton, NJ/Sanofi Partnership, Paris, France; Glaxo Smith
Kline, Philadelphia, PA; Intekrin, Los Altos, CA; Merck, Whitehouse
Station, NJ; Merck/Schering Plough Partnership, Kenilworth, NJ; Abbott;
Pfizer; Sanofi-Aventis; Takeda Pharmaceuticals; Merck Research
Laboratories, Rahway, NJ
FX The DEFINE study and the study analyses were funded by Merck Research
Laboratories, Rahway, NJ. The first draft of the manuscript was prepared
by Dr Cannon, with edits and comments provided by all coauthors. The
authors wish to thank Christine McCrary Sisk (Merck Research
Laboratories) for her contributions in editing this manuscript.
NR 22
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U1 0
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD OCT
PY 2009
VL 158
IS 4
BP 513
EP +
DI 10.1016/j.ahj.2009.07.028
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 505PI
UT WOS:000270706100004
PM 19781408
ER
PT J
AU Heidenreich, PA
Lewis, WR
LaBresh, KA
Schwamm, LH
Fonarow, GC
AF Heidenreich, Paul A.
Lewis, William R.
LaBresh, Kenneth A.
Schwamm, Lee H.
Fonarow, Gregg C.
TI Hospital performance recognition with the Get With The Guidelines
Program and mortality for acute myocardial infarction and heart failure
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID TRANSIENT ISCHEMIC ATTACK; ASSOCIATION TASK-FORCE; AMERICAN-COLLEGE;
ST-ELEVATION; QUALITY; INCOME; RATES; IMPROVEMENT; MANAGEMENT; EDUCATION
AB Background Many hospitals enrolled in the American Heart Association's Get With The Guidelines (GWTG) Program achieve high levels of recommended care for heart failure, acute myocardial infarction (MI) and stroke. However, it is unclear if outcomes are better in those hospitals recognized by the GWTG program for their processes of care.
Methods We compared hospitals enrolled in GWTG and receiving achievement awards for high levels of recommended processes of care with other hospitals using data on risk-adjusted 30-day survival for heart failure and acute MI reported by the Center for Medicare and Medicaid Services.
Results Among the 3,909 hospitals with 30-day data reported by Center for Medicare and Medicaid Services 355 (9%) received GWTG achievement awards. Risk-adjusted mortality for hospitals receiving awards was lower for both heart failure (11.0% vs 11.2%, P = .0005) and acute MI (16.1% vs 16.5%, P < .0001) compared to those not receiving awards. After additional adjustment for hospital characteristics and noncardiac performance measures, the reduction in mortality remained significantly lower for GWTG award hospitals for acute myocardial infraction (-0.19%, 95% CI -0.33 to -0.05), but not for heart failure (-0.11%, 95% CI -0.25 to 0.02). Additional adjustment for cardiac processes of care reduced the benefit of award hospitals by 28% for heart failure mortality and 43% for acute MI mortality.
Conclusions Hospitals receiving achievement awards from the GWTG program have modestly lower risk adjusted mortality for acute MI and to a lesser extent, heart failure, explained in part by better process of care. (Am Heart J 2009; 158:546-53.)
C1 [Heidenreich, Paul A.] VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA.
[Lewis, William R.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[LaBresh, Kenneth A.] RTI Int Waltham, Waltham, MA USA.
[Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Fonarow, Gregg C.] Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA.
RP Heidenreich, PA (reprint author), VA Palo Alto Hlth Care Syst, 111C Cardiol,3801 Miranda Ave, Palo Alto, CA 94304 USA.
EM heiden@stanford.edu
RI LaBresh, Kenneth/A-6995-2017;
OI LaBresh, Kenneth/0000-0001-9040-1956; Heidenreich,
Paul/0000-0001-7730-8490; Schwamm, Lee/0000-0003-0592-9145
FU GlaxoSmithKline; Merck/Schering-Plough Partnership
FX Program disclosure: GWTG is a program of the AHA and is Supported in
part by unrestricted educational grants from GlaxoSmithKline and
Merck/Schering-Plough Partnership.
NR 25
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U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD OCT
PY 2009
VL 158
IS 4
BP 546
EP 553
DI 10.1016/j.ahj.2009.07.031
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 505PI
UT WOS:000270706100009
PM 19781413
ER
PT J
AU Mahabadi, AA
Bamberg, F
Toepker, M
Schlett, CL
Rogers, IS
Nagurney, JT
Brady, TJ
Hoffmann, U
Truong, QA
AF Mahabadi, Amir A.
Bamberg, Fabian
Toepker, Michael
Schlett, Christopher L.
Rogers, Ian S.
Nagurney, John T.
Brady, Thomas J.
Hoffmann, Udo
Truong, Quynh A.
TI Association of aortic valve calcification to the presence, extent, and
composition of coronary artery plaque burden: From the Rule Out
Myocardial Infarction using Computer Assisted Tomography (ROMICAT) trial
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID C-REACTIVE PROTEIN; ATHEROSCLEROTIC PLAQUE; STENOSIS; PROGRESSION;
CALCIUM; INFLAMMATION; ANGIOGRAPHY; POPULATION; DISEASE
AB Background Aortic valve calcification (AVC) is associated with cardiovascular risk factors and coronary artery calcification. We sought to determine whether AVC is associated with the presence and extent of overall plaque burden, as well as to plaque composition (calcified, mixed, and noncalcified).
Methods We examined 357 subjects (mean age 53 12 years, 61% male) who underwent contrast-enhanced electrocardiogram-gated 64-slice multidetector computed tomography from the ROMICAT trial for the assessment of presence and extent of coronary plaque burden according to the 17-coronary segment model and presence of AVC.
Results Patients with AVC (n = 37, 10%) were more likely than those without AVC (n = 320, 90%) to have coexisting presence of any coronary plaque (89% vs 46%, P < .001) and had a greater extent of coronary plaque burden (6.4 vs 1.8 segments, P < .001). Those with AVC had >3-fold increase odds of having any plaque (adjusted odds ratio [OR] 3.6, P = .047) and an increase of 2.5 segments of plaque (P < .001) as compared to those without AVC. When stratified by plaque composition, AVC was associated most with calcified plaque (OR 5.2, P = .004), then mixed plaque (OR 3.2, P = .02), but not with noncalcified plaque (P = .96).
Conclusion Aortic valve calcification is associated with the presence and greater extent of coronary artery plaque burden and may be part of the later stages of the atherosclerosis process, as its relation is strongest with calcified plaque, less with mixed plaque, and nonsignificant with noncalcified plaque. If AVC is present, consideration for aggressive medical therapy may be warranted. (Am Heart J 2009;158:562-8.)
C1 [Mahabadi, Amir A.; Toepker, Michael; Schlett, Christopher L.; Rogers, Ian S.; Brady, Thomas J.; Hoffmann, Udo; Truong, Quynh A.] Harvard Univ, Cardiac MR PET CT Program, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Bamberg, Fabian] Univ Munich, Klinikum Grosshadern, Dept Clin Radiol, D-8000 Munich, Germany.
[Rogers, Ian S.; Truong, Quynh A.] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Nagurney, John T.] Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Brady, Thomas J.; Hoffmann, Udo; Truong, Quynh A.] Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
RP Truong, QA (reprint author), Harvard Univ, Cardiac MR PET CT Program, Massachusetts Gen Hosp, Sch Med, 165 Cambridge St,Suite 400, Boston, MA 02114 USA.
EM qtruong@partners.org
FU NHLBI NIH HHS [T32 HL076136, T32 HL076136-05, K23 HL098370, L30
HL093806, L30 HL093806-01, R01 HL080053, R01 HL080053-03]
NR 26
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U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD OCT
PY 2009
VL 158
IS 4
BP 562
EP 568
DI 10.1016/j.ahj.2009.07.027
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 505PI
UT WOS:000270706100011
PM 19781415
ER
PT J
AU Forman, DE
Clare, R
Kitzman, DW
Ellis, SJ
Fleg, JL
Chiara, T
Fletcher, G
Kraus, WE
AF Forman, Daniel E.
Clare, Robert
Kitzman, Dalane W.
Ellis, Stephen J.
Fleg, Jerome L.
Chiara, Toni
Fletcher, Gerald
Kraus, William E.
CA HF-ACTION Investigators
TI Relationship of age and exercise performance in patients with heart
failure: The HF-ACTION study
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID TRIAL INVESTIGATING OUTCOMES; BODY-MASS INDEX; CHRONOTROPIC
INCOMPETENCE; VENTILATORY EFFICIENCY; AEROBIC CAPACITY; EJECTION
FRACTION; VE/VCO2 SLOPE; ADVANCING AGE; HEALTHY-MEN; ARTERIAL
AB Background More than three fourths of patients with heart failure (HF) are 65 years and older, and older age is associated with worse symptoms and prognoses than is younger age. Reduced exercise capacity is a chief HF complaint and indicates poorer prognosis, especially among elderly persons, but the mechanisms underlying functional decline in older patients with HF are largely unknown.
Methods Baseline cardiopulmonary exercise testing data from the HF-ACTION trial were assessed to clarify age effects on peak oxygen consumption (VO(2)) and ventilation-carbon dioxide production (VE/VCO(2)) slope.
Results Among 2,331 New York Heart Association class II-IV patients with HF, increased age corresponded to decreased peak VO(2) (-0.14 mL kg(-1) min(-1) per year >40 years; P<.0001) and increased VE/VCO(2) slope (0.30 U/y>70years; P<.0001). In a multivariable model with 34 other potential determinants, age was the strongest independent predictor of peak VO(2) (partial R(2) 0.130, total R(2) 0.392; P<.001) and a significant but relatively weaker predictor of VE/VCO(2) slope (partial R(2) 0.037, total R(2) 0.199; P<.001). Blunted peak heart rate was also a strong predictor of peak VO(2). Although peak heart rate and age were strongly correlated, both were significant independent predictors of peak VO(2) when analyzed simultaneously in a model. Aggregate comorbidity increased significantly with age but did not account for age effects on peak VO(2).
Conclusions Age is the strongest predictor of peak VO(2) and a significant predictor of VE/VCO(2) slope in the HF-ACTION population. Age-dependent comorbidities do not explain changes in peak VO(2). Age-related changes in cardiovascular physiology, potentially magnified by the HF disease state, should be considered a contributor to the pathophysiology and a target for more effective therapy in older patients with HF. (Am Heart J 2009; 1 58:S6-S15.)
C1 [Kraus, William E.] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA.
[Forman, Daniel E.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Forman, Daniel E.] VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA USA.
[Clare, Robert; Ellis, Stephen J.] Duke Clin Res Inst, Durham, NC USA.
[Kitzman, Dalane W.] Wake Forest Univ Hlth Sci, Dept Internal Med, Cardiol Sect, Winston Salem, NC USA.
[Kitzman, Dalane W.] Wake Forest Univ Hlth Sci, Dept Internal Med, Sect Geriatr, Winston Salem, NC USA.
[Fleg, Jerome L.] NHLBI, Div Cardiovasc Dis, Bethesda, MD 20892 USA.
[Chiara, Toni] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Phys Therapy, Malcom Randall VA Med Ctr, Gainesville, FL USA.
[Fletcher, Gerald] Mayo Clin Jacksonville, Jacksonville, FL 32224 USA.
RP Kraus, WE (reprint author), Duke Univ, Med Ctr, Dept Med, Div Cardiol, POB 3327, Durham, NC 27710 USA.
EM william.kraus@duke.edu
OI Kraus, William E/0000-0003-1930-9684
FU National Institutes of Health [5U01HL063747, 5U01HL068973, 5UO1HL066501,
5U01HL066482, 5U01HL064250, 5U01HL066494, 5U01HL064257, 5U01HL066497,
5U01HL068980, 5U01HL064265, 5U01HL066491, 5U01HL064264, R37AG18915,
P60AG10484]
FX A complete list of the HF-ACTION investigators is available as on
appendix in the introduction of this supplement. This study was
supported by National Institutes of Health grants 5U01HL063747,
5U01HL068973, 5UO1HL066501, 5U01HL066482, 5U01HL064250, 5U01HL066494,
5U01HL064257, 5U01HL066497, 5U01HL068980, 5U01HL064265, 5U01HL066491,
5U01HL064264, R37AG18915, and P60AG10484.
NR 40
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Z9 18
U1 0
U2 8
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD OCT
PY 2009
VL 158
IS 4
BP S6
EP S15
DI 10.1016/j.ahj.2009.07.018
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 505PG
UT WOS:000270705800002
PM 19782790
ER
PT J
AU Spies, C
Farzaneh-Far, R
Na, B
Kanaya, A
Schiller, NB
Whooley, MA
AF Spies, Christian
Farzaneh-Far, Ramin
Na, Beeya
Kanaya, Alka
Schiller, Nelson B.
Whooley, Mary A.
TI Relation of Obesity to Heart Failure Hospitalization and Cardiovascular
Events in Persons With Stable Coronary Heart Disease (from the Heart and
Soul Study)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID BODY-MASS INDEX; DEPRESSIVE SYMPTOMS; ABDOMINAL OBESITY; RISK;
MORTALITY; WEIGHT; DYSFUNCTION; DISORDERS; ADIPOSITY; INSULIN
AB Obesity is an independent risk factor for recurrent events among patients with established coronary heart disease (CHD). The goal of the present study was to identify potential mechanisms underlying this association. We measured the waist-to-hip ratio and body mass index in 979 outpatients with stable CHD and followed them for a mean of 4.9 years. We used proportional hazards models to evaluate the extent to which the association of obesity with subsequent heart failure (HF) hospitalization or cardiovascular (CV) events (myocardial infarction, stroke, or CHD death) was explained by baseline co-morbidities, cardiac disease severity, inflammation, insulin resistance, neurohormones and adipokines. Of the 979 participants, 128 (13%) were hospitalized for HF and 152 (16%) developed a CV event. Each standard deviation (SD) increase in the waist-to-hip ratio was associated with a 30% increased risk of HF hospitalization (unadjusted hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.1 to 1.6). This association was not attenuated after adjustment for potential mediators (HR 1.6, 95% CI 1.2 to 2.1.). Likewise, each SD increase in the waist-to-hip ratio was associated with a 20% greater risk of CV events (unadjusted HR 1.2, 95% CI 1.0 to 1.4), and this remained unchanged after adjustment for potential mediators (adjusted HR 1.3, 95% CI 1.0 to 1.5). The body mass index was not associated with the risk of HF or CV events. In conclusion, abdominal obesity is an independent predictor of HF hospitalization and recurrent CV events in patients with stable CHD. This association does not appear to be mediated by co-morbid conditions, cardiac disease severity, insulin resistance, inflammation, neurohormones, or adipokines. (C) 2009 Elsevier Inc. All rights reserved. (Am J Cardiol 2009;104:883-889)
C1 [Farzaneh-Far, Ramin; Na, Beeya; Whooley, Mary A.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
[Spies, Christian] Queens Med Ctr, Honolulu, HI USA.
[Farzaneh-Far, Ramin; Kanaya, Alka; Schiller, Nelson B.; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Whooley, Mary A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP Farzaneh-Far, R (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
EM rfarzanehfar@medicine.ucsf.edu
FU Department of Veterans Affairs, Washington, DC; National Heart Lung and
Blood Institute [RO 1 HL079235]
FX The Heart and Soul Study was funded by the Department of Veterans
Affairs, Washington, DC; the National Heart Lung and Blood Institute,
Grant RO 1 HL079235, Bethesda, Maryland; the American Federation for
Aging Research (Paul Beeson Scholars Program), New York, New York; the
Robert Wood Johnson Foundation (Faculty Scholars Program), Princeton,
New Jersey; and the Nancy Kirwan Heart Research Fund, San Francisco,
California. Dr. Farzaneh-Far was supported by an American Heart
Association Fellow-to-Faculty Transition Award (Dallas, Texas).
NR 30
TC 11
Z9 12
U1 1
U2 4
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD OCT 1
PY 2009
VL 104
IS 7
BP 883
EP 889
DI 10.1016/j.amjcard.2009.05.027
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 503MG
UT WOS:000270537800003
PM 19766751
ER
PT J
AU Yosefy, C
Hung, J
Chua, S
Vaturi, M
Ton-Nu, TT
Handschumacher, MD
Levine, RA
AF Yosefy, Chaim
Hung, Judy
Chua, Sarah
Vaturi, Mordehay
Ton-Nu, Thanh-Thao
Handschumacher, Mark D.
Levine, Robert A.
TI Direct Measurement of Vena Contracta Area by Real-Time 3-Dimensional
Echocardiography for Assessing Severity of Mitral Regurgitation
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID QUANTITATIVE DOPPLER ASSESSMENT; FLOW MAPPING PREDICTS; CHRONIC
ANIMAL-MODEL; COLOR DOPPLER; ORIFICE AREA; VALVULAR REGURGITATION;
AORTIC REGURGITATION; JET AREA; QUANTIFICATION; VOLUME
AB We tested the hypothesis that the vena contracta (VC) cross-sectional area in patients with mitral regurgitation (MR) can be reproducibly measured by real-time 3-dimensional (3D) echocardiography and correlates well with the volumetric effective regurgitant orifice area (EROA). Earlier MR repair requires accurate noninvasive measures, but practically, the VC area is difficult to image in 2-dimensional views, which are often oblique to it. 3D echocardiography can provide an otherwise unobtainable true cross-sectional view. In 45 patients with mild or greater MR, 44% eccentric, 2-dimensional and 3D VC areas were measured and correlated with the EROA derived from the regurgitant stroke volume. Real-time 3D echocardiography of the VC area correlated and agreed well with the EROA for both central and eccentric jets (r(2) = 0.86, SEE 0.02 cm(2), difference 0.04 +/- 0.06 cm(2), p = NS). For eccentric jets, 2-dimensional echocardiography overestimated the VC width compared with 3D echocardiography (p = 0.024) and correlated more poorly with the EROA (r(2) = 0.61 vs 0.85, p <0.001), causing clinical misclassification in 45% of patients with eccentric MR. The interobserver variability for the 3D VC area was 0.03 cm(2) (7.5% of the mean, r = 0.95); the intraobserver variability was 0.01 cm(2) (2.5% of the mean, r = 0.97). In conclusion, real-time 3D echocardiography accurately and reproducibly quantified the vena contracta cross-sectional area in patients with both central and eccentric MR. Rapid acquisition and intuitive analysis promote practical clinical application of this central, directly visualized, measure and its correlation with outcome. (C) 2009 Elsevier Inc. All rights reserved. (Am J Cardiol 2009;104:978-983)
C1 [Yosefy, Chaim; Hung, Judy; Chua, Sarah; Vaturi, Mordehay; Ton-Nu, Thanh-Thao; Handschumacher, Mark D.; Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02115 USA.
RP Levine, RA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02115 USA.
EM rlevine@partners.org
FU NHLBI NIH HHS [K24 HL067434, K24 HL067434-08, R01 HL038176, R01
HL038176-14, R01 HL072265, R01 HL072265-04]
NR 30
TC 47
Z9 49
U1 0
U2 1
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD OCT 1
PY 2009
VL 104
IS 7
BP 978
EP 983
DI 10.1016/j.amjcard.2009.05.043
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 503MG
UT WOS:000270537800019
PM 19766767
ER
PT J
AU Imamura, F
Lichtenstein, AH
Dallal, GE
Meigs, JB
Jacques, PF
AF Imamura, Fumiaki
Lichtenstein, Alice H.
Dallal, Gerard E.
Meigs, James B.
Jacques, Paul F.
TI Generalizability of dietary patterns associated with incidence of type 2
diabetes mellitus
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID FOOD-FREQUENCY QUESTIONNAIRE; CORONARY-HEART-DISEASE; TRANS-FATTY-ACIDS;
SUGAR-SWEETENED BEVERAGES; MIDDLE-AGED ADULTS; ALCOHOL-CONSUMPTION; MEAT
INTAKE; INSULIN-RESISTANCE; WHITEHALL-II; RISK
AB Background: Reduced rank regression (RRR) has been used to derive dietary pattern scores that predict linear combinations of disease biomarkers. The generalizability of these patterns to independent populations remains unknown.
Objective: The goal was to examine the generalizability of dietary patterns from the following prior studies using RRR to predict type 2 diabetes mellitus (T2DM): the Nurses' Health Study (NHS), European Prospective Investigation into Cancer and Nutrition Germany (EPIC), and Whitehall II Study (WS).
Design: The relative weights of food groups of each dietary pattern were used to generate each dietary pattern score in the Framingham Offspring Study (n = 2879). Each of the external scores (confirmatory scores) was examined to determine whether it could predict incident T2DM during 7 y of follow-up as well as scores developed internally in the Framingham Offspring Study using a Cox-proportional hazard model adjusted for T2DM risk factors.
Results: Intakes of meat products, refined grains, and soft drinks (caloric and noncaloric) were found to be common predictive components of all confirmatory scores, but fried foods, eggs, and alcoholic beverages were predictive in some, but not in all, confirmatory scores. On the basis of a continuous increase in the score by 1 SD, the NHS-based confirmatory score predicted T2DM risk (hazard ratio: 1.44; 95% CI: 1.25, 1.66). However, T2DM risk was only weakly predicted by the EPIC-based score (hazard ratio: 1.14; 95% CI: 0.99, 1.32) and the WS-based score (hazard ratio: 1.16; 95% CI: 1.00, 1.35).
Conclusions: The study suggested that dietary patterns that predict T2DM risk in different populations may not be generalizable to different populations. Additional dietary pattern studies should be conducted with regard to generalizability. Am J Clin Nutr 2009;90:1075-83.
C1 [Imamura, Fumiaki; Lichtenstein, Alice H.; Dallal, Gerard E.; Jacques, Paul F.] Tufts Univ, Jean Meyer USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA.
[Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
RP Jacques, PF (reprint author), Tufts Univ, Jean Meyer USDA, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA.
EM paul.jacques@tufts.edu
OI Imamura, Fumiaki/0000-0002-6841-8396
FU US Department of Agriculture, Agricultural Research Service
[58-1950-7-707]; National Institutes of Health [N01-HC-25195]; NIDDK
[K24 DK080140]
FX Supported in part by the US Department of Agriculture, Agricultural
Research Service, under agreement no. 58-1950-7-707 and the Framingham
Heart Study of the National Heart Lung and Blood Institute of the
National Institutes of Health (contract no. N01-HC-25195). JBM was
supported by NIDDK K24 DK080140.
NR 49
TC 32
Z9 32
U1 0
U2 4
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD OCT 1
PY 2009
VL 90
IS 4
BP 1075
EP 1083
DI 10.3945/ajcn.2009.28009
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 496GC
UT WOS:000269956700025
PM 19710193
ER
PT J
AU Wagner, PL
Perner, S
Rickman, DS
LaFargue, CJ
Kitabayashi, N
Johnstone, SF
Weir, BA
Meyerson, M
Altorki, NK
Rubin, MA
AF Wagner, Patrick L.
Perner, Sven
Rickman, David S.
LaFargue, Christopher J.
Kitabayashi, Naoki
Johnstone, Stephen F.
Weir, Barbara A.
Meyerson, Matthew
Altorki, Nasser K.
Rubin, Mark A.
TI In Situ Evidence of KRAS Amplification and Association With Increased
p21 Levels in Non-Small Cell Lung Carcinoma
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
DE Lung cancer; KRAS; EGFR; p21; Gene amplification
ID COMPARATIVE GENOMIC HYBRIDIZATION; EML4-ALK FUSION; KI-RAS; GENE
AMPLIFICATION; COPY NUMBER; CANCER; ADENOCARCINOMA; MUTATIONS;
PROTOONCOGENES; ABERRATIONS
AB Recent advances in the characterization of the lung cancer genome have suggested that KRAS may frequently be amplified, although little is known regarding the significance of this finding. This is in contrast with activating mutations of KRAS, which occur in approximately 20% of non-small cell lung carcinomas (NSCLCs).
We used fluorescence in situ hybridization to provide direct evidence of KRAS amplification for the first time in clinical specimens. We detected amplification in 7 of 100 consecutive NSCLCs, with a concurrent activating KRAS mutation in 4 cases. KRAS amplification was associated with greater expression of p21 as assessed by quantitative immunohistochemical analysis (P =. 015).
Our data indicate that a sizable subgroup of NSCLCs harbor KRAS amplification, some of which also contain point mutations, and suggest that an increased KRAS copy number may drive p21 overexpression. KRAS amplification may define a unique clinicopathologic subset of NSCLCs with potentially altered responsiveness to targeted therapies
C1 [Wagner, Patrick L.; Perner, Sven; Rickman, David S.; LaFargue, Christopher J.; Kitabayashi, Naoki; Johnstone, Stephen F.; Rubin, Mark A.] Cornell Univ, Weill Med Coll, Dept Pathol & Lab Med, New York, NY 10021 USA.
[Wagner, Patrick L.; Altorki, Nasser K.] Cornell Univ, Weill Med Coll, Dept Cardiothorac Surg, New York, NY 10021 USA.
[Weir, Barbara A.; Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Wagner, PL (reprint author), 525 E 68 St,K-707, New York, NY 10021 USA.
RI Meyerson, Matthew/E-7123-2012;
OI Rubin, Mark/0000-0002-8321-9950
NR 22
TC 14
Z9 14
U1 0
U2 0
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD OCT
PY 2009
VL 132
IS 4
BP 500
EP 505
DI 10.1309/AJCPF10ZUNSOLIFG
PG 6
WC Pathology
SC Pathology
GA 503AQ
UT WOS:000270503500002
PM 19762526
ER
PT J
AU Cannizzo, E
Bellio, E
Dorn, ME
Sadowski, C
Bucci, JJ
Petrini, M
Carulli, G
Preffer, F
AF Cannizzo, Elisa
Bellio, Emanuele
Dorn, Michelle E.
Sadowski, Craig
Bucci, Janessa J.
Petrini, Mario
Carulli, Giovanni
Preffer, Frederic
TI The Diagnostic Role of Multiparameter Immunophenotyping by Flow
Cytometry in Multiple Myeloma: A New Model
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Meeting Abstract
CT AJCP Resident Research Symposium and Poster Sessions/Annual Meeting of
the American-Society-for-Clinical-Pathology
CY OCT 28-NOV 01, 2009
CL Chicago, IL
SP Amer Soc Clin Pathol
C1 [Cannizzo, Elisa; Dorn, Michelle E.; Sadowski, Craig; Bucci, Janessa J.; Preffer, Frederic] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Cannizzo, Elisa; Dorn, Michelle E.; Sadowski, Craig; Bucci, Janessa J.; Preffer, Frederic] Harvard Univ, Sch Med, Boston, MA USA.
[Cannizzo, Elisa; Bellio, Emanuele; Petrini, Mario; Carulli, Giovanni] Univ Pisa, Sect Hematol, Dept Oncol Transplants & Advances Med, Pisa, Italy.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD OCT
PY 2009
VL 132
IS 4
MA 39
BP 634
EP 634
PG 1
WC Pathology
SC Pathology
GA 503AQ
UT WOS:000270503500056
ER
PT J
AU Coniglio, I
Garcia-Godoy, F
Magni, E
Carvalho, CA
Ferrari, M
AF Coniglio, Ivanovic
Garcia-Godoy, Franklin
Magni, Elisa
Carvalho, Carlos Augusto
Ferrari, Marco
TI Resin cement thickness in oval-shaped canals: Oval vs. circular fiber
posts in combination with different tips/drills for post space
preparation
SO AMERICAN JOURNAL OF DENTISTRY
LA English
DT Article
ID ENDODONTICALLY TREATED TEETH; CLINICAL-PERFORMANCE; ROOT CANALS;
INSTRUMENTS; STRENGTH; DENTIN; LAYER; HAND
AB Purpose: To evaluate the cement thickness around oval and circular posts luted in oval post spaces prepared with different drills/tips. Methods: Extracted premolars were endodontically treated and obturated, then randomly divided into three groups (n = 5) according to the tips/drills used for post-space preparation and to the type of fiber post luted: medium grit oval tip + oval posts, fine grit oval tip + oval posts, Mtwo Post File drill + circular posts. The specimens were sectioned in horizontal slices; one slice per canal third was chosen for each post-space, resulting in three slices for each specimen. The distances between the canal wall and the post perimeter were measured on SEM images of each slice. Results: The fine grit tip + oval post group obtained statistically significant lower cement thicknesses than the other groups (P < 0.05), in particular in the apical third. The MtwoPF + circular post group showed the highest cement thickness, comparable to that of the medium tip + oval post group. A good post fitting in oval-shaped canals can be obtained using a fine grit oval tip combined with oval posts. (Am J Dent 2009;22:290-294).
C1 [Coniglio, Ivanovic; Magni, Elisa; Ferrari, Marco] Univ Siena, Policlin Le Scotte, Sch Dent Med, Dept Fixed Prosthodont & Dent Mat, I-53100 Siena, Italy.
[Garcia-Godoy, Franklin] Univ Tennessee, Coll Dent, Biosci Res Ctr, Memphis, TN USA.
[Garcia-Godoy, Franklin] Forsyth Inst, Boston, MA USA.
[Carvalho, Carlos Augusto] Univ Sao Paulo, Bauru Sch Dent, Dept Operat Dent, Bauru, Brazil.
[Ferrari, Marco] Univ Siena, Sch Dent Med, Dept Dent Mat & Restorat Dent, I-53100 Siena, Italy.
[Ferrari, Marco] Tufts Univ, Sch Dent Med, Boston, MA 02111 USA.
RP Ferrari, M (reprint author), Univ Siena, Policlin Le Scotte, Sch Dent Med, Dept Fixed Prosthodont & Dent Mat, Viale Bracci, I-53100 Siena, Italy.
EM md3972@mclink.it
NR 22
TC 21
Z9 25
U1 0
U2 0
PU MOSHER & LINDER, INC
PI WESTON
PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA
SN 0894-8275
J9 AM J DENT
JI Am. J. Dent.
PD OCT
PY 2009
VL 22
IS 5
BP 290
EP 294
PG 5
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 548JO
UT WOS:000273958100009
PM 20225472
ER
PT J
AU Chapman, J
Pallin, D
Ferrara, L
Mortell, S
Pliakas, J
Shear, M
Thomas, S
AF Chapman, Jacob
Pallin, Daniel
Ferrara, Larisa
Mortell, Sarah
Pliakas, John
Shear, Melissa
Thomas, Stephen
TI Endotracheal tube cuff pressures in patients intubated before transport
SO AMERICAN JOURNAL OF EMERGENCY MEDICINE
LA English
DT Article
ID BLOOD-FLOW
AB Introduction: Prolonged endotracheal tube cuff pressures (ETTCPs) greater than 30 cm H(2)O cause complications ranging from sore throat to rare cases of tracheoesophageal fistula. In a series of patients, we sought to determine the proportion of patients with overinflated cuffs and to determine whether overinflation was associated with demographics, diagnostic category, or intubator credentials.
Methods: Between July 2007 and April 2008, we measured cuff pressures on a convenience sample of patients drawn from 2 groups. The "helicopter group" had pressure measured before transport by a single aeromedical transport service. The "hospital group" had pressure measured upon arrival to I of 2 emergency departments after being intubated before transport.
