FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Sugimoto, H Mundel, TM Kieran, MW Kalluri, R AF Sugimoto, Hikaru Mundel, Thomas M. Kieran, Mark W. Kalluri, Raghu TI Identification of fibroblast heterogeneity in the tumor microenvironment SO CANCER BIOLOGY & THERAPY LA English DT Article DE fibroblast heterogeneity; CAF; cancer; micro-environment; NG2; SMA; FSP1; S100A4; PDGFR ID BASEMENT-MEMBRANE COLLAGEN; ENDOTHELIAL-CELLS; NG2 PROTEOGLYCAN; TISSUE; MYOFIBROBLASTS; CANCER; EXPRESSION; PERICYTES; PROTEIN; GROWTH AB Tumors are unorganized organs that contain many different cell types. In the recent years, many studies have reported that primary tumors contain fibroblasts/myofibroblasts (carcinoma-associated fibroblasts), mesenchymal cells such as pericytes/mural cells and other vascular smooth muscle cells. Several different markers are used routinely to identify carcinoma-associated fibroblasts (CAFs) such as alpha-smooth muscle actin (alpha-SMA), vimentin, S100A4 protein/fibroblast specific protein-1 (FSP1) and type I collagen. Likewise markers such as platelet derived growth factor receptor-beta (PDGFR beta) and NG2 chondroitin sulfate proteoglycan (NG2) are used to identify mesenchymal cells such as pericytes and other vasculature associated smooth muscle cells. It is still unknown whether these markers overlap with each other or identify a unique population of cells within the tumor microenvironment. Therefore in the present study we utilized two different mouse models of cancer, the Rip1Tag2 mice that develop progressive pancreatic cancer and an orthotopic 4T1 breast cancer model, to study the overlap between six different mesenchymal markers commonly used in mouse cancer research. Our study demonstrates that among all the markers, S100A4/FSP1 identifies a unique population of fibroblasts with minimal overlap with markers for alpha SMA, PDGFR beta and NG2. Vimentin and type I collagen are not specific markers for fibroblasts in these tumors. alpha SMA, PDGFR beta and NG2 significantly overlap with each other in identifying a mixed population of fibroblasts (activated or resting), myofibroblasts, pericytes and vascular smooth muscle cells. Collectively, this study demonstrates that tumor microenvironment associated fibroblasts are a heterogeneous population and thus, the use of alpha SMA or vimentin as the only markers will not identify all the CAFs. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Matrix Biol,Dept Med, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Kalluri, R (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Matrix Biol,Dept Med, 330 Brookline Ave,DANA 514, Boston, MA 02215 USA. EM rkalluri@bidmc.harvard.edu RI thomson, axel/A-7893-2013; Kalluri, Raghu/E-2677-2015; OI Kalluri, Raghu/0000-0002-2190-547X; Kieran, Mark/0000-0003-2184-7692 FU NIAAA NIH HHS [AA13913]; NIDDK NIH HHS [DK61688, DK55001, DK62987] NR 25 TC 251 Z9 256 U1 3 U2 36 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD DEC PY 2006 VL 5 IS 12 BP 1640 EP 1646 DI 10.4161/cbt.5.12.3354 PG 7 WC Oncology SC Oncology GA 160DK UT WOS:000245919000020 PM 17106243 ER PT J AU Bishnupuri, KS Luo, QZ Korzenik, JR Henderson, JO Houchen, CW Anant, S Dieckgraefe, BK AF Bishnupuri, Kumar S. Luo, Qizhi Korzenik, Joshua R. Henderson, Jeffrey O. Houchen, Courtney W. Anant, Shrikant Dieckgraefe, Brian K. TI Dysregulation of Reg gene expression occurs early in gastrointestinal tumorigenesis and regulates anti-apoptotic genes SO CANCER BIOLOGY & THERAPY LA English DT Article DE regenerating gene; tumorigenesis; colorectal; adenocarcinoma; apoptosis; resistance; Bcl-2 ID PANCREATITIS-ASSOCIATED PROTEIN; HORMONE-RELEASING HORMONE; COLORECTAL CARCINOMAS; IV; CANCER; FAMILY; ADENOCARCINOMAS; DIFFERENTIATION; OVEREXPRESSION; LOCALIZATION AB Expression of anti-apoptotic genes is frequently elevated in tumors, where they increase resistance to chemotherapeutic agents and predict poor patient outcomes. However, key cellular factors regulating anti-apoptotic genes in tumors remain unknown. Increased expression of the regenerating (Reg) genes is commonly observed in gastrointestinal (GI) malignancies including colorectal cancer (CRC). We therefore examined Reg gene expression and associated changes in anti-apoptotic genes in an animal model of GI tumorigenesis. Using real time RT-PCR, we measured expression of Reg genes in human colorectal adenocarcinoma specimens, colon adenocarcinoma cell lines and adenomas from multiple intestinal neoplasia (min) mice heterozygous for a germ-line mutation of the adenomatous polyposis coli (APC) gene. Expression of Reg genes is increased in human colorectal adenocarcinomas and in the intestine of APC(min/+) mice at four weeks of age, a time preceding the spontaneous second mutation in the APC gene. Individual Reg genes exhibited regional expression profiles across the GI tract in mice. Adenomas from 14-week old mice had significant increases in at least one member of the Reg gene family, most commonly Reg IV and an associated increase in expression of the anti-apoptotic gene, Bcl-2. Addition of exogenous recombinant human Reg IV to human colon adenocarcinoma cells significantly increased Bcl-2 and Bcl-x(L) expression and induced resistance to ionizing radiation. These results show that dysregulation of Reg genes occur early in tumorigenesis. Furthermore, increased expression of Reg genes, specifically Reg IV contribute to adenoma formation and lead to increased resistance to apoptotic cell death in CRC. C1 Washington Univ, Dept Internal Med, Div Gastroenterol, Sch Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA. Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA USA. Tabor Coll, Dept Biol, Hillsboro, KS USA. Univ Oklahoma, Hlth Sci Ctr, Dept Internal Med, Oklahoma City, OK USA. RP Dieckgraefe, BK (reprint author), Washington Univ, Dept Internal Med, Div Gastroenterol, Sch Med, 660 S Euclid Ave,CSRB,NT929, St Louis, MO 63110 USA. EM dieck@im.wustl.edu FU NCI NIH HHS [CA109269]; NIDDK NIH HHS [DK62265, DK060106, P30 DK52574] NR 29 TC 18 Z9 23 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD DEC PY 2006 VL 5 IS 12 BP 1714 EP 1720 DI 10.4161/cbt.5.12.3469 PG 7 WC Oncology SC Oncology GA 160DK UT WOS:000245919000032 PM 17106246 ER PT J AU Bardeesy, N Sharpless, NE AF Bardeesy, Nabeel Sharpless, Norman E. TI RAS unplugged: Negative feedback and oncogene-induced senescence SO CANCER CELL LA English DT Editorial Material ID CELLULAR SENESCENCE; PATHWAY; P16 AB Many normal cells respond to certain stresses, such as oncogene activation, by undergoing a permanent form of growth arrest known as senescence, an intrinsic tumor suppressor program. The predominant view has been that senescence is caused in some settings through a mutant oncogene's ability to induce activation of high levels of sustained MAP kinase and PI3 kinase signaling. A new study in this issue of Cancer Cell has challenged this model with the surprising finding that aberrant activation of the RAS/RAF pathway can induce a negative feedback loop that globally attenuates MAPK and PI3K signaling and that the reduction of signaling in these pathways is required for senescence. C1 Univ N Carolina, Dept Med, Sch Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Genet, Sch Med, Chapel Hill, NC 27599 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Canc Ctr, Boston, MA 02114 USA. RP Bardeesy, N (reprint author), Univ N Carolina, Dept Med, Sch Med, Chapel Hill, NC 27599 USA. EM nelbardeesy@partners.org; nes@med.unc.edu NR 10 TC 21 Z9 21 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD DEC PY 2006 VL 10 IS 6 BP 451 EP 453 DI 10.1016/j.ccr.2006.11.015 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 118PA UT WOS:000242953000001 PM 17157783 ER PT J AU Courtois-Cox, S Williams, SMG Reczek, EE Johnson, BW McGillicuddy, LT Johannessen, CM Hollstein, PE MacCollin, M Cichowski, K AF Courtois-Cox, Stephanie Williams, Sybil M. Genther Reczek, Elizabeth E. Johnson, Bryan W. McGillicuddy, Lauren T. Johannessen, Cory M. Hollstein, Pablo E. MacCollin, Mia Cichowski, Karen TI A negative feedback signaling network underlies oncogene-induced senescence SO CANCER CELL LA English DT Article ID NF1 TUMOR-SUPPRESSOR; HUMAN-FIBROBLASTS; TYPE-1 NEUROFIBROMATOSIS; CELLULAR SENESCENCE; RAS; CELLS; GROWTH; TRANSCRIPTION; EXPRESSION; OVEREXPRESSION AB Oncogene-induced senescence functions to limit tumor development. However, a complete understanding of the signals that trigger this type of senescence is currently lacking. We found that mutations affecting NF1, Raf, and Ras induce a global negative feedback response that potently suppresses Ras and/or its effectors. Moreover, these signals promote senescence by inhibiting the Ras/PI3K pathway, which can impact the senescence machinery through HDM2 and Ill This negative feedback program is regulated in part by RasGEFs, Sprouty proteins, RasGAPs, and MKPs. Moreover, these signals function in vivo in benign human tumors. Thus, the ultimate response to the aberrant activation of the Ras pathway is a multifaceted negative feedback signaling network that terminates the oncogenic signal and participates in the senescence response. C1 Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp East, Mol Neurogenet Unit, Boston, MA 02129 USA. RP Cichowski, K (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 458C NRB,77 Louis Pasteur Ave, Boston, MA 02115 USA. EM kcichowski@rics.bwh.harvard.edu FU NCI NIH HHS [R01 CA111754, R01 CA111754-01] NR 40 TC 315 Z9 324 U1 3 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD DEC PY 2006 VL 10 IS 6 BP 459 EP 472 DI 10.1016/j.ccr.2006.10.003 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 118PA UT WOS:000242953000005 PM 17157787 ER PT J AU Koushik, A Kraft, P Fuchs, CS Hankinson, SE Willett, WC Giovannucci, EL Hunter, DJ AF Koushik, Anita Kraft, Peter Fuchs, Charles S. Hankinson, Susan E. Willett, Walter C. Giovannucci, Edward L. Hunter, David J. TI Nonsynonymous polymorphisms in genes in the one-carbon metabolism pathway and associations with colorectal cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISM; HOMOCYSTEINE METHYLTRANSFERASE BHMT; METHIONINE SYNTHASE GENE; COLON-CANCER; BETAINE-HOMOCYSTEINE; 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE; MICROSATELLITE INSTABILITY; A1298C POLYMORPHISMS; VASCULAR-DISEASE; ALCOHOL INTAKE AB The Ala(222)Val single nucleotide polymorphism (SNP) in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in one-carbon metabolism, has been associated with colorectal cancer risk. Many enzymes are involved in one-carbon metabolism, and SNPs in the corresponding genes may play a role in colorectal carcinogenesis. We examined 24 nonsynonymous SNPs in 13 genes involved in the one-carbon metabolism pathway in relation to the risk of colorectal cancer in a case-control study nested in the Nurses' Health Study and the Health Professionals Follow-up Study cohorts. Among 376 men and women with colorectal cancer and 849 controls, a reduced risk of colorectal cancer was observed for Val/Val versus Ala carriers of MTHFR Ala(222)Val [odds ratio (OR), 0.66; 95% confidence interval (0), 0.43-1.00]. An increased risk was suggested for the variant carrier genotypes versus homozygous wild-type for betaine hydroxymethyltransferase Arg(239)Gln (OR, 1.40; 95% Cl, 1.07-1.83) and two linked SNPs in methionine synthase reductase, Ser(284) Thr (OR, 1.85; 95% Cl, 1.05-3.27) and Arg(415)Cys (OR, 2.03; 95% CI, 1.15-3.56). The other SNPs were not associated with colorectal cancer risk. Also, none of the SNPs were associated with risk in subgroups of dietary methyl status or were jointly associated with colorectal cancer risk in combination with another SNP, except possibly SNPs in methionine synthase and transcobalamin II. However, these analyses of gene-diet interactions were limited in statistical power. Our results corroborate previous findings for MTHFR Ala(222)Val and suggest that other genes involved in one-carbon metabolism, particularly those that affect DNA methylation, may be associated with colorectal cancer risk. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Hunter, DJ (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM david.hunter@chaming.harvard.edu FU NCI NIH HHS [U54-CA100971, P01-CA055075, P01-CA087969] NR 62 TC 60 Z9 63 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2006 VL 15 IS 12 BP 2408 EP 2417 DI 10.1158/1055-9965.EPI-06-0624 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 119AK UT WOS:000242984400015 PM 17164363 ER PT J AU Rajaraman, P Stewart, PA Samet, JM Schwartz, BS Linet, MS Zahm, SH Rothman, N Yeager, M Fine, HA Black, PM Loeffler, J Shapiro, WR Selker, RG Inskip, PD AF Rajaraman, Preetha Stewart, Patricia A. Samet, Jonathan M. Schwartz, Brian S. Linet, Martha S. Zahm, Shelia Hoar Rothman, Nathaniel Yeager, Meredith Fine, Howard A. Black, Peter M. Loeffler, Jay Shapiro, William R. Selker, Robert G. Inskip, Peter D. TI Lead, genetic susceptibility, and risk of adult brain tumors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID AMINOLEVULINIC-ACID DEHYDRATASE; SMELTER WORKERS; BLOOD LEAD; 5-AMINOLEVULINIC ACID; ALAD POLYMORPHISM; NERVOUS-SYSTEM; OCCUPATIONAL EXPOSURES; HUMAN ERYTHROCYTES; CANCER-MORTALITY; UNITED-STATES AB Background: Although few etiologic factors for brain tumors have been identified, limited data suggest that lead may increase the risk of brain tumors, particularly meningioma. The ALAD G177C polymorphism affects the toxicokinetics of lead and may confer genetic susceptibility to adverse effects of lead exposure. Methods: We examined occupational exposure to lead and risk of brain tumors in a multisite, hospital-based, case-control study of 489 patients with glioma, 197 with meningioma, and 799 non-cancer controls frequency matched on hospital, age, sex, race/ethnicity, and residential proximity to hospital. ALAD genotype was assessed by a Taqman assay for 355 glioma patients, 151 meningioma patients, and 505 controls. Exposure to lead was estimated using a rigorous questionnaire-based exposure assessment strategy incorporating lead measurement and other occupational data abstracted from published articles and reports. Results: Increased risk of meningioma with occupational lead exposure (estimated by odds ratios and 95% confidence intervals) was most apparent in individuals with the ALAD2 variant allele, for whom risk increased from 1.1 (0.3-4.5) to 5.6 (0.7-45.5) and 12.8 (1.4-120.8) for estimated cumulative lead exposures of 1 to 49 mu g/m(3)-y, 50 to 99 mu g/m(3)-y, and >= 100 mu g/m(3)-y, respectively, compared with unexposed individuals (two-sided P trend = 0.06). This relationship became stronger after excluding occupational lead exposures characterized by a low confidence level or occurring in the 10 years before meningioma diagnosis. Occupational lead exposure was not associated with glioma risk. Conclusions: Although our results indicate that lead may be implicated in meningioma risk in genetically susceptible individuals, these results need to be interpreted with caution given the small numbers of exposed cases with a variant genotype. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, NeuroOncol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. St Josephs Hosp, Barrow Neurol Inst, Phoenix, AZ USA. Western Penn Hosp, Pittsburgh, PA 15224 USA. RP Rajaraman, P (reprint author), NCI, Radiat Epidemiol Branch, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS Room 7085, Bethesda, MD 20892 USA. EM rajarama@mail.nih.gov RI Zahm, Shelia/B-5025-2015 NR 54 TC 38 Z9 40 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2006 VL 15 IS 12 BP 2514 EP 2520 DI 10.1158/1055-9965.EPI-06-0482 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 119AK UT WOS:000242984400032 PM 17164378 ER PT J AU Muthusamy, V Duraisamy, S Bradbury, CM Hobbs, C Curley, DP Nelson, B Bosenberg, M AF Muthusamy, Viswanathan Duraisamy, Sekhar Bradbury, C. Matthew Hobbs, Cara Curley, David P. Nelson, Betsy Bosenberg, Marcus TI Epigenetic silencing of novel tumor suppressors in malignant melanoma SO CANCER RESEARCH LA English DT Article ID DNA METHYLATION PATTERNS; HUMAN BREAST-CANCER; TYROSINE KINASE; ABERRANT METHYLATION; CUTANEOUS MELANOMA; GLUTAMINYL CYCLASE; PROSTATE-CANCER; CPG ISLANDS; GENE; SYK AB Malignant melanoma is a common and frequently lethal disease. Current therapeutic interventions have little effect on survival, emphasizing the need for a better understanding of the genetic, epigenetic, and phenotypic changes in melanoma formation and progression. We identified 17 genes that were not previously known to be silenced by methylation in melanoma using a microarray-based screen following treatment of melanoma cell lines with the DNA methylation inhibitor 5-Aza-2'-deoxycytidine. Eight of these genes have not been previously shown to undergo DNA methylation in any form of cancer. Three of the genes, QPCT, CYP1B1, and LXN, are densely methylated in > 95% of uncultured melanoma tumor samples. Reexpression of either of two of the silenced genes, HOXB13 and SYK, resulted in reduced colony formation in vitro and diminished tumor formation in vivo, indicating that these genes function as tumor suppressors in melanoma. C1 Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Bosenberg, M (reprint author), Univ Vermont, Coll Med, Dept Pathol, 323 Hlth Sci Res Facil,149 Beaumont Ave, Burlington, VT 05405 USA. EM marcus.bosenberg@uvm.edu FU NCI NIH HHS [R01 CA112054, K08CA89124, P30CA22435]; NCRR NIH HHS [P20 RR16462] NR 46 TC 98 Z9 102 U1 0 U2 11 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 DEC 1 PY 2006 VL 66 IS 23 BP 11187 EP 11193 DI 10.1158/0008-5472.CAN-06-1274 PG 7 WC Oncology SC Oncology GA 113RF UT WOS:000242614300017 PM 17145863 ER PT J AU Torres-Arzayus, MI Yuan, J DellaGatta, JL Lane, H Kung, AL Brown, M AF Torres-Arzayus, Maria I. Yuan, Jing DellaGatta, Jamie L. Lane, Heidi Kung, Andrew L. Brown, Myles TI Targeting the AIB1 oncogene through mammalian target of rapamycin inhibition in the mammary gland SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER; CELL-GROWTH; TRANSLATION INITIATION; HUMAN-DISEASE; MTOR; ESTROGEN; PATHWAY; TOR; ACTIVATION; TRANSFORMATION AB Amplified in breast cancer 1 (AIB1), an estrogen receptor (ER) coactivator, is frequently amplified or overexpressed in human breast cancer. We previously developed a transgenic mouse model in which AIB1 can act as an oncogene, giving rise to a premalignant hyperplastic mammary phenotype as well as to a high incidence of mammary tumors that are primarily ER+. In this model, the AIB1 transgene is responsible for continued activation of the insulin-like growl factor-1 receptor, suggesting a role for the activation of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway in the premalignant phenotype and tumor development. Here we show that treatment of AIB1 transgenic mice with the mTOR inhibitor RAD001 reverts the premalignant phenotype. Furthermore, treatment of cell lines derived from AIB1-dependent mammary tumors with RAD001 in culture leads to a G, cell cycle arrest. Lastly, tumor growth after injection of ER+ AIB1 tumor cell lines into wild-type animals is inhibited by RAD001 treatment. In this ER+ model, inhibition of tumor growth by RAD001 was significantly better than inhibition by the antiestrogen 4-hydroxytamoxifen alone, whereas a combination of both RAD001 and 4-hydroxytamoxifen was most effective. Based on these results, we propose that the combination of mTOR inhibition and ER-targeted endocrine therapy may improve the outcome of the subset of ER+ breast cancers overexpressing AIB1. These studies provide preclinical support for the clinical development of RAD001 and suggest that AIB1 may be a predictive factor of RAD001 response. C1 Dana Farber Canc Inst, Div Mol & Cell Oncol, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Novartis Pharma AG, Basel, Switzerland. RP Brown, M (reprint author), Dana Farber Canc Inst, Div Mol & Cell Oncol, Dept Med Oncol, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658; Kung, Andrew/0000-0002-9091-488X FU NCI NIH HHS [5 P01 CA801105] NR 29 TC 34 Z9 34 U1 0 U2 0 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 DEC 1 PY 2006 VL 66 IS 23 BP 11381 EP 11388 DI 10.1158/0008-5472.CAN-06-2316 PG 8 WC Oncology SC Oncology GA 113RF UT WOS:000242614300040 PM 17145884 ER PT J AU Kobayashi, S Shimamura, T Monti, S Steidl, U Hetherington, CJ Lowell, AM Golub, T Meyerson, M Tenen, DG Shapiro, GI Halmos, B AF Kobayashi, Susumu Shimamura, Takeshi Monti, Stefano Steidl, Ulrich Hetherington, Christopher J. Lowell, April M. Golub, Todd Meyerson, Matthew Tenen, Daniel G. Shapiro, Geoffrey I. Halmos, Balazs TI Transcriptional profiling identifies cyclin D1 as a critical downstream effector of mutant epidermal growth factor receptor signaling SO CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR; EGF RECEPTOR; ACQUIRED-RESISTANCE; GEFITINIB TREATMENT; DOMAIN MUTATIONS; GENE-MUTATIONS; SENSITIVITY; ACTIVATION; ERLOTINIB AB Activating mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain determine responsiveness to EGFR tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer (NSCLC). The modulation of transcriptional pathways by mutant EGFR signaling is not fully understood. Previously, we and others identified a single base pair change leading to a threonine to methionine (T790M) amino acid alteration in the ATP-binding pocket of the EGFR as a common mechanism of acquired resistance. The gefitinib resistant, T790M-mutant H1975 NSCLC cell line undergoes prominent growth arrest and apoptosis when treated with the irreversible EGFR inhibitor, CL-387,785. We did a transcriptional profiling study of mutant EGFR target genes that are differentially expressed in the "resistant" gefitinib-treated and the "sensitive" CL387,785-treated H1975 cells to identify the pivotal transcriptional changes in NSCLC with EGFR-activating mutations. We identified a small subset of early gene changes, including significant reduction of cyclin D1 as a result of EGFR inhibition by CL-387,785 but not by gefitinib. The reduction in cyclin D1 transcription was associated with subsequent suppression of E2F-responsive genes, consistent with proliferation arrest. Furthermore, cyclin D1 expression was higher in EGFR-mutant lung cancer cells compared with cells with wild-type EGFR. EGFR-mutant cells were routinely sensitive to the cyclin-dependent kinase inhibitor flavopiridol, confirming the functional relevance of the cyclin D axis. These studies suggest that cyclin D1 may contribute to the emergence of EGFR-driven tumorigenesis and can be an alternative target of therapy. C1 Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Tenen, DG (reprint author), Harvard Univ, Inst Med, Room 954,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM geoffrey_shapiro@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; OI Monti, Stefano/0000-0002-9376-0660; Tenen, Daniel/0000-0002-6423-3888 FU NCI NIH HHS [1R01 CA116010, P20 CA90578, PA20-CA090578-01A1] NR 52 TC 69 Z9 72 U1 1 U2 1 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 DEC 1 PY 2006 VL 66 IS 23 BP 11389 EP 11398 DI 10.1158/0008-5472.CAN-06-2318 PG 10 WC Oncology SC Oncology GA 113RF UT WOS:000242614300041 PM 17145885 ER PT J AU Maher, EA Brennan, C Wen, PY Durso, L Ligon, KL Richardson, A Khatry, D Feng, B Sinha, R Louis, DN Quackenbush, J Black, PM Chin, L DePinho, RA AF Maher, Elizabeth A. Brennan, Cameron Wen, Patrick Y. Durso, Laura Ligon, Keith L. Richardson, Aaron Khatry, Deepak Feng, Bin Sinha, Raktim Louis, David N. Quackenbush, John Black, Peter McL. Chin, Lynda DePinho, Ronald A. TI Marked genomic differences characterize primary and secondary glioblastoma subtypes and identify two distinct molecular and clinical secondary glioblastoma entities SO CANCER RESEARCH LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; SQUAMOUS-CELL CARCINOMA; HYBRIDIZATION ANALYSIS; BREAST-CANCER; HIGH-GRADE; GENE; EXPRESSION; IDENTIFICATION; SUBGROUPS; PROFILES AB Glioblastoma is classified into two subtypes on the basis of clinical history: "primary glioblastoma arising de novo without detectable antecedent disease and "secondary glioblastoma" evolving from a low-grade astrocytoma. Despite their distinctive clinical courses, they arrive at an indistinguishable clinical and pathologic end point highlighted by widespread invasion and resistance to therapy and, as such, are managed clinically as if they are one disease entity. Because the life history of a cancer cell is often reflected in the pattern of genomic alterations, we sought to determine whether primary and secondary glioblastomas evolve through similar or different molecular pathogenetic routes. Clinically annotated primary and secondary glioblastoma samples were subjected to high-resolution copy number analysis using oligonucleotide-based array comparative genomic hybridization. Unsupervised classification using genomic nonnegative matrix factorization methods identified three distinct genomic subclasses. Whereas one corresponded to clinically defined primary glioblastomas, the remaining two stratified secondary glioblastoma into two genetically distinct cohorts. Thus, this global genomic analysis showed wide-scale differences between primary and secondary glioblastomas that were previously unappreciated, and has shown for the first time that secondary glioblastoma is heterogeneous in its molecular pathogenesis. Consistent with these findings, analysis of regional recurrent copy number alterations revealed many more events unique to these subclasses than shared. The pathobiological significance of these shared and subtype-specific copy number alterations is reinforced by their frequent occurrence, resident genes with clear links to cancer, recurrence in diverse cancer types, and apparent association with clinical outcome. We conclude that glioblastoma is composed of at least three distinct molecular subtypes, including novel subgroups of secondary glioblastoma, which may benefit from different therapeutic strategies. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Appl Canc Sci, Belfer Inst Innovat Canc Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Cornell Univ, Mem Sloan Kettering Canc Ctr, Weill Med Coll, Neurosurg Serv, New York, NY USA. Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM ron_depinho@dfci.harvard.edu OI Khatry, Deepak/0000-0002-2388-9434; Brennan, Cameron/0000-0003-4064-8891 FU NCI NIH HHS [R01CA99041, CA57683, 5P01CA95616, P01 CA095616, R01 CA099041] NR 48 TC 121 Z9 125 U1 0 U2 3 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 DEC 1 PY 2006 VL 66 IS 23 BP 11502 EP 11513 DI 10.1158/0008-5472.CAN-06-2072 PG 12 WC Oncology SC Oncology GA 113RF UT WOS:000242614300055 PM 17114236 ER PT J AU Stay, RM vanSonnenberg, E Goodacre, BW Ozkan, OS Wittich, GR AF Stay, Rourke M. vanSonnenberg, Eric Goodacre, Brian W. Ozkan, Orhan S. Wittich, Gerhard R. TI Removal of a trapped endoscopic catheter from the gallbladder via percutaneous transhepatic cholecystostomy: Technical innovation SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE biliary; catheters; cholecystostomy; endoscopy; gallbladder; interventional radiology; percutaneous AB Background: Percutaneous cholecystostomy is used for a variety of clinical problems. Methods: Percutaneous cholecystostomy was utilized in a novel setting to resolve a problematic endoscopic situation. Observations: Percutaneous cholecystostomy permitted successful removal of a broken and trapped endoscopic biliary catheter, in addition to helping treat cholecystitis. Conclusion: Another valuable use of percutaneous cholecystostomy is demonstrated, as well as emphasizing the importance of the interplay between endoscopists and interventional radiologists. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Radiol, Boston, MA 02115 USA. Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. Victoria Gen Hosp, Dept Radiol, Victoria, BC V8Z 6R5, Canada. Ankara Univ, Dept Radiol, TR-06100 Ankara, Turkey. Bay Shore Med Ctr, Dept Radiol, Pasadena, TX 77504 USA. RP vanSonnenberg, E (reprint author), Dana Farber Canc Inst, Dept Radiol, 44 Binney St, Boston, MA 02115 USA. EM evansonnenberg@yahoo.com NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD DEC PY 2006 VL 29 IS 6 BP 1097 EP 1099 DI 10.1007/s00270-003-0101-2 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 099OY UT WOS:000241606000027 PM 16786201 ER PT J AU Arany, Z Novikov, M Chin, S Ma, YH Rosenzweig, A Spiegelman, BM AF Arany, Zoltan Novikov, Mikhail Chin, Sherry Ma, Yanhong Rosenzweig, Anthony Spiegelman, Bruce M. TI Transverse aortic constriction leads to accelerated heart failure in mice lacking PGC-1 alpha SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-3206 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD DEC PY 2006 VL 20 IS 6 BP 398 EP 399 PG 2 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 124JT UT WOS:000243364800008 ER PT J AU Kalva, SP Wicky, S AF Kalva, Sanjeeva P. Wicky, Stephan TI Mediastinal bronchial artery aneurysms: Endovascular therapy in two patients SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE EMBO-embolization; IMAG-imaging (CT/MR); bronchial artery aneurysm AB We report two patients with cystic fibrosis and mediastinal bronchial artery aneurysms treated by means of endovascular coil embolization. In one case, the presence of a long segment of bronchial artery proximal to the aneurysm allowed coil embolization with regular steel coils. In the second case, the aneurysm was near the origin of the bronchial artery from the aorta. We used detachable coils to occlude this aneurysm for more precise embolization. (C) 2006 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kalva, SP (reprint author), GRB-290,MGH,55 Fruit St, Boston, MA 02114 USA. EM skalva@partners.org NR 13 TC 5 Z9 7 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD DEC PY 2006 VL 68 IS 6 BP 858 EP 861 DI 10.1002/ccd.20902 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 112FX UT WOS:000242512200007 PM 17086528 ER PT J AU Maree, A Palacios, IF Lago, RM AF Maree, Andrew Palacios, Igor F. Lago, Rodrigo M. TI Transcatheter closure of atrial septal defects in adults using two devices: An angiographic overview SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE atrial septal defect, ASD; percutaneous closure; transcatheter closure; multiple closure devices AB Atrial septal defects are a common congenital cardiac abnormality in adults. Individuals with atrial septal defects carry the risk to develop cardiac problems such as right ventricle volume overload, pulmonary hypertension, atrial fibrillation, and more rarely paradoxical embolic events. Surgery was the standard treatment for symptomatic patients with atrial septal defects for decades. More recently, percutaneous transcatheter closure of atrial septal defects in adults using a closure device has become an alternative to surgery in selected patients. (C) 2006 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Div Cardiol, Intervent Cardiol Dept, Boston, MA 02114 USA. RP Lago, RM (reprint author), 33 Auburn St 08, Framingham, MA 01701 USA. EM rmarinasdolago@partners.org NR 7 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD DEC PY 2006 VL 68 IS 6 BP 946 EP 947 DI 10.1002/ccd.20891 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 112FX UT WOS:000242512200022 PM 17086521 ER PT J AU Wildenberg, GA Dohn, MR Carnahan, RH Davis, MA Lobdell, NA Settleman, J Reynolds, AB AF Wildenberg, Gregg A. Dohn, Michael R. Carnahan, Robert H. Davis, Michael A. Lobdell, Nichole A. Settleman, Jeffrey Reynolds, Albert B. TI p120-catenin and p190RhoGAP regulate cell-cell adhesion by coordinating antagonism between Rac and Rho SO CELL LA English DT Article ID P120 CATENIN; FAMILY GTPASES; ACTIN CYTOSKELETON; INHIBITION; MODULATION; EXPRESSION; P120RASGAP; PROTEIN; ABL AB Integration of receptor tyrosine kinase, integrin, and cadherin activities is crucial for normal cell growth, motility, and adhesion. Here, we describe roles for p120-catenin (p120) and p190RhoGAP that coordinate crosstalk between these systems and regulate cadherin function. Surprisingly, PDGFR-induced actin remodeling in NIH3T3 cells is blocked in the absence of p120, and the cells are partially transformed via constitutive activation of Rho. We have traced the mechanism to unexpected codependent roles for p120 and