Results: Three hundred patients aged 4 to 92 years (median, 57) were studied: 59.7% were male; and diagnostic categories were neurologic (33.7%), trauma (32.7%), cardiac (12.7%), and general medical/surgical (21.0%). Intubation occurred 1 to 28 000 minutes before ETTCP assessment (median, 60). Endotracheal tube cuff pressure was greater than 30 cm H(2)O in 64.7% and ranged from 10 to 180 (median, 40). Forty-nine percent of patients had ETTCP greater than 40 cm H(2)O. There was no association between ETTCP and age group, sex, diagnostic category, ETT size, time between intubation and ETTCP assessment, or intubator credentials.
Conclusions: The most compelling results of the study are the high rates of elevated ETTCPs. Furthermore, there were no clear risk factors for elevated ETTCP. Although the risk of elevated ETTCP in the prehospital to acute care time frame is unclear, it seems reasonable to measure ETTCP after intubation in all patients. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Chapman, Jacob; Shear, Melissa; Thomas, Stephen] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Chapman, Jacob; Pallin, Daniel] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA.
[Pallin, Daniel] Childrens Hosp, Dept Emergency Med, Boston, MA 02115 USA.
[Ferrara, Larisa] Massachusetts Gen Hosp, Dept Resp Therapy, Boston, MA 02114 USA.
[Mortell, Sarah] Brigham & Womens Hosp, Dept Resp Therapy, Boston, MA 02115 USA.
[Pliakas, John; Thomas, Stephen] Boston MedFlight, Boston, MA USA.
RP Chapman, J (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
OI Pallin, Daniel/0000-0002-8517-9702
NR 9
TC 15
Z9 16
U1 1
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 0735-6757
J9 AM J EMERG MED
JI Am. J. Emerg. Med.
PD OCT
PY 2009
VL 27
IS 8
BP 980
EP 982
DI 10.1016/j.ajem.2008.07.025
PG 3
WC Emergency Medicine
SC Emergency Medicine
GA 503WZ
UT WOS:000270573900014
PM 19857418
ER
PT J
AU Singh, H
Daci, K
Petersen, LA
Collins, C
Petersen, NJ
Shethia, A
El-Serag, HB
AF Singh, Hardeep
Daci, Kuang
Petersen, Laura A.
Collins, Clyde
Petersen, Nancy J.
Shethia, Anila
El-Serag, Hashem B.
TI Missed Opportunities to Initiate Endoscopic Evaluation for Colorectal
Cancer Diagnosis
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID IRON-DEFICIENCY ANEMIA; PRIMARY-CARE; GASTROINTESTINAL-TRACT;
MALPRACTICE CLAIMS; DELAY; COLON; POPULATION; CARCINOMA; SYMPTOMS;
ERRORS
AB OBJECTIVES: Delayed diagnosis of colorectal cancer (CRC) is among the most common reasons for ambulatory diagnostic malpractice claims in the United States. Our objective was to describe missed opportunities to diagnose CRC before endoscopic referral, in terms of patient characteristics, nature of clinical clues, and types of diagnostic-process breakdowns involved.
METHODS: We conducted a retrospective cohort study of consecutive, newly diagnosed cases of CRC between February 1999 and June 2007 at a tertiary health-care system in Texas. Two reviewers independently evaluated the electronic record of each patient using a standardized pretested data collection instrument. Missed opportunities were defined as care episodes in which endoscopic evaluation was not initiated despite the presence of one or more clues that warrant a diagnostic workup for CRC. Predictors of missed opportunities were evaluated in logistic regression. The types of breakdowns involved in the diagnostic process were also determined and described.
RESULTS: Of the 513 patients with CRC who met the inclusion criteria, both reviewers agreed on the presence of at least one missed opportunity in 161 patients. Among these patients there was a mean of 4.2 missed opportunities and 5.3 clues. The most common clues were suspected or confirmed iron deficiency anemia, positive fecal occult blood test, and hematochezia. The odds of a missed opportunity were increased in patients older than 75 years (odds ratio (OR) = 2.3; 95% confidence interval (CI) 1.3-4.1) or with iron deficiency anemia (OR = 2.2; 95 % CI 1.3-3.6), whereas the odds of a missed opportunity were lower in patients with abnormal flexible sigmoidoscopy (OR = 0.06; 95 % CI 0.01-0.51), or imaging suspicious for CRC (OR = 0.3; 95 % CI 0.1-0.9). Anemia was the clue associated with the longest time to endoscopic referral (median = 393 days). Most process breakdowns occurred in the provider-patient clinical encounter and in the follow-up of patients or abnormal diagnostic test results.
CONCLUSIONS: Missed opportunities to initiate workup for CRC are common despite the presence of many clues suggestive of CRC diagnosis. Future interventions are needed to reduce the process breakdowns identified.
C1 [El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Houston VA HSR&D Ctr Excellence, Houston, TX 77030 USA.
[Singh, Hardeep; Petersen, Laura A.; Petersen, Nancy J.; Shethia, Anila] Michael E DeBakey Vet Affairs Med Ctr, Ctr Inquiry Improve Outpatient Safety Effect Elec, Houston, TX USA.
[Singh, Hardeep; Petersen, Laura A.; Petersen, Nancy J.; Shethia, Anila] Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA.
[El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA.
RP Singh, H (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM hardeeps@bcm.edu
FU NIH K23 [K23CA125585]; Houston VA HSR&D Center of Excellence [HFP90-020]
FX This work was supported by an NIH K23 career development award
(K23CA125585) to Dr Singh, and in part by the Houston VA HSR&D Center of
Excellence (HFP90-020). These sources had no role in study design or
execution, collection of data, the writing of the paper, or the decision
to submit the paper for publication.
NR 44
TC 46
Z9 49
U1 0
U2 1
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 2009
VL 104
IS 10
BP 2543
EP 2554
DI 10.1038/ajg.2009.324
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 507KY
UT WOS:000270853300022
PM 19550418
ER
PT J
AU Chavalitdhamrong, D
Kijsirichareanchai, K
Sul, J
Jutabha, R
AF Chavalitdhamrong, Disaya
Kijsirichareanchai, Kunut
Sul, James
Jutabha, Rome
TI The Self-administered Capsule Endoscopy is Useful for the Obscure
Gastrointestinal Bleeding Cases
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 74th Annual Scientific Meeting and Postgraduate Course of the
American-College-of-Gastroenterology
CY OCT 23-28, 2009
CL San Diego, CA
SP Amer Coll Gastroenterol
C1 [Kijsirichareanchai, Kunut; Sul, James; Jutabha, Rome] Univ Calif Los Angeles, Med Ctr, Capsule Endoscopy Serv, Los Angeles, CA 90024 USA.
[Chavalitdhamrong, Disaya] Mt Sinai Sch Med Program, James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 2009
VL 104
SU 3
MA 1435
BP S539
EP S540
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 507LA
UT WOS:000270853601423
ER
PT J
AU Chavalitdhamrong, D
Kijsirichareanchai, K
Sul, J
Jutabha, R
AF Chavalitdhamrong, Disaya
Kijsirichareanchai, Kunut
Sul, James
Jutabha, Rome
TI Endoscopic Placement of a Capsule Endoscope by Using Mini-snare
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 74th Annual Scientific Meeting and Postgraduate Course of the
American-College-of-Gastroenterology
CY OCT 23-28, 2009
CL San Diego, CA
SP Amer Coll Gastroenterol
C1 [Kijsirichareanchai, Kunut; Sul, James; Jutabha, Rome] Univ Calif Los Angeles, Capsule Endoscopy Serv, Los Angeles, CA USA.
[Chavalitdhamrong, Disaya] Mt Sinai Sch Med Program, James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 2009
VL 104
SU 3
MA 1066
BP S392
EP S392
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 507LA
UT WOS:000270853601055
ER
PT J
AU Flicker, M
Weber, H
AF Flicker, Michael
Weber, Horst
TI Endoscopic Hemostasis in a Case of Bleeding from Zenker's Diverticulum
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 74th Annual Scientific Meeting and Postgraduate Course of the
American-College-of-Gastroenterology
CY OCT 23-28, 2009
CL San Diego, CA
SP Amer Coll Gastroenterol
C1 [Flicker, Michael; Weber, Horst] VA Boston Healthcare Syst, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 2009
VL 104
SU 3
MA 1011
BP S371
EP S371
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 507LA
UT WOS:000270853601001
ER
PT J
AU Halley, L
Lahr, C
Subramony, C
Kothari, T
Schmieg, R
Spree, D
Eriator, I
Kasser, C
Kedar, A
Abell, T
AF Halley, Lindsey
Lahr, Christopher
Subramony, Charu
Kothari, Truptesh
Schmieg, Robert
Spree, Danielle
Eriator, Ike
Kasser, Christine
Kedar, Archana
Abell, Thomas
TI Pain and Gastroparesis: Not a Contraindication for a Trial of Gastric
Electrical Stimulation
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 74th Annual Scientific Meeting and Postgraduate Course of the
American-College-of-Gastroenterology
CY OCT 23-28, 2009
CL San Diego, CA
SP Amer Coll Gastroenterol
C1 [Halley, Lindsey; Lahr, Christopher; Subramony, Charu; Schmieg, Robert; Spree, Danielle; Eriator, Ike; Kedar, Archana; Abell, Thomas] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Kasser, Christine] Univ Tennessee, Memphis, TN USA.
[Kothari, Truptesh] James J Peters VA Med Ctr, Bronx, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 2009
VL 104
SU 3
MA 112
BP S45
EP S45
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 507LA
UT WOS:000270853600112
ER
PT J
AU Harris, M
Buscaglia, J
DiMaio, C
Pollack, M
Shin, EJ
Richards, R
Chak, A
Kantsevoy, S
Jagannath, S
Okolo, P
AF Harris, Michael
Buscaglia, Jonathan
DiMaio, Christopher
Pollack, Michael
Shin, Eun Ji
Richards, Robert
Chak, Amitabh
Kantsevoy, Sergey
Jagannath, Sanjay
Okolo, Patrick
TI Are Large Side Holes Associated with Reduced Rates of Pancreatic Stent
Occlusion? Results of a Prospective, Multi-centered Study
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 74th Annual Scientific Meeting and Postgraduate Course of the
American-College-of-Gastroenterology
CY OCT 23-28, 2009
CL San Diego, CA
SP Amer Coll Gastroenterol
C1 [Buscaglia, Jonathan; Kantsevoy, Sergey; Jagannath, Sanjay; Okolo, Patrick] Johns Hopkins Sch Med, Baltimore, MD USA.
[DiMaio, Christopher; Shin, Eun Ji] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Pollack, Michael; Chak, Amitabh] Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Cleveland, OH 44106 USA.
[Harris, Michael] Stony Brook Med Ctr, Stony Brook, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 2009
VL 104
SU 3
MA 204
BP S79
EP S80
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 507LA
UT WOS:000270853600204
ER
PT J
AU Heyman, M
Ferry, G
Aronstein, W
Ajayi, F
Balan, G
Kuzmak, B
Smith-Hall, N
Winter, H
AF Heyman, Melvin
Ferry, George
Aronstein, William
Ajayi, Funmi
Balan, Guhan
Kuzmak, Barbara
Smith-Hall, Nancy
Winter, Harland
TI A Randomized, Open-Label, Parallel-Group Study to Determine the
Pharmacokinetics (PK), Safety and Tolerability of Delayed-Release
Mesalamine Tablets in Children and Adolescents with Active Ulcerative
Colitis (UC)
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 74th Annual Scientific Meeting and Postgraduate Course of the
American-College-of-Gastroenterology
CY OCT 23-28, 2009
CL San Diego, CA
SP Amer Coll Gastroenterol
C1 [Heyman, Melvin] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Ferry, George] Texas Childrens Hosp, Houston, TX 77030 USA.
[Aronstein, William] CTI Clin Trial & Consulting Serv Inc, Cincinnati, OH USA.
[Ajayi, Funmi; Balan, Guhan; Kuzmak, Barbara; Smith-Hall, Nancy] Procter & Gamble Pharmaceut Inc, Mason, OH USA.
[Winter, Harland] Mass Gen Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 2009
VL 104
SU 3
MA 1452
BP S546
EP S546
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 507LA
UT WOS:000270853601440
ER
PT J
AU Hughes, J
Lahr, C
Subramony, C
Kothari, T
Schmieg, R
Spree, D
Cutts, T
Kedar, A
Abell, T
AF Hughes, Joy
Lahr, Christopher
Subramony, Charu
Kothari, Truptesh
Schmieg, Robert
Spree, Danielle
Cutts, Teresa
Kedar, Archana
Abell, Thomas
TI Depression and Gastroparesis: A Histological, Physiological and Clinical
Outcome Analysis in Response to Gastric Stimulation
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 74th Annual Scientific Meeting and Postgraduate Course of the
American-College-of-Gastroenterology
CY OCT 23-28, 2009
CL San Diego, CA
SP Amer Coll Gastroenterol
C1 [Hughes, Joy; Lahr, Christopher; Subramony, Charu; Schmieg, Robert; Spree, Danielle; Kedar, Archana; Abell, Thomas] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Kothari, Truptesh] James J Peters VA Med Ctr, Bronx, NY USA.
[Cutts, Teresa] Univ Tennessee, Memphis, TN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 2009
VL 104
SU 3
MA 113
BP S45
EP S45
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 507LA
UT WOS:000270853600113
ER
PT J
AU Isani, M
Lahr, C
Subramony, C
Kothari, T
Schmieg, R
Spree, D
Vedanarayanan, V
Kedar, A
Abell, T
AF Isani, Mubina
Lahr, Christopher
Subramony, Charu
Kothari, Truptesh
Schmieg, Robert
Spree, Danielle
Vedanarayanan, Vetta
Kedar, Archana
Abell, Thomas
TI Migraines and Gastroparesis: A Histologic, Physiologic, and Clinical
Analysis with Temporary Gastric Stimulation
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 74th Annual Scientific Meeting and Postgraduate Course of the
American-College-of-Gastroenterology
CY OCT 23-28, 2009
CL San Diego, CA
SP Amer Coll Gastroenterol
C1 [Isani, Mubina; Lahr, Christopher; Subramony, Charu; Schmieg, Robert; Spree, Danielle; Vedanarayanan, Vetta; Kedar, Archana; Abell, Thomas] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Kothari, Truptesh] James J Peters VA Med Ctr, Bronx, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 2009
VL 104
SU 3
MA 111
BP S44
EP S44
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 507LA
UT WOS:000270853600111
ER
PT J
AU Kane, S
Panaccione, R
Colombel, JF
Sands, B
Rubin, D
Lewis, J
Nag, A
Hass, S
Panjabi, S
AF Kane, Sunanda
Panaccione, Remo
Colombel, Jean-Frederic
Sands, Bruce
Rubin, David
Lewis, James
Nag, Arpita
Hass, Steven
Panjabi, Sumeet
TI TOUCH (TM) Study Patient Outcomes: The Impact of Natalizumab on
Utilization of Healthcare Resources by the Patients and Their Associated
Treatment Satisfaction
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 74th Annual Scientific Meeting and Postgraduate Course of the
American-College-of-Gastroenterology
CY OCT 23-28, 2009
CL San Diego, CA
SP Amer Coll Gastroenterol
C1 [Kane, Sunanda] Mayo Clin, Rochester, MN USA.
[Panaccione, Remo] Univ Calgary, Rochester, AB, Canada.
[Colombel, Jean-Frederic] Ctr Hosp Reg & Univ Lille, Hop Huriez, F-59037 Lille, France.
[Sands, Bruce] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rubin, David] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Lewis, James] Univ Penn, Philadelphia, PA 19104 USA.
[Nag, Arpita; Hass, Steven; Panjabi, Sumeet] Elan Pharmaceut Inc, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 2009
VL 104
SU 3
MA 1130
BP S416
EP S416
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 507LA
UT WOS:000270853601119
ER
PT J
AU Kothari, T
Hughes, J
Lahr, C
Subramony, C
Schmieg, R
Spree, D
Uwaifo, G
Kedar, A
Abell, T
AF Kothari, Truptesh
Hughes, Joy
Lahr, Christopher
Subramony, Charu
Schmieg, Robert
Spree, Danielle
Uwaifo, Gabriel
Kedar, Archana
Abell, Thomas
TI Diabetes and Gastroparesis: A Histologic, Physiologic and Clinical
Analysis in Response to Temporary and Subsequent Permanent Gastric
Stimulation
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 74th Annual Scientific Meeting and Postgraduate Course of the
American-College-of-Gastroenterology
CY OCT 23-28, 2009
CL San Diego, CA
SP Amer Coll Gastroenterol
C1 [Hughes, Joy; Lahr, Christopher; Subramony, Charu; Schmieg, Robert; Spree, Danielle; Uwaifo, Gabriel; Kedar, Archana; Abell, Thomas] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Kothari, Truptesh] James J Peters VA Med Ctr, Bronx, NY USA.
RI Uwaifo, Gabriel/M-2361-2016
OI Uwaifo, Gabriel/0000-0002-6962-9304
NR 0
TC 0
Z9 0
U1 0
U2 1
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 2009
VL 104
SU 3
MA 114
BP S46
EP S46
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 507LA
UT WOS:000270853600114
ER
PT J
AU Panaccione, R
Kane, S
Lewis, J
Colombel, JF
Sands, B
Rubin, D
Nag, A
Hass, S
Panjabi, S
Eisenberg, D
AF Panaccione, Remo
Kane, Sunanda
Lewis, James
Colombel, Jean-Frederic
Sands, Bruce
Rubin, David
Nag, Arpita
Hass, Steven
Panjabi, Sumeet
Eisenberg, Debra
TI TOUCH (TM) Study Patient Outcomes: The Impact of Natalizumab on Common
Measures of Quality of Life in CD patients
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 74th Annual Scientific Meeting and Postgraduate Course of the
American-College-of-Gastroenterology
CY OCT 23-28, 2009
CL San Diego, CA
SP Amer Coll Gastroenterol
C1 [Panaccione, Remo] Univ Calgary, Calgary, AB, Canada.
[Kane, Sunanda] Mayo Clin, Rochester, MN USA.
[Lewis, James] Univ Penn, Philadelphia, PA 19104 USA.
[Colombel, Jean-Frederic] Ctr Hosp Reg & Univ Lille, Hop Huriez, F-59037 Lille, France.
[Sands, Bruce] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rubin, David] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Nag, Arpita; Hass, Steven; Panjabi, Sumeet] Elan Pharmaceut Inc, San Francisco, CA USA.
[Eisenberg, Debra] HealthCore Inc, Wilmington, DE USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 2009
VL 104
SU 3
MA 1135
BP S418
EP S418
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 507LA
UT WOS:000270853601124
ER
PT J
AU Ramirez, F
Leung, F
AF Ramirez, Francisco
Leung, Felix
TI Water Method for Colonoscopy in Sedated Patients is Easy to Learn for an
Experienced Colonoscopist and May Minimize the Need for Technical
Assistance
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 74th Annual Scientific Meeting and Postgraduate Course of the
American-College-of-Gastroenterology
CY OCT 23-28, 2009
CL San Diego, CA
SP Amer Coll Gastroenterol
C1 [Ramirez, Francisco] Carl T Hayden VA Med Ctr, Phoenix, AZ USA.
[Leung, Felix] Univ Calif Los Angeles, David Geffen Sch Med, Sepulveda Ambulatory Care Ctr, VA Greater Healthcare Syst, Los Angeles, CA 90095 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
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 2009
VL 104
SU 3
MA 1399
BP S525
EP S525
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 507LA
UT WOS:000270853601387
ER
PT J
AU Rubin, D
Sands, B
Lewis, J
Kane, S
Panaccione, R
Colombel, JF
Nag, A
Hass, S
Panjabi, S
AF Rubin, David
Sands, Bruce
Lewis, James
Kane, Sunanda
Panaccione, Remo
Colombel, Jean-Frederic
Nag, Arpita
Hass, Steven
Panjabi, Sumeet
TI TOUCH (TM) Study Patient Outcomes: The Impact of Natalizumab on Crohn's
Disease Severity
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 74th Annual Scientific Meeting and Postgraduate Course of the
American-College-of-Gastroenterology
CY OCT 23-28, 2009
CL San Diego, CA
SP Amer Coll Gastroenterol
C1 [Rubin, David] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Sands, Bruce] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Lewis, James] Univ Penn, Philadelphia, PA 19104 USA.
[Kane, Sunanda] Mayo Clin, Rochester, MN USA.
[Panaccione, Remo] Univ Calgary, Calgary, AB, Canada.
[Colombel, Jean-Frederic] Ctr Hosp Reg & Univ Lille, Hop Huriez, F-59037 Lille, France.
[Nag, Arpita; Hass, Steven; Panjabi, Sumeet] Elan Pharmaceut Inc, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 2009
VL 104
SU 3
MA 1139
BP S420
EP S420
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 507LA
UT WOS:000270853601128
ER
PT J
AU Rubin, D
Lewis, J
Kane, S
Panaccione, R
Colombel, JF
Sands, B
Nag, A
Hass, S
Panjabi, S
AF Rubin, David
Lewis, James
Kane, Sunanda
Panaccione, Remo
Colombel, Jean-Frederic
Sands, Bruce
Nag, Arpita
Hass, Steven
Panjabi, Sumeet
TI TOUCH (TM) Study Patient Outcomes: Workforce Participation, Productivity
and the Impact of Natalizumab
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 74th Annual Scientific Meeting and Postgraduate Course of the
American-College-of-Gastroenterology
CY OCT 23-28, 2009
CL San Diego, CA
SP Amer Coll Gastroenterol
C1 [Rubin, David] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Lewis, James] Univ Penn, Philadelphia, PA 19104 USA.
[Kane, Sunanda] Mayo Clin, Rochester, MN USA.
[Panaccione, Remo] Univ Calgary, Calgary, AB, Canada.
[Colombel, Jean-Frederic] Ctr Hosp Reg & Univ Lille, Hop Huriez, F-59037 Lille, France.
[Sands, Bruce] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Nag, Arpita; Hass, Steven; Panjabi, Sumeet] Elan Pharmaceut Inc, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 2009
VL 104
SU 3
MA 1134
BP S417
EP S418
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 507LA
UT WOS:000270853601123
ER
PT J
AU Sandborn, W
Kane, S
Korzenik, J
Lashner, B
Leighton, J
Mahadevan, U
Marion, J
Safdi, M
Sninsky, C
Ramsey, D
AF Sandborn, William
Kane, Sunanda
Korzenik, Joshua
Lashner, Bret
Leighton, Jonathan
Mahadevan, Uma
Marion, James
Safdi, Michael
Sninsky, Charles
Ramsey, David
TI Once Daily Dosing of Delayed-Release Oral Mesalamine (400 mg Tablet) is
as Effective as Twice Daily Dosing for Maintenance of Remission of
Ulcerative Colitis: Results of the QDIEM Study
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 74th Annual Scientific Meeting and Postgraduate Course of the
American-College-of-Gastroenterology
CY OCT 23-28, 2009
CL San Diego, CA
SP Amer Coll Gastroenterol
C1 [Sandborn, William; Kane, Sunanda] Mayo Clin, Rochester, MN USA.
[Korzenik, Joshua] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Lashner, Bret] Cleveland Clin, Cleveland, OH 44106 USA.
[Leighton, Jonathan] Mayo Clin Arizona, Scottsdale, AZ USA.
[Mahadevan, Uma] Univ Calif San Francisco, Ctr Colitis & Crohns Dis, San Francisco, CA 94143 USA.
[Marion, James] Mt Sinai Sch Med, New York, NY USA.
[Safdi, Michael] Gastroenterol & Liver Inst, Cincinnati, OH USA.
[Sninsky, Charles] Digest Dis Associates, Gainesville, FL USA.
[Ramsey, David] Procter & Gamble Pharmaceut Inc, Mason, OH USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
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 2009
VL 104
SU 3
MA 1185
BP S438
EP S439
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 507LA
UT WOS:000270853601174
ER
PT J
AU Siegel, C
Sands, B
Feagan, B
Sandborn, W
Hass, S
Niecko, T
AF Siegel, Corey
Sands, Bruce
Feagan, Brian
Sandborn, William
Hass, Steven
Niecko, Timothy
TI Natalizumab Reduces the Rate of Hospitalization in Moderate to Severe
Crohn's Patients: Data from the ENACT and ENCORE Trials
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 74th Annual Scientific Meeting and Postgraduate Course of the
American-College-of-Gastroenterology
CY OCT 23-28, 2009
CL San Diego, CA
SP Amer Coll Gastroenterol
C1 [Siegel, Corey] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
[Sands, Bruce] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Feagan, Brian] Univ Western Ontario, Robarts Res Inst, London, ON, Canada.
[Sandborn, William] Mayo Clin, Rochester, MN USA.
[Hass, Steven] Elan Pharmaceut Inc, San Francisco, CA USA.
[Niecko, Timothy] Niecko Hlth Econ, Escondido, CA USA.
RI Feagan, Brian/M-4283-2015
NR 0
TC 0
Z9 0
U1 0
U2 0
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 2009
VL 104
SU 3
MA 1258
BP S470
EP S470
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 507LA
UT WOS:000270853601246
ER
PT J
AU Siegel, C
Finlayson, S
Sands, B
Tosteson, A
AF Siegel, Corey
Finlayson, Samuel
Sands, Bruce
Tosteson, Anna
TI A Decision Analysis to Define the Thresholds at Which the Risks of
Combination Infliximab and Azathioprine Therapy Outweigh Its Benefits
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Meeting Abstract
CT 74th Annual Scientific Meeting and Postgraduate Course of the
American-College-of-Gastroenterology
CY OCT 23-28, 2009
CL San Diego, CA
SP Amer Coll Gastroenterol
C1 [Siegel, Corey] Dartmouth Hitchcock Med Ctr, IBD Ctr, Lebanon, NH 03766 USA.
[Finlayson, Samuel; Tosteson, Anna] Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH USA.
[Sands, Bruce] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 2009
VL 104
SU 3
MA 1257
BP S469
EP S470
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 507LA
UT WOS:000270853601245
ER
PT J
AU Shah, K
Qureshi, SU
Johnson, M
Parikh, N
Schulz, PE
Kunik, ME
AF Shah, Kairav
Qureshi, Salah U.
Johnson, Michael
Parikh, Niraj
Schulz, Paul E.
Kunik, Mark E.
TI Does Use of Antihypertensive Drugs Affect the Incidence or Progression
of Dementia? A Systematic Review
SO AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY
LA English
DT Review
DE incidence or progression of dementia; antihypertensive drugs
ID PLACEBO-CONTROLLED TRIAL; COGNITIVE FUNCTION; BLOOD-PRESSURE;
ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; MEDICATION-USE; HYPERTENSION;
RISK; PREVALENCE; PREVENTION
AB Background: Hypertension appears to contribute to the development of dementia. Antihypertensive drugs may play an important role in altering the incidence or progression of dementia, particularly dementia of the vascular type; however, the neuroprotective effects of these agents in other types of dementia are not well characterized.
Objectives: The main aims of this review were to examine the relationship between use of antihypertensive agents and the incidence and progression of Alzheimer's dementia (AD), vascular dementia (VaD), and unspecified dementia, and to consider whether these agents may be neuroprotective. Methods: A search of the English-language literature (January 1996-August 2009) was conducted using PubMed, Ovid MEDLINE, EBSCO MEDLINE, and the Cochrane Database of Systematic Reviews for publications mentioning both antihypertensive drugs and dementia. A combination of searches was performed using the following terms: antihypertensive drugs, dementia, cognitive impairment, Alzheimer's dementia, vascular dementia, progression of cognitive impairment, severity of cognitive impairment, severity of dementia, prevalence, and incidence. Searches were also performed using the names of antihypertensive drug classes. The bibliographies of all retrieved articles were reviewed for additional relevant publications. The focus was on randomized controlled trials, cohort studies, and case-control studies, excluding studies in animals, patients aged <45 years, drugs other than antihypertensive agents, and the role in cognition of hormones, receptors, and enzymes.
Results: Sixty-five potentially relevant articles were identified from the 536 publications retrieved by the literature search. After application of the exclusion criteria, 12 original studies were included in the review, all published between 1999 and 2008 and most involving patients with AD or VaD. The most frequently studied antihypertensive agents were calcium channel blockers (7 studies), diuretics (6 studies), and angiotensin-converting enzyme (ACE) inhibitors (6 studies). Overall, these medications appeared to be beneficial in dementia, but only ACE inhibitors and diuretics significantly reduced the risk for and progression of dementia in the majority of studies.
Conclusions: Antihypertensive medications-particularly ACE inhibitors and diuretics-may be helpful in reducing the risk for and progression of dementia. Large randomized clinical trials are warranted to further explore the relationship between antihypertensive drugs and dementia. (Am J Geriatr Pharmacother. 2009;7:250-261) (C) 2009 Excerpta Medica Inc.
C1 [Shah, Kairav; Qureshi, Salah U.; Schulz, Paul E.; Kunik, Mark E.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA.
[Shah, Kairav] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
[Qureshi, Salah U.; Kunik, Mark E.] Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA.
[Qureshi, Salah U.; Schulz, Paul E.; Kunik, Mark E.] Baylor Coll Med, Houston, TX 77030 USA.
[Qureshi, Salah U.; Kunik, Mark E.] Vet Affairs S Cent Mental Illness Res Educ & Clin, Houston, TX USA.
[Johnson, Michael] Univ Houston, Coll Pharm, Dept Clin Sci & Adm, Houston, TX 77030 USA.
[Parikh, Niraj] Anal Grp Inc, Boston, MA USA.
RP Kunik, ME (reprint author), Michael E DeBakey VAMC 151, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM mkunik@bcm.tmc.edu
FU Houston Veterans Affairs Health Services Research and Development Center
of Excellence [HFP90-020]
FX This work was supported in part by the Houston Veterans Affairs Health
Services Research and Development Center of Excellence (HFP90-020). The
views expressed are those of the authors and do not necessarily reflect
those of the Department of Veterans Affairs (Baylor College of
Medicine), with which 3 of the authors are affiliated.
NR 34
TC 61
Z9 61
U1 3
U2 11
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 1543-5946
J9 AM J GERIATR PHARMAC
JI Am. J. Geriatr. Pharmacother.
PD OCT
PY 2009
VL 7
IS 5
BP 250
EP 261
DI 10.1016/j.amjopharm.2009.11.001
PG 12
WC Geriatrics & Gerontology; Pharmacology & Pharmacy
SC Geriatrics & Gerontology; Pharmacology & Pharmacy
GA 525XU
UT WOS:000272251900002
PM 19948301
ER
PT J
AU Wright, RM
Sloane, R
Pieper, CF
Ruby-Scelsi, C
Twersky, J
Schmader, KE
Hanlon, JT
AF Wright, Rollin M.
Sloane, Richard
Pieper, Carl F.
Ruby-Scelsi, Christine
Twersky, Jack
Schmader, Kenneth E.
Hanlon, Joseph T.
TI Underuse of Indicated Medications Among Physically Frail Older US
Veterans at the Time of Hospital Discharge: Results of a Cross-Sectional
Analysis of Data From the Geriatric Evaluation and Management Drug Study
SO AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY
LA English
DT Article
DE medication use; underutilization; comorbidity; transition of care; frail
elderly
ID QUALITY-OF-CARE; PHARMACOLOGICAL CARE; CONTROLLED-TRIAL; POLYPHARMACY;
INPATIENTS; DISEASES; PEOPLE; COMORBIDITY; OUTPATIENTS; VALIDATION
AB Background: Medication underutilization, or the omission of a potentially beneficial medication indicated for disease management, is common among older adults but poorly understood.
Objectives: The aims of this work were to assess the prevalence of medication underuse and to determine whether polypharmacy or comorbidity was associated with medication underuse among physically frail older veterans transitioning from the hospital to the community.
Methods: This was a cross-sectional analysis of patients who were discharged from 11 US veterans' hospitals to outpatient care, based on data from the Geriatric Evaluation and Management Drug Study, a substudy of the Veterans Affairs Cooperative Study of geriatric evaluation and management. Patients were enrolled between August 31, 1995, and January 31, 1999. To qualify for the study, patients had to be aged >= 65 years, hospitalized in a medical or surgical ward for >48 hours, and meet >= 2 of the following criteria: moderate functional disability; recent cerebrovascular accident with residual neurological deficit; history of >= 1 fall in the previous 3 months; documented difficulty with walking (ie, requiring personal assistance or equipment), not including preadmission use of a wheelchair with ability to transfer to and from chair independently; malnutrition (admission serum albumin of 3.5 g/dL, <80% of ideal body weight, or recent >= 15-lb weight loss reported in admission history); dementia; depression; documented diagnosis of new fracture or revision needed of older fracture; unplanned admission within 3 months of previous admission; and prolonged bed rest. Clinical pharmacist/physician pairs reviewed medical records and medication lists and independently applied the Assessment of Underutilization (AOU) index to determine omissions of indicated medications. Discordances in index ratings were resolved during clinical consensus conferences. The primary outcome measure was the percentage of patients with >= 1 medication omission detected by the AOU. Multivariable logistic regression analyses identified factors associated with underuse.
Results: A total of 384 patients were included in the study. The majority (53.6%) were between the ages of 65 and 74 years, and the mean (SD) Charlson comorbidity index was 2.44 (1.93). Overall, 374 patients (97.4%) were men and 274 (71.4%) were white. Medication undertreatment occurred in 238 participants (62.0%). Diseases of the circulatory, endocrine/nutritional, musculoskeletal, and respiratory systems were the most commonly undertreated conditions. The indicated medications most likely to be omitted were nitrates for those with a history of myocardial infarction, multivitamins in those with malnutrition, and inhaled anticholinergics for chronic obstructive airways disease. Statistically significant factors associated with medication underuse included limitations in activities of daily living (adjusted odds ratio [AOR], 2.17 [95% CI, 1.27-3.71]; P = 0.01), being white (AOR, 1.70 [95% CI, 1.06-2.71]; P = 0.03), and Charlson comorbidity index (AOR, 1.13 for each 1-point increase [95% CI, 1.00-1.27]; P = 0.04). Discharge from a general medicine service as opposed to a surgical service was associated with lower risk of medication underuse (AOR, 0.61 [95% CI, 0.38-0.98]; P = 0.04).
Conclusions: Medication underuse was relatively common in this study. Patients with greater comorbidity, but not polypharmacy, had increased odds of undertreatment. (Am J Geriatr Pharmacother 2009;7:271280) (C) 2009 Excerpta Medica Inc.
C1 [Wright, Rollin M.; Ruby-Scelsi, Christine; Hanlon, Joseph T.] Univ Pittsburgh, Div Geriatr Med, Dept Med, Sch Med, Pittsburgh, PA 15213 USA.
[Sloane, Richard; Pieper, Carl F.; Twersky, Jack; Schmader, Kenneth E.] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC 27710 USA.
[Pieper, Carl F.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA.
[Ruby-Scelsi, Christine; Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA.
[Twersky, Jack; Schmader, Kenneth E.] Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC USA.
[Twersky, Jack; Schmader, Kenneth E.] Duke Univ, Med Ctr, Dept Med, Div Geriatr Med, Durham, NC 27710 USA.
[Hanlon, Joseph T.] Vet Affairs Pittsburgh Hlth Care Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Hanlon, Joseph T.] Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA.
RP Hanlon, JT (reprint author), Univ Pittsburgh, Div Geriatr Med, Dept Med, Sch Med, Kaufmann Med Bldg,Suite 500,3471 5th Ave, Pittsburgh, PA 15213 USA.
EM jth14@pitt.edu
FU Veterans Affairs Cooperative Study Program 006; National Institute on
Aging [R01-AG-027017, P30 AG024827]; National Institute of Allergy and
Infectious Diseases [K24-AI-51324-01]; John A. Hartford Foundation
Center of Excellence in Geriatrics; [R01-AG-15432]
FX Financial support was provided by the grant R01-AG-15432 and the
Veterans Affairs Cooperative Study Program 006. Additional support was
provided by R01-AG-027017 and P30 AG024827 from the National Institute
on Aging, K24-AI-51324-01 from the National Institute of Allergy and
Infectious Diseases, and from the John A. Hartford Foundation Center of
Excellence in Geriatrics.
NR 37
TC 20
Z9 22
U1 0
U2 8
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 1543-5946
J9 AM J GERIATR PHARMAC
JI Am. J. Geriatr. Pharmacother.
PD OCT
PY 2009
VL 7
IS 5
BP 271
EP 280
DI 10.1016/j.amjopharm.2009.11.002
PG 10
WC Geriatrics & Gerontology; Pharmacology & Pharmacy
SC Geriatrics & Gerontology; Pharmacology & Pharmacy
GA 525XU
UT WOS:000272251900004
PM 19948303
ER
PT J
AU Snow, AL
Chandler, JF
Kunik, ME
Davila, JA
Balasubramanyam, V
Steele, AB
Morgan, RO
AF Snow, A. Lynn
Chandler, Joseph F.
Kunik, Mark E.
Davila, Jessica A.
Balasubramanyam, Valli
Steele, Avila B.
Morgan, Robert O.
TI Self-Reported Pain in Persons With Dementia Predicts Subsequent
Decreased Psychosocial Functioning
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Article
DE Pain; dementia; psychosocial functioning
ID LOW-BACK-PAIN; QUALITY-OF-LIFE; NURSING-HOME RESIDENTS; LONG-TERM-CARE;
ALZHEIMERS-DISEASE; MARITAL SATISFACTION; BEHAVIORAL TREATMENT;
DEPRESSION; ASSOCIATION; AGITATION
AB Objectives: Pain self-report is the assessment gold standard in cognitively intact populations but has been discouraged in persons with dementia because of significant evidence that pain intensity is often underreported by persons with dementia. However, most community-dwelling persons with dementia are cared for in primary care settings where a more in depth pain assessment is unlikely. Therefore, it is vital to know the clinical predictive value of self-report pain assessment in this population. Psychosocial functioning is a meaningful focus for clinical prediction, because psychosocial constructs are integrally related to quality of life, physical functioning, and one's ability to function in the presence of pain. The purpose of this study was to investigate the degree to which answers to simple self-report pain questions can predict changes in psychosocial functioning 4 months later in community-dwelling older adults with dementia. Design: Longitudinal. Patients and caregivers were assessed every 4 months for 24 months. Setting: Veterans Affairs Medical Center, Houston, TX. Participants: One hundred seventy-one patients over age 60 years diagnosed with dementia in the previous year and with no previous aggression were recruited from Veterans Administration clinics. Measurements: Pain, agitation, depression, involvement in pleasant events, caregiver burden, psychosis, and patient/caregiver relationship quality (mutuality). Results: Pain scores at each time period were predictive of increased agitation and depression and decreased pleasant event frequency 4 months later. Conclusions: Our results suggest that persons with dementia who affirmatively respond to pain questions are at higher risk for developing negative psychosocial states. (Am J Geriatr Psychiatry 2009; 17:873-880)
C1 [Snow, A. Lynn; Chandler, Joseph F.] Univ Alabama, Ctr Mental Hlth & Aging, Dept Psychol, Tuscaloosa, AL 35487 USA.
[Snow, A. Lynn] Tuscaloosa Vet Affairs Med Ctr, Res & Dev Serv, Tuscaloosa, AL USA.
[Kunik, Mark E.; Davila, Jessica A.; Balasubramanyam, Valli; Steele, Avila B.] Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA.
[Kunik, Mark E.; Davila, Jessica A.; Balasubramanyam, Valli; Steele, Avila B.] Baylor Coll Med, Hlth Serv Res & Dev Serv, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
[Kunik, Mark E.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
[Kunik, Mark E.; Davila, Jessica A.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Snow, A. Lynn; Kunik, Mark E.] Vet Affairs S Cent Mental Illness Res Educ & Clin, N Little Rock, AR USA.
[Morgan, Robert O.] Univ Texas Sch Publ Hlth, Div Management Policy & Community Hlth, Houston, TX USA.
RP Snow, AL (reprint author), Univ Alabama, Ctr Mental Hlth & Aging, Dept Psychol, 207 Osband Hall,Box 870315, Tuscaloosa, AL 35487 USA.
EM LSNOW@bama.ua.edu
FU Department of Veterans Affairs; Veterans Health Administration; Health
Services Research and Development Service, Washington, DC [IIR 01-159-2,
HFP 90-020]
FX The study sponsors had no role in the design, conduct, analysis,
interpretation, writing, or decision to publish this study.
NR 47
TC 15
Z9 15
U1 5
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD OCT
PY 2009
VL 17
IS 10
BP 873
EP 880
DI 10.1097/JGP.0b013e3181ad4f73
PG 8
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 501LG
UT WOS:000270382800007
PM 19910876
ER
PT J
AU Schillerstrom, JE
Salazar, R
Regwan, H
Bonugli, RJ
Royall, DR
AF Schillerstrom, Jason E.
Salazar, Ricardo
Regwan, Heather
Bonugli, Rebecca J.
Royall, Donald R.
TI Executive Function in Self-Neglecting Adult Protective Services
Referrals Compared With Elder Psychiatric Outpatients
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Article
DE Adult protective services; executive function; depression
ID CONSENT
AB Objective: Psychometric performance, with an emphasis on executive function, was compared between adult protective services (APS) clients referred for a decision-making capacity consultation and elders seen in an outpatient geriatric psychiatry clinic. Methods: The authors performed a retrospective medical records review extracting general, executive, and visuospatial cognitive performance and depression symptom burden in APS referrals (N = 63) and geriatric psychiatry outpatients (N = 58). Results: After adjusting for age and education, APS clients had worse mean executive performance as measured by the Executive Interview (24.3 [SD 6.4] versus 17.3 [SD 7.6], F([1, 87]) 15.7, p < 0.001) and CLOX1 (7.4 [SD 4.0] versus 9.3 [SD 4.2], F([1, 92]) 4.79, p = 0.03). There were no differences in visuospatial or general cognitive abilities. The self-neglect subgroup had worse cognitive performance on each measure than other APS referrals. Conclusions: Compared with routine geriatric psychiatry patients, APS referrals are more likely to be executively impaired but less depressed. General cognitive screens do not distinguish these two groups. (Am J Geriatr Psychiatry 2009; 17:907-910)
C1 [Schillerstrom, Jason E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Royall, Donald R.] S Texas Vet Healthcare Syst, Audie L Murphy Div, San Antonio, TX USA.
RP Schillerstrom, JE (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM schillerstr@uthscsa.edu; royall@uthscsa.edu
NR 10
TC 8
Z9 8
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD OCT
PY 2009
VL 17
IS 10
BP 907
EP 910
DI 10.1097/JGP.0b013e3181b4bf64
PG 4
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 501LG
UT WOS:000270382800011
PM 19910879
ER
PT J
AU Aspinall, SL
Banthin, JS
Good, CB
Miller, GE
Cunningham, FE
AF Aspinall, Sherrie L.
Banthin, Jessica S.
Good, Chester B.
Miller, G. Edward
Cunningham, Francesca E.
TI VA Pharmacy Users: How They Differ From Other Veterans
SO AMERICAN JOURNAL OF MANAGED CARE
LA English
DT Article
ID MENTAL-HEALTH PROBLEMS; CARE; EXPENDITURES; MEDICARE; ACCESS; IRAQ
AB Objective: To compare users and nonusers of Veterans Affairs (VA) pharmacy services by age group. Study Design: Cross-sectional.
Methods: We used data on sociodemographics, health status, and medical conditions from the Medical Expenditure Panel Survey (MEPS) to compare users and nonusers of VA pharmacies for medications. Data were pooled for 2003-2005 to ensure adequate sample sizes. Student t tests were used to compare the means for each variable, and all analyses were adjusted for the complex sample design of the MEPS.
Results: Among both nonelderly (18-64 years) and elderly (> 65 years) veterans, a higher proportion who used VA pharmacy services versus those who did not use VA pharmacy services (1) were black (nonelderly: 17.7% vs 7.4%, P < .001; elderly: 9.4% vs 4.7%, P < .001); (2) had no alternative insurance (nonelderly: 27.2% vs 4.8%, P < .001; elderly: 36.3% vs 19.9%, P < .001); (3) had lower incomes (nonelderly: 32.4% vs 11.5%, P < .001; elderly: 32.4% vs 25.4%, P = .01); (4) had less than a high school education (nonelderly: 13.0% vs 6.5%, P < .001; elderly: 27.5% vs 17.6%, P < .001); (5) were disabled; and (6) reported poorer health. A higher percentage of nonelderly users reported a mental health condition (31.6% vs 19.4%, P < .001).
Conclusions: Veterans who use VA pharmacy services appear to be more ill than those who do not use VA pharmacy services. In addition, the VA appears to be a safety net for uninsured veterans who have mental health problems. (Am J Manag Care. 2009; 15(10): 701-708)
C1 [Aspinall, Sherrie L.; Good, Chester B.] VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA.
[Aspinall, Sherrie L.; Good, Chester B.; Cunningham, Francesca E.] VA Ctr Medicat Safety, Hines, IL USA.
[Aspinall, Sherrie L.; Good, Chester B.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA 15260 USA.
[Good, Chester B.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA.
[Banthin, Jessica S.; Miller, G. Edward] Agcy Healthcare Res & Qual, Ctr Financing Access & Cost Trends, Washington, DC USA.
RP Aspinall, SL (reprint author), VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, 7180 Highland Dr, Pittsburgh, PA 15206 USA.
EM sherrie.aspinall@va.gov
NR 13
TC 3
Z9 3
U1 1
U2 1
PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC
PI PLAINSBORO
PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA
SN 1088-0224
J9 AM J MANAG CARE
JI Am. J. Manag. Care
PD OCT
PY 2009
VL 15
IS 10
BP 701
EP 708
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Medicine,
General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 508YN
UT WOS:000270975300004
PM 19845422
ER
PT J
AU Ross, JS
Keyhani, S
Korenstein, D
AF Ross, Joseph S.
Keyhani, Salomeh
Korenstein, Deborah
TI Appropriateness of Collaborations between Industry and the Medical
Profession: Physicians' Perceptions
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Attitude of health personnel; Biomedical research; Drug industry
ID EDUCATIONAL INTERVENTION; GIFTS
AB BACKGROUND: Physicians' ratings of the appropriateness of collaboration and of receiving payment for collaboration with the pharmaceutical and medical device industries may differ.
METHODS: We administered an anonymous, cross-sectional survey to a convenience sample of faculty and postgraduate physicians from all departments within the 11 hospitals affiliated with the Mount Sinai School of Medicine in New York City and New Jersey. We examined 12 collaborations with the pharmaceutical and medical device industries using 4-point Likert scales, ranging from very appropriate to very inappropriate.
RESULTS: Surveys were distributed to physicians within 35 departments at 11 hospitals; 590 surveys were completed by physicians at 9 hospitals, yielding a 67% response rate. Physicians' assessment of appropriateness varied among the different collaborations, ranging from nearly all rating developing a drug or device (92%) and designing a drug/device trial (91%) as appropriate to fewer rating preparing a manuscript of a drug/device trial (60%) and recruiting patients for a drug/device trial (65%) as appropriate for physicians not involved in trial design. Physicians consistently rated receiving payment for collaboration as appropriate less often than they rated the collaboration itself as appropriate and ratings varied among the collaborations. For example, 81% rated receiving payment to develop a drug or device as appropriate, whereas 38% rated receiving payment to recruit patients for a drug/device trial when the physician was not involved in trial design as appropriate.
CONCLUSIONS: Physicians' broadly perceived most collaboration with the pharmaceutical and medical device industries, and of receiving payment for collaboration, as appropriate. Published by Elsevier Inc. . The American Journal of Medicine (2009) 122, 955-960
C1 [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA.
[Ross, Joseph S.; Keyhani, Salomeh] James J Peters VA Med Ctr, HSR&D Res Enhancement Award Program, Bronx, NY USA.
James J Peters VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA.
[Keyhani, Salomeh] Mt Sinai Sch Med, Dept Hlth Policy, New York, NY USA.
[Korenstein, Deborah] Mt Sinai Sch Med, Dept Med, New York, NY USA.
RP Ross, JS (reprint author), Mt Sinai Sch Med, Dept Geriatr & Adult Dev, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA.
EM joseph.ross@mssm.edu
FU Attorney General Consumer and Prescriber
FX Data collection for this work was partially supported by the Attorney
General Consumer and Prescriber Grant Program administered by the State
of Oregon. Dr. Ross was compensated for his work as a consultant at the
request of plaintiffs in litigation against Merck and Co., Inc. related
to rofecoxib from 2006-2007.
NR 14
TC 8
Z9 8
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD OCT
PY 2009
VL 122
IS 10
BP 955
EP 960
DI 10.1016/j.amjmed.2009.04.013
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 501UV
UT WOS:000270409200015
PM 19786162
ER
PT J
AU Sampat, MP
Berger, AM
Healy, BC
Hildenbrand, P
Vass, J
Meier, DS
Chitnis, T
Weiner, HL
Bakshi, R
Guttmann, CRG
AF Sampat, M. P.
Berger, A. M.
Healy, B. C.
Hildenbrand, P.
Vass, J.
Meier, D. S.
Chitnis, T.
Weiner, H. L.
Bakshi, R.
Guttmann, C. R. G.
TI Regional White Matter Atrophy-Based Classification of Multiple Sclerosis
in Cross-Sectional and Longitudinal Data
SO AMERICAN JOURNAL OF NEURORADIOLOGY
LA English
DT Article
ID SPINAL-CORD ATROPHY; HUMAN CORPUS-CALLOSUM; COGNITIVE IMPAIRMENT; BRAIN
ATROPHY; DIAGNOSTIC-CRITERIA; CLINICAL-RELEVANCE; SEX-DIFFERENCES;
AXONAL LOSS; MRI; SECONDARY
AB BACKGROUND AND PURPOSE: The different clinical subtypes of multiple sclerosis (MS) may reflect underlying differences in affected neuroanatomic regions, Our aim was to analyze the effectiveness of jointly using the inferior subolivary medulla oblongata volume (MOV) and the cross-sectional area of the corpus callosum in distinguishing patients with relapsing-remitting multiple sclerosis (RRMS), secondary-progressive multiple sclerosis (SPMS), and primary-progressive multiple sclerosis (PPMS).
MATERIALS AND METHODS: We analyzed a cross-sectional dataset of 64 patients (30 RRMS, 14 SPMS, 20 PPMS) and a separate longitudinal dataset of 25 patients (114 MR imaging examinations). Twelve patients in the longitudinal dataset had converted from RRMS to SPMS. For all images, the MOV and corpus callosum were delineated manually and the corpus callosum was parcellated into 5 segments. Patients from the cross-sectional dataset were classified as FIRMS, SPMS, or PPMS by using a decision tree algorithm with the following input features: brain parenchymal fraction, age, disease duration, MOV, total corpus callosum area and areas of 5 segments of the corpus callosum. To test the robustness of the classification technique, we applied the results derived from the cross-sectional analysis to the longitudinal dataset.
RESULTS: MOV and central corpus callosum segment area were the 2 features retained by the decision tree. Patients with MOV >0.94 cm(3) were classified as having RRMS. Patients with progressive MS were further subclassified as having SPMS if the central corpus callosum segment area was <55.12 mm(2), and as having PPMS otherwise. In the cross-sectional dataset, 51/64 (80%) patients were correctly classified. For the longitudinal dataset, 88/114 (77%) patient time points were correctly classified as FIRMS or SPMS.
CONCLUSIONS: Classification techniques revealed differences in affected neuroanatomic regions in subtypes of multiple sclerosis. The combination of central corpus callosum segment area and MOV provides good discrimination among patients with FIRMS, SPMS, and PPMS.
C1 [Sampat, M. P.; Berger, A. M.; Vass, J.; Meier, D. S.; Bakshi, R.; Guttmann, C. R. G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Imaging, Boston, MA 02115 USA.
[Healy, B. C.; Chitnis, T.; Weiner, H. L.; Bakshi, R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Partners Multiple Sclerosis Ctr, Boston, MA 02115 USA.
[Healy, B. C.] Massachusetts Gen Hosp, Dept Neurol, Ctr Biostat, Boston, MA 02114 USA.
[Hildenbrand, P.] Lahey Clin Fdn, Burlington, MA USA.
RP Guttmann, CRG (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Imaging, 221 Longwood Ave,RF 394, Boston, MA 02115 USA.
EM guttmann@bwh.harvard.edu
FU NCRR NIH HHS [P41 RR013218, P41 RR013218-010009, P41 RR13218-01]
NR 56
TC 8
Z9 8
U1 0
U2 0
PU AMER SOC NEURORADIOLOGY
PI OAK BROOK
PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA
SN 0195-6108
J9 AM J NEURORADIOL
JI Am. J. Neuroradiol.
PD OCT
PY 2009
VL 30
IS 9
BP 1731
EP 1739
DI 10.3174/ajnr.A1659
PG 9
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 509PV
UT WOS:000271031300021
PM 19696139
ER
PT J
AU Pasadhika, S
Kempen, JH
Newcomb, CW
Liesegang, TL
Pujari, SS
Rosenbaum, JT
Thorne, JE
Foster, CS
Jabs, DA
Levy-Clarke, GA
Nussenblatt, RB
Suhler, EB
AF Pasadhika, Sirichai
Kempen, John H.
Newcomb, Craig W.
Liesegang, Teresa L.
Pujari, Siddharth S.
Rosenbaum, James T.
Thorne, Jennifer E.
Foster, C. Stephen
Jabs, Douglas A.
Levy-Clarke, Grace A.
Nussenblatt, Robert B.
Suhler, Eric B.
TI Azathioprine for Ocular Inflammatory Diseases
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID LONG-TERM; IMMUNOSUPPRESSIVE THERAPY; BEHCETS-SYNDROME; CONTROLLED
TRIAL; DRUGS; MANAGEMENT; PREGNANCY; ARTHRITIS; UVEITIS; AGENTS
AB PURPOSE: To evaluate treatment outcomes of azathioprine for noninfectious ocular inflammatory diseases.
DESIGN: Retrospective cohort study.
METHODS: Medical records of 145 patients starting azathioprine as a sole noncorticosteroid immunosuppressant at 4 tertiary uveitis services were reviewed. Main outcome measures included control of ocular inflammation, sustained control after tapering prednisone to <= 10 mg/day, and discontinuation of treatment because of side effects.
RESULTS: Among 145 patients (255 eyes) treated with azathioprine, 63% had uveitis, 23% had mucous membrane pemphigoid, 11% bad scleritis, and 3% had other inflammatory diseases. By Kaplan-Meier analysis, 62% (95% confidence interval [CI], 50% to 74%) of patients with active disease initially gained complete inactivity of inflammation sustained over at least 28 days within 1 year of therapy, and 47% (95% CI, 37% to 58%) tapered systemic corticosteroids to <= 10 mg daily while maintaining control of inflammation within 1 year of therapy. Treatment success was most common for intermediate uveitis (90% with sustained inactivity within 1 year; 95% CI, 64% to 99%). Over the median follow-up of 230 days (interquartile range, 62 to 679 days), azathioprine was discontinued at a rate of 0.45 per person,years (/PY): 0.16/PY because of side effects, 0.10/PY because of ineffectiveness, 0.09/PY because of disease remission, and 0.10/PY because of unspecified causes.
CONCLUSIONS: Azathioprine was moderately effective as a single corticosteroid-sparing immunosuppressive agent in terms of control of inflammation and corticosteroid-sparing benefits, but required several months to achieve treatment goals; it seems especially useful for patients with intermediate uveitis. Treatment-limiting side effects occurred in approximately one-fourth of patients within 1 year, but typically were reversible. (Am J Ophthalmol 2009;148:500-509. (C) 2009 by Elsevier Inc. All rights reserved.)
C1 [Kempen, John H.] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA.
[Pasadhika, Sirichai; Liesegang, Teresa L.; Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA.
[Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97201 USA.
[Kempen, John H.] Univ Penn, Scheie Eye Inst, Ocular Inflammat Serv, Philadelphia, PA 19104 USA.
[Kempen, John H.; Newcomb, Craig W.] Univ Penn, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Pujari, Siddharth S.; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA.
[Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA.
[Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA.
[Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
[Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA.
[Levy-Clarke, Grace A.] St Lukes Cataract & Laser Inst, Tarpon Springs, FL USA.
[Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA.
RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA.
EM john.kempen@uphs.upenn.edu
FU NATIONAL EYE INSTITUTE, BETHESDA, MARYLAND [EY-014943]; Research to
Prevent Blindness; Veterans' Administration; Genentech; Eyegate; Lux
Biosciences; Abbott
FX THIS STUDY WAS SUPPORTED BY THE NATIONAL EYE INSTITUTE, BETHESDA,
MARYLAND, GRANT NO. EY-014943 (DR KEMPEN); the Paul and Evanina Mackall
Foundation, New York, New York; and Research to Prevent Blindness Inc,
New York, New York. Dr Kempen is a Research to Prevent Blindness James
S. Adams Special Scholar Award recipient. Drs Jabs and Rosenbaum are
recipients of Research to Prevent Blindness Senior Scientific
Investigator Awards. Dr Levy-Clarke previously was supported by and Dr
Nussenblatt is supported by intramural funds of the National Eye
Institute, Bethesda, Maryland. Dr Sublet also received support from the
Veterans' Administration. Dr Foster has served as a consultant to
Allergan, Bausch & Lomb, and Sirion; owns equity or stock options in
Eyegate; and h is received speaking fees from Alcon, Allergan, Inspire,
Ista, Bausch & Lomb, and Centocor. Dr Jabs has served as a consultant to
Abbott, Genzyme Corporation, Novartis, Allergan, the Emmes Corporation
(DSMC member), and the Johns Hopkins University Dana Center for
Preventive Ophthalmology. Dr Kempen has served as a Consultant to Lux
Biosciences and has participated in clinical trials funded by Allergan
and Eyegate. Dr Rosenbaum has served as a Consultant to Abbott, Amgen,
Allergan, Lux Biosciences, and Novartis; holds equity ownership/stock
options in Amgen; and has received research Support from Genentech, Lux
Biosciences, and Abbott. Dr Suhler has received research support from
Eyegate, Genentech, Lux Biosciences, and Abbott. Involved in design of
study (S.P., J.H.K., C.W.N.); conduct of study (S.P., J.H.K., E.B.S.);
collection of data (S.P., J.H.K., CW.N., T.L.L., S.S.P., J.T.R., J.E.T.,
C.S.F., D.A.J., G.A.L.-C., R.B.N., E.B.S.); management (S.P., J.H.K.,
JT.R., J.E.T., C.S.F., D.A.]., G.A.L.-C., R.B.N., E.B.S.), analysis, and
interpretation of data (S.P., J.H.K., CW.N., E.B.S.); and preparation
(S.P., J.H.K., E.B.S.), review, and approval of the manuscript (S.P.,
J.H.K., C.W.N., T.L.L., S.S.P., J.T.R., J.E.T., C.S.F., D.A.J.,
G.A.L.-C., R.B.N., E.B.S.). The protocol was approved by Institutional
Review Boards of all participating institutions and was conducted in
accordance with the principles of the Declaration of Helsinki and the
Health Insurance Portability and Accountability Act.
NR 26
TC 68
Z9 71
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD OCT
PY 2009
VL 148
IS 4
BP 500
EP 509
DI 10.1016/j.ajo.2009.05.008
PG 10
WC Ophthalmology
SC Ophthalmology
GA 503MI
UT WOS:000270538000006
PM 19570522
ER
PT J
AU Taft, CT
Weatherill, RP
Woodward, HE
Pinto, LA
Watkins, LE
Miller, MW
Dekel, R
AF Taft, Casey T.
Weatherill, Robin P.
Woodward, Halley E.
Pinto, Lavinia A.
Watkins, Laura E.
Miller, Mark W.
Dekel, Rachel
TI Intimate Partner and General Aggression Perpetration Among Combat
Veterans Presenting to a Posttraumatic Stress Disorder Clinic
SO AMERICAN JOURNAL OF ORTHOPSYCHIATRY
LA English
DT Article
DE aggression; domestic violence; veterans; posttraumatic stress disorder
ID PHYSICAL AGGRESSION; RELATIONSHIP ABUSE; DOMESTIC VIOLENCE; VIETNAM
VETERANS; BEHAVIOR; COUPLES; ANGER; MEN; SYMPTOMATOLOGY; CONFLICT
AB This study examined rates and correlates of intimate partner and general aggression perpetration among 236 male combat veterans seeking services in a Veteran's Affairs posttraumatic stress disorder (PTSD) clinic. Approximately 33% of those in an intimate relationship reported perpetrating partner physical aggression in the previous year, and 91% reported partner psychological aggression. Comparable rates were found for general aggression perpetration among partnered and nonpartnered veterans. PTSD symptoms as well as symptoms of depression were associated with aggression across subgroups and forms of aggression, and PTSD symptoms reflecting arousal and lack of control were generally the strongest predictor of aggression. Findings indicate a need for additional aggression screening and intervention development for this population, and highlight the targeting of heightened arousal and lack of behavioral control in aggression interventions.
C1 [Taft, Casey T.; Weatherill, Robin P.; Woodward, Halley E.; Pinto, Lavinia A.; Watkins, Laura E.; Miller, Mark W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA.
[Taft, Casey T.; Weatherill, Robin P.; Miller, Mark W.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA.
[Dekel, Rachel] Bar Ilan Univ, Louis & Gabi Weisfeld Sch Social Work, IL-52100 Ramat Gan, Israel.
RP Taft, CT (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA.
EM casey.taft@va.gov
RI Miller, Mark/G-7322-2011
OI Miller, Mark/0000-0001-6393-8563
FU NIMH NIH HHS [R01 MH079806]
NR 45
TC 48
Z9 48
U1 4
U2 13
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-9432
J9 AM J ORTHOPSYCHIAT
JI Am. J. Orthopsychiatr.