p190RhoGAP in regulating Rac-dependent antagonism of Rho. Receptor-induced Rac activity causes translocation of p190RhoGAP to adherens junctions (AJs), where it couples to the cadherin complex via interaction with p120. AJ formation is dependent on this p120-p190RhoGAP interaction and fails altogether if either of these proteins are compromised. We propose that Rac activation links diverse signaling systems to AJ assembly by controlling transient p190RhoGAP interactions with p120 and localized inhibition of Rho. C1 Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37232 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Reynolds, AB (reprint author), Vanderbilt Univ, Dept Canc Biol, 438 Preston Bldg, Nashville, TN 37232 USA. EM al.reynolds@vanderbilt.edu RI Carnahan, Robert/N-7429-2013 OI Carnahan, Robert/0000-0001-5230-1532 FU NCI NIH HHS [CA04-013, R01-CA111947, R01-CA55724, T32 CA009592] NR 36 TC 264 Z9 266 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD DEC 1 PY 2006 VL 127 IS 5 BP 1027 EP 1039 DI 10.1016/j.cell.2006.09.046 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 113RA UT WOS:000242613800018 PM 17129786 ER PT J AU Jones, R Capen, D Jacobson, M Munn, L AF Jones, Rosemary Capen, Diane Jacobson, Margaretha Munn, Lance TI PDGF and microvessel wall remodeling in adult rat lung: imaging PDGF-AA and PDGF-R alpha molecules in progenitor smooth muscle cells developing in experimental pulmonary hypertension SO CELL AND TISSUE RESEARCH LA English DT Article DE pulmonary hypertension; lung; smooth muscle; microvessels; PDGF-AA; PDGF-R alpha; rat (Sprague Dawley, male) ID GROWTH-FACTOR RECEPTOR; DEFICIENT MICE; PROLIFERATION; ALVEOGENESIS; FIBROBLASTS; HYPERPLASIA; ISOFORMS; SIGNAL; GENES; BETA AB Smooth muscle cells are mostly absent from the walls of microvessels in the adult lung but develop in large numbers as part of the pathology of human and experimental pulmonary hypertensions (PHs). We have previously shown, In an in vivo model of experimental PH, that mesenchymal (interstitial) fibroblasts and intermediate cells are the progenitors of these cells. Although smooth muscle cell development is a defining pathophysiological feature of human PH, little is known about the angiogenic signaling molecules responsible. Here, we report data for platelet-derived growth factor AA (PDGF-AA) and PDGFR alpha, two components of an important signaling pathway for fibroblast and myofibroblast proliferation and migration. Using antibodies linked to protein-A gold and high-resolution imaging techniques, we analyzed the expression of these molecules as smooth muscle cells developed from progenitor cell populations and in endothelial cells of the same microvessels. PDGF-AA was highly expressed by each cell type in control lung. As PH developed, the number of antigenic sites for PDGF-AA decreased with time. PDGF-R alpha expression levels in the control lung were low, relative to the ligand, and fell in PH. These data show, for the first time, a marked phenotypic shift in expression levels of the PDGF-AA isoform and its receptor tyrosine kinase in the progenitor smooth muscle cells developing in the microvessels of the adult hypertensive lung. C1 Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jones, R (reprint author), Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, MGH E,Bldg 149,13th St, Charlestown, MA 02129 USA. EM jones@etherdome.mgh.harvard.edu FU NHLBI NIH HHS [R01HL070866, R01HL064240] NR 34 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD DEC PY 2006 VL 326 IS 3 BP 759 EP 769 DI 10.1007/s00441-006-0177-5 PG 11 WC Cell Biology SC Cell Biology GA 120GT UT WOS:000243073200009 PM 16794827 ER PT J AU Vianna, CR Huntgeburth, M Coppari, R Choi, CS Lin, JD Krauss, S Barbatelli, G Tzameli, I Kim, YB Cinti, S Shulman, GI Spiegelman, BM Lowell, BB AF Vianna, Claudia R. Huntgeburth, Michael Coppari, Roberto Choi, Cheol Soo Lin, Jiandie Krauss, Stefan Barbatelli, Giorgio Tzameli, Iphigenia Kim, Young-Bum Cinti, Saverio Shulman, Gerald I. Spiegelman, Bruce M. Lowell, Bradford B. TI Hypomorphic mutation of PGC-1 beta causes mitochondrial dysfunction and liver insulin resistance SO CELL METABOLISM LA English DT Article ID TRANSCRIPTIONAL COACTIVATOR; DIABETIC PARENTS; GENE-EXPRESSION; RECEPTOR-ALPHA; PIMA-INDIANS; MUSCLE-CELLS; ERR-ALPHA; GLUCOSE; PGC-1-ALPHA; BIOGENESIS AB PGC-1 beta is a transcriptional coactivator that potently stimulates mitochondrial biogenesis and respiration of cells. Here, we have generated mice lacking exons 3 to 4 of the Pgc-1 beta gene (Pgc-1 beta(E3,4-/E3,4-) mice). These mice express a mutant protein that has reduced coactivation activity on a subset of transcription factors, including ERR alpha, a major target of PGC-1 beta in the induction of mitochondrial gene expression. The mutant mice have reduced expression of OXPHOS genes and mitochondrial dysfunction in liver and skeletal muscle as well as elevated liver triglycerides. Euglycemic-hyperinsulinemic clamp and insulin signaling studies show that PGC-1 beta mutant mice have normal skeletal muscle response to insulin but have hepatic insulin resistance. These results demonstrate that PGC-1 beta is required for normal expression of OXPHOS genes and mitochondrial function in liver and skeletal muscle. Importantly, these abnormalities do not cause insulin resistance in skeletal muscle but cause substantially reduced insulin action in the liver. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Univ Cologne, Clin Internal Med 3, D-50937 Cologne, Germany. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA. Univ Marche, Fac Med, Inst Normal Human Morphol, I-60020 Ancona, Italy. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu; blowell@bidmc.harvard.edu RI vianna, claudia /I-4991-2012; Coppari, Roberto/B-4799-2014 FU NIDDK NIH HHS [DK49569, DK61562, R01 DK040936, R01 DK049569, R01 DK061562, U24 DK059635] NR 43 TC 122 Z9 130 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD DEC PY 2006 VL 4 IS 6 BP 453 EP 464 DI 10.1016/j.cmet.2006.11.003 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 115RM UT WOS:000242751500009 PM 17141629 ER PT J AU Wright, CI Williams, D Feczko, E Barrett, LF Dickerson, BC Schwartz, CE Wedig, MM AF Wright, Christopher I. Williams, Danielle Feczko, Eric Barrett, Lisa Feldman Dickerson, Bradford C. Schwartz, Carl E. Wedig, Michelle M. TI Neuroanatomical correlates of extraversion and neuroticism SO CEREBRAL CORTEX LA English DT Review DE amygdala; emotion; human; magnetic resonance imaging; personality; prefrontal cortex ID OBSESSIVE-COMPULSIVE DISORDER; BORDERLINE PERSONALITY-DISORDER; PAVLOVIAN-INSTRUMENTAL TRANSFER; HUMAN CEREBRAL-CORTEX; 5-FACTOR MODEL; PREFRONTAL CORTEX; ORBITOFRONTAL CORTEX; DOUBLE DISSOCIATION; INDIVIDUAL-DIFFERENCES; BEHAVIORAL-INHIBITION AB Introversion/extraversion and neuroticism are 2 important and frequently studied dimensions of human personality. These dimensions describe individual differences in emotional responding across a range of situations and may contribute to a predisposition for psychiatric disorders. Recent neuroimaging research has begun to provide evidence that neuroticism and introversion/extraversion have specific functional and structural neural correlates. Previous studies in healthy adults have reported an association between neuroticism, introversion/extraversion, and the activity of the prefrontal cortex and amygdala. Studies of individuals with psychopathological states have also indicated that anatomic variations in these brain areas may relate to extraversion and neuroticism. The purpose of the present study was to examine selected structural correlates of neuroticism and extraversion in healthy subjects (n = 28) using neuroanatomic measures of the cerebral cortex and amygdala. We observed that the thickness of specific prefrontal cortex regions correlates with measures of extraversion and neuroticism. In contrast, no such correlations were observed for the volume of the amygdala. The results suggest that specific aspects of regional prefrontal anatomy are associated with specific personality traits. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Neuroimaging Res Program, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gerontol Res Unit, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Neurol, Div Cognit & Behav Neurol, Boston, MA 02115 USA. Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dev Psychopathol Unit, Charlestown, MA 02129 USA. RP Wright, CI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Neuroimaging Res Program, 13th St,bldg 149,CNY-2628, Charlestown, MA 02129 USA. EM ciwright@partners.org FU NIMH NIH HHS [K23MH64806] NR 102 TC 109 Z9 113 U1 5 U2 27 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD DEC PY 2006 VL 16 IS 12 BP 1809 EP 1819 DI 10.1093/cercor/bhj118 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 103OO UT WOS:000241896800015 PM 16421327 ER PT J AU Frutos-Vivar, F Ferguson, ND Estaban, A Epstein, SK Arabi, Y Apezteguia, C Gonzalez, M Hill, NS Nava, S D'Empaire, G Anzueto, A AF Frutos-Vivar, Fernando Ferguson, Niall D. Estaban, Andres Epstein, Scott K. Arabi, Yaseen Apezteguia, Carlos Gonzalez, Marco Hill, Nichola S. Nava, Stefano D'Empaire, Gabriel Anzueto, Antonio TI Risk factors for extubation failure in patients following a successful spontaneous breathing trial SO CHEST LA English DT Article DE artificial respiration; extubation; predictive index; reintubation; ventilator weaning ID VENTILATOR-ASSOCIATED PNEUMONIA; MECHANICAL VENTILATION; OUTCOMES; SUPPORT; DURATION; COUGH AB Background: To assess the factors associated with reintubation in patients who had successfully passed a spontaneous breathing trial. Methods: We used logistic regression and recursive partitioning analyses of prospectively collected clinical data from adults admitted to ICUs of 37 hospitals in eight countries, who had undergone invasive mechanical ventilation for > 48 h and were deemed ready for extubation. Results: Extubation failure occurred in 121 of the 900 patients (13.4%). The logistic regression analysis identified the following associations with reintubation: rapid shallow breathing index (RSBI) [odds ratio (OR), 1.009 per unit; 95% confidence interval (CI), 1.003 to 1.015]; positive fluid balance (OR, 1.70; 95% CI, 1.15 to 2.53); and pneumonia as the reason for initiating mechanical ventilation (OR, 1.77; 95% CI, 1.10 to 2.84). The recursive partitioning analysis allowed the separation of patients into different risk groups for extubation failure: (1) RSBI of > 57 breaths/L/min and positive fluid balance (OR, 3.0; 95% CI, 1.8 to 4.8); (2) RSBI of < 57 breaths/L/min and pneumonia as reason for mechanical ventilation (OR, 2.0; 95% CI, 1.1 to 3.6); (3) RSBI of > 57 breaths/Umin and negative fluid balance (OR, 1.4; 95% CI, 0.8 to 2.5); and (4) RSBI of < 57 breaths/L/min (OR, 1 [reference value]). Conclusions: Among routinely measured clinical variables, RSBI, positive fluid balance 24 h prior to extubation, and pneumonia at the initiation of ventilation were the best predictors of extubation failure. However, the combined predictive ability of these variables was weak. C1 Univ Madrid, Hosp Getafe, Intens Care Unit, Madrid 28905, Spain. Univ Toronto, Univ Hlth Network, Div Respirol, Dept Med, Toronto, ON, Canada. Univ Toronto, Univ Hlth Network, Interdepartmental Div Crit Care Med, Toronto, ON, Canada. Tufts Univ, Sch Med, Caritas St Elizabeths Med Ctr, Dept Med, Boston, MA 02111 USA. King Abdulaziz Med City, Riyadh, Saudi Arabia. Hosp Prof Posadas, Buenos Aires, DF, Argentina. Hosp Gen Medellin, Medellin, Colombia. Tufts Univ, New England Med Ctr, Dept Med, Div Pulm & Crit Care,Sch Med, Boston, MA 02111 USA. Hosp Clin, Caracas, Venezuela. Fdn S Maugeri, Ist Sci Pavia, Resp Intens Care Unit, Pavia, Italy. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Frutos-Vivar, F (reprint author), Univ Madrid, Hosp Getafe, Intens Care Unit, Carretera Toledo Km 12,500, Madrid 28905, Spain. EM ffrutos@ucigetafe.com OI Frutos-Vivar, Fernando/0000-0002-4648-9636; Ferguson, Niall/0000-0002-6213-5264 NR 26 TC 112 Z9 120 U1 2 U2 5 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2006 VL 130 IS 6 BP 1664 EP 1671 DI 10.1378/chest.130.6.1664 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 117MB UT WOS:000242876200010 PM 17166980 ER PT J AU Mularski, RA Asch, SM Shrank, WH Kerr, EA Setodji, CM Adams, JL Keesey, J McGlynn, EA AF Mularski, Richard A. Asch, Steven M. Shrank, William H. Kerr, Eve A. Setodji, Claude M. Adams, John L. Keesey, Joan McGlynn, Elizabeth A. TI The quality of obstructive lung disease care for adults in the United States as measured by adherence to recommended processes SO CHEST LA English DT Article ID IMPROVING PRIMARY-CARE; OF-CARE; PULMONARY-DISEASE; HEALTH-CARE; STANDARDIZED PATIENTS; CHRONIC ILLNESS; ASTHMA; MANAGEMENT; COPD; PHYSICIANS AB Background: The extent to which patients with obstructive lung disease receive recommended processes of care is largely unknown. We assessed the quality of care delivered to a national sample of the US population. Methods: We extracted medical records for 2 prior years from consenting participants in a random telephone survey in 12 communities and measured the quality of care provided with 45 explicit, process-based quality indicators for asthma and COPD developed using the modified Delphi expert panel methodology. Multivariate logistic regression evaluated effects of patient demographics, insurance, and other characteristics on the quality of health care. Results: We identified 2,394 care events among 260 asthma participants and 1,664 events among 169 COPD participants. Overall, participants received 55.2% of recommended care for obstructive lung disease. Asthma patients received 53.5% of recommended care; routine management was better (66.9%) than exacerbation care (47.8%). COPD patients received 58.0% of recommended care but received better exacerbation care (60.4%) than routine care (46.1%). Variation was seen in mode of care with considerable deficits in documenting recommended aspects of medical history (41.4%) and use of diagnostic studies (40.1%). Modeling demonstrated modest variation between racial groups, geographic areas, insurance types, and other characteristics. Conclusions: Americans with obstructive lung disease received only 55% of recommended care. The deficits and variability in the quality of care for obstructive lung disease present ample opportunity for quality improvement. Future endeavors should assess reasons for low adherence to recommended processes of care and assess barriers in delivery of care. C1 Kaiser Permanente NW, Ctr Hlth Res, Portland, OR 97227 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RAND Hlth, Los Angeles, CA USA. Ann Arbor Healthcare Syst, Ctr Practice Management & Outcomes Res, Ann Arbor, MI USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. RP Mularski, RA (reprint author), Kaiser Permanente NW, Ctr Hlth Res, 3800 N Interstate,WIN 1060, Portland, OR 97227 USA. EM Richard.Mularski@kpchr.org NR 50 TC 68 Z9 68 U1 0 U2 4 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2006 VL 130 IS 6 BP 1844 EP 1850 DI 10.1378/chest.130.6.1844 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 117MB UT WOS:000242876200037 PM 17167007 ER PT J AU Frank, JA Parsons, PE Matthay, MA AF Frank, James A. Parsons, Polly E. Matthay, Michael A. TI Pathogenetic significance of biological markers of ventilator-associated lung injury in experimental and clinical studies SO CHEST LA English DT Review DE ARDS; critical care; ventilation; ventilator-induced lung injury ID RESPIRATORY-DISTRESS-SYNDROME; TIDAL VOLUME VENTILATION; NECROSIS-FACTOR-ALPHA; PULMONARY-EDEMA FLUID; VON-WILLEBRAND-FACTOR; SURFACTANT PROTEIN-A; MECHANICAL VENTILATION; BRONCHOALVEOLAR LAVAGE; INFLAMMATORY CYTOKINES; ENDOTHELIAL INJURY AB For patients with acute lung injury, positive pressure mechanical ventilation is life saving. However, considerable experimental and clinical data have demonstrated that how clinicians set the tidal volume, positive end-expiratory pressure, and plateau airway pressure influences lung injury severity and patient outcomes including mortality. In order