PD OCT
PY 2009
VL 79
IS 4
BP 461
EP 468
DI 10.1037/a0016657
PG 8
WC Psychiatry; Social Work
SC Psychiatry; Social Work
GA V15HM
UT WOS:000207793100005
PM 20099937
ER
PT J
AU Jaafar, F
Righi, E
Lindstrom, V
Linton, C
Nohadani, M
Van Noorden, S
Lloyd, T
Poznansky, J
Stamp, G
Dina, R
Coleman, DV
Poznansky, MC
AF Jaafar, Fatimah
Righi, Elda
Lindstrom, Victoria
Linton, Christine
Nohadani, Mahrokh
Van Noorden, Susan
Lloyd, Tyler
Poznansky, Joshua
Stamp, Gordon
Dina, Roberto
Coleman, Dulcie V.
Poznansky, Mark C.
TI Correlation of CXCL12 Expression and FoxP3(+) Cell Infiltration with
Human Papillomavirus Infection and Clinicopathological Progression of
Cervical Cancer
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID REGULATORY T-CELLS; CHEMOKINE RECEPTOR CXCR4; LYMPH-NODE METASTASIS;
OVARIAN-CARCINOMA; ACTIVE MOVEMENT; TUMOR-CELLS; ADENOCARCINOMA;
INVOLVEMENT; PROGNOSIS; NEOPLASIA
AB Human cervical cancer is an immunogenic tumor with a defined pattern of histopathological and clinical progression. Tumor-infiltrating T cells contribute to immune control of this tumor; however, cervical cancer dysregulates this immune response both through its association with human papillomavirus (HPV) infection and by producing cytokines and chemokines. Animal tumor models have revealed associations between overproduction of the chemokine stromal cell-derived factor-1 (SDF-1 or CXCL12) and dys-regulation of tumor-specific immunity. We therefore proposed that CXCL12 expression by cervical precancerous and cancerous lesions correlates with histopathological progression, loss of immune control of the tumor, and HPV infection. We found a significant association between cancer stage and CXCL12 expression for squamous and glandular lesions as well as with the HPV16+ (high-risk) status of the neoplastic lesions. Cancer progression was correlated with increasing levels of FoxP3 T-cell infiltration in the tumor. FoxP3 and CXCL12 expression significantly correlated for squamous and glandular neoplastic lesions. These observations were supported by enzyme-linked immunosorbent assay and Western blotting. In addition, we demonstrated CXCL12 expression by dyskaryotic cells in ThinPrep cervical smears. This study robustly links increased CXCL12 expression and FoxP3(+)-cell infiltration to HPV infection and progression of cervical cancer. It supports the detection of CXCL12 in cervical smears and biopsies as an additional biomarker for this disease. (Am J Pathol 2009, 175:1525-1535; DOI: 10.2353/ajpath.2009.090295)
C1 [Righi, Elda; Lindstrom, Victoria; Linton, Christine; Poznansky, Mark C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Righi, Elda; Lindstrom, Victoria; Linton, Christine; Poznansky, Mark C.] Massachusetts Gen Hosp, Dana Farber Harvard Canc Ctr, Boston, MA 02114 USA.
[Jaafar, Fatimah; Nohadani, Mahrokh; Van Noorden, Susan; Lloyd, Tyler; Poznansky, Joshua; Stamp, Gordon; Dina, Roberto; Coleman, Dulcie V.] Hammersmith Hosp, Imperial Coll, Fac Med, Dept Histopathol & Cytol, London, England.
RP Poznansky, MC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp East, 149 Bldg,13th St, Charlestown, MA 02129 USA.
EM d.v.coleman@ic.ac.uk; mpoznansky@partners.org
FU U.S. Public Health Service [R01 A149757]; Marsha Rivkin Center;
philanthropic funds; Imperial College Trust Fund; Government of Brunei,
Darussalam
FX Supported by the U.S. Public Health Service (grant R01 A149757), the
Marsha Rivkin Center, and philanthropic funds (M.C.P. and E.R.), the
Imperial College Trust Fund (D.N.C.), and the Government of Brunei,
Darussalam (F.J.).
NR 33
TC 33
Z9 33
U1 1
U2 12
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 2009
VL 175
IS 4
BP 1525
EP 1535
DI 10.2353/ajpath.2009.090295
PG 11
WC Pathology
SC Pathology
GA 503AM
UT WOS:000270503100019
PM 19808652
ER
PT J
AU Ho-Tin-Noe, B
Carbo, C
Demers, M
Cifuni, SM
Goerge, T
Wagner, DD
AF Ho-Tin-Noe, Benoit
Carbo, Carla
Demers, Melanie
Cifuni, Stephen M.
Goerge, Tobias
Wagner, Denisa D.
TI Innate Immune Cells Induce Hemorrhage in Tumors during Thrombocytopenia
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID HUMAN PLATELETS; NEUTROPHIL FUNCTIONS; ENDOTHELIAL BARRIER;
NECROSIS-FACTOR; MICE; INFLAMMATION; ANGIOGENESIS; MACROPHAGES; RELEASE;
PRODUCTS
AB Platelets are crucial regulators of tumor vascular homeostasis and continuously prevent tumor hemorrhage through secretion of their granules. However, the reason for tumor bleeding in the absence of platelets remains unknown. Tumors are associated with inflammation, a cause of hemorrhage in thrombocytopenia. Here, we investigated the role of the inflamed tumor microenvironment in the induction of tumor vessel injury in thrombocytopenic mice. Using s.c. injections of vascular endothelial growth factor or tumor necrosis factor-a combined with depletion of neurtrophils, we demonstrate that enhancing the opening of endothelial cell junctions was not sufficient to cause bleeding in the absence of platelets; instead, induction of tissue hemorrhage in thrombocytopenia required recruitment of leukocytes. immunohistology revealed that thrombocytopenia-induced tumor hemorrhage occurs at sites of macrophage and neutrophil accumulation. Mice deficient in beta(2) or beta(3) integrins, which have decreased neutrophil and/or macrophage infiltration in their tumor stroma, were protected from thrombocytopenia-induced tumor hemorrhage, indicating that, in the absence of platelets, stroma-infiltrating leukocytes induced tumor vessel injury. This injury was independent of reactive oxygen species generation and of complement activation, as suggested by the persistence of tumor hemorrhage in C3- and nicotinamide adenine dinucleotide phosphate oxidase-deficient thrombocytopenic mice. Our results show that platelets counteract tumor-associated inflammation and that the absence of this platelet function elicits vascular injuries by tumor-infiltrating innate immune cells. (Am J Pathol 2009, 175:1699-1708; DOI: 10.2353/ajpath.2009.090460)
C1 [Ho-Tin-Noe, Benoit; Carbo, Carla; Demers, Melanie; Cifuni, Stephen M.; Goerge, Tobias; Wagner, Denisa D.] Immune Dis Inst, Boston, MA 02115 USA.
[Ho-Tin-Noe, Benoit; Carbo, Carla; Demers, Melanie; Cifuni, Stephen M.; Goerge, Tobias; Wagner, Denisa D.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Ho-Tin-Noe, Benoit; Carbo, Carla; Demers, Melanie; Goerge, Tobias; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Carbo, Carla] Univ Barcelona, Hosp Clin, Serv Hemoterapia Hemostasia, Barcelona, Spain.
RP Wagner, DD (reprint author), Immune Dis Inst, 3 Blackfan Circle, Boston, MA 02115 USA.
EM wagner@idi.harvard.edu
FU National Heart, Lung, and Blood Institute of the National Institutes of
Health [R37 HL041002, P01 HI066105]; La Fonclation pour la Recherche
Medicale; Terry Fox Foundation through the National Cancer Institute of
Canada [TF018748]; Deutsche Forschungsgemeinschaft [GO1360/4-1]
FX Supported by grants from the National Heart, Lung, and Blood Institute
of the National Institutes of Health (R37 HL041002 and P01 HI066105; to
D.D.W.), La Fonclation pour la Recherche Medicale (to B.H.), the Terry
Fox Foundation through the National Cancer Institute of Canada
(TF018748; to M.D.), and from the Deutsche Forschungsgemeinschaft
(GO1360/4-1; to T.G.).
NR 58
TC 31
Z9 32
U1 1
U2 1
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD OCT
PY 2009
VL 175
IS 4
BP 1699
EP 1708
DI 10.2353/ajpath.2009.090460
PG 10
WC Pathology
SC Pathology
GA 503AM
UT WOS:000270503100035
PM 19729481
ER
PT J
AU Jones, JA
Beck, C
Barbour, JR
Zavadzkas, JA
Mukherjee, R
Spinale, FG
Ikonomidis, JS
AF Jones, Jeffrey A.
Beck, Christy
Barbour, John R.
Zavadzkas, Jouzas A.
Mukherjee, Rupak
Spinale, Francis G.
Ikonomidis, John S.
TI Alterations in Aortic Cellular Constituents during Thoracic Aortic
Aneurysm Development Myofibroblast-Mediated Vascular Remodeling
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID MATRIX PROTEIN EXPRESSION; EXTRACELLULAR-MATRIX; ASCENDING AORTA; MURINE
MODEL; MONOCLONAL-ANTIBODY; METALLOPROTEINASES; VALVE; MACROPHAGE;
APOPTOSIS; PATTERNS
AB The present study tested the hypothesis that changes in the resident endogenous cellular population accompany alterations in aortic collagen and elastin content during thoracic aortic aneurysm (TAA) development in a murine model. Descending thoracic aortas were analyzed at various time points (2, 4, 8, and 16 weeks) post-TAA induction (0-5 M CaCl(2), 15 minutes). Aortic tissue sections were subjected to histological staining and morphometric analysis for collagen and elastin, as well as immunostaining for cell-type-specific markers to quantify fibroblasts, myofibroblasts, and smooth-muscle cells. Results were compared with reference control mice processed in die same fashion. Aortic dilatation was accompanied by changes in the elastic architecture that included: a decreased number of elastic lamellae (from 6 to 4); altered area fraction of elastin (elevated at 4 weeks and decreased at 16 weeks); and a decreased area between elastic lamellae (minimum reached at 4 weeks). Total collagen content did not change over time. increased immunoreactivity for fibroblast and myofibroblast markers was observed at 8- and 16-week post-TAA-induction, whereas immunoreactivity for smooth-muscle cell markers peaked at 4 weeks and returned to baseline by 16 weeks. Therefore, this study demonstrated that changes in aortic elastin content were accompanied by the emergence of a subset of fibroblast-derived myofibroblasts whose altered phenotype may play a significant role in TAA development through the enhancement of extracellular matrix proteolysis. (Am J Pathol 2009, 175:1746-1756; DOI: 10.2353/ajpath.2009.081141)
C1 [Jones, Jeffrey A.; Beck, Christy; Barbour, John R.; Zavadzkas, Jouzas A.; Mukherjee, Rupak; Spinale, Francis G.; Ikonomidis, John S.] Med Univ S Carolina, Dept Surg, Div Cardiothorac Surg Res, Charleston, SC 29425 USA.
[Jones, Jeffrey A.; Spinale, Francis G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
RP Jones, JA (reprint author), Med Univ S Carolina, Dept Surg, Div Cardiothorac Surg Res, Strom Thurmond Res Bldg,114 Doughty St,Suite 625, Charleston, SC 29425 USA.
EM jonesja@musc.edu
FU National Institutes of Health/National Heart, Lung, and Blood Institute
[R01 HL075488-05]; Department of Veterans Affairs [BLRD-CDA-2]
FX Supported by National Institutes of Health/National Heart, Lung, and
Blood Institute grant R01 HL075488-05 and a Career Development Award
(BLRD-CDA-2) from the Department of Veterans Affairs.
NR 50
TC 27
Z9 28
U1 1
U2 5
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD OCT
PY 2009
VL 175
IS 4
BP 1746
EP 1756
DI 10.2353/ajpath.2009.081141
PG 11
WC Pathology
SC Pathology
GA 503AM
UT WOS:000270503100039
PM 19729479
ER
PT J
AU Yang, ZH
Yan, K
Williams, S
Lew, HL
AF Yang, Zhaohui
Yan, Kun
Williams, Steve
Lew, Henry L.
TI An Unusual Cause of Abdominal Pain in a Patient with Severe Traumatic
Brain Injury (TBI): Intussusception of the Jejunum
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Editorial Material
C1 [Yan, Kun; Lew, Henry L.] VA Boston Healthcare Syst, Phys Med & Rehabil Serv, Boston, MA 02130 USA.
[Yang, Zhaohui; Williams, Steve] Boston Univ, Med Ctr, Dept Phys Med & Rehabil, Boston, MA USA.
[Lew, Henry L.] Harvard Univ, Sch Med, Boston, MA USA.
RP Lew, HL (reprint author), VA Boston Healthcare Syst, Phys Med & Rehabil Serv, 150 S Huntington Ave, Boston, MA 02130 USA.
NR 4
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-9115
J9 AM J PHYS MED REHAB
JI Am. J. Phys. Med. Rehabil.
PD OCT
PY 2009
VL 88
IS 10
BP 864
EP 865
DI 10.1097/PHM.0b013e3181b32b31
PG 2
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 506FV
UT WOS:000270760600011
PM 19661775
ER
PT J
AU Sussman, CR
Zhao, JH
Plata, C
Lu, J
Daly, C
Angle, N
DiPiero, J
Drummond, IA
Liang, JO
Boron, WF
Romero, MF
Chang, MH
AF Sussman, Caroline R.
Zhao, Jinhua
Plata, Consuelo
Lu, Jing
Daly, Christopher
Angle, Nathan
DiPiero, Jennifer
Drummond, Iain A.
Liang, Jennifer O.
Boron, Walter F.
Romero, Michael F.
Chang, Min-Hwang
TI Cloning, localization, and functional expression of the electrogenic Na+
bicarbonate cotransporter (NBCe1) from zebrafish
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE intracellular pH; acid base; membrane current; bicarbonate transport;
Xenopus oocyte; teleost; Danio rerio; cellular buffering;
immunohistochemistry; in situ; electrophysiology
ID RENAL TUBULAR-ACIDOSIS; NA+-HCO3-COTRANSPORTER; ANION-EXCHANGER;
NA+/HCO3-COTRANSPORTER; ENVIRONMENTAL HYPERCAPNIA; MISSENSE MUTATION;
BRAIN VENTRICLES; INTRACELLULAR PH; BASE REGULATION; GENE SLC4A4
AB Sussman CR, Zhao J, Plata C, Lu J, Daly C, Angle N, DiPiero J, Drummond IA, Liang JO, Boron WF, Romero MF, Chang M-H. Cloning, localization, and functional expression of the electrogenic Na+ bicarbonate cotransporter (NBCe1) from zebrafish. Am J Physiol Cell Physiol 297: C865-C875, 2009. First published July 22, 2009; doi:10.1152/ajpcell.00679.2008.-Mutations in the electrogenic Na+/nHCO(3)(-) cotransporter (NBCe1, SLC4A4) cause severe proximal renal tubular acidosis, glaucoma, and cataracts in humans, indicating NBCe1 has a critical role in acid-base homeostasis and ocular fluid transport. To better understand the homeostatic roles and protein ontogeny of NBCe1, we have cloned, localized, and downregulated NBCe1 expression in zebrafish, and examined its transport characteristics when expressed in Xenopus oocytes. Zebrafish NBCe1 (zNBCe1) is 80% identical to published mammalian NBCe1 cDNAs. Like other fish NBCe1 clones, zebrafish NBCe1 is most similar to the pancreatic form of mammalian NBC (Slc4a4-B) but appears to be the dominant isoform found in zebrafish. In situ hybridization of embryos demonstrated mRNA expression in kidney pronephros and eye by 24 h postfertilization (hpf) and gill and brain by 120 hpf. Immunohistochemical labeling demonstrated expression in adult zebrafish eye and gill. Morpholino knockdown studies demonstrated roles in eye and brain development and caused edema, indicating altered fluid and electrolyte balance. With the use of microelectrodes to measure membrane potential (V-m), voltage clamp (V-C), intracellular pH (pH(i)), or intracellular Na+ activity (aNa(i)), we examined the function of zNBCe1 expressed in Xenopus oocytes. Zebrafish NBCe1 shared transport properties with mammalian NBCe1s, demonstrating electrogenic Na+ and HCO3- transport as well as similar drug sensitivity, including inhibition by 4,4'-diiso-thiocyano-2,2'-disulfonic acid stilbene and tenidap. These data indicate that NBCe1 in zebrafish shares many characteristics with mammalian NBCe1, including tissue distribution, importance in systemic water and electrolyte balance, and electrogenic transport of Na+ and HCO3-. Thus zebrafish promise to be useful model system for studies of NBCe1 physiology.
C1 [Sussman, Caroline R.; Romero, Michael F.; Chang, Min-Hwang] Mayo Clin, Coll Med, Rochester, MN 55905 USA.
[Sussman, Caroline R.; Plata, Consuelo; Lu, Jing; Daly, Christopher; Angle, Nathan; DiPiero, Jennifer; Liang, Jennifer O.; Boron, Walter F.; Romero, Michael F.; Chang, Min-Hwang] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Zhao, Jinhua] Cleveland Vet Affairs Med Ctr, Cleveland, OH USA.
[Zhao, Jinhua; Drummond, Iain A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nephrol Div,Dept Med, Charlestown, MA USA.
[Plata, Consuelo] Inst Nacl Ciencias Med & Nutr Nefrol & Metab Mine, Mexico City, DF, Mexico.
[Lu, Jing; Daly, Christopher; Boron, Walter F.] Yale Univ, Sch Med, New Haven, CT USA.
[Liang, Jennifer O.] Univ Minnesota, Duluth, MN 55812 USA.
RP Chang, MH (reprint author), Mayo Clin, Coll Med, 200 1st St SW, Rochester, MN 55905 USA.
EM chang.minhwang@mayo.edu
RI Plata, Consuelo/M-4482-2015
OI Plata, Consuelo/0000-0001-9340-8950
FU National Institute of Diabetes and Digestive and Kidney Diseases
[DK-56218, DK-60845, EY-017732, DK-30344, DK-070263]; Wadsworth
Foundation New Investigator Award; American Heart Association (AHA) [SDG
06-30137N]; PKD foundation fellowship [38a2f]; AHA postdoctoral
fellowships
FX This work was supported by National Institute of Diabetes and Digestive
and Kidney Diseases Grants DK-56218, DK-60845, and EY-017732 (to M. F.
Romero), DK-30344 (to W. F. Boron), DK-070263 (to I. A. Drummond),
Wadsworth Foundation New Investigator Award and American Heart
Association (AHA) SDG 06-30137N (to C. R. Sussman), PKD foundation
fellowship 38a2f (to J. Zhao), and AHA postdoctoral fellowships (to
M.-H. Chang and J. Lu).
NR 52
TC 15
Z9 16
U1 3
U2 10
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 2009
VL 297
IS 4
BP C865
EP C875
DI 10.1152/ajpcell.00679.2008
PG 11
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 501KY
UT WOS:000270381900009
PM 19625604
ER
PT J
AU Akiba, Y
Watanabe, C
Mizumori, M
Kaunitz, JD
AF Akiba, Yasutada
Watanabe, Chikako
Mizumori, Misa
Kaunitz, Jonathan D.
TI Luminal L-glutamate enhances duodenal mucosal defense mechanisms via
multiple glutamate receptors in rats
SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
LA English
DT Article
DE intracellular alkalinization; mucus secretion; bicarbonate secretion;
monosodium glutamate; taste receptor
ID CALCIUM-SENSING RECEPTOR; MUCUS GEL THICKNESS; BITTER TASTE RECEPTORS;
INTRACELLULAR PH; GASTROINTESTINAL-TRACT; CA2+-SENSING RECEPTOR;
CARBONIC-ANHYDRASES; CHORDA TYMPANI; BLOOD-FLOW; ACID
AB Akiba Y, Watanabe C, Mizumori M, Kaunitz JD. Luminal L-glutamate enhances duodenal mucosal defense mechanisms via multiple glutamate receptors in rats. Am J Physiol Gastrointest Liver Physiol 297: G781-G791, 2009. First published July 30, 2009; doi: 10.1152/ajpgi.90605.2008.-Presence of taste receptor families in the gastrointestinal mucosa suggests a physiological basis for local and early detection of a meal. We hypothesized that luminal L-glutamate, which is the primary nutrient conferring fundamental umami or proteinaceous taste, influences mucosal defense mechanisms in rat duodenum. We perfused the duodenal mucosa of anesthetized rats with L-glutamate (0.1-10 mM). Intracellular pH (pH(i)) of the epithelial cells, blood flow, and mucus gel thickness (MGT) were simultaneously and continuously measured in vivo. Some rats were pretreated with indomethacin or capsaicin. Duodenal bicarbonate secretion (DBS) was measured with flow-through pH and CO(2) electrodes. We tested the effects of agonists or antagonists for metabotropic glutamate receptor (mGluR) 1 or 4 or calcium-sensing receptor (CaSR) on defense factors. Luminal L-glutamate dose dependently increased pHi and MGT but had no effect on blood flow in the duodenum. L-glutamate (10 mM)-induced cellular alkalinization and mucus secretion were inhibited by pretreatment with indomethacin or capsaicin. L-glutamate effects on pH(i) and MGT were mimicked by mGluR4 agonists and inhibited by an mGluR4 antagonist. CaSR agonists acidified cells with increased MGT and DBS, unlike L-glutamate. Perfusion of L-glutamate with inosinate (inosine 5'-monophosphate, 0.1 mM) enhanced DBS only in combination, suggesting synergistic activation of the L-glutamate receptor, typical of taste receptor type 1. L-leucine or L-aspartate had similar effects on DBS without any effect on pHi and MGT. Preperfusion of L-glutamate prevented acid-induced cellular injury, suggesting that L-glutamate protects the mucosa by enhancing mucosal defenses. Luminal L-glutamate may activate multiple receptors and afferent nerves and locally enhance mucosal defenses to prevent subsequent injury attributable to acid exposure in the duodenum.
C1 [Akiba, Yasutada; Kaunitz, Jonathan D.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA.
[Akiba, Yasutada; Watanabe, Chikako; Mizumori, Misa; Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA.
[Akiba, Yasutada; Watanabe, Chikako; Mizumori, Misa; Kaunitz, Jonathan D.] Brentwood Biomed Res Inst, Los Angeles, CA USA.
RP Akiba, Y (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM yasuakiba@hotmail.com
FU Ajinomoto, Japan; Department of Veterans Affairs Merit Review Award,
NIH-NIDDK [R01 DK54221, P30 DK0413]
FX This work was supported by a research grant from Ajinomoto, Japan (Y.
Akiba), Department of Veterans Affairs Merit Review Award, NIH-NIDDK R01
DK54221 (J. Kaunitz), and the animal core of NIH-NIDDK P30 DK0413 (J. E.
Rozengurt).
NR 48
TC 58
Z9 62
U1 0
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1857
J9 AM J PHYSIOL-GASTR L
JI Am. J. Physiol.-Gastroint. Liver Physiol.
PD OCT
PY 2009
VL 297
IS 4
BP G781
EP G791
DI 10.1152/ajpgi.90605.2008
PG 11
WC Gastroenterology & Hepatology; Physiology
SC Gastroenterology & Hepatology; Physiology
GA 498LI
UT WOS:000270141400017
PM 19643955
ER
PT J
AU Waxman, AB
Kolliputi, N
AF Waxman, Aaron B.
Kolliputi, Narasaiah
TI IL-6 Protects against Hyperoxia-Induced Mitochondrial Damage via
Bcl-2-Induced Bak Interactions with Mitofusions
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE lung injury; mitochondria; apoptosis; cytochrome c; Bax
ID ACUTE LUNG INJURY; CELL-DEATH; OXYGEN-TOXICITY; GENE-EXPRESSION;
DNA-DAMAGE; BCL-2; APOPTOSIS; FAMILY; INTERLEUKIN-11; INHIBITION
AB overexpression of IL-6 markedly diminishes hyperoxic lung injury, hyperoxia-induced cell death, and DNA fragmentation, and enhances Bcl-2 expression. We hypothesized that changes in the interactions between Bcl-2 family members play an important role in the IL-6-mediated protective response to oxidative stress. Consistent with this hypothesis, we found that IL-6 induced Bcl-2 expression, both in vivo and in vitro, disrupted interactions between proapoptotic and antiapoptotic factors, and suppressed H(2)O(2)-induced loss of mitochondrial membrane potential in vitro. In addition, IL-6 overexpression in mice protects against hyperoxia-induced lung mitochondrial damage. The overexpression of Bcl-2 in vivo prolonged the survival of mice exposed to hyperoxia and inhibited alveolar capillary protein leakage. In addition, apoptosis-associated DNA fragmentation was substantially reduced in these animals. This IL-6-mediated protection was lost when Bcl-2 was silenced, demonstrating that Bcl-2 is an essential mediator of IL-6 cytoprotection. Finally, Bcl-2 blocked the dissociation of Bak from mitofusion protein (Mfn) 2, and inhibited the interaction between Bak and Mfn1. Taken together, our results suggest that IL-6 induces Bcl-2 expression to perform cytoprotective functions in response to oxygen toxicity, and that this effect is mediated by alterations in the interactions between Bak and Mfns.
C1 [Waxman, Aaron B.; Kolliputi, Narasaiah] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Pulm Crit Care Unit, Boston, MA 02114 USA.
RP Waxman, AB (reprint author), Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Pulm Crit Care Unit, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA.
EM abwaxman@partners.org
RI Kolliputi, Narasaiah/I-6050-2012
OI Kolliputi, Narasaiah/0000-0002-2654-1900
FU National Institutes of Health [RO1HL074859]
FX This work was supported by National Institutes of Health grant
RO1HL074859 (A.B.W.).
NR 32
TC 45
Z9 50
U1 0
U2 3
PU AMER THORACIC SOC
PI NEW YORK
PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA
SN 1044-1549
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD OCT
PY 2009
VL 41
IS 4
BP 385
EP 396
DI 10.1165/rcmb.2008-0302OC
PG 12
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 499BJ
UT WOS:000270191200002
PM 19168699
ER
PT J
AU Medoff, BD
Okamoto, Y
Leyton, P
Weng, MQ
Sandall, BP
Raher, MJ
Kihara, S
Bloch, KD
Libby, P
Luster, AD
AF Medoff, Benjamin D.
Okamoto, Yoshihisa
Leyton, Patricio
Weng, Meiqian
Sandall, Barry P.
Raher, Michael J.
Kihara, Shinji
Bloch, Kenneth D.
Libby, Peter
Luster, Andrew D.
TI Adiponectin Deficiency Increases Allergic Airway Inflammation and
Pulmonary Vascular Remodeling
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE asthma; obesity; pulmonary hypertension
ID ACTIVATED PROTEIN-KINASE; OBESITY HYPOVENTILATION-SYNDROME; BODY-MASS
INDEX; NF-KAPPA-B; SMOOTH-MUSCLE; ARTERIAL-HYPERTENSION;
EPITHELIAL-CELLS; STIMULATES ANGIOGENESIS; EOTAXIN EXPRESSION;
INSULIN-RESISTANCE
AB Obesity is associated with an increased incidence and severity of asthma, as well as other lung disorders, such as pulmonary hypertension. Adiponectin (APN), an antiinflammatory adipocytokine, circulates at lower levels in the obese, which is thought to contribute to obesity-related inflammatory diseases. We sought to determine the effects of APN deficiency in a murine model of chronic asthma. Allergic airway inflammation was induced in APN-deficient mice (APN(-/-)) using sensitization without adjuvant followed by airway challenge with ovalbumin. The mice were then analyzed for changes in inflammation and lung remodeling. APN(-/-) mice in this model develop increased allergic airway inflammation compared with wildtype mice, with greater accumulation of eosinophils and monocytes in the airways associated with elevated lung chemokine levels. Surprisingly, APN-/- mice developed severe pulmonary arterial muscularization and pulmonary arterial hypertension in this model, whereas wild-type mice had only mild vascular remodeling and comparatively less pulmonary arterial hypertension. Our findings demonstrate that APN modulates allergic inflammation and pulmonary vascular remodeling in a model of chronic asthma. These data provide a possible mechanism for the association between obesity and asthma, and suggest a potential novel link between obesity, inflammatory lung disease, and pulmonary hypertension.
C1 [Medoff, Benjamin D.; Weng, Meiqian; Sandall, Barry P.; Luster, Andrew D.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA.
[Medoff, Benjamin D.; Weng, Meiqian] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Charlestown, MA 02129 USA.
[Leyton, Patricio; Raher, Michael J.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
[Leyton, Patricio; Raher, Michael J.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Charlestown, MA 02129 USA.
[Leyton, Patricio; Raher, Michael J.; Bloch, Kenneth D.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Okamoto, Yoshihisa; Libby, Peter] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.
[Okamoto, Yoshihisa; Libby, Peter] Harvard Univ, Sch Med, Boston, MA USA.
[Kihara, Shinji] Osaka Univ, Grad Sch Med, Dept Metab Med, Osaka, Japan.
RP Medoff, BD (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, CNY 8301,149 13th St, Charlestown, MA 02129 USA.
EM bmedoff@partners.org; aluster@mgh.harvard.edu
FU National Institutes of Health [HL072775, HL088297, A140618, HL34636,
HL074352]; Donald W. Reynolds Foundation; American Heart Association and
Eli Lilly (International Fellowship)
FX This work was supported by National Institutes of Health grants HL072775
and HL088297 (B.D.M.), A140618 (A.D.L.), HL34636 (P.L.), and HL074352
(K.D.B.), the Donald W. Reynolds Foundation (P.L.), and the American
Heart Association and Eli Lilly (International Fellowship) (Y.O.).
NR 86
TC 87
Z9 88
U1 1
U2 5
PU AMER THORACIC SOC
PI NEW YORK
PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA
SN 1044-1549
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD OCT
PY 2009
VL 41
IS 4
BP 397
EP 406
DI 10.1165/rcmb.2008-0415OC
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 499BJ
UT WOS:000270191200003
PM 19168697
ER
PT J
AU Baier, ND
Hahn, PF
Gervais, DA
Samir, A
Halpern, EF
Mueller, PR
Harisinghani, MG
AF Baier, Nina D.
Hahn, Peter F.
Gervais, Debra A.
Samir, Anthony
Halpern, Elkan F.
Mueller, Peter R.
Harisinghani, Mukesh G.
TI Fine-Needle Aspiration Biopsy of Thyroid Nodules: Experience in a Cohort
of 944 Patients
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE fine-needle aspiration biopsy; sonography; thyroid cancer; thyroid
nodules; ultrasound-guided biopsy
ID ULTRASONOGRAPHY; CARCINOMA; SONOGRAPHY; US; ASSOCIATION; PREVALENCE;
MALIGNANCY; MANAGEMENT; DIAGNOSIS; SOLITARY
AB OBJECTIVE. The objective of our study was to determine the likelihood of malignancy in thyroid nodules and the risk of a nondiagnostic fine-needle aspiration biopsy (FNAB) on the basis of the demographic characteristics of the patients and sonographic features of the nodules.
MATERIALS AND METHODS. Between January 2002 and November 2007, 2,338 ultrasound-guided thyroid, thyroid bed, and cervical lymph node FNABs were performed at a tertiary referral center. Entry criteria for our retrospective study were adult patients who underwent thyroid nodule FNAB and had previously undergone diagnostic sonography. From previous reports for 944 thyroid nodules (739 nodules in women and 205 nodules in men), four sonographic features were recorded: longest dimension, morphology, presence of micro-calcifications, and presence of lymphadenopathy. The final diagnosis of each nodule was classified as benign, malignant, or nondiagnostic on the basis of surgical pathology when available and cytology otherwise and was analyzed for correlation with individual sonographic features and combinations of features.
RESULTS. The prevalence of malignancy and of nondiagnostic FNAB in this study was 11.0% and 11.8%, respectively. Statistically significant (p < 0.05) findings in malignant nodules were younger patient age (<= 45 years; odds ratio [OR], 1.54) and solid nodule morphology (OR, 2.38). The significant predictors of a nondiagnostic-quality FNAB were older patient age (> 75 years; OR, 1.95) and a nodule >= 10 mm (OR, 1.45). Adding information about the other evaluated ultrasound features did not lead to a significant result.
CONCLUSION. Malignant thyroid nodules tend to be solid (86.5%). Patients older than 75 years showed a clearly increased risk of nondiagnostic FNAB, but to predict a higher risk of malignancy or of nondiagnostic FNAB using ultrasound remains difficult.
C1 [Baier, Nina D.; Hahn, Peter F.; Gervais, Debra A.; Samir, Anthony; Mueller, Peter R.; Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA.
[Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
RP Baier, ND (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA.
OI Samir, Anthony/0000-0002-7801-8724
NR 20
TC 45
Z9 45
U1 0
U2 0
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 2009
VL 193
IS 4
BP 1175
EP 1179
DI 10.2214/AJR.08.1840
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 497CZ
UT WOS:000270033300035
PM 19770344
ER
PT J
AU Samphao, S
Wheeler, AJ
Rafferty, E
Michaelson, JS
Specht, MC
Gadd, MA
Hughes, KS
Smith, BL
AF Samphao, Srila
Wheeler, Amanda J.
Rafferty, Elizabeth
Michaelson, James S.
Specht, Michelle C.
Gadd, Michele A.
Hughes, Kevin S.
Smith, Barbara L.
TI Diagnosis of breast cancer in women age 40 and younger: delays in
diagnosis result from underuse of genetic testing and breast imaging
SO AMERICAN JOURNAL OF SURGERY
LA English
DT Article; Proceedings Paper
CT 10th Annual Meeting of the American-Society-of-Breast-Surgeons
CY APR 23, 2009
CL San Diego, CA
SP Amer Soc Breast Surg
DE Breast cancer; Young women; Genetic testing; Digital mammography;
Magnetic resonance imaging
ID HIGH FAMILIAL RISK; SOCIETY GUIDELINES; BRCA2 MUTATIONS; MAMMOGRAPHY;
MRI; CARCINOMA; SENSITIVITY; PERFORMANCE; POPULATION; FEATURES
AB BACKGROUND: The impact of newer breast imaging technologies and genetic testing on the detection of breast cancer in women age 40 and younger remains unknown.
METHODS: A records review identified 628 women age 40 and younger diagnosed with breast cancer from 1996 to 2008. Patient and tumor characteristics, means of diagnosis, imaging results, and genetic testing were examined.
RESULTS: Tumors were first detected by self-examination in 71%, with a median invasive tumor size of 2.0 cm. Imaging performed at or after diagnosis visualized most tumors; mammography visualized 86%, magnetic resonance imaging (MRI) visualized 96%, and mammography plus MRI visualized more than 98% of tumors. For 81% of patients, the mammogram at diagnosis was their first mammogram. Although 50% had a family history of breast or ovarian cancer, few underwent genetic testing before their cancer diagnosis; 61 of 247 (25%) ultimately tested had a BRCA mutation.
CONCLUSIONS: Better use of genetic testing, mammography, and MRI could improve breast cancer detection in young women. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Samphao, Srila; Wheeler, Amanda J.; Michaelson, James S.; Specht, Michelle C.; Gadd, Michele A.; Hughes, Kevin S.; Smith, Barbara L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Surg Oncol, Boston, MA 02114 USA.
[Rafferty, Elizabeth] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA.
[Michaelson, James S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA.
RP Smith, BL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Surg Oncol, Yawkey 9A,55 Fruit St, Boston, MA 02114 USA.
EM blsmith1@partners.org
OI Hughes, Kevin/0000-0003-4084-6484
NR 33
TC 27
Z9 29
U1 0
U2 5
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9610
J9 AM J SURG
JI Am. J. Surg.
PD OCT
PY 2009
VL 198
IS 4
BP 538
EP 543
DI 10.1016/j.amjsurg.2009.06.010
PG 6
WC Surgery
SC Surgery
GA 509YU
UT WOS:000271056000016
PM 19800464
ER
PT J
AU Maguire, AA
Greenson, JK
Lauwers, GY
Ginsburg, RE
Williams, GT
Brown, IS
Riddell, RH
O'Donoghue, D
Sheahan, KD
AF Maguire, Aoife A.
Greenson, Joel K.
Lauwers, Greg Y.
Ginsburg, Richard E.
Williams, Geraint T.
Brown, Ian S.
Riddell, Robert H.
O'Donoghue, Diarmuid
Sheahan, Kieran D.
TI Collagenous Sprue A Clinicopathologic Study of 12 Cases
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE collagenous sprue; complicated celiac disease; small intestine
ID T-CELL LYMPHOMA; REFRACTORY CELIAC-DISEASE; NONSTEROIDAL
ANTIINFLAMMATORY DRUGS; GLUTEN-FREE DIET; INTRAEPITHELIAL LYMPHOCYTES;
GASTROINTESTINAL-TRACT; NEOPLASTIC POPULATION; ULCERATIVE JEJUNITIS;
SMALL-INTESTINE; COLITIS
AB Collagenous sprue is a rare form of small bowel enteropathy characterized by chronic diarrhea and progressive malabsorption with little data available on its natural history. The pathologic lesion consists of subepithelial collagen deposition associated with variable alterations in villous architecture. The small bowel biopsies of 12 cases were reviewed. Clinical details, celiac serology, and T-cell receptor gene rearrangement study results, when available, were collated. There were 8 females and 4 males (age ranged from 41 to 84 y) who presented with chronic diarrhea and weight loss. Small intestinal biopsies showed subepithelial collagen deposition with varying degrees of villous atrophy and varying numbers of intraepithelial lymphocytes. Four patients had previous biopsies showing enteropathic changes without collagen deposition. Seven cases were associated with collagenous colitis and I also had features of lymphocytic colitis. Three patients also had collagen deposition in gastric biopsies. One case was associated with lymphocytic gastritis. Celiac disease (CD, gluten-sensitive enteropathy) was documented in 4 patients. Five patients made a clinical improvement with combinations of a gluten-free diet and immunosuppressive therapy. Two patients died of complications of malnutrition and I of another illness. Clonal T-cell populations were identified in 5 of 6 cases tested. Four of these patients improved clinically after treatment but I has died. Collagenous sprue evolved on a background of CID in 4 cases. There was no history of CD in others and these cases may be the result of a biologic insult other than gluten sensitivity. None has developed clinical evidence of lymphoma to date.
C1 [Maguire, Aoife A.; Sheahan, Kieran D.] St Vincents Univ Hosp, Dept Histopathol, Dublin 4, Ireland.
[Greenson, Joel K.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA.
[Lauwers, Greg Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Ginsburg, Richard E.] Montgomery Gastroenterol Specialists, Montgomery, AL USA.
[Williams, Geraint T.] Cardiff Univ, Sch Med, Dept Pathol, Cardiff, S Glam, Wales.
[Brown, Ian S.] Sullivan Nicolaides Pathol, Brisbane, Qld, Australia.
[Riddell, Robert H.] Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada.
[O'Donoghue, Diarmuid] St Vincents Univ Hosp, Dept Gastroenterol, Dublin 4, Ireland.
RP Maguire, AA (reprint author), St Vincents Univ Hosp, Dept Histopathol, Elm Pk, Dublin 4, Ireland.
EM Aoife.maguire@ucd.ie
RI Riddell, Robert/J-5557-2016; Brown, Ian/R-7763-2016
OI Brown, Ian/0000-0001-6329-2547
NR 54
TC 20
Z9 20
U1 0
U2 2
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 2009
VL 33
IS 10
BP 1440
EP 1449
PG 10
WC Pathology; Surgery
SC Pathology; Surgery
GA 501RQ
UT WOS:000270399700002
PM 19641452
ER
PT J
AU Braaten, KM
Young, RH
Ferry, JA
AF braaten, Kristina M.
Young, Robert H.
Ferry, Judith A.
TI Viral-type Orchitis A Potential Mimic of Testicular Neoplasia
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE testis; orchitis; lymphoma; leukemia; intratubular neoplasia
ID TESTIS; LYMPHOMA; SARCOMA; TUMORS
AB Orchitis of viral or presumed viral etiology is an uncommon Cause of testicular pain or enlargement. Rarely orchitis is clinically or radiographically suggestive of neoplasia, resulting in a testicular biopsy or orchiectomy being performed. Between 1978 and 2004, 10 cases submitted in consultation were diagnosed as orchitis at the Massachusetts General Hospital. The patients were from 18 to 37 years of age and presented with testicular enlargement or a mass, pain, or both. Radiographic Studies were suspicious for a neoplasm in all 5 cases in which results were available. The patients underwent testicular biopsy (2 cases), orchiectomy (6 cases), biopsy immediately followed by orchiectomy (I case), or biopsy followed by orchiectomy 3 weeks later (I case). The cases were Submitted with diagnoses that included intratubular seminoma, intratubular germ cell neoplasia, unspecified, Sertoli cell hyperplasia, myeloid sarcoma, and lymphoma. Microscopic examination revealed preservation of the architecture of the testicular parenchyma, typically with hemorrhage and edema, with patchy inflammation in the form of a lymphohistiocytic infiltrate within seminiferous tubules and also between tubules. The intratubular infiltrate usually predominated. Immunohistochemical studies, performed in 7 cases showed a mixture of CD68+ histiocytes and CD3+ T cells, with few B cells (CD20+) and few granulocytes. Follow-up was available in 5 cases; all 5 patients were alive and well I I months to 10 years after diagnosis. In the rare instance in which a testicular specimen with orchitis is Submitted for pathologic evaluation, diagnosis may be difficult. Familiarity with the pathologic changes characteristic of orchitis will help avoid misdiagnosis.
C1 [braaten, Kristina M.; Young, Robert H.; Ferry, Judith A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs,Dept Pathol, Boston, MA 02114 USA.
RP Ferry, JA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs,Dept Pathol, 55 Fruit St, Boston, MA 02114 USA.
EM jferry@partners.org
NR 21
TC 4
Z9 4
U1 0
U2 0
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 2009
VL 33
IS 10
BP 1477
EP 1484
PG 8
WC Pathology; Surgery
SC Pathology; Surgery
GA 501RQ
UT WOS:000270399700006
PM 19623033
ER
PT J
AU Farris, AB
Hasserjian, RP
Zukerberg, LR
Amrein, PC
Greene, RE
Mark, EJ
Kradin, RL
AF Farris, Alton B., III
Hasserjian, Robert P.
zukerberg, Lawrence R.
Amrein, Philip C.
Greene, Reginald E.
Mark, Eugene J.
Kradin, Richard L.
TI Diffuse Cellular and Fibrosing Interstitial Pneumonitis With
Desquamative Interstitial Pneumonitis-like Features Associated With
Myeloid Neoplasia
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE interstitial pneumonia; myelodysplastic syndromes; acute myeloid
leukemia
ID BONE-MARROW-TRANSPLANTATION; IDIOPATHIC PNEUMONIA; MYELODYSPLASTIC
SYNDROME; PROGNOSTIC-SIGNIFICANCE; LUNG INJURY; LENALIDOMIDE; SPECTRUM;
DISEASE
AB Patients with preleukemic myeloid neoplasia can develop nonhematologic disease. Five patients with the myelodysplastic syndrome presented with interstitial lung disease that heralded acute leukemia in 3. Chest radiographs showed diffuse interstitial opacities, and the lung biopsies showed diffuse Cellular interstitial and fibrosing pneumonitis with prominent alveolar filling by macrophages. There was no evidence to support a drug-induced or infectious etiology, and all cases lacked an identifiable leukemic infiltration. The inflammatory infiltrates and fibrosis were analyzed morphometrically, and this revealed a trend toward an indirect correlation between both CD68(+) cells and MPO-positive inflammatory cells and pulmonary fibrosis. We conclude that preleukemic myeloid neoplasia can be associated with an interstitial pneumonitis with histopathologic features that are distinguishable from both leukemic infiltration and "usual" nonspecific interstitial pneumonia.
C1 [Farris, Alton B., III; Hasserjian, Robert P.; zukerberg, Lawrence R.; Mark, Eugene J.; Kradin, Richard L.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA.
[Amrein, Philip C.] Massachusetts Gen Hosp, Dept Med, Hematol Oncol Unit, Boston, MA 02114 USA.
[Greene, Reginald E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Kradin, Richard L.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA.
RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Pathol Serv, 55 Fruit St,Warren 2, Boston, MA 02114 USA.
EM rkradin@partners.org
NR 34
TC 4
Z9 4
U1 0
U2 0
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 2009
VL 33
IS 10
BP 1485
EP 1493
PG 9
WC Pathology; Surgery
SC Pathology; Surgery
GA 501RQ
UT WOS:000270399700007
PM 19654503
ER
PT J
AU Hsu, M
Young, RH
Misdraji, J
AF Hsu, Maylee
Young, Robert H.
Misdraji, Joseph
TI Ruptured Appendiceal Diverticula Mimicking Low-grade Appendiceal
Mucinous Neoplasms
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE appendix; diverticular disease; mucinous neoplasm; pseudomyxoma
peritonei
ID VERMIFORM APPENDIX; NEUROMAS; LESIONS
AB Low-grade appendiceal mucinous neoplasms may rupture and seed the peritoneum with bland neoplastic mucinous epithelium resulting, when grossly evident, in the well-known process pseudomyxoma peritonei. Appendiceal diverticula may also rupture, resulting in mucin on the appendiceal serosa, which may raise concern for,in underlying appendiceal mucinous neoplasm. We report I I cases of ruptured appendiceal diverticula that were initially either misdiagnosed as appendiceal mucinous neoplasms, raised concern for a neoplasm, or were thought to exhibit localized pseudomyxoma peritonei. Two cases showed eversion or the appendiceal lining onto the serosa; I showed collision between the diverticulum and endosalpingiosis, and 3 had rare nonneoplastic epithelial cells in extra-appendiceal mucin. Most cases showed mucosal hyperplasia, mild crypt disarray, and variable reactive atypia. Eight cases had mucosal neuromas or other neural changes. None of the patients progressed to pseudomyxoma peritonei during the follow-up interval (mean 23 mo). Pathologists Should be aware that ruptured appendiceal diverticula may be associated with serosal mucin and even extra-appendiceal epithelium. Failure to distinguish this process from a mucosal neoplasm with rupture may result in unnecessary therapy and Cause the patient undue alarm.
C1 [Misdraji, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs,Dept Pathol, Boston, MA 02114 USA.
RP Misdraji, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs,Dept Pathol, Warren Bldg 105F, Boston, MA 02114 USA.
EM jmisdraji@partners.org
NR 22
TC 9
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 2009
VL 33
IS 10
BP 1515
EP 1521
PG 7
WC Pathology; Surgery
SC Pathology; Surgery
GA 501RQ
UT WOS:000270399700010
PM 19623035
ER
PT J
AU Jasuja, D
Mor, MK
Hartwig, KC
Palevsky, PM
Fine, MJ
Weisbord, SD
AF Jasuja, Deepak
Mor, Maria K.
Hartwig, Kathryn C.
Palevsky, Paul M.
Fine, Michael J.
Weisbord, Steven D.
TI Provider Knowledge of Contrast-Induced Acute Kidney Injury
SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES
LA English
DT Article
DE Contrast; Acute kidney injury; Providers; Knowledge
ID RADIOCONTRAST-INDUCED NEPHROPATHY; RANDOMIZED CONTROLLED-TRIAL;
ACUTE-RENAL-FAILURE; CORONARY INTERVENTION; CARDIAC ANGIOGRAPHY;
RISK-FACTORS; MEDIA; PREVENTION; NEPHROTOXICITY; INSUFFICIENCY
AB Background Although past research has elucidated the principal risk factors and efficacy of preventive interventions for contrast-induced acute kidney injury (CIAKI), provider awareness of this empiric evidence base is largely unknown. We sought to assess provider knowledge of the risk factors and preventive interventions for CIAKI. Methods: We asked medical providers caring for patients undergoing procedures with intravascular iodinated contrast to complete a survey designed to assess their knowledge of the risk factors and preventive interventions,for CIAKI. Results: Of the 87 participating providers, nearly all (n = 85; 98%) recognized chronic kidney disease and intravascular volume depletion as risk factors. However, 35 (41%) incorrectly identified allergy to contrast media as a risk factor and 8 (10%) incorrectly identified intravenous (IV) water as an effective preventive intervention. Compared with those with little or no prior training on CIAKI, those with substantial prior training correctly reported that peripheral vascular disease and atrial fibrillation are not risk factors and that fenoldopam and IV water are ineffective preventive interventions (P < 0.05). Trainees were more likely than those who had completed their postgraduate medical training to correctly report that IV saline and sodium bicarbonate are effective preventive interventions and that fenoldopam, dopamine, mannitol, and IV water are ineffective measures (P < 0.05). Conclusions: There is wide variability in providers' knowledge of CIAKI. Providers with more training on CIAKI and trainees had greater knowledge of the risk factors and preventive interventions for CIAKI. These findings underscore the need to standardize and intensify provider education of this costly and preventable iatrogenic condition.
C1 [Mor, Maria K.; Hartwig, Kathryn C.; Fine, Michael J.; Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA.
[Jasuja, Deepak] Univ Pittsburgh, Dept Gen Internal Med, Med Ctr McKeesport, Pittsburgh, PA USA.
[Palevsky, Paul M.; Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Renal Sect, Med Specialty Serv Line, Pittsburgh, PA 15240 USA.
[Palevsky, Paul M.; Weisbord, Steven D.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA.
[Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA.
RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Mailstop 111F-U,7E Room 120, Pittsburgh, PA 15240 USA.
EM weisbordsd@upmc.edu
OI Palevsky, Paul/0000-0002-7334-5400
FU NIAID NIH HHS [K24 AI001769]
NR 27
TC 4
Z9 4
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0002-9629
J9 AM J MED SCI
JI Am. J. Med. Sci.
PD OCT
PY 2009
VL 338
IS 4
BP 280
EP 286
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 511OE
UT WOS:000271174300006
PM 19641454
ER
PT J
AU Reese, PP
Feldman, HI
Asch, DA
Halpern, SD
Blumberg, EA
Thomasson, A
Shults, J
Bloom, RD
AF Reese, P. P.
Feldman, H. I.
Asch, D. A.
Halpern, S. D.
Blumberg, E. A.
Thomasson, A.
Shults, J.
Bloom, R. D.
TI Transplantation of Kidneys from Donors at Increased Risk for Blood-Borne
Viral Infection: Recipient Outcomes and Patterns of Organ Use
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE Centers for Disease Control (CDC); kidney transplantation; viral
infection
ID EXPANDED CRITERIA DONORS; CARDIAC DEATH; INFORMING CANDIDATES; SURVIVAL;
DIALYSIS; DONATION; INMATES
AB Kidney transplantation from deceased donors classified as increased risk for viral infection by the Centers for Disease Control (CDC) is controversial. Analyses of Organ Procurement and Transplantation Network (OPTN) data from 7/1/2004 to 7/1/2006 were performed. The primary cohort included 48 054 adults added to the kidney transplant wait list. Compared to receiving a standard criteria donor (SCD) kidney or remaining wait-listed, CDC recipients (HR 0.80, p = 0.18) had no significant difference in mortality. In a secondary cohort of 19 872 kidney recipients at 180 centers, SCD (reference) and CDC (HR 0.91, p = 0.16) recipients had no difference in the combined endpoint of allograft failure or death. Among centers performing > 10 kidney transplants during the study period, the median proportion of CDC transplants/total transplants was 7.2% (range 1.1-35.6%). Higher volume transplant centers were more likely to use CDC kidneys compared to low and intermediate volume centers (p < 0.01). An analysis of procured kidneys revealed that 6.8% of SCD versus 7.8% of CDC (p = 0.13) kidneys were discarded. In summary, center use of CDC kidneys varied widely, and recipients had good short-term outcomes. OPTN should collect detailed data about long-term outcomes and recipient viral testing so the potential risks of CDC kidneys can be fully evaluated.
C1 [Reese, P. P.; Feldman, H. I.; Halpern, S. D.; Bloom, R. D.] Univ Penn, Dept Med, Div Renal, Philadelphia, PA 19104 USA.
[Reese, P. P.; Feldman, H. I.; Halpern, S. D.; Thomasson, A.; Shults, J.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Reese, P. P.; Asch, D. A.; Halpern, S. D.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Asch, D. A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
[Blumberg, E. A.] Univ Penn, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA.
RP Reese, PP (reprint author), Univ Penn, Dept Med, Div Renal, Philadelphia, PA 19104 USA.
EM peter.reese@uphs.upenn.edu
OI Asch, David/0000-0002-7970-286X
FU NIH [K23 - DK078688-01, K24 - DK002651]; Greenwall Foundation
FX The authors acknowledge Stacey Doll for her helpful suggestions for the
study. Dr. Reese is supported by NIH grant K23 - DK078688-01. Dr.
Feldman is supported by NIH grant K24 - DK002651. Dr. Halpern is
supported by a Greenwall Foundation Faculty Scholar Award in Bioethics.
NR 23
TC 17
Z9 18
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD OCT
PY 2009
VL 9
IS 10
BP 2338
EP 2345
DI 10.1111/j.1600-6143.2009.02782.x
PG 8
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 494GY
UT WOS:000269801000018
PM 19702645
ER
PT J
AU Rozet, I
Tontisirin, N
Vavilala, MS
Treggiari, MM
Lee, LA
Lam, AM
AF Rozet, Irene
Tontisirin, Nuj
Vavilala, Monica S.
Treggiari, Miriam M.
Lee, Lorri A.
Lam, Arthur M.
TI Prolonged Propofol Anesthesia Is Not Associated with an Increase in
Blood Lactate
SO ANESTHESIA AND ANALGESIA
LA English
DT Article
ID HEPATIC GLUCOSE-PRODUCTION; FREE FATTY-ACIDS; INFUSION SYNDROME;
METABOLIC-ACIDOSIS; LACTIC-ACIDOSIS; ISOFLURANE ANESTHESIA; HALOTHANE
ANESTHESIA; CONSCIOUS DOGS; SEVOFLURANE; CHILDREN
AB BACKGROUND: Lactic acidosis is considered an early sign of propofol infusion syndrome. In this study, we investigated the changes in lactate and pH with propofol versus volatile anesthesia (VA) of long duration.
METHODS: Demographic and intraoperative data were recorded retrospectively from the anesthesia records of patients who underwent elective spine surgery longer than 8 h. Propofol patients were matched 1:2 to VA patients, based on anesthesia time (AT) (+/- 30 min) and blood loss (BL) (+/- 500 mL).
RESULTS: Of 246 patients identified, 50 received propofol (AT 10 +/- 2 h, BL = 1955 +/- 1409 mL) and were matched to 100 VA cases (AT = 10 +/- 1 h, BL = 1801 +/- 1543 mL), and of those, 40 and 72 patients, respectively, had complete lactate data at baseline and at 8 h after anesthesia and were included in the main analysis. The propofol group received 8.8 +/- 2 mg.kg(-1).h(-1) of propofol. The VA group age was older than the propofol group (58 +/- 12 vs 51 +/- 15 yr, respectively, P = 0.002), but there was no difference between the groups in gender, ASA grade, intraoperative hemodynamic variables, and use of vasopressors. After 8 h, the VA group had a larger increase in arterial lactate from baseline compared with the propofol group (change from baseline: propofol, 0.48 +/- 0.72 mmol/L; VA, 1.2 +/- 1.2 mmol/L, P = 0.001).
CONCLUSIONS: During prolonged spine surgery > 8 h, VA was associated with higher serum lactate, when compared with propofol infusion. Prospective studies are needed to elucidate the exact mechanisms and clinical implications of this finding. (Anesth Analg 2009;109:1105-10)
C1 [Rozet, Irene] Univ Washington, Dept Anesthesiol, VA Puget Sound Hlth Care Syst, Harborview Med Ctr, Seattle, WA 98108 USA.
[Vavilala, Monica S.] Univ Washington, Dept Pediat, Harborview Med Ctr, Seattle, WA 98108 USA.
[Vavilala, Monica S.; Treggiari, Miriam M.; Lee, Lorri A.; Lam, Arthur M.] Univ Washington, Dept Neurol Surg, Harborview Med Ctr, Seattle, WA 98108 USA.
RP Rozet, I (reprint author), Univ Washington, Dept Anesthesiol, VA Puget Sound Hlth Care Syst, Harborview Med Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA.
EM irozet@u.washington.edu
NR 38
TC 7
Z9 7
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD OCT
PY 2009
VL 109
IS 4
BP 1105
EP 1110
DI 10.1213/ANE.0b013e3181b5a220
PG 6
WC Anesthesiology
SC Anesthesiology
GA 499HL
UT WOS:000270209100020
PM 19641048
ER
PT J
AU Bartels, K
Moss, DR
Peterfreund, RA
AF Bartels, Karsten
Moss, David R.
Peterfreund, Robert A.
TI An Analysis of Drug Delivery Dynamics via a Pediatric Central Venous
Infusion System: Quantification of Delays in Achieving Intended Doses
SO ANESTHESIA AND ANALGESIA
LA English
DT Article
ID SYRINGE PUMPS; DEAD-VOLUME; FLOW-RATE; FLUCTUATIONS
AB BACKGROUND: Pediatric patients frequently receive continuous infusions of drugs via central venous catheters in the intensive care unit and the operating room. This study characterized drug delivery profiles in a quantitative laboratory model of a standard pediatric central venous infusion system.
METHODS: We evaluated drug delivery via a standard pediatric 8-cm, 4-F double-lumen catheter. One syringe pump infused normal saline as the carrier fluid through a limb of a Y-piece connected to the catheter's 22-gauge distal lumen. Through the other limb of the Y-piece, a second syringe pump infused methylene blue, the model drug, at a constant rate of 0.5 mL/h. The volume delivered was collected every minute for quantitative analysis. We compared 2 mL/h and 12 mL/h total flow rates to mimic volume delivery to a 3-kg infant, and priming of the Y-piece with the model drug, to mimic resumption of a stopped drug infusion, versus no priming, to mimic a new infusion. Drug pump system start-up performance was measured to estimate this factor's contribution to infusion onset profiles.
RESULTS: When initiating a new infusion of the model drug, the time to steady-state delivery at the catheter's end varied significantly among the studied scenarios as measured by the time to reach half of the targeted dose (t(50)). Onset of delivery with a low total flow was much slower (t(50) = 23.5 +/- 2.1 min) than with the high flow rate (t(50) = 15.7 +/- 2.9 min). Priming the drug limb of the connecting Y-piece with methylene blue substantially shortened the time to steady state (low flow t(50) = 12.7 +/- 0.6 min, high flow t(50) = 5.2 +/- 0.8 min). Time to cessation of drug delivery to the end of the catheter after stopping the drug pump was substantially shorter using the high carrier flow rate (t(50) = 3 +/- 0.5 min) compared with the low carrier flow rate (t(50) = 11.6 +/- 0.8 min). Drug pump system start-up performance contributed to onset delay.
CONCLUSIONS: Current infusion techniques in the pediatric care setting can result in significant, unrecognized, and potentially hazardous delays in achieving delivery of intended drug doses to the patient. Total flow rate, priming of the infusion system, the dead volume of the fluid path, and the start-up performance of the infusion pump system contribute to delays in achieving targeted rates of drug delivery. (Anesth Analg 2009;109:1156-61)
C1 [Bartels, Karsten; Moss, David R.; Peterfreund, Robert A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
RP Peterfreund, RA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Jackson 439,55 Fruit St, Boston, MA 02114 USA.
EM rpeterfreund@partners.org
NR 8
TC 16
Z9 16
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD OCT
PY 2009
VL 109
IS 4
BP 1156
EP 1161
DI 10.1213/ane.0b013e3181b220c9
PG 6
WC Anesthesiology
SC Anesthesiology
GA 499HL
UT WOS:000270209100026
PM 19762743
ER
PT J
AU Rathmell, JP
Miller, MJ
AF Rathmell, James P.
Miller, Matthew J.
TI Death after Initiation of Intrathecal Drug Therapy for Chronic Pain
Assessing Risk and Designing Prevention
SO ANESTHESIOLOGY
LA English
DT Editorial Material
ID RESPIRATORY DEPRESSION; CANCER PAIN; DELIVERY; MORPHINE; MANAGEMENT
C1 [Rathmell, James P.] Massachusetts Gen Hosp, Div Pain Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Rathmell, James P.] Harvard Univ, Sch Med, Boston, MA USA.
[Miller, Matthew J.] Harvard Univ, Sch Publ Hlth, Harvard Injury Control Res Ctr, Boston, MA 02115 USA.
RP Rathmell, JP (reprint author), Massachusetts Gen Hosp, Div Pain Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
EM jrathmell@partners.org
RI miller, matthew/H-4624-2011
OI miller, matthew/0000-0002-3267-6510
NR 12
TC 6
Z9 7
U1 0
U2 0
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 2009
VL 111
IS 4
BP 706
EP 708
PG 3
WC Anesthesiology
SC Anesthesiology
GA 499HS
UT WOS:000270210100009
PM 20029248
ER
PT J
AU Zhen, Y
Dong, YL
Wu, X
Xu, ZP
Lu, Y
Zhang, YY
Norton, D
Tian, M
Li, SR
Xie, ZC
AF Zhen, Yu
Dong, Yuanlin
Wu, Xu
Xu, Zhipeng
Lu, Yan
Zhang, Yiying
Norton, David
Tian, Ming
Li, Shuren
Xie, Zhongcong
TI Nitrous Oxide Plus Isoflurane Induces Apoptosis and Increases
beta-Amyloid Protein Levels
SO ANESTHESIOLOGY
LA English
DT Article
ID INHALATION ANESTHETIC ISOFLURANE; NEURONAL CELL-DEATH;
ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; CASPASE-3 ACTIVATION; GLYCINE
RECEPTORS; PEPTIDE; GAMMA; INVOLVEMENT; EXPOSURE
AB Background: Some anesthetics have been suggested to induce neurotoxicity, including promotion of Alzheimer's disease neuro-pathogenesis. Nitrous oxide and isoflurane are common anesthetics. The authors set out to assess the effects of nitrous oxide and/or isoflurane on apoptosis and beta-amyloid (A beta) levels in H4 human neuroglioma cells and primary neurons from naive mice. Methods: The cells or neurons were exposed to 70% nitrous oxide and/or 1% isoflurane for 6 h. The cells or neurons and
Methods: The cells or neurons were exposed to 70% nitrous oxide and/or 1% isoflurane for 6 h. The cells or neurons and conditioned media were harvested at the end of the treatment. Caspase-3 activation, apoptosis, processing of amyloid precursor protein, and A beta levels were determined.