to better identify ventilator-associated lung injury (VALI), clinical investigators have sought to measure blood-borne and airspace biological markers of VALI. At the same time, several laboratory-based studies have focused on biological markers of inflammation and organ injury in experimental models in order to clarify the mechanisms of ventilator-induced lung injury (VILI) and VALI. This review summarizes data on biological markers of VALI and VILI from both clinical and experimental studies with an emphasis on markers identified in patients and in the experimental setting. This analysis suggests that measurement of some of these biological markers may be of value in diagnosing VALI and in understanding its pathogenesis. C1 Univ Calif San Francisco, Div Pulm & Crit Care Med, Med Intens Care Unit, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. Univ Vermont, Dept Med, Div Pulm & Crit Care, Burlington, VT USA. RP Frank, JA (reprint author), Univ Calif San Francisco, Div Pulm & Crit Care Med, Med Intens Care Unit, San Francisco VA Med Ctr, 4150 Clement St,Mail Stop 111D, San Francisco, CA 94121 USA. EM james.frank@ucsf.edu FU NHLBI NIH HHS [R01 HL051856, K08 HL069900-05, HL 51856, K08 HL069900, R37 HL051856, R37 HL051856-14, R56 HL088440]; PHS HHS [JL 69900] NR 64 TC 57 Z9 61 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2006 VL 130 IS 6 BP 1906 EP 1914 DI 10.1378/chest.130.6.1906 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 117MB UT WOS:000242876200045 PM 17167015 ER PT J AU Wecht, JM Weir, JP Bauman, WA AF Wecht, Jill M. Weir, Joseph P. Bauman, William A. TI Blunted heart rate response to vagal withdrawal in persons with tetraplegia SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE spinal cord injury; head-up tilt; heart rate variability; autonomic nervous system ID BLOOD-PRESSURE VARIABILITY; UP TILT; AUTONOMIC RESPONSES; SPECTRAL-ANALYSIS; INDIVIDUALS; INHIBITION; MECHANISMS; FAILURE; HUMANS; AGE AB Cardiovascular autonomic mechanisms control heart rate (HR) and determination of heart rate variability (HRV) permits the quantitative assessment of relative shifts in autonomic cardiac control during head-up tilt (HUT). The study herein used HRV techniques to determine the vagal and sympathetic contribution to the change in HR during HUT in persons with tetraplegia (T; n = 7) paraplegia (P; n = 7) and a non-spinal cord injured (non-SCI; n = 8) control group. Heart rate (HR) was continuously monitored and cardiovascular autonomic responses were assessed for 5-minutes at supine and at 45 degrees HUT. Change associated with tilt from supine to 45 degrees HUT was calculated for HR (deltaHR), high & low frequency HRV (HF & LF) and the LF/HF ratio. HR and LF power were lower in the T compared to the P and non-SCI groups at 45 degrees HUT, whereas there were no group differences for HF at 45 degrees HUT. The LF/HF ratio was lower in the T compared to the non-SCI group at 45 degrees HUT. The relationship between delta HR and delta HF response differed between groups (significant group x delta HF interaction) such that the slope of this relationship was reduced in the T (-1.026: 95% Cl: -2.623 to 0.571) compared with the non-SCI (-6.985: 95% Cl: -11.25 to 2.72) and P (-5.218: 95% Cl: -8.197 to -2.239) groups. There was no significant interaction effect for the relationships between deltaHR and deltaLF or deltaLF/HF. In summary, although the magnitude of vagal withdrawal was comparable among the groups, the increase in HR was attenuated in the group with tetraplegia, which may reflect reduced sympathetic cardiac modulation or altered SA node responsiveness to vagal withdrawal. C1 James J Peters Med Ctr, Bronx, NY 10468 USA. Vet Affairs Med Ctr, SCI, Bronx, NY USA. Med Serv, Bronx, NY USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Rehabiol Med Serv, New York, NY USA. Des Moines Univ, Osteopath Med Ctr, Des Moines, IA USA. RP Wecht, JM (reprint author), James J Peters Med Ctr, Rm 1E-06,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM jwecht@hotmail.com NR 20 TC 18 Z9 19 U1 0 U2 2 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD DEC PY 2006 VL 16 IS 6 BP 378 EP 383 DI 10.1007/a10286-006-0367-y PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 125GN UT WOS:000243430500005 PM 17066256 ER PT J AU Yang, YS Koontz, AM Triolo, RJ Mercer, JL Boninger, ML AF Yang, Yu-Sheng Koontz, Alicia M. Triolo, Ronald J. Mercer, Jennifer L. Boninger, Michael L. TI Surface electromyography activity of trunk muscles during wheelchair propulsion SO CLINICAL BIOMECHANICS LA English DT Article DE electromyography; muscle recruitment; spinal cord injury; manual wheelchair; wheelchair propulsion; trunk stability; trunk control ID SPINAL-CORD-INJURY; ISOMETRIC AXIAL ROTATION; SHOULDER MUSCLES; BIOMECHANICS; POSITION; LEVEL; USERS; PAIN; ILIOCOSTALIS; STIMULATION AB Background. Trunk instability due to paralysis can have adverse effects on posture and function in a wheelchair. The purpose of this study was to record trunk muscle recruitment patterns using surface electromyography from unimpaired individuals during wheelchair propulsion under various propulsion speed conditions to be able to design trunk muscle stimulation patterns for actual wheelchair users with spinal cord injury. Methods. Fourteen unimpaired subjects propelled a test wheelchair on a dynamometer system at two steady state speeds of 0.9 m/s and 1.8 m/s and acceleration from rest to their maximum speed. Lower back/abdominal surface electromyography and upper body movements were recorded for each trial. Based on the hand movement during propulsion, the propulsive cycle was further divided into five stages to describe the activation patterns. Findings. Both abdominal and back muscle groups revealed significantly higher activation at early push and pre-push stages when compared to the other three stages of the propulsion phase. With increasing propulsive speed, trunk muscles showed increased activation (P < 0.0001). Back muscle activity was significantly higher than abdominal muscle activity across the three speed conditions (P < 0.0005), with lower back muscles predominating. Interpretation. Abdominal and back muscle groups cocontracted at late recovery phase and early push phase to provide sufficient trunk stability to meet the demands of propulsion. This study provides an indication of the amount and duration of stimulation needed for a future application of electrical stimulation of the trunk musculature for persons with spinal cord injury. (c) 2006 Elsevier Ltd. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R1H, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15261 USA. Louis Stokes Cleveland VA Med Ctr, Cleveland FES Ctr, Cleveland, OH 44106 USA. Kaohsiung Med Univ, Fac Occupat Therapy, Coll Hlth Sci, Dept Occupat Therapy, Kaohsiung, Taiwan. RP Koontz, AM (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R1H, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM akoontz@pitt.edu RI Yang, Yu-Sheng/D-4525-2009; OI Yang, Yu-Sheng/0000-0002-2767-9354; Boninger, Michael/0000-0001-6966-919X NR 42 TC 18 Z9 19 U1 2 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD DEC PY 2006 VL 21 IS 10 BP 1032 EP 1041 DI 10.1016/j.clinbiomech.2006.07.006 PG 10 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA 108MN UT WOS:000242244000005 PM 16979271 ER PT J AU Rusby, JE Smith, BL Dominguez, FJ Golshan, M AF Rusby, Jennifer E. Smith, Barbara L. Dominguez, Francisco J. Golshan, Mehra TI Sentinel lymph node biopsy in men with breast cancer: A report of 31 consecutive procedures and review of the literature SO CLINICAL BREAST CANCER LA English DT Review DE axillary lymph node; male breast carcinoma; sentinel lymphadenectomy ID ROUTINE AXILLARY DISSECTION; CARCINOMA; ACCURACY; LYMPHOSCINTIGRAPHY; LYMPHADENECTOMY; INJECTION; SURVIVAL; SUCCESS AB Purpose We present our experience with sentinel lymph node (SLN) biopsy in men with breast cancer and review the literature published to date. Consecutive men with breast cancer undergoing SLN biopsy were identified in our prospectively maintained database. A PubMed search for "male breast cancer" and "sentinel node biopsy" was performed. Patients and Methods: Thirty patients underwent 31 SLN biopsy procedures between 1996 and 2006. Twenty-five patients presented with a palpable mass, and 13 underwent surgical biopsy for diagnosis. The sentinel lymph node was successfully identified in 90%; 61% of SLN biopsies were positive and, in 65% of this group, the sentinel node was the only positive node. Results: Combined data from the literature from 110 procedures resulted in an identification rate of 96%, positive sentinel nodes in 45% and the sentinel node as the only positive node in 56%. Only 13 patients underwent completion axillary node. dissection after a negative SLN biopsy; none were false negatives. This series extends previous knowledge about SLN biopsy in men with respect to diagnostic biopsy, type of mapping agent, lymphoscintigraphy, and location of injection site. The identification rate mirrors that of large randomized trials of women with breast cancer. Conclusion: The high rate of lymph node-positive disease, even in this series of patients with clinically node-negative disease, reflects the later presentation of breast cancer in men. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Golshan, M (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org NR 36 TC 11 Z9 12 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD DEC PY 2006 VL 7 IS 5 BP 406 EP 410 DI 10.3816/CBC.2006.n.058 PG 5 WC Oncology SC Oncology GA 123WP UT WOS:000243327200007 PM 17239266 ER PT J AU Rodig, SJ Abramson, JS Pinkus, GS Treon, SP Dorfman, DM Dong, HY Shipp, MA Kutok, JL AF Rodig, Scott J. Abramson, Jeremy S. Pinkus, Geraldine S. Treon, Steven P. Dorfman, David M. Dong, Henry Y. Shipp, Margaret A. Kutok, Jeffery L. TI Heterogeneous CD52 expression among hematologic neoplasms: Implications for the use of alemtuzumab (CAMPATH-1H) SO CLINICAL CANCER RESEARCH LA English DT Article ID ANTI-CD52 MONOCLONAL-ANTIBODY; NON-HODGKINS-LYMPHOMAS; PHASE-II MULTICENTER; CELL PROLYMPHOCYTIC LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; MULTIPLE-MYELOMA; APLASTIC-ANEMIA; CDW52 ANTIGEN; THERAPY; TRANSPLANTATION AB Purpose: CD52 is a GPI-linked glycoprotein expressed by B cells, T cells, monocytes, and macrophages. The humanized monoclonal antibody alemtuzumab (CAMPATH-1H) is specific for CD52 and is Food and Drug Administration - approved for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL). The utility of CAMPATH in the treatment of other hematologic neoplasms has been explored; however, a comprehensive survey of CD52 expression among a broad spectrum of WHO-defined tumor types has not been completed. Experimental Design: We evaluated 294 hematologic neoplasms for the presence of CD52 using standard immunohistochemical techniques on paraffin-embedded biopsy specimens fixed with formalin, B-Plus, Zenker's acetic acid, or B5-formalin. Results: The vast majority of low-grade B cell lymphoproliferative disorders (CLL/small lymphocytic leukemia, follicular lymphoma, lymphoplasmacytic lymphoma, hairy cell leukemia, and mucosa-associated lymphoid tissue lymphomas) express CD52. In addition, we found that the majority of precursor B cell acute lymphoblastic leukemia/lymphomas express this antigen. In contrast, there is surprising heterogeneity in CD52 expression among more aggressive B cell lymphomas, with 25% of cases of diffuse large B cell lymphoma and Burkitt lymphoma demonstrating no detectable CD52. In addition, the majority of neoplasms of the T cell lineage are negative for the antigen, including most cases of precursor T cell acute lymphoblastic leukemia/ lymphoma, anaplastic large cell lymphoma, and peripheral T cell lymphoma, not otherwise specified. Finally, the vast majority of cases of acute myeloid leukemia, Hodgkin lymphoma, and multiple myeloma are negative for CD52 expression. Conclusion: In contrast with CLL, the variable expression of CD52 among other hematologic malignancies suggests that target validation on a case-by-case basis will likely be necessary to guide the rational analysis of CAMPATH therapy. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Genzyme Genet, New York, NY USA. RP Kutok, JL (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM Jkutok@partners.org NR 25 TC 85 Z9 87 U1 1 U2 3 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 DEC 1 PY 2006 VL 12 IS 23 BP 7174 EP 7179 DI 10.1158/1078-0432.CCR-06-1275 PG 6 WC Oncology SC Oncology GA 114UL UT WOS:000242691000043 PM 17145843 ER PT J AU Zhou, W Heist, RS Liu, G Asomaning, K Miller, DP Neuberg, DS Wain, JC Lynch, TJ Christiani, DC AF Zhou, Wei Heist, Rebecca S. Liu, Geoffrey Asomaning, Kofi Miller, David P. Neuberg, Donna S. Wain, John C. Lynch, Thomas J. Christiani, David C. TI Second hand smoke exposure and survival in early-stage non-small-cell lung cancer patients SO CLINICAL CANCER RESEARCH LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; PASSIVE SMOKING; OCCUPATIONAL EXPOSURE; NEVER SMOKERS; RISK; MULTICENTER; MORTALITY; WOMEN; P53; CARCINOGENS AB Purpose: Second hand smoke (SHS) exposure is associated with higher risk of lung cancer. However, the role of SHS in lung cancer survival is not clear. Experimental Design: We examined the association between self-reported SHS exposure before diagnosis and overall survival and recurrence-free survival in 393 early-stage non-small-cell lung cancer patients. SHS exposure was analyzed by both duration and location of exposure using log-rank test and Cox proportional hazard models, adjusting for covariates including pack-years of smoking. Results: The median follow-up time was 66 months (range, 0.2-140 months). There were 135 recurrences and 213 deaths. The 5-year overall survival rates were 71% [95% confidence interval (95% CI), 62-81%], 61% (51-72%), 49% (38-60%), and 47% (37-58%), respectively, for patients with the lowest to highest quartile of SHS exposure durations (P < 0.001, log-rank test), with the adjusted hazard ratio (AHR) of 1.57 (95% CI, 1.02-2.41) for the highest versus lowest quartile of SHS exposure durations (P-trend = 0.04). For different SHS exposure locations, a stronger association was found for SHS exposure at work (AHR of the highest versus lowest quartile, 1.71; 95% CI, 1.12-2.61; P-trend = 0.03) than for exposure at home (AHR, 1.26; 95% CI, 0.86-1.86; P-trend = 0.20) or leisure places (AHR,1.28; 95% CI, 0.83-1.95; P-trend = 0.16). Similar associations were observed when SHS exposure durations were dichotomized into two or three groups and between SHS exposure and recurrence-free survival. Conclusions: SHS exposure is associated with worse survival in early-stage non-small-cell lung cancer patients, especially for SHS exposure at the work. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Thorac Surg Unit, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA USA. RP Zhou, W (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM wzhou@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA090578, CA074386, ES/CA 06409, CA092824]; NIEHS NIH HHS [ES00002] NR 30 TC 8 Z9 8 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 DEC 1 PY 2006 VL 12 IS 23 BP 7187 EP 7193 DI 10.1158/1078-0432.CCR-06-1460 PG 7 WC Oncology SC Oncology GA 114UL UT WOS:000242691000045 PM 17145845 ER PT J AU Gralnek, IM Dulai, GS Fennerty, MB Spiegel, BMR AF Gralnek, Ian M. Dulai, Gareth S. Fennerty, M. Brian Spiegel, Brennan M. R. TI Esomeprazole versus other proton pump inhibitors in erosive esophagitis: A meta-analysis of randomized clinical trials SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; PANTOPRAZOLE 40 MG; LANSOPRAZOLE 30 MG; ACID CONTROL; OMEPRAZOLE; SYMPTOMS; EFFICACY; EQUIVALENT; RELIEF; SAFETY AB Background & Aims: There are limited data comparing the effectiveness of available proton pump inhibitors (PPIs) in erosive esophagitis (EE). We performed a mesa-analysis to calculate the pooled effect of esomeprazole on healing rates, symptom relief, and adverse events versus competing PPIs in EE. Methods: We performed a structured electronic search of MEDLINE and EMBASE and reviewed published abstracts to identify English-language, randomized clinical trials from 1995-2005, comparing rates of endoscopic healing, symptom relief, and adverse events with esomeprazole versus alternative PPIs in the treatment of gastroesophageal reflux disease (GERD)/EE. We then performed meta-analysis to compare the relative risk (RR) of EE healing, symptom relief, and adverse events between study arms and calculated the absolute risk reduction and number needed to treat (NNT) for each outcome. Results: Meta-analysis was performed on 10 studies (n = 15,316). At 8 weeks, there was a 5% (RR, 1.05; 95% confidence interval, 1.02-1.08) relative increase in the probability of healing of EE with esomeprazole, yielding an absolute risk reduction of 4% and NNT of 25. The calculated NNTs by Los Angeles grade of EE (grades A-D) were 50, 33, 14, and 8, respectively. Last, esomeprazole conferred an 8% (RR, 1.08; 95% confidence interval, 1.05-1.11) relative increase in the probability of GERD symptom relief at 4 weeks. Conclusions: As compared with other PPIs, esomeprazole confers a statistically significant improvement, yet, clinically, only a modest overall benefit in 8-week healing and symptom relief in all-comers with EE. The clinical benefit of esomeprazole appears negligible in less severe erosive disease but might be important in more severe disease. C1 Technion Israel Inst Technol, Rappaport Fac Med, GI Outcomes Unit,Dept Gastroenterol, Rambam Med Ctr, Haifa, Israel. Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ, Los Angeles, CA USA. CURE Digest Dis Res Ctr, Los Angeles, CA USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. So Calif Permanente Med Grp, Bellflower, CA USA. RP Gralnek, IM (reprint author), Technion Israel Inst Technol, Rappaport Fac Med, GI Outcomes Unit,Dept Gastroenterol, Rambam Med Ctr, Haifa, Israel. EM i_gralnek@rambam.health.gov.il FU NIDDK NIH HHS [2P30 DK 041301-17] NR 26 TC 60 Z9 63 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD DEC PY 2006 VL 4 IS 12 BP 1452 EP 1458 DI 10.1016/j.cgh.2006.09.013 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 119CN UT WOS:000242989900009 PM 17162239 ER PT J AU Oh, DS Wang, HS Ohning, GV Pisegna, JR AF Oh, David S. Wang, Hank S. Ohning, Gordon V. Pisegna, Joseph R. TI Validation of a new endoscopic technique to assess acid output in Zollinger-Ellison syndrome SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID ESOPHAGEAL-PERFORATION; NASOGASTRIC INTUBATION; GASTRIC-SECRETION; ANESTHETIC AGENTS; HYPERGASTRINEMIA; PENTAGASTRIN; AGREEMENT; DIAGNOSIS; STOMACH; BASAL AB Background & Aims: To safely manage the hypersecretory state in patients with Zollinger-Ellison syndrome, both upper endoscopy and gastric analysis are required to titrate optimal medical therapy. Conventional gastric analysis requires more than 1 hour to perform and results in significant patient dissatisfaction. In this study, we have validated endoscopic gastric analysis as a novel technique that can effectively replace conventional gastric analysis. Methods: In a prospective, crossover study. 12 patients with Zollinger-Ellison syndrome underwent gastric analysis, first by the conventional method and then by an endoscopic technique performed on the same day. Acid concentration was determined by titration, volume output was recorded, and acid output was calculated using standard methodologies and formulas. Agreement was assessed following the Bland-Altman method. To assess repeatability, both techniques were repeated on the same day in a subset of patients. Results: Excellent agreement was reported between acid output (95% limits of agreement, -1.27 to 1.61 mEq/h) and acid concentration (95% limits of agreement, -0.01 to 0.01 mEq/mL), although poor agreement was observed between volume output measured. Endoscopic gastric analysis showed greater reproducibility regarding acid and volume output measured. Conclusions: Wee introduce a new, rapid, reproducible, and accurate endoscopic technique to measure acid output in patients with Zollinger-Ellison syndrome who require both annual endoscopy and gastric analysis. The data presented here suggest that endoscopic gastric analysis would be equally effective in determining acid output in other hypersecretory states. Additional analysis of cost effectiveness is needed to evaluate its use as a screening tool in select populations. C1 VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol & Hepatol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. RP Pisegna, JR (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol & Hepatol, 691-1110,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jpisegna@ucla.edu NR 31 TC 4 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD DEC PY 2006 VL 4 IS 12 BP 1467 EP 1473 DI 10.1016/j.cgh.2006.08.015 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 119CN UT WOS:000242989900011 PM 17101299 ER PT J AU Nodit, L McGrath, KM Zahid, M Jani, N Schoedel, KE Ohori, NP Carty, S Finkelstein, S Khalid, A AF Nodit, Laurentia McGrath, Kevin M. Zahid, Maliha Jani, Niraj Schoedel, Karen E. Ohori, N. Paul Carty, Sally Finkelstein, Sydney Khalid, Asif TI Endoscopic ultrasound-guided fine needle aspirate microsatellite loss analysis and pancreatic endocrine tumor outcome SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID NEUROENDOCRINE TUMORS; DELETION; PROGRESSION; MALIGNANCY; NEOPLASMS; PATHOLOGY; CYTOLOGY; MARKER AB Background & Aims: The clinical course of pancreatic endocrine tumor (PET) varies depending on tumor aggressiveness, disease extent, and possibly accumulated molecular alterations. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) results, although accurate in diagnosing PET, correlate poorly with PET outcome. The role of detecting key molecular abnormalities in predicting PET behavior and clinical outcome from EUS-FNA material remains unknown. Methods: Patients with confirmed PET who underwent EUS-FNA during a 32-month period were included. Patient demographics and clinical data were recorded and follow-up information was obtained by contacting their physician to evaluate disease progression. Representative tumor cells were microdissected from the FNA material. DNA was harvested and amplified, targeting a panel of 17 polymorphic microsatellite markers on chromosomes 1p, 3p, 5q, 9p, 10q, 11q, 17p, 17q, 21q, and 22q. The polymerase chain reaction products were subjected to fluorescent capillary gel electrophoresis to detect microsatellite loss. The fractional allelic loss (FAL) was calculated. Results: Twenty-five patients were studied. Thirteen were classified histologically as benign PET limited to the pancreas and 12 as malignant PET (invasive or metastatic). The mean FAL in the benign and malignant PET was 0.03 and 0.37 (P < .0001), respectively. In addition, the mean FAL was significantly greater in those with disease progression as compared with patients with stable disease (0.45 vs 0.09 respectively, P < .0001). Conclusions: Microsatellite loss analysis of EUS-FNA material from PET can be performed reliably and an FAL value of more than 0.2 is associated with disease progression. This technique may have value in the preoperative assessment and risk stratification of patients with PET. C1 Univ Pittsburgh, Med Ctr, VA Pittsburgh Hlth Care Syst, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. RedPath Integrated Pathol Inc, Pittsburgh, PA USA. RP Khalid, A (reprint author), Univ Pittsburgh, Med Ctr, VA Pittsburgh Hlth Care Syst, Div Gastroenterol Hepatol & Nutr, M2,C-Wing,PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM khalida@upmc.edu NR 24 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD DEC PY 2006 VL 4 IS 12 BP 1474 EP 1478 DI 10.1016/j.cgh.2006.07.017 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 119CN UT WOS:000242989900012 PM 16996803 ER PT J AU Rutherford, A Davern, T Hay, JE Murray, NG Hassanein, T Lee, WM Chung, RT AF Rutherford, Anna Davern, Tim Hay, J. Eileen Murray, Natalie G. Hassanein, Tarek Lee, William M. Chung, Raymond T. CA Acute Liver Failure Study Grp TI Influence of high body mass index on outcome in acute liver failure SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID NONALCOHOLIC STEATOHEPATITIS; UNITED-STATES; DIABETES-MELLITUS; HEPATIC-FAILURE; OBESITY; ACETAMINOPHEN; PREVALENCE; CONJUGATION; SURVIVAL; RISK AB Background & Aims: Diabetes and obesity affect development of nonalcoholic fatty liver disease. Nonalcoholic fatty liver disease increases susceptibility to hepatic injury and limits regenerative capacity, which might increase adverse outcomes in acute liver failure. There is no difference in the prevalence of diabetes in acute liver failure patients when compared with the general population, but no large studies have examined the relationship of obesity to incidence or outcome of acute liver failure. Methods: Seven hundred eighty-two adult patients with acute liver failure were prospectively enrolled from 1998-2004. Body mass index, history of diabetes, and outcome were recorded. Multivariable logistic regression was used for the analysis. Results: Compared with 30.4% of adults in the National Health and Nutrition Examination Survey III, 29.1% of adult patients with acute liver failure were obese (P = .542). Obese patients had 1.63 times the odds of transplantation or death as nonobese patients (1.04-2.55, P = .033). Severely obese patients had 1.93 times the odds of transplantation or death (1.02-3.62, P = .042). There were no differences in the proportion of patients listed for transplantation, with body mass index greater or less than 30, 35, or 40 (P = .264, P = .112, P = .244, respectively). Obese patients had 3.4 times the odds of dying after transplantation (1.29-8.87, P = .01). Conclusions: Obesity does not appear to be more prevalent in acute liver failure. However, obese and severely obese patients had significantly poorer outcomes when they developed acute liver failure. This difference is not explained by weight discrimination in listing patients for transplantation, despite evidence for poorer post-transplant outcomes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, GI Unit, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Gastroenterol, San Francisco, CA 94143 USA. Mayo Clin, Rochester, MN USA. Baylor Univ, Med Ctr, Baylor All St Transplant Serv, Ft Worth, TX USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dallas, TX USA. RP Chung, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, GI Unit, GRJ 825,55 Fruit St, Boston, MA 02114 USA. EM RTChung@partners.org FU NIDDK NIH HHS [R01 DK058369, 2 U01 DK058369] NR 24 TC 23 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD DEC PY 2006 VL 4 IS 12 BP 1544 EP 1549 DI 10.1016/j.cgh.2006.07.014 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 119CN UT WOS:000242989900022 PM 16996806 ER PT J AU Oates, JC Gilkeson, GS AF Oates, Jim C. Gilkeson, Gary S. TI The biology of nitric oxide and other reactive intermediates in systemic lupus erythematosus SO CLINICAL IMMUNOLOGY LA English DT Review DE nitric oxide; lupus; reactive oxygen species; reactive nitrogen species; 3-nitrotyrosine; lipid peroxidation; apoptosis; autoantigens ID MRL-LPR/LPR MICE; MESSENGER-RNA EXPRESSION; CELL-ADHESION MOLECULE-1; MRL/LPR MICE; DISEASE-ACTIVITY; RENAL-DISEASE; DIMINISHES GLOMERULOSCLEROSIS; PHARMACOLOGICAL INHIBITION; 3-NITROTYROSINE LEVELS; MYCOPHENOLATE-MOFETIL AB Formation of reactive nitrogen and oxygen intermediates (RNI and ROI) is an essential part of the innate immune response. Markers of systemic RNI production are increased in the setting of systemic lupus erythematosus (SLE) activity. Several tines of evidence suggest mechanisms through which the activity of inducible nitric oxide synthase (iNOS) is pathogenic in SLE, including the ability of peroxynitrite (ONOO-, a product of iNOS activity) to modify proteins, lipids, and DNA. These modifications can alter enzyme activity and may increase the immunogenicity of self antigens, leading to a break in immune tolerance. In humans, observational data suggest that overexpression of iNOS and increased production of ONOO- lead to glomerular and vascular pathology. Therapies designed to target iNOS activity or scavenge ROI and RNI are in development and may provide the means to reduce the pathogenic consequences of ROI and RNI in SLE. (c) 2006 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Oates, JC (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol, 96 Jonathan Lucas St,Suite 912,POB 250637, Charleston, SC 29425 USA. EM oatesjc@musc.edu FU NCRR NIH HHS [M01 RR001070-270263, M01 RR001070-25A1S20263, M01 RR001070-315777, M01 RR001070-290263, M01 RR001070-230263, M01 RR001070-260263, M01 RR001070-25A1S10263, M01 RR001070-280263, M01 RR001070-220263, M01 RR001070-30A15146, M01 RR001070-25A10263, M01 RR001070-24S50263, M01 RR001070-240263, M01 RR001070]; NIAMS NIH HHS [K08 AR002193, K08 AR002193-03, K08 AR002193-05, K08 AR002193-02, K08 AR002193-01A1, K08 AR002193-04] NR 77 TC 35 Z9 35 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD DEC PY 2006 VL 121 IS 3 BP 243 EP 250 DI 10.1016/j.clim.2006.06.001 PG 8 WC Immunology SC Immunology GA 111VZ UT WOS:000242484800001 PM 16861040 ER PT J AU Binder, LM Storzbach, D Salinsky, MC AF Binder, Laurence M. Storzbach, Daniel Salinsky, Martin C. TI MMPI-2 profiles of persons with multiple chemical sensitivity SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article; Proceedings Paper CT Meeting of the American-Academy-of-Clinical-Neuropsychology CY JUN 10, 2004 CL Minneapolis, MN ID IDIOPATHIC ENVIRONMENTAL INTOLERANCES; FAKE BAD SCALE; SYMPTOMS; SEIZURES; MODEL AB We compared the MMPI-2 profiles of adults with multiple chemical sensitivity (MCS), epileptic seizures (ES), and nonepileptic seizures (NES). Both NES and MCS are medically unexplained conditions. In previous studies profiles associated with NES were elevated on scales Hs and Hy, compared with profiles associated with ES. We predicted that profiles associated with MCS would be elevated on Hs and Hy compared with the ES group. Patients with ES and NES were diagnosed after intensive EEG monitoring using published criteria. MCS was diagnosed if there was a complaint of illness in response to multiple common odors at levels that are not noxious to most people. All the MCS cases had legal claims for injury related to chemical exposures. The results showed that on MMPI-2 scales Hs, D, and Hy the MCS group had means significantly higher than both the ES and NES groups. Fake Bad Scale scores were elevated in 11 MCS cases, and regression-based estimates of Fake Bad Scale scores showed elevation in the MCS group compared with both seizure groups. We conclude that MMPI-2 data, obtained from people seeking financial compensation, indicate that there is a strong psychological component to MCS symptoms. C1 Oregon Hlth Sci Univ, Beaverton, OR USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Binder, LM (reprint author), 4900 SW Griffith Dr Suite 244, Beaverton, OR 97005 USA. EM pdxlarry@aol.com NR 30 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD DEC PY 2006 VL 20 IS 4 BP 848 EP 857 DI 10.1080/13854040500246927 PG 10 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 085IE UT WOS:000240597000018 PM 16980266 ER PT J AU Harris, WH AF Harris, William H. TI An integrated solution to acetabular revision surgery SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL HIP-ARTHROPLASTY; LOW-FRICTION ARTHROPLASTY; CROSS-LINKED POLYETHYLENE; CONCISE FOLLOW-UP; CEMENTED CUP; FEMORAL COMPONENT; RECONSTRUCTION; DISLOCATION; REPLACEMENT; MINIMUM AB The three salient reasons for failure of acetabular revision surgery have been failure of fixation, wear and lysis, and dislocation. This review focuses on the major progress made in addressing these three items, leading to an overall approach integrating three contemporary techniques with a strong likelihood of improving acetabular revision surgery. These three techniques are the use of hemispheric cementless acetabular components, alternate bearings, and big heads. C1 Massachusetts Gen Hosp, Harris Orthoped Biomech & Biomat Lab, Boston, MA 02114 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Harris Orthoped Biomech & Biomat Lab, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. EM wharris.obbl@partners.org NR 48 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2006 IS 453 BP 178 EP 182 DI 10.1097/01.blo.0000246546.80068.04 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 113PU UT WOS:000242610600031 ER PT J AU Talmo, CT Shanbhag, AS Rubash, HE AF Talmo, Carl T. Shanbhag, Arun S. Rubash, Harry E. TI Nonsurgical management of osteolysis SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL HIP-ARTHROPLASTY; DEBRIS-INDUCED OSTEOLYSIS; NECROSIS-FACTOR-ALPHA; BONE-MINERAL DENSITY; REVISION TOTAL HIP; PERIPROSTHETIC ACETABULAR OSTEOLYSIS; PARTICLE-INDUCED OSTEOCLASTOGENESIS; VOLUMETRIC COMPUTERIZED-TOMOGRAPHY; PERIPHERAL-BLOOD MONOCYTES; WEAR DEBRIS AB Osteolysis remains a common mode of total hip arthroplasty failure. In vitro and animal models have been used to determine the pathophysiology of osteolysis by carefully dissecting the biochemical pathways leading to particulate wear debris and periprosthetic bone loss. Numerous cytokines and inflammatory mediators, including TNF-alpha and IL-1, are critical participants in this cascade and may represent prime targets for pharmacologic intervention. Osteoclasts, the end effector cells involved in the osteolytic process, also represent potential targets. Cell surface receptors on osteoclast precursors, such as receptor activator of NF-kappa B (RANK) (on osteoclasts) and RANK-ligand (RANKL) (on stromal cells), provide opportunities to arrest osteoclast maturation. Enhancing the naturally occurring osteoprotegerin is another recent attempt at modulating osteoclast behavior and a possible target for pharmacologic therapies. Other nonoperative strategies include intercepting tumor necrosis factor-alpha activity, interfering with the RANK-RANKL interaction necessary for osteoclast development and maturation, bisphosphonate therapy, and using viral vectors to deliver genes. Although each of these approaches has potential benefits, there are substantial challenges to effective implementation. Until there is convincing evidence of efficacy in human clinical trials, we recommend vigilant screening and appropriate surgery with component loosening or substantial likelihood of loosening, periprosthetic fracture, or major bone loss. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02114 USA. RP Rubash, HE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg, 55 Fruit St,YAW 3B, Boston, MA 02114 USA. EM HRUBASH@partners.org NR 99 TC 23 Z9 23 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2006 IS 453 BP 254 EP 264 DI 10.1097/01.blo.0000246531.59876.a8 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 113PU UT WOS:000242610600042 PM 17016218 ER PT J AU Moye, J Gurrera, RJ Karel, MJ Edelstein, B O'Connell, C AF Moye, Jennifer Gurrera, Ronald J. Karel, Michele J. Edelstein, Barry O'Connell, Christopher TI Empirical advances in the assessment of the capacity to consent to medical treatment: Clinical implications and research needs SO CLINICAL PSYCHOLOGY REVIEW LA English DT Review DE informed consent; competence; aging ID ADULT AGE-DIFFERENCES; DECISION-MAKING CAPACITY; SUSTAINING TREATMENT DECISIONS; MACARTHUR TREATMENT COMPETENCE; PHYSICIANS LEGAL STANDARD; MILD ALZHEIMERS-DISEASE; HEALTH-CARE DECISION; INFORMED CONSENT; PERSONAL JUDGMENTS; COGNITIVE MODELS AB The clinical evaluation of capacity to consent to treatment occurs in the medical setting and is based on legal foundations of informed consent and capacity. Clinical judgment is still the "gold standard" for capacity determination, although it can be unreliable. In the past 10 years the empirical basis for these assessments has been advanced considerably by the introduction of a number of instruments designed to assess capacity to consent to treatment. In this paper, we review studies, mostly with older adult populations, that consider the cognitive and non-cognitive correlates of consent capacity, rates of impaired capacity in various patient groups, the relation of instrument-based to clinician-based capacity assessment, and the inter-rater and test-retest reliability of consent capacity assessment. We also overview key research focusing on factors influencing, and procedural and processing variables involved in, medical decision-making. We conclude that these studies have yielded quite varied results, and promote no consensus regarding the reliability and validity of instrument-based consent capacity assessment. Overall, the results of these studies provide some guidance for clinicians, but, at present, practitioners should view these instruments as supplemental resources rather than benchmarks for assessment. However, this first generation of instruments provides a good foundation for future research, which should continue to systematically study aspects of reliability and validity, most especially construct validity, in well-defined patient populations. Published by Elsevier Ltd. C1 VA Boston Healthcare Syst, Brockton, MA 02301 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. W Virginia Univ, Dept Psychol, Morgantown, WV 26506 USA. RP Moye, J (reprint author), VA Boston Healthcare Syst, Brockton Campus,940 Belmont St, Brockton, MA 02301 USA. EM jennifer.moye@med.va.gov RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X FU NIMH NIH HHS [R29 MH057104] NR 115 TC 35 Z9 38 U1 2 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD DEC PY 2006 VL 26 IS 8 BP 1054 EP 1077 DI 10.1016/j.cpr.2005.04.013 PG 24 WC Psychology, Clinical SC Psychology GA 114FK UT WOS:000242651900008 PM 16137811 ER PT J AU Ramnath, VR Hess, DR Thompson, BT AF Ramnath, Venktesh R. Hess, Dean R. Thompson, B. Taylor TI Conventional mechanical ventilation in acute lung injury and acute respiratory distress syndrome SO CLINICS IN CHEST MEDICINE LA English DT Article ID END-EXPIRATORY PRESSURE; TIDAL VOLUME VENTILATION; ELECTRICAL-IMPEDANCE TOMOGRAPHY; HYPERCAPNIC ACIDOSIS; PERMISSIVE HYPERCAPNIA; PROTECTIVE-VENTILATION; CRITICALLY-ILL; TRANSPULMONARY PRESSURES; MOISTURE EXCHANGERS; LIMITED VENTILATION AB Acute lung injury and acute respiratory distress syndrome are inflammatory conditions involving a broad spectrum of lung injury from mild respiratory abnormality to severe respiratory derangement. Regardless of cause (direct or indirect lung injury), pulmonary physiology and mechanics are altered, leading to hypoxemic respiratory failure. The use of positive pressure ventilation itself may cause lung injury (ventilator-induced lung injury, or VILI). VILI may amplify preexisting injury, delay lung recovery, and result in adverse outcomes. This article examines the evidence supporting lung-protective ventilation strategies and addresses the methods, outcomes, and potential obstacles to implementation of such approaches. C1 Massachusetts Gen Hosp, Dept Resp Care, Pulm Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Med Intens Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Thompson, BT (reprint author), Massachusetts Gen Hosp, Dept Resp Care, Pulm Crit Care Unit, Bulfinch Bldg 148,Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM tthompson1@partners.org NR 68 TC 18 Z9 19 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 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD DEC PY 2006 VL 27 IS 4 BP 601 EP + DI 10.1016/j.ccm.2006.06.009 PG 14 WC Respiratory System SC Respiratory System GA 109NE UT WOS:000242314200007 PM 17085249 ER PT J AU Anzueto, A Guntapalli, K AF Anzueto, Antonio Guntapalli, Kalapatha TI Adjunctive therapy to mechanical ventilation: Surfactant therapy, liquid ventilation, and prone position SO CLINICS IN CHEST MEDICINE LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; INHALED NITRIC-OXIDE; FREQUENCY OSCILLATORY VENTILATION; TUMOR-NECROSIS-FACTOR; N-ACETYLCYSTEINE; REGIONAL DISTRIBUTION; ADULT PATIENTS; SEVERE SEPSIS; DOUBLE-BLIND AB Acute lung injury and acute respiratory distress syndrome are associated with significant morbidity and mortality in critically ill patients. Although lung protective mechanical ventilation is the only therapy shown to reduce mortality and development of organ failure, several biologic pathways have been identified and provided an opportunity for therapeutic interventions. No pharmacologic or adjunctive treatments are available. Clinical studies demonstrated that prone position results in significant and clinically relevant improvement in oxygenation and ventilation, which persist when patients are returned to supine position; the beneficial response is not limited to patients turned early in disease course. Few complications are associated with prone ventilation. Clinical experience suggests that prone ventilation may protect the lung from potential detrimental effects of mechanical ventilation. Further studies are needed. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Anzueto, A (reprint author), S Texas Vet Hlth Care Syst, 111E,7400 Merton Mintner Blvd, San Antonio, TX 78229 USA. EM anzueto@uthscsa.edu NR 94 TC 2 Z9 2 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 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD DEC PY 2006 VL 27 IS 4 BP 637 EP + DI 10.1016/j.ccm.2006.07.004 PG 19 WC Respiratory System SC Respiratory System GA 109NE UT WOS:000242314200010 PM 17085252 ER PT J AU Mick, TM Hollander, E AF Mick, Thomas M. Hollander, Eric TI Impulsive-compulsive sexual behavior SO CNS SPECTRUMS LA English DT Review ID PARAPHILIA-RELATED DISORDERS; SEROTONIN REUPTAKE INHIBITORS; BUSPIRONE HYDROCHLORIDE; ADDICTION; COMORBIDITY; MALES; MEN; HYPERSEXUALITY; CLOMIPRAMINE; DEFINITION AB Impulsive-compulsive sexual behavior is a little studied clinical phenomenon which affects similar to 5% to 6% of the population. In the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision, it is classified as an impulse control disorder not otherwise specified or a sexual disorder not otherwise specified. It may be placed in a possible new category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition called substance and behavioral addictions. This clinical entity is reviewed and the merit of classifying it as an addiction is assessed. Information is presented regarding its diagnostic criteria, epidemiology, types of behavior it can involve, relationship to hypersexuality, comorbidities, treatment, and etiology. The data regarding this disorder and its overlap with chemical addiction is limited. If the two disorders are to be grouped together, further data are needed. C1 Mt Sinai Sch Med, New York, NY 10029 USA. Mt Sinai Med Ctr, Dept Psychiat, New York, NY 10029 USA. James J Peter Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. Seaver & New York Autism Ctr Excellence, New York, NY USA. RP Mick, TM (reprint author), Mt Sinai Sch Med, 1 Gustave Levy Pl,Box 1230, New York, NY 10029 USA. EM Thomas.Mick@mssm.edu RI Arens, Johannes/F-1296-2010 NR 56 TC 42 Z9 43 U1 0 U2 13 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD DEC PY 2006 VL 11 IS 12 BP 944 EP 955 PG 14 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 123CD UT WOS:000243273000012 PM 17146408 ER PT J AU Kan, IP Biran, I Thompson-Schill, SL Chatterjee, A AF Kan, Irene P. Biran, Iftah Thompson-Schill, Sharon L. Chatterjee, Anjan TI Letter selection and letter assembly in acquired dysgraphia SO COGNITIVE AND BEHAVIORAL NEUROLOGY LA English DT Article DE dysgraphia; graphemic buffer; spelling disorder; neuropsychology; case study ID GRAPHEMIC BUFFER; SPELLING-ERRORS; IMPAIRMENT AB Objective: We explored the constituents of the graphemic buffer in a patient with acquired dysgraphia and tested the hypothesis that the graphemic buffer is composed of 2 dissociable components: letter selection and letter assembly. Background: Research on dysgraphia has established the graphemic buffer as a component of the spelling mechanism, and the buffer is considered a short-term memory store that is critical for letter production. However, little is known about the components within the buffer. Method: We devised 2 spelling tasks that rely differentially on letter selection and letter assembly. In the selection task, our patient produced the letters that composed a target word, but she did not have to provide serial position information. In the assembly task, B.H. was given all the letters of a target word and was asked to spell the word by arranging the letters in the proper serial order. Results: Compared to spelling to dictation, our patient did not benefit from being given letter identity information (ie, assembly task), but her performance improved significantly when position information was available (ie, selection task). Conclusions: Based on these data, and the comparison of her performance with another dysgraphic patient, we propose that the graphemic buffer engages in both letter selection and letter assembly. C1 Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Univ Penn, Ctr Cognit Neurosci, Philadelphia, PA 19104 USA. RP Kan, IP (reprint author), Boston VA Healthcare Syst, Memory Disorders Res Ctr, 151-A,150 S Huntington Ave, Boston, MA 02130 USA. EM ikan@bu.edu RI Thompson-Schill, Sharon/M-1788-2013 FU NIDCD NIH HHS [R01 DC 004817]; NIMH NIH HHS [R01 MH 60414, R01 MH 67008] NR 26 TC 7 Z9 7 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1543-3633 J9 COGN BEHAV NEUROL JI Cogn. Behav. Neurol. PD DEC PY 2006 VL 19 IS 4 BP 225 EP 236 DI 10.1097/01.wnn.0000213918.18138.f2 PG 12 WC Behavioral Sciences; Clinical Neurology SC Behavioral Sciences; Neurosciences & Neurology GA 120AF UT WOS:000243054900011 PM 17159621 ER PT J AU Cumming, TB Patterson, K Verfaellie, M Graham, KS AF Cumming, Toby B. Patterson, Karalyn Verfaellie, Mieke Graham, Kim S. TI One bird with two stones: Abnormal word length effects in pure alexia and semantic dementia SO COGNITIVE NEUROPSYCHOLOGY LA English DT Article ID BY-LETTER DYSLEXIA; ALZHEIMERS-DISEASE; IMPAIRMENT; APHASIA; LATENCY; SOUND AB In pure alexia (PA)-an acquired reading disorder consequent on posterior left-hemisphere stroke the hallmark is a pronounced and abnormal impact of word length on reading speed. Some patients with semantic dementia ( SD)-a neurodegenerative condition affecting semantic memory-have also been reported to show an abnormal word length effect (AWLE) in reading, even though they are not thought to have the basic visual-processing deficits hypothesized to underlie this phenomenon in PA. In the current study, an AWLE in reading was consistently observed in both PA and SD patients, but further manipulations demonstrated marked differences between the groups in the conditions that produce the length effect, its specific manifestation, and the pattern of other deficits accompanying it. All of the results are compatible with the twin hypotheses that the AWLE in reading arises from a visual-processing deficit in PA but from reduced top-down lexical/semantic support for word identification in SD. In other words, the AWLE in the two patient groups appears to be a common symptom arising from different underlying deficits: one bird with two stones. C1 MRC, Cognit & Brain Sci Unit, Cambridge CB2 2EF, England. Boston VA Healthcare Syst, Memory Disorders Res Ctr, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Graham, KS (reprint author), MRC, Cognit & Brain Sci Unit, 15 Chaucer Rd, Cambridge CB2 2EF, England. EM kim.graham@mrc-cbu.cam.ac.uk RI Graham, Kim/A-1672-2010; OI Cumming, Toby/0000-0001-7530-2837; Verfaellie, Mieke/0000-0001-5535-4584; Graham, Kim/0000-0002-1512-7667 FU Medical Research Council [MC_U105579220, MC_U105579219] NR 51 TC 11 Z9 11 U1 1 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0264-3294 J9 COGN NEUROPSYCHOL JI Cogn. Neuropsychol. PD DEC PY 2006 VL 23 IS 8 BP 1130 EP 1161 DI 10.1080/02643290600674143 PG 32 WC Psychology; Psychology, Experimental SC Psychology GA 112IB UT WOS:000242518100003 PM 21049371 ER PT J AU Palevsky, PM AF Palevsky, Paul M. TI Off-pump cardiac surgery and acute kidney injury SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE acute kidney injury; cardiac surgery; coronary artery bypass; off pump; estimated glomerular filtration rate ID MORTALITY C1 Univ Pittsburgh, Sch Med, Renal Sect, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. RP