Results: Treatment with a combination of 70% nitrous oxide and 1% isoflurane for 6 h induced caspase-3 activation and apoptosis In H4 naive cells and primary neurons from naive mice. The 70% nitrous oxide plus 1% isoflurane, but neither alone, for 6 h Induced caspase-3 activation and apoptosis, and increased levels of beta-site amyloid precursor protein-cleaving enzyme and A beta in H4-amyloid precursor protein cells. In addition, the nitrous oxide plus isoflurane-induced A beta generation was reduced by a broad caspase inhibitor, Z-VAD. Finally, the nitrous oxide plus isoflurane-induced caspase-3 activation was attenuated by gamma-secretase inhibitor L-685,458, but potentiated by exogenously added A beta.
Conclusion: These results suggest that the common anesthetics nitrous oxide plus isoflurane may promote neurotoxicity by inducing apoptosis and increasing A beta levels. The generated A beta may further potentiate apoptosis to form another round of apoptosis and A beta generation. More studies, especially the in vivo confirmation of these in vitro findings, are needed.
C1 [Zhen, Yu; Dong, Yuanlin; Norton, David; Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA.
[Zhen, Yu; Dong, Yuanlin; Norton, David; Xie, Zhongcong] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Zhen, Yu; Tian, Ming; Li, Shuren] Capital Med Univ, Beijing Friendship Hosp, Dept Anesthesia, Beijing, Peoples R China.
[Wu, Xu] China Med Univ, Dept Forens Pathol, Fac Forens Med, Shenyang, Peoples R China.
[Lu, Yan] China Med Univ, Affiliated Shengjing Hosp, Key Lab Hlth Minist Congenital Malformat, Shenyang, Liaoning, Peoples R China.
RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, 114 16th St,3750, Charlestown, MA 02129 USA.
EM zxie@partners.org
FU NIA NIH HHS [R21 AG029856-01A2, R21 AG029856]; NIGMS NIH HHS [R01
GM088801-01A1, R01 GM088801]; NINDS NIH HHS [K08 NS048140-04, K08
NS048140, K08 NS048140-05]
NR 61
TC 48
Z9 54
U1 1
U2 5
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 2009
VL 111
IS 4
BP 741
EP 752
PG 12
WC Anesthesiology
SC Anesthesiology
GA 499HS
UT WOS:000270210100015
PM 19741497
ER
PT J
AU Desai, R
Ruesch, D
Forman, SA
AF Desai, Rooma
Ruesch, Dirk
Forman, Stuart A.
TI gamma-Amino Butyric Acid Type A Receptor Mutations at beta 2N265 Alter
Etomidate Efficacy While Preserving Basal and Agonist-dependent Activity
SO ANESTHESIOLOGY
LA English
DT Article
ID GENERAL ANESTHETIC ETOMIDATE; NICOTINIC ACETYLCHOLINE-RECEPTORS; GATED
ION CHANNELS; GABA(A) RECEPTOR; BINDING-SITE; AZI-ETOMIDATE; SUBUNIT;
ACTIVATION; MECHANISMS; BENZODIAZEPINES
AB Background: Etomidate acts at gamma-Aminobutyric acid type A (GABA(A)) receptors containing beta 2 or beta 3, but not beta 1 subunits. Mutations at beta residue 265 (Ser in beta 1; Asn in beta 2 or beta 3) profoundly affect etomidate sensitivity. Whether these mutations alter etomidate binding remains uncertain.
Methods: Heterologously expressed alpha 1 beta 2 gamma 2L GAB(A) receptors and receptors with beta 2(N265S) or beta 2(N265M) mutations were studied electrophysiologically in both Xenopus oocytes and HEK293 cells. Experiments quantified the impact of beta 2N265 mutations or substituting beta 1 for beta 2 on basal channel activation, GABA EC(50), maximal GABA efficacy, etomidate-induced leftward shift in GABA responses, etomidate direct activation, and rapid macrocurrent kinetics. Results were analyzed in the context of an established allosteric coagonist mechanism.
Results: Mutations produced only small changes in basal channel activity, GABA EC(50), maximal GABA efficacy, and macrocurrent kinetics. Relative to wild-type, beta 2(N265S) reduced etomidate enhancement of apparent GABA affinity six-fold, and it reduced etomidate direct activation efficacy 14-fold. beta 2(N265M) totally eliminated both etomidate modulation of GABA responses and direct channel activation. Mechanism-based analysis showed that the function of both mutants remains consistent with the allosteric coagonist model and that beta 2(N265S) reduced etomidate allosteric efficacy five-fold, whereas etomidate-binding affinity dropped threefold. Experiments swapping beta 2 subunits for beta 1 indicated that etomidate efficacy is reduced 34-fold, whereas binding affinity drops less than two-fold.
Conclusions. Mutations at beta 2N265 profoundly alter etomidate sensitivity with only small changes in basal and GABA-dependent channel activity. Mutations at the beta 2N265 residue or replacement of beta 2 with beta 1 Influence etomidate efficacy much more than binding to inactive receptors.
C1 [Forman, Stuart A.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Ruesch, Dirk] Univ Hosp Giessen Marburg, Dept Anesthesia & Crit Care, Marburg, Germany.
RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
EM saforman@partners.org
FU National Institutes of Health, Bethesda, Maryland [P0IGM58448,
R01GM66724]; Department of Anesthesia & Critical Care, Massachusetts
General Hospital, Boston, Massachusetts
FX Supported by grants P0IGM58448 and R01GM66724 from the National
Institutes of Health, Bethesda, Maryland, and by the Department of
Anesthesia & Critical Care, Massachusetts General Hospital, Boston,
Massachusetts.
NR 42
TC 27
Z9 27
U1 0
U2 1
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 2009
VL 111
IS 4
BP 774
EP 784
PG 11
WC Anesthesiology
SC Anesthesiology
GA 499HS
UT WOS:000270210100019
PM 19741491
ER
PT J
AU Sulemanji, D
Marchese, A
Garbarini, P
Wysocki, M
Kacmarek, RM
AF Sulemanji, Demet
Marchese, Andrew
Garbarini, Paul
Wysocki, Marc
Kacmarek, Robert M.
TI Adaptive Support Ventilation An Appropriate Mechanical Ventilation
Strategy for Acute Respiratory Distress Syndrome?
SO ANESTHESIOLOGY
LA English
DT Article
ID ACUTE LUNG INJURY; VOLUME-CONTROLLED VENTILATION; CARDIAC-SURGERY;
PROTECTIVE-VENTILATION; BREATHING PATTERN; MORTALITY; FAILURE; ARDS
AB Background: Adaptive support ventilation (ASV) allows the clinician to set a maximum plateau pressure (PP) and automatically adjusts tidal volume to keep PP below the set maximum.
Methods: ASV was compared to a fixed tidal volume of 6 ml/kg. ASV determined the respiratory rate and tidal volume based on its algorithms. Maximum airway pressure limit was 28 CM H(2)O in ASV. Six sets of lung mechanics were simulated for two ideal body weights: 60 kg, Group I; 80 kg, Group II. Positive end expiratory pressure was 8, 12, and 16 cm 1120, and target minute volume 120%, 150%, and 200% of predicted minute volume.
Results: ASV "sacrificed" tidal volume and minute ventilation to maintain PP in 9 (17%) of 54 scenarios in Group I and 20 (37%) of 54 scenarios in Group U. In Group I, the number of scenarios with PP of 28 cm H(2)O or more was 14 for ASV (26%) and 19 for 6 ml/kg (35%). in these scenarios, mean PP were ASV 28.8 +/- 0.86 cm H(2)O (min 28, max 30.3) and 6 ml/kg 33.01 +/- 3.48 cm H(2)O (min 28, max 37.8) (P = 0.000). In group II, the number of scenarios PP of 28 cm H(2)O or more was 10 for ASV (19%) and 21 for 6 ml/kg (39%). in these cases, mean PP values were ASV 28.78 +/- 0.54 cm H(2)O (min 28, max 29.6) and 6 ml/kg 32.66 +/- 3.37 cm H(2)O (min 28.2, max 38.2) (P = 0.000).
Conclusion: In a lung model with varying mechanics, ASV is better able to prevent the potential damaging effects of excessive PP (greater than 28 cm 1120) than a fixed tidal volume of 6 ml/kg by automatically adjusting airway pressure, resulting in a decreased tidal volume.
C1 [Marchese, Andrew; Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA.
RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Resp Care, 55 Fruit St,Ellison 401, Boston, MA 02114 USA.
EM rkacmarek@partners.org
NR 30
TC 16
Z9 16
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 2009
VL 111
IS 4
BP 863
EP 870
PG 8
WC Anesthesiology
SC Anesthesiology
GA 499HS
UT WOS:000270210100029
PM 19741490
ER
PT J
AU Tsai, CL
Rowe, BH
Sullivan, AF
Camargo, CA
AF Tsai, Chu-Lin
Rowe, Brian H.
Sullivan, Ashley F.
Camargo, Carlos A., Jr.
TI Factors associated with delayed use or nonuse of systemic
corticosteroids in emergency department patients with acute asthma
SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY
LA English
DT Article
ID MYOCARDIAL-INFARCTION; METHYLPREDNISOLONE; REPERFUSION; THERAPY
AB Background: Little is known about factors associated with systemic corticosteroid (SC) use in emergency department (ED) patients with acute asthma.
Objective: To determine the patient and system factors associated with delayed use or nonuse of SCs in the ED.
Methods: We analyzed the asthma component of the National Emergency Department Safety Study. Patients with acute asthma in 62 urban EDs in 23 US states between 2003 and 2006 were identified. The primary outcome measure was the pattern of SC use in the ED, which was categorized as timely use (<= 60 minutes), delayed use (>60 minutes), or nonuse. Multinomial logistic regression was performed to identify factors associated with delayed use or nonuse of SCs.
Results: A total of 2,559 of 3,798 patients with acute asthma (67.4%) received SCs. Of these, the median door-to-SC time was 62 minutes (interquartile range, 35-100 minutes), with 1,319 patients (51.5%) having delayed SC treatment. Nonuse of SCs was largely explained by markers of asthma exacerbations (never intubated for asthma, lower respiratory rate, and higher oxygen saturation). In contrast, in addition to these factors, delayed SC treatment was associated with age of 40 years or older, female sex, longer duration of symptoms, ED presentation between 8 Am and 11:59 Pm, and ED with a longer average patient wait time.
Conclusions: Physicians in the ED seem to appropriately administer SCs to higher-acuity asthmatic patients; however, the additional nonmedical factors represent opportunities to improve the timeliness of SC treatment in the ED. Ann Allergy Asthma Immunol. 2009;103:318-324.
C1 [Tsai, Chu-Lin; Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA.
[Rowe, Brian H.] Univ Alberta, Dept Emergency Med, Edmonton, AB, Canada.
[Rowe, Brian H.] Univ Alberta, Sch Publ Hlth, Edmonton, AB, Canada.
RP Tsai, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA.
OI TSAI, CHU-LIN/0000-0003-4639-1513
FU Agency for Healthcare Research and Quality [R01 HS-13099]; National
Institutes of Health [R01 HL-84401]; Government of Canada
FX This study was supported by grant R01 HS-13099 from the Agency for
Healthcare Research and Quality, grant R01 HL-84401 from the National
Institutes of Health (Dr Camargo), and a 21st Century Research Chair
from the Government of Canada (Dr Rowe).
NR 32
TC 4
Z9 5
U1 0
U2 0
PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY
PI ARLINGTON HTS
PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA
SN 1081-1206
J9 ANN ALLERG ASTHMA IM
JI Ann. Allergy Asthma Immunol.
PD OCT
PY 2009
VL 103
IS 4
BP 318
EP 324
PG 7
WC Allergy; Immunology
SC Allergy; Immunology
GA 509YP
UT WOS:000271055500008
PM 19852196
ER
PT J
AU Kang, HK
Bullman, TA
AF Kang, Han K.
Bullman, Tim A.
TI Is There an Epidemic of Suicides among Current and Former US Military
Personnel?
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
ID PERSIAN-GULF-WAR; VIETNAM VETERANS; MORTALITY; RISK; ARMY
C1 [Kang, Han K.; Bullman, Tim A.] Environm Epidemiol Serv, US Dept Vet Affairs, Washington, DC 20420 USA.
[Kang, Han K.] DC VA Med Ctr, War Related Illness & Injury Study Ctr, Washington, DC USA.
[Kang, Han K.] George Washington Univ, Washington, DC 20052 USA.
RP Kang, HK (reprint author), Environm Epidemiol Serv, US Dept Vet Affairs, 810 Vermont Ave NW, Washington, DC 20420 USA.
EM han.kang@va.gov
NR 20
TC 34
Z9 34
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD OCT
PY 2009
VL 19
IS 10
BP 757
EP 760
DI 10.1016/j.annepidem.2009.05.004
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 499BR
UT WOS:000270192000011
PM 19628411
ER
PT J
AU Hawker, K
O'Connor, P
Freedman, MS
Calabresi, PA
Antel, J
Simon, J
Hauser, S
Waubant, E
Vollmer, T
Panitch, H
Zhang, JM
Chin, P
Smith, CH
AF Hawker, Kathleen
O'Connor, Paul
Freedman, Mark S.
Calabresi, Peter A.
Antel, Jack
Simon, Jack
Hauser, Stephen
Waubant, Emmanuelle
Vollmer, Timothy
Panitch, Hillel
Zhang, Jiameng
Chin, Peter
Smith, Craig H.
CA OLYMPUS Trial Grp
TI Rituximab in Patients with Primary Progressive Multiple Sclerosis
Results of a Randomized Double-Blind Placebo-Controlled Multicenter
Trial
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID INNATE IMMUNE-SYSTEM; INTERFERON BETA-1A; AGED MICE; B-CELLS;
INFLAMMATION; DAMAGE; EVENT; MRI; NEUROINFLAMMATION; AUTOANTIBODIES
AB Objective: Rituximab, a monoclonal antibody selectively depleting CD20+ B cells, has demonstrated efficacy in reducing disease activity in relapsing-remitting multiple sclerosis (MS). We evaluated rituximab in adults with primary progressive MS (PPMS) through 96 weeks and safety through 122 weeks.
Methods: Using 2:1 randomization, 439 PPMS patients received two 1,000mg intravenous rituximab or placebo infusions every 24 weeks, through 96 weeks (4 courses). The primary endpoint was time to confirmed disease progression (CDP), a prespecified increase in Expanded Disability Status Scale sustained for 12 weeks. Secondary endpoints were change from baseline to week 96 in T2 lesion volume and total brain volume on magnetic resonance imaging scans.
Results: Differences in time to CDP between rituximab and placebo did not reach significance (96-week rates: 38.5% placebo, 30.2% rituximab; p = 0.14). From baseline to week 96, rituximab patients had less (p < 0.001) increase in T2 lesion volume; brain volume change was similar (p = 0.62) to placebo. Subgroup analysis showed time to CDP was delayed in rituximab-treated patients aged <51 years (hazard ratio [HR] = 0.52; p = 0.010), those with gadolinium-enhancing lesions (HR = 0.41; P = 0.007), and those aged <51 years with gadolinium-enhancing lesions (HR = 0.33; p = 0.009) compared with placebo. Adverse events were comparable between groups; 16.1% of rituximab and 13.6% of placebo patients reported serious events. Serious infections occurred in 4.5% of rituximab and <1.0% of placebo patients. Infusion-related events, predominantly mild to moderate, were more common with rituximab during the first course, and decreased to rates comparable to placebo on successive courses.
Interpretation: Although time to CDP between groups was not significant, overall subgroup analyses suggest selective B-cell depletion may affect disease progression in younger patients, particularly those with inflammatory lesions.
C1 [Hawker, Kathleen] Ohio State Univ, Dept Neurol, Med Ctr, Columbus, OH 43210 USA.
[O'Connor, Paul] Univ Toronto, Dept Med, Toronto, ON, Canada.
[Freedman, Mark S.] Ottawa Hosp, Dept Med, Ottawa, ON, Canada.
[Calabresi, Peter A.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD USA.
[Antel, Jack] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada.
[Simon, Jack] Portland VA Med Ctr, Dept Neurol, Portland, OR USA.
[Hauser, Stephen; Waubant, Emmanuelle] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Vollmer, Timothy] Univ Colorado, Dept Neurol, Denver, CO 80202 USA.
[Panitch, Hillel] Univ Vermont, Dept Neurol, Burlington, VT USA.
[Zhang, Jiameng; Chin, Peter; Smith, Craig H.] Genentech Inc, San Francisco, CA 94080 USA.
RP Hawker, K (reprint author), Eli Lilly & Co, 450 S Meridian St, Indianapolis, IN 46225 USA.
EM hawkerks@lilly.com
FU Clinicaltrials.gov [NCT00087529]; Genentech, Inc.; Biogen Idec, Inc.
FX This study was supported by Clinicaltrials.gov under "A Study to
Evaluate the Safety and Efficacy of Rituximab in Adults With Primary
Progressive Multiple Sclerosis" (grant NCT00087529), by Genentech, Inc.,
and by Biogen Idec, Inc.
NR 38
TC 245
Z9 248
U1 3
U2 10
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD OCT
PY 2009
VL 66
IS 4
BP 460
EP 471
DI 10.1002/ana.21867
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 507SJ
UT WOS:000270874700006
PM 19847908
ER
PT J
AU Jimenez, M
Krall, EA
Garcia, RI
Vokonas, PS
Dietrich, T
AF Jimenez, Monik
Krall, Elizabeth A.
Garcia, Raul I.
Vokonas, Pantel S.
Dietrich, Thomas
TI Periodontitis and Incidence of Cerebrovascular Disease in Men
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID SERUM INFLAMMATORY MARKERS; CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN;
CARDIOVASCULAR-DISEASE; PLASMA-FIBRINOGEN; SMOKING HISTORY;
ISCHEMIC-STROKE; RISK-FACTOR; POPULATION; ASSOCIATIONS
AB Objective: To identify associations between periodontitis and incidence of cerebrovascular disease.
Methods: We analyzed data of 1, 137 dentate men in the Veterans Affairs Normative Aging and Dental Longitudinal Study who were followed with triennial medical/dental exams for up to 34 years (mean, 24 years). We evaluated incidence of cerebrovascular events consistent with stroke or transient ischemic attack in relation to mean radiographic alveolar bone loss (a measure of periodontitis history) and cumulative periodontal probing depth (a measure of current periodontal inflammation). Cox proportional hazards models were Fit controlling for age, baseline socioeconomic status, and time-varying effects of established cardiovascular risk factors.
Results: Eighty incident cases of cerebrovascular disease Occurred from 27,506 person-years. Periodontal bone loss was significantly associated with an increased hazard rate (HR) of cerebrovascular disease (HR, 3.52; 95% confidence interval [Cl], 1.59-7.81 comparing highest to lowest bone loss category; p for trend, <0.001). There was a stronger effect among men aged <65 years (HR, 5.81; 95% CI, 1.63-20.7) as compared with men aged >= 65 years (HR, 2.39; 95% CI, 0.91-6.25). Periodontal probing depth was not associated with a significantly increased rate of cerebrovascular disease in the combined or age-stratified analyses.
Interpretation: These results Support an association between history of periodontitis-but not current periodontal inflammation-and incidence of cerebrovascular disease in men, independent of established cardiovascular risk factors, particularly among men aged <65 years.
C1 [Dietrich, Thomas] Univ Birmingham, Sch Dent, Dept Oral Surg, Birmingham B4 6NN, W Midlands, England.
[Jimenez, Monik; Krall, Elizabeth A.; Garcia, Raul I.; Dietrich, Thomas] Boston Univ, Dept Hlth Policy & Hlth Serv Res, Goldman Sch Dent Med, Boston, MA 02215 USA.
[Jimenez, Monik] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Jimenez, Monik] Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA.
[Garcia, Raul I.; Vokonas, Pantel S.] VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA.
[Vokonas, Pantel S.] Boston Univ, Sch Med, Dept Med, Dept Epidemiol, Boston, MA 02118 USA.
RP Dietrich, T (reprint author), Univ Birmingham, Sch Dent, Dept Oral Surg, St Chads Queensway, Birmingham B4 6NN, W Midlands, England.
EM t.dietrich@bham.ac.uk
OI Garcia, Raul/0000-0003-2153-4629; Kaye, Elizabeth/0000-0001-7529-2501;
Dietrich, Thomas/0000-0002-2557-7645
FU Veterans Affairs Cooperative Studies Program; National Institutes of
Health [R03 DE016357, K24 DE00419]; National Institute of Dental and
Craniofacial Research; US Department of Veterans Affairs Career
Development Award in Health Services Research; Veterans Affairs Merit
Review Award
FX The Veterans Affairs Normative Aging Study and Veterans Affairs Dental
Longitudinal Study are components of the Massachusetts Veterans
Epidemiology Research and Information Center, supported by the Veterans
Affairs Cooperative Studies Program. This work was supported by National
Institutes of Health grant R03 DE016357 from the National Institute of
Dental and Craniofacial Research (T.D.), and by a US Department of
Veterans Affairs Career Development Award in Health Services Research
from the Veterans Affairs Health Services Research & Development
Service, a Veterans Affairs Merit Review Award, and National Institutes
of Health grant K24 DE00419 from the National Institute of Dental and
Craniofacial Research (R.I.G.).
NR 32
TC 42
Z9 43
U1 0
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD OCT
PY 2009
VL 66
IS 4
BP 505
EP 512
DI 10.1002/ana.21742
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 507SJ
UT WOS:000270874700010
PM 19847898
ER
PT J
AU Eikermann-Haerter, K
Baum, MJ
Ferrari, MD
van den Maagdenberg, AMJM
Moskowitz, MA
Ayata, C
AF Eikermann-Haerter, Katharina
Baum, Michael J.
Ferrari, Michel D.
van den Maagdenberg, Arn M. J. M.
Moskowitz, Michael A.
Ayata, Cenk
TI Androgenic Suppression of Spreading Depression in Familial Hemiplegic
Migraine Type 1 Mutant Mice
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID ESTROGEN-RECEPTOR-ALPHA; PYRAMIDAL CELLS; TESTOSTERONE; POPULATION;
DANAZOL; 17-BETA-ESTRADIOL; SUSCEPTIBILITY; PREVALENCE; DISORDERS;
MUTATIONS
AB Familial hemiplegic migraine type 1 (FHM1), a severe migraine with aura variant, is caused by mutations in the CACNA1A gene. Mutant mice carrying the FHM1 R192Q mutation exhibit increased propensity for cortical spreading depression (CSD), a propagating wave of neuroglial depolarization implicated in migraine aura. The CSD phenotype is stronger in female R192Q mutants and diminishes after ovariectomy. Here, we show that orchiectomy reciprocally increases CSD susceptibility in R192Q mutant mice. Chronic testosterone replacement restores CSD susceptibility by an androgen receptor-dependent mechanism. Hence, androgens modulate genetically-enhanced CSD susceptibility and may provide a novel prophylactic target for migraine.
C1 [Eikermann-Haerter, Katharina; Moskowitz, Michael A.; Ayata, Cenk] Boston Univ, Stroke & Neurovasc Regulat Lab, Dept Radiol, Boston, MA 02215 USA.
[Baum, Michael J.] Boston Univ, Dept Biol, Boston, MA 02215 USA.
[Ferrari, Michel D.; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands.
[van den Maagdenberg, Arn M. J. M.] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands.
[van den Maagdenberg, Arn M. J. M.] Harvard Univ, Massachusetts Gen Hosp, Stroke Serv & Neurosci Intens Care Unit, Sch Med,Dept Neurol, Charlestown, MA USA.
RP Ayata, C (reprint author), Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA.
EM cayata@partners.org
FU Deutsche Forschungsgemeinschaft [Ha5085/1-1]; National Institutes of
Health [NS061505, NS35611]; Netherlands Organization for Scientific
Research [903-52-291, Vici 918-56.602]; EU [CT-2004-504837]; Centre for
Medical Systems Biology (CMSB)
FX This work was supported by the Deutsche Forschungsgemeinschaft
(Ha5085/1-1; K.E.-H.), National Institutes of Health (NS061505, C.A.;
NS35611, M.A.M), Netherlands Organization for Scientific Research
(903-52-291 and Vici 918-56.602; M.D.F.), EU "EUROHEAD" grant
(LSHM-CT-2004-504837; M.D.F. and A.M.J.M.v.d.M.), and the Centre for
Medical Systems Biology (CMSB) in the framework of the Netherlands
Genomics Initiative (NGI).
NR 30
TC 38
Z9 38
U1 0
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD OCT
PY 2009
VL 66
IS 4
BP 564
EP 568
DI 10.1002/ana.21779
PG 5
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 507SJ
UT WOS:000270874700018
PM 19847904
ER
PT J
AU Nannini, M
Astolfi, A
Pantaleo, MA
Di Battista, M
Santini, D
Catena, F
Heinrich, MC
Saponara, M
Lolli, C
Maleddu, A
Formica, S
Biasco, G
AF Nannini, Margherita
Astolfi, Annalisa
Pantaleo, Maria A.
Di Battista, Monica
Santini, Donatella
Catena, Fausto
Heinrich, Mike C.
Saponara, Maristella
Lolli, Cristian
Maleddu, Alessandra
Formica, Serena
Biasco, Guido
TI HIGH RESOLUTION COPY NUMBER ANALYSIS OF GASTROINTESTINAL STROMAL TUMORS
(GISTs) WITH AFFYMETRIX TECHNOLOGY
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
C1 [Nannini, Margherita; Pantaleo, Maria A.; Di Battista, Monica; Saponara, Maristella; Lolli, Cristian; Maleddu, Alessandra; Biasco, Guido] Univ Bologna, Dept Hematol & Oncol Sci LA Seragnoli, I-40126 Bologna, Italy.
[Astolfi, Annalisa; Formica, Serena; Biasco, Guido] Univ Bologna, Interdept Ctr Canc Res G Prodi, I-40126 Bologna, Italy.
[Santini, Donatella] Univ Bologna, Pathol Unit, St Orsola Malpighi Hosp, I-40126 Bologna, Italy.
[Catena, Fausto] Univ Bologna, Emergency Surg & Transplant Dept, St Orsola Malpighi Hosp, I-40126 Bologna, Italy.
[Heinrich, Mike C.] Oregon Hlth & Sci Univ, Dept Med, Portland VA Med Ctr, Portland, OR 97201 USA.
[Heinrich, Mike C.] Oregon Hlth & Sci Univ, Oregon Hlth & Sci Univ Knight Canc Inst, Portland, OR 97201 USA.
RI Saponara, Maristella/J-9904-2016; nannini, margherita/J-9866-2016
OI Saponara, Maristella/0000-0003-0715-171X;
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD OCT
PY 2009
VL 20
SU 8
PG 2
WC Oncology
SC Oncology
GA V15CV
UT WOS:000207781000221
ER
PT J
AU Pantaleo, MA
Astolfi, A
Di Battista, M
Paterini, P
Santini, D
Catena, F
Heinrich, MC
Nannini, M
Saponara, M
Lolli, C
Maleddu, A
Formica, S
Biasco, G
AF Pantaleo, Maria A.
Astolfi, Annalisa
Di Battista, Monica
Paterini, Paola
Santini, Donatella
Catena, Fausto
Heinrich, Mike C.
Nannini, Margherita
Saponara, Maristella
Lolli, Cristian
Maleddu, Alessandra
Formica, Serena
Biasco, Guido
TI IGF1R OVEREXPRESSION IN WILD TYPE GASTROINETSTINAL STROMAL TUMOR (GISTS)
STUDIED WITH GENOME ARRAY ANALYSES AND WESTERN BLOTTING
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
C1 [Pantaleo, Maria A.; Di Battista, Monica; Nannini, Margherita; Saponara, Maristella; Lolli, Cristian; Maleddu, Alessandra; Biasco, Guido] Univ Bologna, Dept Hematol & Oncol Sci LA Seragnoli, I-40126 Bologna, Italy.
[Astolfi, Annalisa; Paterini, Paola; Formica, Serena] Univ Bologna, Interdept Ctr Canc Res G Prodi, I-40126 Bologna, Italy.
[Santini, Donatella] Univ Bologna, Pathol Unit, St Orsola Malpighi Hosp, I-40126 Bologna, Italy.
[Catena, Fausto] Univ Bologna, Emergency Surg & Transplant Dept, St Orsola Malpighi Hosp, I-40126 Bologna, Italy.
[Heinrich, Mike C.] Oregon Hlth & Sci Univ, Dept Med, Portland VA Med Ctr, Portland, OR 97201 USA.
[Heinrich, Mike C.] Oregon Hlth & Sci Univ, Oregon Hlth & Sci Univ Knight Canc Inst, Portland, OR 97201 USA.
RI Saponara, Maristella/J-9904-2016; nannini, margherita/J-9866-2016
OI Saponara, Maristella/0000-0003-0715-171X;
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD OCT
PY 2009
VL 20
SU 8
PG 1
WC Oncology
SC Oncology
GA V15CV
UT WOS:000207781000219
ER
PT J
AU Lin, HW
Quesnel, AM
Holman, AS
Curry, WT
Rho, MB
AF Lin, Harrison W.
Quesnel, Alicia M.
Holman, Allison S.
Curry, William T., Jr.
Rho, Michael B.
TI Hypertrophic Anterior Cervical Osteophytes Causing Dysphagia and Airway
Obstruction
SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY
LA English
DT Article
DE airway obstruction; anterior cervical osteophyte; dysphagia
ID IDIOPATHIC SKELETAL HYPEROSTOSIS; FORESTIERS-DISEASE; DISH;
MANIFESTATIONS; DYSPNEA
AB Hyperostosis of anterior cervical vertebral osteophytes can produce otolaryngological symptoms ranging from mild dysphagia, dysphonia, and foreign body sensation to severe food impaction and stridulous dyspnea. Airway compromise necessitating a tracheostomy is very rare. We discuss the case of an elderly man who presented with progressive dysphagia and a large hypopharyngeal mass as his initial manifestations of hypertrophic anterior cervical osteophytes. After a biopsy of the mass, the patient went into airway distress due to bilateral vocal fold fixation by the enlarging mass and consequently required a surgical airway. A combined team approach to the removal of the osteophytes successfully resolved his symptoms. The clinical, diagnostic, radiologic, and therapeutic principles involved in this case are presented and discussed. The recognition of hypertrophic osteophytes as a potential cause of common otolaryngological symptoms in the elderly population is paramount, as these symptoms can rapidly progress and lead to life-threatening airway obstruction. Medical and surgical interventions can be employed for the treatment of hypertrophic anterior cervical osteophytes, and they often result in favorable outcomes.
C1 [Lin, Harrison W.; Quesnel, Alicia M.; Rho, Michael B.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Lin, Harrison W.; Quesnel, Alicia M.; Rho, Michael B.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Holman, Allison S.] Massachusetts Gen Hosp, Dept Speech Language & Swallowing Disorders, Boston, MA 02114 USA.
[Curry, William T., Jr.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
RP Lin, HW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
NR 22
TC 12
Z9 12
U1 0
U2 1
PU ANNALS PUBL CO
PI ST LOUIS
PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA
SN 0003-4894
J9 ANN OTO RHINOL LARYN
JI Ann. Otol. Rhinol. Laryngol.
PD OCT
PY 2009
VL 118
IS 10
BP 703
EP 707
PG 5
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 509UZ
UT WOS:000271045500004
PM 19894397
ER
PT J
AU Johnson, ML
Petersen, LA
Sundaravaradan, R
Byrne, MM
Hasche, JC
Osemene, NI
Wei, II
Morgan, RO
AF Johnson, Michael L.
Petersen, Laura A.
Sundaravaradan, Raji
Byrne, Margaret M.
Hasche, Jennifer C.
Osemene, Nora I.
Wei, Iris I.
Morgan, Robert O.
TI The Association of Medicare Drug Coverage with Use of Evidence-Based
Medications in the Veterans Health Administration
SO ANNALS OF PHARMACOTHERAPY
LA English
DT Article
DE managed care; Medicare; pharmacy; veterans
ID ACUTE MYOCARDIAL-INFARCTION; ACCESS; VA; IDENTIFICATION; POPULATIONS;
PREVALENCE; OUTCOMES; HMOS; CARE
AB BACKGROUND: Veterans with Medicare managed-care plans have access to pharmacy benefits outside the Veterans Health Administration (VA), but how this coverage affects use of medications for specific disease conditions within the VA is unclear.
OBJECTIVE: To examine patterns of pharmacotherapy among patients with diabetes mellitus, ischemic heart disease, and chronic heart failure enrolled in fee-for-service (FFS) or managed-care (HMO) plans and to test whether pharmacy benefit coverage within Medicare is associated with the receipt of evidence-based medications in the VA.
METHODS: A retrospective analysis of veterans dually enrolled in the VA and Medicare healthcare systems was conducted. We used VA and Medicare administrative data from 2002 in multivariable logistic regression analysis to determine the unique association of enrollment in Medicare FFS or managed-care plans on the use of medications, after adjusting for sociodemographic, geographic, and patient clinical factors.
RESULTS: A total of 369,697 enrollees met inclusion criteria for diabetes, ischemic heart disease, or chronic heart failure. Among patients with diabetes, adjusted odds ratios (ORs) of receiving angiotensin-converting enzyme (ACE) inhibitors and oral hypoglycemics in the FFS group were, respectively, 0.86 and 0.80 (p < 0.001). Among patients with ischemic heart disease, FFS patients were generally less likely to receive beta-blockers, antianginals, and statins. Among patients with chronic heart failure, adjusted ORs of receiving ACE inhibitors, angiotensin-receptor blockers, and statins in the FFS group were, respectively, 0.90, 0.78, and 0.79 (all p < 0.05). There were few systematic differences within HMO coverage levels.
CONCLUSIONS: FFS-enrolled veterans were generally less likely to be receiving condition-related medications from the VA, compared with HMO-enrolled veterans with lower levels of prescription drug coverage. Pharmacy prescription coverage within Medicare affects the use of evidence-based medications for specific disease conditions in the VA.
C1 [Johnson, Michael L.] Univ Houston, Coll Pharm, Dept Clin Sci & Adm, Houston, TX 77030 USA.
[Johnson, Michael L.; Petersen, Laura A.; Sundaravaradan, Raji; Hasche, Jennifer C.; Morgan, Robert O.] Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA.
[Petersen, Laura A.] Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA.
[Byrne, Margaret M.] Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL USA.
[Osemene, Nora I.] Texas So Univ, Coll Pharm & Hlth Sci, Houston, TX 77004 USA.
[Wei, Iris I.] Ctr Medicare Serv, Off Res Dev & Informat, Res & Evaluat Grp, Div Res Hlth Plans & Drugs, Baltimore, MD USA.
[Wei, Iris I.] Ctr Medicaid Serv, Off Res Dev & Informat, Res & Evaluat Grp, Div Res Hlth Plans & Drugs, Baltimore, MD USA.
RP Johnson, ML (reprint author), 1441 Moursund St, Houston, TX 77030 USA.
EM mikejohnson@uh.edu
NR 30
TC 2
Z9 2
U1 0
U2 0
PU HARVEY WHITNEY BOOKS CO
PI CINCINNATI
PA PO BOX 42696, CINCINNATI, OH 45242 USA
SN 1060-0280
J9 ANN PHARMACOTHER
JI Ann. Pharmacother.
PD OCT
PY 2009
VL 43
IS 10
BP 1565
EP 1575
DI 10.1345/aph.1L606
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 503YR
UT WOS:000270579100001
PM 19706740
ER
PT J
AU Arriaga, AF
Lancaster, RT
Berry, WR
Regenbogen, SE
Lipsitz, SR
Kaafarani, HMA
Elbardissi, AW
Desai, P
Ferzoco, SJ
Belday, R
Breen, E
Kastrinakis, WV
Rubin, MS
Gawande, AA
AF Arriaga, Alexander F.
Lancaster, Robert T.
Berry, William R.
Regenbogen, Scott E.
Lipsitz, Stuart R.
Kaafarani, Haytham M. A.
Elbardissi, Andrew W.
Desai, Priya
Ferzoco, Stephen J.
Belday, Ronald
Breen, Elizabeth
Kastrinakis, William V.
Rubin, Marc S.
Gawande, Atul A.
TI The Better Colectomy Project Association of Evidence-Based Best-Practice
Adherence Rates to Outcomes in Colorectal Surgery
SO ANNALS OF SURGERY
LA English
DT Article
ID QUALITY IMPROVEMENT PROGRAM; SURGERY; SAFETY; MORBIDITY; MORTALITY;
CANCER
AB objective: To evaluate whether adherence to evidence-based best practices in colorectal surgery predicts improved postoperative Outcomes
Summary and Background Data: Over a quarter of a million colon and rectal resections are performed annually in the United States The average postoperative complication rate for these procedures approaches 3 0
Methods: A panel of colorectal and general surgeons from 3 hospitals (I academic medical center and 2 community hospitals) was assembled to ascertain a set of 37 evidence-based practices that they felt were the most pertinent to the evaluation and management of a patient undergoing a colorectal resection. Fifteen of these practices were classified as "key processes" for the prevention of complications We then retrospectively reviewed medical records for 370 consecutive patients undergoing colorectal resection at these institutions We evaluated the a. association of best-practice adherence to complications in the subset of patients with outcome data available through the American College of Surgeons National Surgical Quality Improvement Program
Results: Nonadherence rates exceeded 40% for 11 practices (including 2 key processes avoidance of unnecessary blood transfusions and timely removal of central venous catheters) Among 198 patients with American College of Surgeons National Surgical Quality Improvement Program outcomes data. 38 (19%) experienced complications, of which 31 (82%) involved postoperative infection Nonadherence it) key-processes significantly predicted the occurrence of a complication (P = 0.002) Each additional process missed increased the odds of a postoperative complication by 60% (odds ratio 1:6. 95% confidence interval 1.2-2.2)
Conclusions: Failures of adherence with best practices in colorectal surgery is associated with an increased occurrence of complications This study merits further research to confirm that improvement in compliance with perioperative best practices will reduce complication rates significantly
C1 [Arriaga, Alexander F.; Lancaster, Robert T.; Berry, William R.; Regenbogen, Scott E.; Kaafarani, Haytham M. A.; Elbardissi, Andrew W.; Desai, Priya; Gawande, Atul A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Arriaga, Alexander F.; Lipsitz, Stuart R.; Elbardissi, Andrew W.; Desai, Priya; Belday, Ronald; Breen, Elizabeth; Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Lancaster, Robert T.; Regenbogen, Scott E.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Kaafarani, Haytham M. A.] Vet Affairs Boston Healthcare Syst, Dept Surg, Boston, MA USA.
[Ferzoco, Stephen J.] Faulkner Hosp, Dept Surg, Boston, MA USA.
[Kastrinakis, William V.; Rubin, Marc S.] N Shore Med Ctr, Dept Surg, Salem, MA USA.
RP Arriaga, AF (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA.
EM aarriaga@partners.org
OI Gawande, Atul/0000-0002-1824-9176
NR 14
TC 29
Z9 29
U1 2
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-4932
J9 ANN SURG
JI Ann. Surg.
PD OCT
PY 2009
VL 250
IS 4
BP 507
EP 513
DI 10.1097/SLA.0b013e3181b672bc
PG 7
WC Surgery
SC Surgery
GA 504FA
UT WOS:000270599800001
PM 19734778
ER
PT J
AU Cobb, JP
Moore, EE
Hayden, DL
Minei, JP
Cuschieri, J
Yang, JY
Li, Q
Lin, N
Brownstein, BH
Hennessy, L
Mason, PH
Schierding, WS
Dixon, DJ
Tompkins, RG
Warren, HS
Schoenfeld, DA
Maier, RV
AF Cobb, J. Perren
Moore, Ernest E.
Hayden, Doug L.
Minei, Joseph P.
Cuschieri, Joseph
Yang, Jingyun
Li, Qing
Lin, Nan
Brownstein, Bernard H.
Hennessy, Laura
Mason, Philip H.
Schierding, William S.
Dixon, David J.
Tompkins, Ronald G.
Warren, H. Shaw
Schoenfeld, David A.
Maier, Ronald V.
TI Validation of the Riboleukogram to Detect Ventilator-Associated
Pneumonia After Severe Injury
SO ANNALS OF SURGERY
LA English
DT Article
DE trauma; sepsis; micro array; genechip; diagnosis; RNA; glue grant
ID GENE-EXPRESSION PROFILES; INTENSIVE-CARE-UNIT; SEPSIS; BLOOD;
MICROARRAYS; DIAGNOSIS; RESPONSES; INFLAMMATION; ACTIVATION; PREDICTION
AB Objective: We hypothesized that circulating leukocyte RNA profiles or 'riboleukograrns" detect ventulator-associaied pneumonia after blunt trauma
Summary Background Data: A pilot microarray Study of 11 ventilator-associated pneumonia (VAP) patients suggested that 85 leukocyte genes can be used to diagnose VAII. Validation of this gene set to detect VAP was tested using data from an independent patient cohort
Methods: A total of 158 intubated blunt trauma patients were enrolled at 5 centers. where 57 (36%) developed VAP. Patient age was 34.2 +/- 11.1 years. 65% were male Circulating leukocyte GeneChip U 133 2 0 expression values were measured at time 0.5. 1, 4, 7, 14, 21 and 28 days after injury DChip normalized leukocyte transcriptional profiles were analyzed using repeated measures logistic regression A compound covariate model based on leukocyte gene transcriptional profiles in a training subset of patients was tested to determine predictive accuracy for VAII 4 days prior to (clinical diagnosis in the test subset.
Results: Using gene expression values measured on each study (lay at all FDR <0.05, 27 (32%) of the 85 genes were associated with Lhe diagnosis of VAP 1 to 4 days before diagnosis However, the compound covariate model based on these 85-genes did not predict VAP in the test cohort better than chance (P = 027) 111 contrast, a compound covariate model based upon de novo transcriptional analysis of the 158 patients predicted VAP better than chance 4 days before diagnosis with a sensitivity of 57% and a specificity of 69%.
Conclusion: Our results validate those described in I pilot study, confirming that riboleukograms are associated with the development of VAP days prior to clinical diagnosis Similarly. a riboleukogram predictive model tested oil a larger cohort of 158 patients was better than chance at predicting VAP (lays prior to clinical diagnosis
C1 Washington Univ, Ctr Crit Illness & Hlth Engn, St Louis, MO USA.
Massachusetts Gen Hosp, NIGMS Inflammat & Host Response Injury Program, Boston, MA 02114 USA.
RP Cobb, JP (reprint author), Campus Box 8109,660 S Euclid Ave, St Louis, MO 63110 USA.
FU NIGMS NIH HHS [U54 GM062119, R01 GM081524, R01GM081524, R01 GM081524-04,
R21 GM075023, R21GM075023, U54GM6211906]
NR 53
TC 15
Z9 16
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-4932
J9 ANN SURG
JI Ann. Surg.
PD OCT
PY 2009
VL 250
IS 4
BP 531
EP 539
DI 10.1097/SLA.0b013e3181b81bd5
PG 9
WC Surgery
SC Surgery
GA 504FA
UT WOS:000270599800004
PM 19730236
ER
PT J
AU Gee, JR
Burmeister, CB
Havighurst, TC
Kim, K
AF Gee, Jason R.
Burmeister, Corrie B.
Havighurst, Thomas C.
Kim, Kyungmann
TI Cyclin-mediated G1 Arrest by Celecoxib Differs in Low-versus High-grade
Bladder Cancer
SO ANTICANCER RESEARCH
LA English
DT Article
DE Cyclooxygenase (COX)-2; celecoxib; bladder cancer; chemoprevention
ID COLON-CARCINOMA CELLS; CYCLOOXYGENASE-2 INHIBITORS; INDUCED APOPTOSIS;
COX-2 EXPRESSION; INDUCE APOPTOSIS; URINARY-BLADDER; AKT ACTIVATION;
LUNG-CANCER; IN-VITRO; GROWTH
AB Background: Celecoxib and other non-steroidal anti-inflammatory drugs (NSAIDs) are being evaluated in the prevention of bladder and other cancers. Here we investigate molecular effects of celecoxib independent of cyclooxygenase (COX)-2 expression levels in urothelial carcinoma of the bladder. Materials and Methods: Low-grade RT-4 and high-grade UM-UC-3 bladder cancer cells were treated with 0-50,mu M celecoxib. Growth, cell cycle and apoptosis were measured by crystal violet elution and flow cytometry. Western analysis was performed for COX-2, Rb, cyclin B1/D1, and phosphocyclin B1/D1 COX-2 induction was achieved with phorbol ester. Results: Celecoxib inhibited growth of RT-4 and UM-UC-3, with G(1) cell cycle arrest and altered cyclin B1/D1 expression in RT-4, whereas Rb up-regulation occurred in UM-UC-3. Apoptosis occurred in both cell lines. Conclusion: Celecoxib induces G(1) cell cycle arrest in low- and high-grade bladder cancer by different pathways. This heterogeneous molecular response supports combination approaches to prevention and treatment.
C1 [Gee, Jason R.] Univ Wisconsin, Dept Urol, Sch Med & Publ Hlth, Clin Sci Ctr G5 342, Madison, WI 53792 USA.
[Havighurst, Thomas C.; Kim, Kyungmann] Univ Wisconsin, Dept Biostat & Informat, Madison, WI 53792 USA.
[Gee, Jason R.] William S Middleton Mem Vet Adm Med Ctr, Dept Urol, Madison, WI USA.
RP Gee, JR (reprint author), Univ Wisconsin, Dept Urol, Sch Med & Publ Hlth, Clin Sci Ctr G5 342, 600 Highland Ave, Madison, WI 53792 USA.
EM Gee@urology.wisc.edu
FU Office of Research and Development, Biomedical Laboratory R&D Service,
Department of Veterans Affairs [P30 CA 14520]
FX This work is supported by the Office of Research and Development,
Biomedical Laboratory R&D Service, Department of Veterans Affairs (J.R.
Gee) and by P30 CA 14520 (T. Havighurst & K. Kim).
NR 40
TC 7
Z9 7
U1 0
U2 1
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
J9 ANTICANCER RES
JI Anticancer Res.
PD OCT
PY 2009
VL 29
IS 10
BP 3769
EP 3775
PG 7
WC Oncology
SC Oncology
GA 515QL
UT WOS:000271487400005
PM 19846907
ER
PT J
AU Rivas, DA
Lessard, SJ
Coffey, VG
AF Rivas, Donato A.
Lessard, Sarah J.
Coffey, Vernon G.
TI mTOR function in skeletal muscle: a focal point for overnutrition and
exercise
SO APPLIED PHYSIOLOGY NUTRITION AND METABOLISM-PHYSIOLOGIE APPLIQUEE
NUTRITION ET METABOLISME
LA English
DT Review
DE nutrients; insulin action; metabolism; training
ID INDUCED INSULIN-RESISTANCE; FREE FATTY-ACIDS; NUTRIENT SENSING PATHWAY;
P70 S6 KINASE; AMINO-ACID; MAMMALIAN TARGET; PROTEIN-SYNTHESIS;
GLUCOSE-UPTAKE; ENDURANCE EXERCISE; CELL-GROWTH
AB The mammalian target of rapamycin (mTOR) is a highly conserved atypical serine-threonine kinase that controls numerous functions essential for cell homeostasis and adaptation in mammalian cells via 2 distinct protein complex formations. Moreover, mTOR is a key regulatory protein in the insulin signalling cascade and has also been characterized as an insulin-independent nutrient sensor that may represent a critical mediator in obesity-related impairments of insulin action in skeletal muscle. Exercise characterizes a remedial modality that enhances mTOR activity and subsequently promotes beneficial metabolic adaptation in skeletal muscle. Thus, the metabolic effects of nutrients and exercise have the capacity to converge at the mTOR protein complexes and subsequently modify mTOR function. Accordingly, the aim of the present review is to highlight the role of mTOR in the regulation of insulin action in response to overnutrition and the capacity for exercise to enhance mTOR activity in skeletal muscle.
C1 [Rivas, Donato A.; Coffey, Vernon G.] RMIT Univ, Sch Med Sci, Exercise Metab Grp, Bundoora, Vic 3083, Australia.
[Lessard, Sarah J.] Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02215 USA.
[Lessard, Sarah J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA.
RP Coffey, VG (reprint author), RMIT Univ, Sch Med Sci, Exercise Metab Grp, Bundoora, Vic 3083, Australia.
EM vernon.coffey@rmit.edu.au
OI Rivas, Donato/0000-0002-4500-6233
NR 109
TC 19
Z9 19
U1 2
U2 11
PU NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS
PI OTTAWA
PA BUILDING M 55, OTTAWA, ON K1A 0R6, CANADA
SN 1715-5312
J9 APPL PHYSIOL NUTR ME
JI Appl. Physiol. Nutr. Metab.
PD OCT
PY 2009
VL 34
IS 5
BP 807
EP 816
DI 10.1139/H09-073
PG 10
WC Nutrition & Dietetics; Physiology; Sport Sciences
SC Nutrition & Dietetics; Physiology; Sport Sciences
GA 541LW
UT WOS:000273418200001
PM 19935842
ER
PT J
AU Huebschmann, AG
Reis, EN
Emsermann, C
Dickinson, LM
Reusch, JEB
Bauer, TA
Regensteiner, JG
AF Huebschmann, Amy G.
Reis, Erin N.
Emsermann, Caroline
Dickinson, L. Miriam
Reusch, Jane E. B.
Bauer, Timothy A.
Regensteiner, Judith G.
TI Women with type 2 diabetes perceive harder effort during exercise than
nondiabetic women
SO APPLIED PHYSIOLOGY NUTRITION AND METABOLISM-PHYSIOLOGIE APPLIQUEE
NUTRITION ET METABOLISME
LA English
DT Article
DE ratings of perceived exertion scale of Borg; type 2 diabetes mellitus;
overweight; obesity; physical activity; exercise
ID HABITUAL PHYSICAL-ACTIVITY; CAUSE-SPECIFIC MORTALITY; CARDIORESPIRATORY
FITNESS; GLUCOSE-TOLERANCE; SKELETAL-MUSCLE; OXYGEN-UPTAKE; US ADULTS;
MEN; SCALE; PREVALENCE
AB Regular exercise is a cornerstone of diabetes treatment; however, people with type 2 diabetes (T2D) are commonly sedentary. It is possible that a harder rate of perceived exertion (RPE) during exercise for those with T2D as compared with nondiabetics may be a barrier to physical activity. This study examined RPE (Borg scale, ordinal range 6-20) during submaximal exercise at identical absolute work rates to test the hypothesis that women with T2D demonstrate harder RPE during exercise than nondiabetic controls. In a prespecified analysis of existing data from equivalently sedentary women, RPE during submaximal exercise was compared among women with uncomplicated T2D (n = 13, mean body mass index (BMI) 34.2, mean hemoglobin A1c 9%), overweight controls (OC, n = 13, mean BMI 30.7), and normal-weight controls (NWC, n = 13, mean BMI 23.1). Subjects performed three 7 min, constant-load exercise tests at 20 W and 30 W. Mixed-effects general linear modeling was used to test for differences in mean RPE estimates among groups with and without adjustment for relative work intensity, age, habitual physical activity, or BMI. Subjects with T2D perceived harder effort during bicycling exercise than controls, as measured by RPE at 20 W and 30 W (p < 0.05 for T2D vs. OC and for T2D vs. NWC). Adjusting for relative work intensity eliminated significant group RPE differences at 30 W, but group RPE differences at 20 W remained significant. Harder perceived effort during exercise may be a barrier to physical activity for those with T2D.
C1 [Huebschmann, Amy G.; Reis, Erin N.; Bauer, Timothy A.; Regensteiner, Judith G.] Univ Colorado, Denver Sch Med, Div Gen Internal Med, Aurora, CO 80045 USA.
[Huebschmann, Amy G.; Reusch, Jane E. B.; Regensteiner, Judith G.] Univ Colorado, Denver Sch Med, Ctr Womens Hlth Res, Dept Med, Aurora, CO 80045 USA.
[Emsermann, Caroline; Dickinson, L. Miriam] Univ Colorado, Denver Sch Med, Div Family Med, Aurora, CO 80045 USA.
[Reusch, Jane E. B.] Univ Colorado, Denver Sch Med, Div Endocrinol, Aurora, CO 80045 USA.
[Reusch, Jane E. B.] Univ Colorado, Denver Sch Med, Denver VAMC, Denver, CO 80220 USA.
[Regensteiner, Judith G.] Univ Colorado, Denver Sch Med, Div Cardiol, Aurora, CO 80045 USA.
RP Huebschmann, AG (reprint author), Univ Colorado, Denver Sch Med, Div Gen Internal Med, POB 6511,Mailstop B180, Aurora, CO 80045 USA.
EM Amy.Huebschmann@ucdenver.edu
FU General Internal Medicine Division of the University of Colorado Denver
(UCD) School of Medicine; American Diabetes Association; Health
Resources and Services Administration faculty development grant; UCD
Center for Women's Health Research Junior Faculty Research Development
Award; Armstrong Family Foundation grant; National Research Service
Award [F32 DK088413-01]; American Diabetes Association award; Veteran
Affairs Merit award; National Institutes of Health [DK064741]
FX As noted in the manuscript, the demographic and (V) over dotO2
peak data have been published previously by Regensteiner et al.
(1998). RPE data were presented in abstract form only at the 2007
American Diabetes Association 67th Scientific Sessions and the 2007
National Diabetes Health Disparities Conference. The analysis of RPE
data was supported by a small grant from the General Internal Medicine
Division of the University of Colorado Denver (UCD) School of Medicine,
and the primary data acquisition for this study was funded by the
American Diabetes Association. A. G. H. is supported by a Health
Resources and Services Administration faculty development grant, by the
UCD Center for Women's Health Research Junior Faculty Research
Development Award, and by an Armstrong Family Foundation grant; T. A. B.
is supported by National Research Service Award F32 DK088413-01; J. G.
R. is supported by an American Diabetes Association award; J. E. B. R.
is supported by a Veteran Affairs Merit award and National Institutes of
Health grant DK064741. We are also grateful to Vermed, Inc., for their
generous donation of ECG electrodes for all of our exercise studies.
NR 45
TC 19
Z9 19
U1 0
U2 0
PU NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS
PI OTTAWA
PA BUILDING M 55, OTTAWA, ON K1A 0R6, CANADA
SN 1715-5312
J9 APPL PHYSIOL NUTR ME
JI Appl. Physiol. Nutr. Metab.
PD OCT
PY 2009
VL 34
IS 5
BP 851
EP 857
DI 10.1139/H09-074
PG 7
WC Nutrition & Dietetics; Physiology; Sport Sciences
SC Nutrition & Dietetics; Physiology; Sport Sciences
GA 541LW
UT WOS:000273418200005
PM 19935846
ER
PT J
AU Shin, LM
Lasko, NB
Macklin, ML
Karpf, RD
Milad, MR
Orr, SP
Goetz, JM
Fischman, AJ
Rauch, SL
Pitman, RK
AF Shin, Lisa M.
Lasko, Natasha B.
Macklin, Michael L.
Karpf, Rachel D.
Milad, Mohammed R.
Orr, Scott P.
Goetz, Jared M.
Fischman, Alan J.
Rauch, Scott L.
Pitman, Roger K.
TI Resting Metabolic Activity in the Cingulate Cortex and Vulnerability to
Posttraumatic Stress Disorder
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID CHILDHOOD SEXUAL-ABUSE; SCRIPT-DRIVEN IMAGERY; CEREBRAL-BLOOD-FLOW;
MONOZYGOTIC TWINS DISCORDANT; MEDIAL PREFRONTAL CORTEX; FUNCTIONAL MRI;
COMBAT EXPOSURE; ENVIRONMENTAL-INFLUENCES; NEUROIMAGING RESEARCH;
HIPPOCAMPAL FUNCTION
AB Context: Recent neuroimaging research has revealed functional abnormalities in the anterior cingulate cortex, amygdala, and hippocampus in individuals with post-traumatic stress disorder (PTSD).
Objective: To determine whether resting functional abnormalities found in PTSD are acquired characteristics or familial risk factors.
Design: Cross-sectional design including identical twins discordant for trauma exposure.
Setting: Academic medical center.
Participants: Combat-exposed veterans with PTSD (n = 14) and their identical co-twins not exposed to combat (n = 14) as well as combat-exposed veterans without PTSD (n = 19) and their identical co-twins not exposed to combat (n = 19).
Main Outcome Measures: We used positron emission tomography and fluorodeoxyglucose 18 to examine resting regional cerebral metabolic rate for glucose (rCMRglu).
Results: Veterans with PTSD and their co-twins had significantly higher resting rCMRglu in the dorsal anterior cingulate cortex/midcingulate cortex (dACC/MCC) compared with veterans without PTSD and their co-twins. Resting rCMRglu in the dACC/MCC in unexposed co-twins was positively correlated with combat exposure severity, PTSD symptom severity, and alcohol use in their exposed twins.
Conclusions: Enhanced resting metabolic activity in the dACC/MCC appears to represent a familial risk factor for developing PTSD after exposure to psychological trauma.
C1 [Shin, Lisa M.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA.
[Shin, Lisa M.; Lasko, Natasha B.; Karpf, Rachel D.; Milad, Mohammed R.; Orr, Scott P.; Goetz, Jared M.; Rauch, Scott L.; Pitman, Roger K.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Rauch, Scott L.] Harvard Univ, Sch Med, Boston, MA USA.
[Lasko, Natasha B.; Macklin, Michael L.; Orr, Scott P.] Vet Affairs Res Serv, Manchester, NH USA.
[Rauch, Scott L.] McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA.
[Fischman, Alan J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Shin, LM (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA.
EM lisa.shin@tufts.edu
FU US Public Health Service [R01MH54636]; US Department of Veterans
Affairs; Vietnam Era Twin Registry
FX This work was supported by grant R01MH54636 from the US Public Health
Service (Dr Pitman). The US Department of Veterans Affairs provided
financial support for the development and maintenance of the Vietnam Era
Twin Registry. Through their support of the Vietnam Era Twin Registry,
numerous other US organizations also provided invaluable assistance,
including the Department of Defense; National Personnel Records Center,
National Archives and Records Administration; Internal Revenue Service;
National Institutes of Health; National Opinion Research Center;
National Research Council, National Academy of Sciences; and Institute
for Survey Research, Temple University.
NR 94
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U1 10
U2 18
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-990X
J9 ARCH GEN PSYCHIAT
JI Arch. Gen. Psychiatry
PD OCT
PY 2009
VL 66
IS 10
BP 1099
EP 1107
PG 9
WC Psychiatry
SC Psychiatry
GA 502YE
UT WOS:000270496100007
PM 19805700
ER
PT J
AU Martell, BA
Orson, FM
Poling, J
Mitchell, E
Rossen, RD
Gardner, T
Kosten, TR
AF Martell, Bridget A.
Orson, Frank M.
Poling, James
Mitchell, Ellen
Rossen, Roger D.
Gardner, Tracie
Kosten, Thomas R.
TI Cocaine Vaccine for the Treatment of Cocaine Dependence in
Methadone-Maintained Patients A Randomized, Double-blind,
Placebo-Controlled Efficacy Trial
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID CHOLERA B-SUBUNIT; WHOLE-CELL VACCINE; CONTINGENCY MANAGEMENT;
IMMUNOLOGICAL MEMORY; ACTIVE IMMUNIZATION; MONOCLONAL-ANTIBODY; SWEDISH
VOLUNTEERS; SMOKING-CESSATION; IMMUNE FUNCTION; IMMUNOGENICITY
AB Context: Cocaine dependence, which affects 2.5 million Americans annually, has no US Food and Drug Administration-approved pharmacotherapy.
Objectives: To evaluate the immunogenicity, safety, and efficacy of a novel cocaine vaccine to treat cocaine dependence.
Design: A 24-week, phase 2b, randomized, double-blind, placebo-controlled trial with efficacy assessed during weeks 8 to 20 and follow-up to week 24.
Setting: Cocaine- and opioid-dependent persons recruited from October 2003 to April 2005 from greater New Haven, Connecticut.
Participants: One hundred fifteen methadone-maintained subjects (67% male, 87% white, aged 18-46 years) were randomized to vaccine or placebo, and 94 subjects (82%) completed the trial. Most smoked crack cocaine along with using marijuana (18%), alcohol (10%), and nonprescription opioids (44%).
Intervention: Over 12 weeks, 109 of 115 subjects received 5 vaccinations of placebo or succinylnorcocaine linked to recombinant cholera toxin B-subunit protein.
Main Outcome Measure: Semiquantitative urinary cocaine metabolite levels measured thrice weekly with a positive cutoff of 300 ng/mL.
Results: The 21 vaccinated subjects (38%) who attained serum IgG anticocaine antibody levels of 43 mu g/mL or higher (ie, high IgG level) had significantly more cocaine-free urine samples than those with levels less than 43 mu g/mL (ie, low IgG level) and the placebo-receiving subjects during weeks 9 to 16 (45% vs 35% cocaine-free urine samples, respectively). The proportion of subjects having a 50% reduction in cocaine use was significantly greater in the subjects with a high IgG level than in subjects with a low IgG level (53% of subjects vs 23% of subjects, respectively) (P = .048). The most common adverse effects were injection site induration and tenderness. There were no treatment-related serious adverse events, withdrawals, or deaths.
Conclusions: Attaining high (>= 43 mu g/mL) IgG anticocaine antibody levels was associated with significantly reduced cocaine use, but only 38% of the vaccinated subjects attained these IgG levels and they had only 2 months of adequate cocaine blockade. Thus, we need improved vaccines and boosters.
C1 [Orson, Frank M.; Rossen, Roger D.; Gardner, Tracie; Kosten, Thomas R.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
[Martell, Bridget A.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA.
[Poling, James; Mitchell, Ellen] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Martell, Bridget A.; Poling, James; Mitchell, Ellen] Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA.
[Gardner, Tracie; Kosten, Thomas R.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Gardner, Tracie; Kosten, Thomas R.] Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA.
[Gardner, Tracie; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
RP Kosten, TR (reprint author), Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe,Bldg 110,Room 229, Houston, TX 77030 USA.
EM kosten@bcm.edu
OI Poling, James/0000-0002-0133-3136
FU National Institute on Drug Abuse [1 R01 DA15477, K05-DA 0454,
P50-DA12762]; Veterans Affairs Mental Illness Research, Education, and
Clinical Center (New England MIRECC); Veteran's Affairs Office of
Research and Development/Cooperative Studies Program Career Development
Award [733A]
FX This work was supported by grants 1 R01 DA15477, K05-DA 0454 (Dr
Kosten), and P50-DA12762 from the National Institute on Drug Abuse and
by the Veterans Affairs Mental Illness Research, Education, and Clinical
Center (New England MIRECC). Dr Martell was provided salary support by
the Veteran's Affairs Office of Research and Development/Cooperative
Studies Program Career Development Award CRCD # 733A at the time the
research was conducted. Celtic Pharmaceuticals supplied the
succinylnorcocaine recombinant cholera toxin B-subunit vaccine and gave
Dr Kosten travel fees for consultative services.
NR 53
TC 109
Z9 111
U1 0
U2 15
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-990X
J9 ARCH GEN PSYCHIAT
JI Arch. Gen. Psychiatry
PD OCT
PY 2009
VL 66
IS 10
BP 1116
EP 1123
PG 8
WC Psychiatry
SC Psychiatry
GA 502YE
UT WOS:000270496100009
PM 19805702
ER
PT J
AU Middleton, LE
Yaffe, K
AF Middleton, Laura E.
Yaffe, Kristine
TI Promising Strategies for the Prevention of Dementia
SO ARCHIVES OF NEUROLOGY
LA English
DT Review
ID COGNITIVE FUNCTION; ALZHEIMER-DISEASE; OLDER-ADULTS; PHYSICAL-ACTIVITY;
RANDOMIZED-TRIAL; BLOOD-PRESSURE; RISK; IMPAIRMENT; DECLINE; MEMORY
AB The incidence and prevalence of dementia are expected to increase several-fold in the coming decades. Given that the current pharmaceutical treatment of dementia can only modestly improve symptoms, risk factor modification remains the cornerstone for dementia prevention. Some of the most promising strategies for the prevention of dementia include vascular risk factor control, cognitive activity, physical activity, social engagement, diet, and recognition of depression. In observational studies, vascular risk factors including diabetes, hypertension, dyslipidemia, and obesity-are fairly consistently associated with increased risk of dementia. In addition, people with depression are at high risk for cognitive impairment. Population studies have reported that intake of antioxidants or polyunsaturated fatty acids may be associated with a reduced incidence of dementia, and it has been reported that people who are cognitively, socially, and physically active have a reduced risk of cognitive impairment. However, results from randomized trials of risk factor modification have been mixed. Most promising, interventions of cognitive and physical activity improve cognitive performance and slow cognitive decline. Future studies should continue to examine the implication of risk factor modification in controlled trials, with particular focus on whether several simultaneous interventions may have additive or multiplicative effects. Arch Neurol. 2009;66(10):1210-1215
C1 [Middleton, Laura E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, Sch Med, San Francisco, CA 94121 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, Sch Med, San Francisco, CA 94121 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, Sch Med, San Francisco, CA 94121 USA.
San Francisco VA Med Ctr, San Francisco, CA USA.
RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Sch Med, 4150 Clement St,Box 181, San Francisco, CA 94121 USA.
EM kristine.yaffe@ucsf.edu
RI Middleton, Laura/C-6024-2009
OI Middleton, Laura/0000-0001-8624-3123
FU National Institute on Aging [AG 031155]
FX This work was supported in part by grant AG 031155 from the National
Institute on Aging (Dr Yaffe).
NR 37
TC 169
Z9 173
U1 2
U2 33
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0003-9942
EI 1538-3687
J9 ARCH NEUROL-CHICAGO
JI Arch. Neurol.
PD OCT
PY 2009
VL 66
IS 10
BP 1210
EP 1215
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 504LA
UT WOS:000270617000004
PM 19822776
ER
PT J
AU Lester, SC
Bose, S
Chen, YY
Connolly, JL
de Baca, ME
Fitzgibbons, PL
Hayes, DF
Kleer, C
O'Malley, FP
Page, DL
Smith, BL
Tan, LK
Weaver, DL
Winer, E
AF Lester, Susan C.
Bose, Shikha
Chen, Yunn-Yi
Connolly, James L.
de Baca, Monica E.
Fitzgibbons, Patrick L.
Hayes, Daniel F.
Kleer, Celina
O'Malley, Frances P.
Page, David L.
Smith, Barbara L.
Tan, Lee K.
Weaver, Donald L.
Winer, Eric
CA Coll Amer Pathologists
TI Protocol for the Examination of Specimens From Patients With Invasive
Carcinoma of the Breast
SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
LA English
DT Article
ID ESTROGEN-RECEPTOR STATUS; IN-SITU HYBRIDIZATION; NEOADJUVANT
CHEMOTHERAPY; PROGESTERONE-RECEPTORS; FORMALIN FIXATION; CANCER;
IMMUNOHISTOCHEMISTRY; RECOMMENDATIONS; DECALCIFICATION; CLASSIFICATION
C1 [Lester, Susan C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Connolly, James L.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA.
[Smith, Barbara L.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA.
[Winer, Eric] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Bose, Shikha] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA.
[Chen, Yunn-Yi] UCSF Med Ctr, Dept Pathol, San Francisco, CA USA.
[de Baca, Monica E.] Phys Lab, Sioux Falls, SD USA.
[Fitzgibbons, Patrick L.] St Jude Med Ctr, Dept Pathol, Fullerton, CA USA.
[Hayes, Daniel F.] Univ Michigan, Dept Med Oncol, Med Ctr, Ann Arbor, MI USA.
[Kleer, Celina] Univ Michigan, Dept Pathol, Med Ctr, Ann Arbor, MI 48109 USA.
[O'Malley, Frances P.] Mt Sinai Hosp, Dept Pathol, Toronto, ON M5G 1X5, Canada.
[Page, David L.] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA.
[Tan, Lee K.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
[Weaver, Donald L.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA.
[Weaver, Donald L.] Univ Vermont, Vermont Canc Ctr, Burlington, VT 05405 USA.
RP Lester, SC (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
EM slester@partners.org
OI Fitzgibbons, Patrick/0000-0002-2998-6913
FU NCI NIH HHS [U01 CA154224]
NR 47
TC 70
Z9 75
U1 0
U2 6
PU COLLEGE AMER PATHOLOGISTS
PI NORTHFIELD
PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA
SN 0003-9985
J9 ARCH PATHOL LAB MED
JI Arch. Pathol. Lab. Med.
PD OCT
PY 2009
VL 133
IS 10
BP 1515
EP 1538
PG 24
WC Medical Laboratory Technology; Medicine, Research & Experimental;
Pathology
SC Medical Laboratory Technology; Research & Experimental Medicine;
Pathology
GA 506ZU
UT WOS:000270819500001
PM 19792042
ER
PT J
AU Monzon, FA
Ogino, S
Hammond, MEH
Halling, KC
Bloom, KJ
Nikiforova, MN
AF Monzon, Federico A.
Ogino, Shuji
Hammond, M. Elizabeth H.
Halling, Kevin C.
Bloom, Kenneth J.
Nikiforova, Marina N.
TI The Role of KRAS Mutation Testing in the Management of Patients With
Metastatic Colorectal Cancer
SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
LA English
DT Review
ID RESOLUTION MELTING ANALYSIS; KI-RAS MUTATIONS; CETUXIMAB THERAPY;
SEQUENCING METHOD; PREDICT RESPONSE; LUNG-CANCER; EGFR; PANITUMUMAB;
EXPRESSION; PCR
AB Context.-KRAS mutations can be detected in approximately 30% to 40% of all patients with colorectal cancer. Several recent studies have shown that patients with KRAS mutations in codons 12 or 13 in metastatic tumors do not benefit from anti-epidermal growth factor receptor therapy with cetuximab or panitumumab.
Objective.-To review the literature on the role of KRAS mutation testing for management of patients with metastatic colorectal cancer and to discuss testing strategies.
Data Sources.-This review is based on published, peer-reviewed literature; available information from medical organizations (eg, National Comprehensive Cancer Network, American Society of Clinical Oncology, College of American Pathologists); and information from clinical laboratories conducting KRAS mutation analysis.
Conclusions.-Multiple methods for detecting KRAS mutations in colorectal tumors are available, and all methods in current clinical use appear to have adequate clinical sensitivity for predicting a lack of response to cetuximab and panitumumab. Pathologist expertise is essential to quality KRAS testing and to determining effective treatment for patients with metastatic colorectal cancer. (Arch Pathol Lab Med. 2009; 133: 1600-1606)
C1 [Monzon, Federico A.] Methodist Hosp, Res Inst, Dept Mol Diagnost, Houston, TX 77030 USA.
[Monzon, Federico A.] Weill Cornell Med Coll, New York, NY USA.
[Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA.
[Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Hammond, M. Elizabeth H.] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA.
[Halling, Kevin C.] Mayo Clin, Dept Pathol & Lab Med, Rochester, MN USA.
[Bloom, Kenneth J.] Clarient Diagnost Serv Lab, Dept Lab, Aliso Viejo, CA USA.
[Nikiforova, Marina N.] Univ Pittsburgh, Dept Pathol, Med Ctr, Pittsburgh, PA USA.
RP Monzon, FA (reprint author), Methodist Hosp, Res Inst, Dept Mol Diagnost, 6565 Fannin St,MS 205, Houston, TX 77030 USA.
EM famonzon@tmhs.org
NR 44
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U1 0
U2 2
PU COLL AMER PATHOLOGISTS
PI NORTHFIELD
PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA
SN 0003-9985
EI 1543-2165
J9 ARCH PATHOL LAB MED
JI Arch. Pathol. Lab. Med.
PD OCT
PY 2009
VL 133
IS 10
BP 1600
EP 1606
PG 7
WC Medical Laboratory Technology; Medicine, Research & Experimental;
Pathology
SC Medical Laboratory Technology; Research & Experimental Medicine;
Pathology
GA 506ZU
UT WOS:000270819500009
PM 19792050
ER
PT J
AU Arterburn, D
Livingston, EH
Schifftner, T
Kahwati, LC
Henderson, WG
Maciejewski, ML
AF Arterburn, David
Livingston, Edward H.
Schifftner, Tracy
Kahwati, Leila C.
Henderson, William G.
Maciejewski, Matthew L.
TI Predictors of Long-term Mortality After Bariatric Surgery Performed in
Veterans Affairs Medical Centers
SO ARCHIVES OF SURGERY
LA English
DT Article
ID GASTRIC BYPASS-SURGERY; RISK-FACTORS; SURGICAL CARE; UNITED-STATES;
DEATH RATES; OBESITY; METAANALYSIS; OVERWEIGHT; QUALITY; EXPENDITURES
AB Hypothesis: The purpose of this study was to examine patient factors associated with mortality among veterans who undergo bariatric surgery.
Design: Prospective study that uses data from the Veterans Affairs (VA) National Surgical Quality Improvement Program.
Setting: Group Health Center for Health Studies, the VA North Texas Health Care System, the Denver VA Medical Center, and the Durham VA Medical Center.
Patients: We identified 856 veterans who had undergone bariatric surgery in 1 of 12 VA bariatric centers from January 1, 2000, through December 31, 2006.
Main Outcome Measures: The risk of death was estimated via Cox proportional hazards.
Results: The 856 veterans had a mean body mass index (BMI) of 48.7, a mean age of 54 years, and a mean DCG score of 0.76; 73.0% were men, 83.9% were white, and 7.0% had an ASA class equal to 4. Fifty-four veterans (6.3%) had died by the end of 2006. In our Cox models, patients with a BMI greater than 50 (superobesity; hazard ratio [HR], 1.8; P=.04) or aDCGscore greater than or equal to 2 (HR, 3.4; P<.001) had an increased risk of death.
Conclusion: Superobese veterans and those with a greater burden of chronic disease had a greater risk of death after bariatric surgery from 2000 through 2006.
C1 [Maciejewski, Matthew L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA.
[Maciejewski, Matthew L.] Univ N Carolina, Sch Pharm, Div Pharmaceut Outcomes & Policy, Chapel Hill, NC USA.
[Arterburn, David] Univ Washington, Ctr Hlth Studies, Grp Hlth, Seattle, WA 98195 USA.
[Arterburn, David] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA.
[Livingston, Edward H.] Univ Texas SW Med Ctr Dallas, Div Gastrointestinal & Endocrine Surg, Dallas, TX 75390 USA.
[Livingston, Edward H.] Vet Adm N Texas Hlth Care Syst, Dallas, TX USA.
[Livingston, Edward H.] Univ Texas Arlington, Arlington, TX USA.
[Schifftner, Tracy; Henderson, William G.] Univ Colorado, Denver Vet Affairs Med Ctr, Denver, CO 80202 USA.
[Henderson, William G.] Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA.
[Henderson, William G.] Univ Colorado, Hlth Sci Ctr, Colorado Hlth Outcomes Program, Denver, CO 80262 USA.
[Kahwati, Leila C.] Off Patient Care Serv, Natl Ctr Hlth Promot & Dis Prevent, Vet Hlth Adm, Dept Vet Affairs, Durham, NC USA.
RP Maciejewski, ML (reprint author), Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Stop Code 152,508 Fulton St, Durham, NC 27705 USA.
EM matthew.maciejewski@va.gov
FU Office of Research and Development, Health Services Research and
Development Service, Department of Veterans Affairs [IIR 05-201]
FX This work was supported by the Office of Research and Development,
Health Services Research and Development Service, Department of Veterans
Affairs, project number IIR 05-201.
NR 33
TC 26
Z9 26
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0004-0010
J9 ARCH SURG-CHICAGO
JI Arch. Surg.
PD OCT
PY 2009
VL 144
IS 10
BP 914
EP 920
PG 7
WC Surgery
SC Surgery
GA 508JJ
UT WOS:000270926400009
PM 19841358
ER
PT J
AU Velmahos, GC
Spaniolas, K
Tabbara, M
Abujudeh, HH
de Moya, M
Gervasini, A
Alam, HB
AF Velmahos, George C.
Spaniolas, Konstantinos
Tabbara, Malek
Abujudeh, Hani H.
de Moya, Marc
Gervasini, Alice
Alam, Hasan B.
TI Pulmonary Embolism and Deep Venous Thrombosis in Trauma Are They
Related?
SO ARCHIVES OF SURGERY
LA English
DT Article
ID INDIRECT CT VENOGRAPHY; THROMBOEMBOLIC DISEASE; VEIN THROMBOSIS;
CRITICALLY-ILL; MAJOR TRAUMA; ANGIOGRAPHY; COMPRESSION; PROPHYLAXIS;
ULTRASOUND; SONOGRAPHY
AB Hypothesis: Pulmonary embolism (PE) and deep venous thrombosis (DVT) in trauma are related.
Design: Retrospective review of medical records.
Setting: Academic level I trauma center.
Patients: Trauma patients who underwent computed tomographic pulmonary angiography (CTPA) with computed tomographic venography (CTV) of the pelvic and proximal lower extremity veins over a 3-year period (January 1, 2004, to December 31, 2006) were reviewed. Data on demographics, injury type and severity, imaging findings, hospital length of stay, and mortality were collected.
Main Outcome Measures: Pulmonary embolism and DVT.
Results: Among 247 trauma patients undergoing CTPA/CTV, PE was diagnosed in 46 (19%) and DVT in 18 (7%). Eighteen PEs were central (main or lobar pulmonary arteries), and 28 PEs were peripheral (segmental or subsegmental branches). Pulmonary embolism occurred within the first week of injury in two-thirds of patients. Seven patients with PE (4 femoral, 2 popliteal, and 1 iliac) had DVT. Pulmonary embolism was central in 5 patients and peripheral in 2 patients. No significant differences were noted in any of the examined variables between patients with PE having DVT and those not having DVT.
Conclusions: Few patients with PE have DVT of the pelvic or proximal lower extremity veins. Pulmonary embolism may not originate from these veins, as commonly believed, but instead may occur de novo in the lungs. These findings have implications for thromboprophylaxis and, particularly, the value of vena cava filters.
C1 [Velmahos, George C.; Spaniolas, Konstantinos; Tabbara, Malek; de Moya, Marc; Gervasini, Alice; Alam, Hasan B.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
[Abujudeh, Hani H.] Massachusetts Gen Hosp, Dept Emergency Radiol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Ste 810, Boston, MA 02114 USA.
EM gvelmahos@partners.org
NR 32
TC 39
Z9 39
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0004-0010
J9 ARCH SURG-CHICAGO
JI Arch. Surg.
PD OCT
PY 2009
VL 144
IS 10
BP 928
EP 932
PG 5
WC Surgery
SC Surgery
GA 508JJ
UT WOS:000270926400013
PM 19841360
ER
PT J
AU Swirski, FK
Weissleder, R
Pittet, MJ
AF Swirski, Filip K.
Weissleder, Ralph
Pittet, Mikael J.
TI Heterogeneous In Vivo Behavior of Monocyte Subsets in Atherosclerosis
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE monocyte; atherosclerosis; imaging
ID LOW-DENSITY-LIPOPROTEIN; PROINFLAMMATORY CD14(+)CD16(+)DR(++) MONOCYTES;
HUMAN PERIPHERAL-BLOOD; BONE-MARROW; T-CELLS; MONONUCLEAR PHAGOCYTES;
MYOCARDIAL-INFARCTION; DENDRITIC CELLS; KNOCKOUT MICE; MACROPHAGES
AB Monocytes and macrophages play active roles in atherosclerosis, a chronic inflammatory disease that is a leading cause of death in the developed world. The prevailing paradigm states that, during human atherogenesis, monocytes accumulate in the arterial intima and differentiate into macrophages, which then ingest oxidized lipoproteins, secrete a diverse array of proinflammatory mediators, and eventually become foam cells, the key constituents of a vulnerable plaque. Yet monocytes are heterogeneous. In the mouse, one subset (Ly-6C(hi)) promotes inflammation, expands in hypercholesterolemic conditions, and selectively gives rise to macrophages in atheromata. A different subset (Ly-6C(lo)) attenuates inflammation and promotes angiogenesis and granulation tissue formation in models of tissue injury, but its role in atherosclerosis is largely unknown. In the human, monocyte heterogeneity is preserved but it is still unresolved how subsets correspond functionally. The contradistinctive properties of these cells suggest commitment for specific function before infiltrating tissue. Such commitment argues for discriminate targeting of deleterious subsets while sparing host defense and repair mechanisms. In addition to advancing our understanding of atherosclerosis, the ability to target and image monocyte subsets would allow us to evaluate drugs designed to selectively inhibit monocyte subset recruitment or function, and to stratify patients at risk for developing complications such as myocardial infarction or stroke. In this review we summarize recent advances of our understanding of the behavioral heterogeneity of monocytes during disease progression and outline emerging molecular imaging approaches to address key questions in the field. (Arterioscler Thromb Vasc Biol. 2009; 29: 1424-1432.)
C1 [Swirski, Filip K.; Weissleder, Ralph; Pittet, Mikael J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA.
RP Swirski, FK (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA.
EM fswirski@mgh.harvard.edu
FU NIH [U01 HL080731, P50 CA86355, R24 CA69246, P01-A154904]; MGH-Center
for Systems Biology
FX This work was supported in part by NIH grants U01 HL080731, P50 CA86355,
R24 CA69246, and P01-A154904 (to R.W.) and the MGH-Center for Systems
Biology (to M.J.P.).
NR 100
TC 89
Z9 92
U1 2
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD OCT
PY 2009
VL 29
IS 10
BP 1424
EP 1432
DI 10.1161/ATVBAHA.108.180521
PG 9
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 494VY
UT WOS:000269848600006
PM 19372462
ER
PT J
AU Nahrendorf, M
Waterman, P
Thurber, G
Groves, K
Rajopadhye, M
Panizzi, P
Marinelli, B
Aikawa, E
Pittet, MJ
Swirski, FK
Weissleder, R
AF Nahrendorf, Matthias
Waterman, Peter
Thurber, Greg
Groves, Kevin
Rajopadhye, Milind
Panizzi, Peter
Marinelli, Brett
Aikawa, Elena
Pittet, Mikael J.
Swirski, Filip K.
Weissleder, Ralph
TI Hybrid In Vivo FMT-CT Imaging of Protease Activity in Atherosclerosis
With Customized Nanosensors
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE FMT-CT; molecular imaging; atherosclerosis; protease activity;
inflammation
ID RAT PERITONEAL-MACROPHAGES; MATRIX METALLOPROTEINASES; PINOCYTOSED
FLUID; KINETIC EVIDENCE; PLAQUE RUPTURE; CATHEPSIN-B; INFLAMMATION;
MOUSE; ENDOCYTOSIS; PLASMA
AB Objective-Proteases are emerging biomarkers of inflammatory diseases. In atherosclerosis, these enzymes are often secreted by inflammatory macrophages, digest the extracellular matrix of the fibrous cap, and destabilize atheromata. Protease function can be monitored with protease activatable imaging probes and quantitated in vivo by fluorescence molecular tomography (FMT). To address 2 major constraints currently associated with imaging of murine atherosclerosis (lack of highly sensitive probes and absence of anatomic information), we compared protease sensors (PS) of variable size and pharmacokinetics and coregistered FMT datasets with computed tomography (FMT-CT).
Methods and Results-Coregistration of FMT and CT was achieved with a multimodal imaging cartridge containing fiducial markers detectable by both modalities. A high-resolution CT angiography protocol accurately localized fluorescence to the aortic root of atherosclerotic apoE(-/-) mice. To identify suitable sensors, we first modeled signal kinetics in-silico and then compared 3 probes with oligo-L-lysine cleavage sequences: PS-5, 5 nm in diameter containing 2 fluorochromes, PS-25, a 25-nm version with an elongated lysine chain and PS-40, a polymeric nanoparticle. Serial FMT-CT showed fastest kinetics for PS-5 but, surprisingly, highest fluorescence in lesions of the aortic root for PS-40. PS-40 robustly reported therapeutic effects of atorvastatin, corroborated by ex vivo imaging and qPCR for the model protease cathepsin B.
Conclusions-FMT-CT is a robust and observer-independent tool for noninvasive assessment of inflammatory murine atherosclerosis. Reporter-containing nanomaterials may have unique advantages over small molecule agents for in vivo imaging. (Arterioscler Thromb Vasc Biol. 2009; 29: 1444-1451.)
C1 [Nahrendorf, Matthias; Waterman, Peter; Thurber, Greg; Panizzi, Peter; Marinelli, Brett; Pittet, Mikael J.; Swirski, Filip K.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02124 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Nahrendorf, Matthias; Waterman, Peter; Panizzi, Peter; Aikawa, Elena; Pittet, Mikael J.; Swirski, Filip K.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA.
Harvard Univ, Sch Med, Charlestown, MA USA.
[Groves, Kevin; Rajopadhye, Milind] VisEn Med Inc, Bedford, MA USA.
RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, CPZN 5206,185 Cambridge St, Boston, MA 02124 USA.
EM rweissleder@mgh.harvard.edu
OI Panizzi, Peter/0000-0003-0141-8807; Thurber, Greg/0000-0001-7570-2080
FU American Heart Association [0835623D]; [R24-CA92782]; [UO1-HL08073]
FX This work was funded in part by R24-CA92782 and UO1-HL08073 (to R.W.)
and by the American Heart Association 0835623D (to M.N.).
NR 50
TC 93
Z9 93
U1 1
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD OCT
PY 2009
VL 29
IS 10
BP 1444
EP U89
DI 10.1161/ATVBAHA.109.193086
PG 16
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 494VY
UT WOS:000269848600009
PM 19608968
ER
PT J
AU Sovershaev, MA
Egorina, EM
Hansen, JB
Osterud, B
Pacher, P
Stasch, JP
Evgenov, OV
AF Sovershaev, Mikhail A.
Egorina, Elena M.
Hansen, John-Bjarne
Osterud, Bjarne
Pacher, Pal
Stasch, Johannes-Peter
Evgenov, Oleg V.
TI Soluble Guanylate Cyclase Agonists Inhibit Expression and Procoagulant
Activity of Tissue Factor
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE tissue factor; procoagulant activity; soluble guanylate cyclase; BAY
41-2272; BAY 58-2667
ID THP-1 MONOCYTIC CELLS; TUMOR-NECROSIS-FACTOR; FACTOR-KAPPA-B;
PULMONARY-HYPERTENSION; ENDOTHELIAL-CELLS; HEART-FAILURE; NITRIC-OXIDE;
CD40 LIGAND; P-SELECTIN; PLATELETS
AB Objective-Tissue factor (TF), a major initiator of blood coagulation, contributes to inflammation, atherosclerosis, angiogenesis, and vascular remodeling. Pharmacological agonists of soluble guanylate cyclase (sGC) attenuate systemic and pulmonary hypertension, vascular remodeling, and platelet aggregation. However, the influence of these novel pharmacophores on TF is unknown.
Methods and Results-We evaluated effects of BAY 41-2272 and BAY 58-2667 on expression and activity of TF in human monocytes and umbilical vein endothelial cells (HUVECs). Both compounds reduced expression of active TF protein in monocytes stimulated with lipopolysaccharide, as demonstrated by immunoblotting and a TF procoagulant activity assay. In-cell Western assay revealed that this effect was associated with a marked reduction of total and surface TF presentation. Furthermore, BAY 41-2272 and BAY 58-2667 decreased TF protein expression and the TF-dependent procoagulant activity in HUVECs stimulated with TNF-alpha. The sGC agonists also suppressed transcriptional activity of NF-kappa B. A siRNA-mediated knockdown of the alpha 1-subunit of sGC in monocytes and HUVECs confirmed that the inhibitory effect of BAY 41-2272 and BAY 58-2667 on TF expression is mediated through the sGC-dependent mechanisms.
Conclusions-Inhibition of TF expression and activity by sGC agonists might provide therapeutic benefits in cardiovascular diseases associated with enhanced procoagulant and inflammatory response. (Arterioscler Thromb Vasc Biol. 2009;29:1578-1586.)
C1 [Sovershaev, Mikhail A.; Egorina, Elena M.; Evgenov, Oleg V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Sovershaev, Mikhail A.; Egorina, Elena M.; Osterud, Bjarne] Univ Tromso, Dept Biochem, Inst Med Biol, N-9001 Tromso, Norway.
[Hansen, John-Bjarne] Univ Tromso, Ctr Atherothrombot Res, Inst Clin Med, N-9001 Tromso, Norway.
[Sovershaev, Mikhail A.; Hansen, John-Bjarne] Univ Hosp No Norway, Dept Med, Tromso, Norway.
[Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA.
[Stasch, Johannes-Peter] Bayer Schering Pharma AG, Inst Cardiovasc Res, Wuppertal, Germany.
RP Evgenov, OV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Gray Bigelow 444, Boston, MA 02114 USA.
EM oevgenov@partners.org
RI Pacher, Pal/B-6378-2008
OI Pacher, Pal/0000-0001-7036-8108
FU Northern Norway Regional Health Authority; NIH/NIAAA
FX This work was supported in part by departmental funds, the Northern
Norway Regional Health Authority ( to M. A. S. and J.B.H.), and the
Intramural Research Program of NIH/NIAAA ( to P. P.).
NR 39
TC 7
Z9 7
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD OCT
PY 2009
VL 29
IS 10
BP 1578
EP U446
DI 10.1161/ATVBAHA.109.192690
PG 27
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 494VY
UT WOS:000269848600029
PM 19592462
ER
PT J
AU Deguchi, JO
Yamazaki, H
Aikawa, E
Aikawa, M
AF Deguchi, Jun-o
Yamazaki, Hiroyuki
Aikawa, Elena
Aikawa, Masanori
TI Chronic Hypoxia Activates the Akt and beta-Catenin Pathways in Human
Macrophages
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE macrophages; hypoxia; inflammation; atherosclerosis; MMP
ID SMOOTH-MUSCLE-CELLS; IN-VIVO; ATHEROSCLEROTIC PLAQUES; MATRIX
METALLOPROTEINASE-7; COLLAGEN ACCUMULATION; INSULIN-RESISTANCE;
SIGNALING PATHWAY; SURVIVAL PATHWAY; OXYGEN-TENSIONS; INFLAMMATION
AB Objective-Macrophage activation contributes importantly to the pathogenesis of inflammatory diseases including atherosclerosis. Macrophages exist chronically under moderate hypoxia (2% to 5% O(2)) in inflamed tissues such as atherosclerotic plaques. However, macrophage phenotypes in such environments remain incompletely understood. This study tested the hypothesis that chronic moderate hypoxia induces macrophage activation and explored the underlying mechanisms.
Methods and Results-We cultured primary human macrophages derived from peripheral blood monocytes in moderate hypoxia (2% O(2) tension) or normoxia (21% O(2)) for 10 days. Moderate hypoxia did not affect macrophage differentiation assessed via expression levels of scavenger receptor A. Chronic moderate hypoxia, but not normoxia, activated Akt and inactivated GSK-3 beta, a negative effector of Akt, thus allowing nuclear translocation of beta-catenin. 2% O(2) tension increased accumulation of hypoxia-inducible factors 1 alpha (HIF-1 alpha) transiently at 3 to 5 days. Hypoxia induced mRNA expression of the beta-catenin-associated genes: MMP-7, CD44, and c-Myc. RNAi of TCF7L2, a cofactor of beta-catenin, suppressed MMP-7 expression induced by hypoxia. Inhibition of Akt phosphorylation with LY294002 abolished hypoxia-induced GSK-3 beta inactivation, beta-catenin activation, and MMP-7 expression. Macrophages under hypoxia were more resistant for oxLDL-induced apoptosis. Moreover, phospho-Akt colocalized with MMP-7 and CD44 expression in macrophages of human atherosclerotic plaques.
Conclusions-Chronic moderate hypoxia induces macrophage activation via the Akt and beta-catenin pathways, providing new insight into the pathogenesis of inflammatory diseases. (Arterioscler Thromb Vasc Biol. 2009;29:1664-1670.)
C1 [Aikawa, Masanori] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Excellence Vasc Biol,Cardiovasc Div,Dept Med, Boston, MA 02115 USA.
[Aikawa, Elena] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA.
RP Aikawa, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Excellence Vasc Biol,Cardiovasc Div,Dept Med, 77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM maikawa@rics.bwh.harvard.edu
FU National Heart, Lung, and Blood Institute [HL66086]; American Heart
Association; Kowa Company Ltd Tokyo, Japan; Donald W. Reynolds
Foundation
FX This work was supported in part by grants from the National Heart, Lung,
and Blood Institute HL66086 and the American Heart Association
Grant-in-Aid, an unrestricted donation from Kowa Company Ltd Tokyo,
Japan ( to M. A.), and a fellowship from the Donald W. Reynolds
Foundation ( to J.D.).
NR 60
TC 25
Z9 25
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD OCT
PY 2009
VL 29
IS 10
BP 1664
EP U628
DI 10.1161/ATVBAHA.109.194043
PG 10
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 494VY
UT WOS:000269848600041
PM 19644051
ER
EF