Palevsky, PM (reprint author), Univ Pittsburgh, Sch Med, Renal Sect, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. OI Palevsky, Paul/0000-0002-7334-5400 NR 7 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2006 VL 34 IS 12 BP 3052 EP 3053 DI 10.1097/01.CCM.0000248904.17516.C4 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 110QH UT WOS:000242393100036 PM 17130705 ER PT J AU Benson, AB Thompson, T Wheeler, A Gordon, B DeBoisblanc, B Wiedemann, H AF Benson, Alexander B. Thompson, Taylor Wheeler, Art Gordon, Bernard DeBoisblanc, Ben Wiedemann, Herb TI Fluid balance in the beneficial conservative fluid management arm of the ARDS Network fluid and catheter treatment trial (FACTT) is substantially different from usual care in both shock and non-shock subsets. SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 36th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 18-21, 2007 CL Orlando, FL SP Soc Crit Care Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. LSU, New Orleans, LA USA. Cleveland Clin, Cleveland, OH 44106 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2006 VL 34 IS 12 SU S SI SI MA 474 BP A132 EP A132 DI 10.1097/00003246-200612002-00455 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 112PZ UT WOS:000242540400453 ER PT J AU Crimi, C Berra, L Bigatello, L Peter, D Velmahos, G AF Crimi, Claudia Berra, Lorenzo Bigatello, Luca Peter, Dunn Velmahos, George TI Effect of bedside percutaneous tracheostomy on icu length of stay- decreasing the time prior to tracheostomy. SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 36th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 18-21, 2007 CL Orlando, FL SP Soc Crit Care Med ID SURGICAL TRACHEOSTOMY C1 Massachusetts Gen Hosp, Boston, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2006 VL 34 IS 12 SU S SI SI MA 331 BP A90 EP A90 DI 10.1097/00003246-200612002-00312 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 112PZ UT WOS:000242540400311 ER PT J AU Douglas, IS Marchlowska, P Rains, R T Kinsella, M Golden, S Randall, A Regan, S Townsend, S Branch, DS Sosnowski, N Levy, MM AF Douglas, Ivor S. Marchlowska, Patricia Rains, Ron T Kinsella, Maria Golden, Suzanne Randall, Ann Regan, Susan Townsend, Sean Branch, Deborah S. Sosnowski, Neal Levy, Mitchell M. TI A statewide implementation of surviving sepsis campaign bundles by the Colorado Critical Care Collaborative. SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 36th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 18-21, 2007 CL Orlando, FL SP Soc Crit Care Med C1 Colorado Crit Care Collaborat, Denver, CO USA. Massachusetts Gen Hosp, Boston, MA USA. Surviving Sepsis Campaign, Des Plaines, IL USA. NR 0 TC 2 Z9 3 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2006 VL 34 IS 12 SU S SI SI MA 363 BP A99 EP A99 DI 10.1097/00003246-200612002-00344 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 112PZ UT WOS:000242540400343 ER PT J AU Elinoff, JM Malhotra, A Subramaniam, TB Goldberger, A Karmpaliotis, D AF Elinoff, Jason M. Malhotra, A. Subramaniam, Talmor B. Goldberger, A. Karmpaliotis, D. TI The effects of mechanical ventilation on the electrocardiogram in healthy subjects. SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 36th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 18-21, 2007 CL Orlando, FL SP Soc Crit Care Med C1 Massachusetts Gen Hosp, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Piedmont Hosp, Atlanta, GA 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2006 VL 34 IS 12 SU S SI SI MA 334 BP A91 EP A91 DI 10.1097/00003246-200612002-00315 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 112PZ UT WOS:000242540400314 ER PT J AU Gallagher, DC Parikh, SM Sukhatme, VP Balonov, K Talmor, D Miller, A AF Gallagher, Diana C. Parikh, Samir M. Sukhatme, Vikas P. Balonov, Konstantin Talmor, Daniel Miller, Andrew TI Circulating angiopoietin 2 correlates with mortality in a surgical population with ALI/ARDS. SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 36th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 18-21, 2007 CL Orlando, FL SP Soc Crit Care Med C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. BIDMC, Boston, MA USA. Brigham & Womens Hosp, 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2006 VL 34 IS 12 SU S SI SI MA 122 BP A28 EP A28 DI 10.1097/00003246-200612002-00103 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 112PZ UT WOS:000242540400104 ER PT J AU Ogilvy, C Chou, S Ayata, C Smith, EE Nogueira, R Rordorf, G AF Ogilvy, Christopher Chou, Sherry Ayata, Cenk Smith, Eric E. Nogueira, Raul Rordorf, Guy TI Safety and feasibility of simvastatin in delayed vasospasm prevention following aneurysmal subarachnoid hemorrhage-a randomized, double-blind, placebo-controlled study. SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 36th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 18-21, 2007 CL Orlando, FL SP Soc Crit Care Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Chou, Sherry/G-5779-2015; Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2006 VL 34 IS 12 SU S SI SI MA 294 BP A80 EP A80 DI 10.1097/00003246-200612002-00275 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 112PZ UT WOS:000242540400274 ER PT J AU Schmidt, U Noto, A Beck, C Kumwilaisak, K Bigatello, L Lewandrowski, K AF Schmidt, Ulrich Noto, Alberto Beck, Claire Kumwilaisak, Kanya Bigatello, Luca Lewandrowski, Kent TI Effect of laboratory testing guidelines on the volume of tests and of physician order entries in a surgical intensive care unit (SICU). SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 36th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 18-21, 2007 CL Orlando, FL SP Soc Crit Care Med C1 Massachusetts Gen Hosp, Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RI Noto, Alberto/G-6468-2012 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2006 VL 34 IS 12 SU S SI SI MA 466 BP A130 EP A130 DI 10.1097/00003246-200612002-00447 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 112PZ UT WOS:000242540400445 ER PT J AU Schmidt, U Gettings, E Allen, K Bigatello, LM Velmahos, GC Stelfax, HT AF Schmidt, Ulrich Gettings, Elise Allen, Kathrin Bigatello, Luca M. Velmahos, George C. Stelfax, Henry T. TI Computed tomography for early and safe removal of cervical spine immobilization in obtunded polytrauma patients. SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 36th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 18-21, 2007 CL Orlando, FL SP Soc Critical Care Med C1 Massachusetts Gen Hosp, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA USA. Univ Calgary, Calgary, AB, Canada. 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2006 VL 34 IS 12 SU S SI SI MA 193 BP A50 EP A50 DI 10.1097/00003246-200612002-00174 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 112PZ UT WOS:000242540400174 ER PT J AU Zhu, YS Bagchi, A Zhao, HL Hajjar, RJ Chao, W Hellman, J Schmidt, U AF Zhu, Yinsheng Bagchi, Aranya Zhao, Huailong Hajjar, Roger J. Chao, Wei Hellman, Judith Schmidt, Ulrich TI Bacterial peptidoglycan-associated lipoprotein (PAL) induces dysfunction in cardiomyocytes through myocardial TLR2/MYD88. SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 36th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 18-21, 2007 CL Orlando, FL SP Soc Crit Care Med C1 Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. Tech Univ Munich, D-8000 Munich, Germany. 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2006 VL 34 IS 12 SU S SI SI MA 114 BP A25 EP A25 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 112PZ UT WOS:000242540400096 ER PT J AU Restrepo, MI Anzueto, A AF Restrepo, Marcos I. Anzueto, Antonio TI The role of new therapies for severe community-acquired pneumonia SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review DE antibiotics; community-acquired pneumonia; Streptococcus pneumoniae ID BACTEREMIC PNEUMOCOCCAL PNEUMONIA; LOWER RESPIRATORY-TRACT; INTENSIVE-CARE-UNIT; RESISTANT STREPTOCOCCUS-PNEUMONIAE; PROGNOSTIC-FACTORS; ANTIMICROBIAL THERAPY; INITIAL MANAGEMENT; ELDERLY-PATIENTS; ADULT PATIENTS; PSEUDOMONAS-AERUGINOSA AB Purpose of review Community-acquired pneumonia (CAP) is associated with significant morbidity and is the most common cause of death from infectious diseases. CAP patients requiring intensive care unit (ICU) admission carry the highest mortality rates. This paper aims to review the current literature regarding epidemiology, risk factors, severity criteria and reasons for admitting the hospitalized patient to the ICU, and the empiric and specific antibiotic therapeutic regimens employed. Recent findings Multiple sets of clinical practice guidelines have been published in the past few years addressing the treatment of CAP. The guidelines all agree that CAP patients admitted to the hospital represent a major concern, and appropriate empiric therapy should be instituted to improve clinical outcomes. Summary The cost, morbidity and mortality of CAP patients requiring ICU admission remain unacceptably high. These are heterogenous groups of patients, so it is important to use risk-stratification based on clinical parameters and prediction tools. Appropriate antibiotic therapy is an important component in the management of both groups of patients. In particular, it is essential to administer an appropriate antimicrobial agent from the initiation of therapy, so that the risks of treatment failure and the morbidity of CAP may be minimized. C1 Univ Texas, Audie L Murphy Div San Antonio, S Texas Vet Healthcare Syst, Hlth Sci Ctr San Antonio,Div Pulm & Crit Care Med, San Antonio, TX 78229 USA. Vet Evidence Based Res Disseminat Implementat Ctr, San Antonio, TX USA. RP Anzueto, A (reprint author), Univ Texas, Audie L Murphy Div San Antonio, S Texas Vet Healthcare Syst, Hlth Sci Ctr San Antonio,Div Pulm & Crit Care Med, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM anzueto@uthscsa.edu NR 105 TC 5 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD DEC PY 2006 VL 19 IS 6 BP 557 EP 564 DI 10.1097/QCO.0b013e3280106b7f PG 8 WC Infectious Diseases SC Infectious Diseases GA 112GI UT WOS:000242513400005 PM 17075331 ER PT J AU Roche, M Kyriakou, H Seiden, M AF Roche, Maria Kyriakou, Helena Seiden, Michael TI Drug evaluation: Tesetaxel - an oral semisynthetic taxane derivative SO CURRENT OPINION IN INVESTIGATIONAL DRUGS LA English DT Article ID HIGHLY-ACTIVE TAXOIDS; 9-BETA-DIHYDROBACCATIN-9,10-ACETALS; RESISTANCE AB Daiichi Sankyo Co Ltd ( formerly Daiichi Seiyaku Co Ltd) was developing the oral semisynthetic taxane derivative tesetaxel for the potential treatment of cancer, including colorectal and gastric cancer. However, despite early signs of promise, in November 2006 tesetaxel was removed from Daiichi's development pipeline for failure to show clear benefit over existing, currently marketed agents for cancer chemotherapy. C1 Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. RP Seiden, M (reprint author), Massachusetts Gen Hosp, Div Hematol & Oncol, 55 Fruit St, Boston, MA 02114 USA. EM seiden.michael@mgh.harvard.edu NR 36 TC 13 Z9 14 U1 0 U2 1 PU THOMSON SCIENTIFIC PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND STREET, LONDON, W1T 4JE, ENGLAND SN 1472-4472 J9 CURR OPIN INVESTIG D JI Curr. Opin. Investig. Drugs PD DEC PY 2006 VL 7 IS 12 BP 1092 EP 1099 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110UV UT WOS:000242407700008 PM 17209527 ER PT J AU Wiviott, SD Cannon, CP AF Wiviott, Stephen D. Cannon, Christopher P. TI The safety and efficacy of achieving very low LDL-cholesterol concentrations with high dose statin therapy SO CURRENT OPINION IN LIPIDOLOGY LA English DT Review DE acute coronary syndrome; cholesterol; coronary artery disease; HMG-CoA reductase inhibitor; safety; statin ID RANDOMIZED CONTROLLED-TRIAL; ACUTE CORONARY SYNDROMES; LOW-DENSITY-LIPOPROTEIN; TO-Z TRIAL; SERUM-CHOLESTEROL; HEART-DISEASE; SIMVASTATIN; ATORVASTATIN; PRAVASTATIN; PREVENTION AB Purpose of review The benefits of lipid lowering with statins are established in patients with or at risk for coronary artery disease. Recent trials with high doses of potent statins have examined treating to very low levels of LDL-cholesterol. Concerns I have been raised about the safety of this strategy. This review examines the safety and efficacy of treating to very low LDL-cholesterol. Recent findings Four clinical trials, Treating to New Targets (TNT) and Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) in stable coronary artery disease and Aggrastat to Zocor (A to Z) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) TIMI 22 following acute coronary syndromes, have examined intensive statin therapy compared to moderate statin therapy. These trials and a meta-analysis demonstrated that intensive statin therapy reduces cardiovascular events. Subsequent analyses from these trials suggest that very low levels of LDL-cholesterol can be achieved safely and may improve clinical outcomes. A note of caution regarding hemorrhagic events following stroke with intensive statin therapy was raised by the Stroke Prevention by Aggressive Reduction of Cholesterol Levels (SPARCL) trial despite impressive reductions in cardiovascular events. Summary A growing body of evidence suggests progressive benefit for lowering LDL-cholesterol aggressively with intensive statin therapy in coronary artery disease. Future trials will be needed to define whether there is a level of LDL-cholesterol beyond which further benefit is not seen or safety concerns emerge. C1 Harvard Univ, Sch Med, TIMI Study Grp, Boston, MA 02115 USA. Brigham & Womens Hosp, Cardiovasc Div, Boston, MA 02115 USA. RP Wiviott, SD (reprint author), Harvard Univ, Sch Med, TIMI Study Grp, 350 Longwood Ave 1st Floor, Boston, MA 02115 USA. EM swiviott@partners.org NR 29 TC 19 Z9 21 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-9672 J9 CURR OPIN LIPIDOL JI Curr. Opin. Lipidology PD DEC PY 2006 VL 17 IS 6 BP 626 EP 630 DI 10.1097/MOL.0b013e328010872d PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral Vascular Disease SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Cardiovascular System & Cardiology GA 115BN UT WOS:000242709700003 PM 17095906 ER PT J AU Roccaro, AM Hideshima, T Richardson, PG Russo, D Ribatti, D Vacca, A Dammacco, F Anderson, KC AF Roccaro, A. M. Hideshima, T. Richardson, P. G. Russo, D. Ribatti, D. Vacca, A. Dammacco, F. Anderson, K. C. TI Bortezomib as an antitumor agent SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY LA English DT Review ID PROTEASOME INHIBITOR PS-341; MULTIPLE-MYELOMA CELLS; NF-KAPPA-B; PANCREATIC-CANCER CELLS; PHASE-I TRIAL; ENDOTHELIAL GROWTH-FACTOR; MEDIATED DRUG-RESISTANCE; NON-HODGKINS-LYMPHOMA; SOLID TUMORS; THERAPEUTIC APPLICATIONS AB The ubiquitin-proteasome pathway (UPP) is the major non-lysosomal proteolytic system in the cytosol and nucleus of all eukaryotic cells. Bortezomib (also known as PS-341 and Velcader (TM)) is a proteasome inhibitor, a novel class of cancer therapies. Bortezomib blocks multi-ubiquitinated protein degradation by inhibiting 26S proteasorne activity, including regulating cell cycle, anti-apoptosis, and inflammation, as well as immune surveillance. In multiple myeloma (MM) cells, bortezomib directly induces cell stress response followed by activation of c-Jun NH2 terminal kinase (JNK)/stress-activated protein kinase (SAPK), and triggers caspase-dependent apoptosis of tumor cells. Recent clinical studies demonstrated that bortezomib had remarkable anti-tumor activity in refractory and relapsed MM, providing the basis to approval by FDA. Its anti-tumor activities earlier in the course, in combination therapies, and in other malignancies is ongoing. C1 Univ Bari, Sch Med, Dept Human Anat & Histol, Bari, Italy. Univ Bari, Sch Med, Dept Internal Med & Oncol, Bari, Italy. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Brescia, Sch Med, Unit Blood Dis & Cell Therapy, Brescia, Italy. RP Ribatti, D (reprint author), Univ Bari, Sch Med, Dept Human Anat & Histol, Bari, Italy. EM ribatti@anatomia.uniba.it RI Russo, Domenico/C-3947-2011 FU NCI NIH HHS [IP50 CA10070, R0-1 CA50947]; PHS HHS [P0-1 78378] NR 72 TC 54 Z9 58 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2010 J9 CURR PHARM BIOTECHNO JI Curr. Pharm. Biotechnol. PD DEC PY 2006 VL 7 IS 6 BP 441 EP 448 DI 10.2174/138920106779116865 PG 8 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 121HU UT WOS:000243149500007 PM 17168660 ER PT J AU Astner, S Gonzalez, S Gonzalez, E AF Astner, Susanne Gonzalez, Salvador Gonzalez, Ernesto TI Noninvasive evaluation of allergic and irritant contact dermatitis by in vivo reflectance confocal microscopy SO DERMATITIS LA English DT Article ID PATCH TEST REACTIONS; SCANNING LASER MICROSCOPY; HYPERSENSITIVITY REACTIONS; REFRACTIVE-INDEX; SKIN; REPRODUCIBILITY; TESTS; MORPHOLOGY; HISTOLOGY; CELLS AB Background: The clinical differentiation of allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD) is often difficult to accomplish. Reflectance-mode confocal microscopy (RCM) is an imaging technique that has previously been used to examine ACD and ICD noninvasively in vivo. Objective: To determine characteristic features of ACD and ICD and their kinetic evolution over time. Ethnic susceptibility to contact irritants such as sodium lauryl sulfate and Ivory dishwashing liquid was evaluated noninvasively, and the sensitivity and specificity of RCM parameters were analyzed in a clinical context and in reference to patch testing. Methods: Subjects were patch-tested with allergens, irritants, and controls. Clinical scoring and RCM evaluation were performed at various time points, assessing stratum corneum (SC) disruption, spongiosis, exocytosis, vesicle formation, and epidermal thickness. Results: RCM features of both ACD and ICD include spongiosis, exocytosis, vesicle formation, and blood vessel dilatation. SC disruption, epidermal necrosis, and hyperproliferation are hallmarks of ICD whereas ACD more typically presents with vesicle formation. Patients with ICD showed a more rapid recovery than those with ACD. When tested with Ivory soap at selected concentrations, Caucasians, when compared to African Americans, showed significantly lower clinical thresholds for ICD and features that were more severe. Conclusions: RCM may be a promising new technology for longitudinal noninvasive studies of contact dermatitis (CD). Using a diagnostic algorithm and those parameters with high sensitivity for CD, RCM may facilitate the differentiation of acute ACD and ICD. RCM can reliably visualize cutaneous changes at subclinical degrees of CD, which suggests a possible role for RCM as an adjunctive tool in CD diagnosis. The results of this pilot study also indicate ethnic differences in the response to contact irritants. However, further studies are needed to substantiate the relevance and clinical applicability of our findings. C1 Harvard Univ, Dept Dermatol, Contact Dermatitis Unit,Med Sch, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Contact Dermatitis Unit, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dermatol Serv, New York, NY 10021 USA. RP Gonzalez, E (reprint author), Harvard Univ, Dept Dermatol, Contact Dermatitis Unit,Med Sch, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02114 USA. EM Gonzalez.ernesto@mgh.harvard.edu FU NIOSH CDC HHS [R01 OH0429] NR 49 TC 36 Z9 36 U1 0 U2 2 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1710-3568 J9 DERMATITIS JI Dermatitis PD DEC PY 2006 VL 17 IS 4 BP 182 EP 191 DI 10.2310/6620.2006.05052 PG 10 WC Dermatology SC Dermatology GA 125VH UT WOS:000243470800002 PM 17150167 ER PT J AU Hayes, GD Frand, AR Ruvkun, G AF Hayes, Gabriel D. Frand, Alison R. Ruvkun, Gary TI The mir-84 and let-7 paralogous microRNA genes of Caenorhabditis elegans direct the cessation of molting via the conserved nuclear hormone receptors NHR-23 and NHR-25 SO DEVELOPMENT LA English DT Article DE miRNAs; microRNAs; mir-84; let-7; heterochronic pathway; molting; nuclear hormone receptors; NHR-23; NHR-25 ID C-ELEGANS; REGULATORY RNA; DROSOPHILA METAMORPHOSIS; HETEROCHRONIC MUTANTS; COMPLEMENTARY SITES; CELL LINEAGES; LIN-4 RNA; EXPRESSION; PROTEIN; TARGET AB The let-7 microRNA ( miRNA) gene of Caenorhabditis elegans controls the timing of developmental events. let-7 is conserved throughout bilaterian phylogeny and has multiple paralogs. Here, we show that the paralog mir-84 acts synergistically with let-7 to promote terminal differentiation of the hypodermis and the cessation of molting in C. elegans. Loss of mir-84 exacerbates phenotypes caused by mutations in let-7, whereas increased expression of mir-84 suppresses a let-7 null allele. Adults with reduced levels of mir-84 and let-7 express genes characteristic of larval molting as they initiate a supernumerary molt. mir-84 and let-7 promote exit from the molting cycle by regulating targets in the heterochronic pathway and also nhr-23 and nhr-25, genes encoding conserved nuclear hormone receptors essential for larval molting. The synergistic action of miRNA paralogs in development may be a general feature of the diversified miRNA gene family. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu RI Hayes, Gabriel/B-9816-2012 FU NIGMS NIH HHS [GM44619] NR 67 TC 65 Z9 78 U1 0 U2 8 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD DEC 1 PY 2006 VL 133 IS 23 BP 4631 EP 4641 DI 10.1242/dev.02655 PG 11 WC Developmental Biology SC Developmental Biology GA 103BA UT WOS:000241857600004 PM 17065234 ER PT J AU Lee, JS Yu, C Shin, JT Sebzda, E Bertozzi, C Chen, M Mericko, P Stadtfeld, M Zhou, D Cheng, L Graf, T MacRae, CA Lepore, JJ Lo, CW Kahn, ML AF Lee, John S. Yu, Cing Shin, Jordan T. Sebzda, Eric Bertozzi, Cara Chen, Mei Mericko, Patti Stadtfeld, Matthias Zhou, Diane Cheng, Lan Graf, Thomas MacRae, Calum A. Lepore, John J. Lo, Cecilia W. Kahn, Mark L. TI KIf2 is an essential regulator of vascular hemodynamic forces in vivo SO DEVELOPMENTAL CELL LA English DT Article ID NONIMMUNE HYDROPS-FETALIS; KRUPPEL-LIKE FACTOR-2; BLOOD-FLOW; GENE-EXPRESSION; MOUSE EMBRYO; MICE LACKING; MECHANISMS; RECEPTOR; KLF2; DIFFERENTIATION AB Hemodynamic responses that control blood pressure and the distribution of blood flow to different organs are essential for survival. Shear forces generated by blood flow regulate hemodynamic responses, but the molecular and genetic basis for such regulation is not known. The transcription factor KLF2 is activated by fluid shear stress in cultured enclothelial cells, where it regulates a large number of vasoactive endothelial genes. Here, we show that KIf2 expression during development mirrors the rise of fluid shear forces, and that enclothelial loss of KIf2 results in lethal embryonic heart failure due to a high-cardiac-output state. KIf2 deficiency does not result in anemia or structural vascular defects, and it can be rescued by administration of phenylephrine, a catecholamine that raises vessel tone. These findings identify KIf2 as an essential hemodynamic regulator in vivo and suggest that hemodynamic regulation in response to fluid shear stress is required for cardiovascular development and function. C1 Univ Penn, Dept Med, Philadelphia, PA 19104 USA. NHLBI, NIH, Dev Biol Lab, Bethesda, MD 20824 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA. RP Kahn, ML (reprint author), Univ Penn, Dept Med, Philadelphia, PA 19104 USA. EM markkahn@mail.med.upenn.edu RI Graf, Thomas/B-4252-2015 OI Graf, Thomas/0000-0003-2774-4117 FU NHLBI NIH HHS [HL081084, HL081654, K08 HL068711]; NIGMS NIH HHS [R21 GM075946] NR 46 TC 126 Z9 132 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD DEC PY 2006 VL 11 IS 6 BP 845 EP 857 DI 10.1016/j.devcel.2006.09.006 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 114KK UT WOS:000242664900013 PM 17141159 ER PT J AU Montero-Balaguer, M Lang, MR Sachdev, SW Knappmeyer, C Stewart, RA De la Guardia, A Hatzopoulos, AK Knapik, EW AF Montero-Balaguer, Mercedes Lang, Michael R. Sachdev, Sherri Weiss Knappmeyer, Christiane Stewart, Rodney A. De la Guardia, Ana Hatzopoulos, Antonis K. Knapik, Ela W. TI The mother superior mutation ablates foxd3 activity in neural crest progenitor cells and depletes neural crest derivatives in zebrafish SO DEVELOPMENTAL DYNAMICS LA English DT Article DE progenitors; neural crest; zebrafish; foxd3; mother superior; craniofacial development ID HELIX TRANSCRIPTIONAL REPRESSOR; EMBRYONIC STEM-CELLS; DANIO-RERIO; WILD-TYPE; XENOPUS EMBRYOS; MUTANT EMBRYOS; EXPRESSION; GENE; INDUCTION; DIFFERENTIATION AB The zebrafish mutation mother superior (mos(m188)) leads to a depletion of neural crest (NC) derivatives including the craniofacial cartilage skeleton, the peripheral nervous system (sympathetic neurons, dorsal root ganglia, enteric neurons), and pigment cells. The loss of derivatives is preceded by a reduction in NC-expressed transcription factors, snail1b, sox9b, sox10, and a specific loss of foxd3 expression in NC progenitor cells. We employed genetic linkage analysis and physical mapping to place the mos(m188) mutation on zebrafish chromosome 6 in the vicinity of the foxd3 gene. Furthermore, we found that mos(m188) does not complement the sym1/foxd3 mutation, indicating that mos(m188) resides within the foxd3 locus. Injection of PAC clones containing the foxd3 gene into mos(m188) embryos restored foxd3 expression in NC progenitors and suppressed the mos(m188) phenotype. However, sequencing the foxd3 transcribed area in mos(m188) embryos did not reveal nucleotide changes segregating with the mos(m188) phenotype, implying that the mutation most likely resides outside the foxd3-coding region. Based on these findings, we propose that the mos(m188) mutation perturbs a NC-specific foxd3 regulatory element. Further analysis of mos(m188) mutants and foxd3 morphants revealed that NC cells are initially formed, suggesting that foxd3 function is required to maintain the pool of NC progenitors. C1 Vanderbilt Univ, Ctr Med, Dept Med, Div Med Genet, Nashville, TN 37232 USA. Vanderbilt Univ, Ctr Med, Dept Cell & Dev Biol, Nashville, TN 37232 USA. Univ Freiburg, Inst Biol 1, D-7800 Freiburg, Germany. Univ Missouri, Div Biochem, Columbia, MO 65211 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Costa Rica, Sch Biol, San Jose, Costa Rica. Vanderbilt Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Nashville, TN 37232 USA. RP Knapik, EW (reprint author), Vanderbilt Univ, Ctr Med, Dept Med, Div Med Genet, 529 Light Hall,2215 Garland Ave, Nashville, TN 37232 USA. EM ela.knapik@vanderbilt.edu RI Hatzopoulos, Antonis/D-2049-2010; Knapik, Ela/J-6172-2014; OI Stewart, Rodney/0000-0003-1220-1830 NR 75 TC 51 Z9 53 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 2006 VL 235 IS 12 BP 3199 EP 3212 DI 10.1002/dvdy.20959 PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 114LL UT WOS:000242667600002 PM 17013879 ER PT J AU Placha, G Poznik, GD Dunn, J Smiles, A Krolewski, B Glew, T Puppala, S Schneider, J Rogus, JJ Rich, SS Duggirala, R Warram, JH Krolewski, AS AF Placha, Grzegorz Poznik, G. David Dunn, Jonathon Smiles, Adam Krolewski, Bozena Glew, Timothy Puppala, Sobha Schneider, Jennifer Rogus, John J. Rich, Stephen S. Duggirala, Ravindranath Warram, James H. Krolewski, Andrzej S. TI A genome-wide linkage scan for genes controlling variation in renal function estimated by serum cystatin C levels in extended families with type 2 diabetes SO DIABETES LA English DT Article ID URINARY ALBUMIN EXCRETION; GLOMERULAR-FILTRATION-RATE; SUSCEPTIBILITY GENES; CHRONIC KIDNEY; DISEASE; NEPHROPATHY; GENOTYPE; GFR; COMPLICATIONS; PROTEINURIA AB We performed a variance components linkage analysis of renal function, measured as glomerular filtration rate (GFR), in 63 extended families with multiple members with type 2 diabetes. GFR was estimated from serum concentrations of cystatin C and creatinine in 406 diabetic and 428 nondiabetic relatives. Results for cystatin C were summarized because they are superior to creatinine results. GFR aggregates in families with significant heritability (h(2)) in diabetic (h(2) = 0.45, P < 1 x 10(-5)) and nondiabetic (h 2 = 0.36, P < 1 x 10(-3)) relatives. Genetic correlation (r(G) = 0.35) between the GFR of diabetic and nondiabetic relatives was less than one (P = 0.01), suggesting that genes controlling GFR variation in these groups are different. Linkage results supported this interpretation. In diabetic relatives, linkage was strong on chromosome 2q (logarithm of odds [LOD] 4.1) and suggestive on 10q (LOD = 3.1) and 18p (LOD 2.2). In nondiabetic relatives, linkage was suggestive on 3q (LOD = 2.2) and 11p (LOD = 2.1). When diabetic and nondiabetic relatives were combined, strong evidence for linkage was found only on 7p (LOD = 4.0). In conclusion, partially distinct sets of genes control GFR variation in relatives with and without diabetes on chromosome 2q, possibly on 10q and 18p in the former, and on 7p in both. None of these genes overlaps with genes controlling variation in urinary albumin excretion. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Warsaw Med Univ, Dept Internal Med & Hypertens, Warsaw, Poland. SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78284 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu FU NIDDK NIH HHS [DK-47475, DK-58549, DK-36836, DK-67638] NR 39 TC 54 Z9 56 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2006 VL 55 IS 12 BP 3358 EP 3365 DI 10.2337/db06-0781 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 111JG UT WOS:000242446800019 PM 17130480 ER PT J AU Williams, DL Baskin, DG Schwartz, MW AF Williams, Diana L. Baskin, Denis G. Schwartz, Michael W. TI Leptin regulation of the anorexic response to glucagon-like peptide-1 receptor stimulation SO DIABETES LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; CAUDAL BRAIN-STEM; FOOD-INTAKE; LITHIUM-CHLORIDE; EXENATIDE EXENDIN-4; NEURAL ACTIVATION; GENE-EXPRESSION; BODY-WEIGHT; ZUCKER RATS; MEAL SIZE AB Leptin reduces food intake in part by enhancing satiety responses to gastrointestinal signals produced in response to food consumption. Glucagon-like peptide 1 (GLP-1), secreted by the intestine when nutrients enter the gut, is one. such putative satiety signal. To investigate whether leptin enhances the anorexic effects of GLP-1, rats received either saline or a subthreshold dose of leptin before intraperitoneal injection of either GLP-1 or Exendin-4 (Ex4; a GLP-1 receptor agonist). Leptin pretreatment strongly enhanced anorexia and weight loss induced by GLP-1 or Ex4 over 24 h. Conversely, fasting attenuated the anorexic response to GLP-1 or Ex4 treatment via a leptin-dependent mechanism, as demonstrated by our finding that the effect of fasting was reversed by physiological leptin replacement. As expected, Ex4 induced expression of c-Fos protein, a marker of neuronal activation, in hindbrain areas that process afferent input from satiety signals, including the nucleus of the solitary tract and area postrema. Unexpectedly, leptin pretreatment blocked this response. These findings identify physiological variation of plasma leptin levels as a potent regulator of GLP-1 receptor-mediated food intake suppression and suggest that the underlying mechanism is distinct from that which mediates interactions between leptin and other satiety signals. C1 Univ Washington, Harborview Med Ctr, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA 98104 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA. RP Williams, DL (reprint author), Univ Washington, Harborview Med Ctr, Div Metab Endocrinol & Nutr, Dept Med, 325 9Th Ave,Box 359675, Seattle, WA 98104 USA. EM dianalw@u.washington.edu RI Schwartz, Michael/H-9950-2012; Williams, Diana/C-1699-2014 OI Williams, Diana/0000-0002-3548-7440 FU NIDDK NIH HHS [DK-52989, DK-68340]; NINDS NIH HHS [NS-32273] NR 36 TC 99 Z9 100 U1 1 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2006 VL 55 IS 12 BP 3387 EP 3393 DI 10.2337/db06-0558 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 111JG UT WOS:000242446800023 PM 17130484 ER PT J AU Xu, J Lee, WNP Phan, J Saad, MF Reue, K Kurland, IJ AF Xu, Jun Lee, W. N. Paul Phan, Jack Saad, Mohammed F. Reue, Karen Kurland, Irwin J. TI Lipin deficiency impairs diurnal metabolic fuel switching SO DIABETES LA English DT Article ID REVERSES INSULIN-RESISTANCE; MASS ISOTOPOMER ANALYSIS; ADIPOSE-TISSUE; GLUCOSE-PRODUCTION; DIABETES-MELLITUS; HEPATIC STEATOSIS; GENE-EXPRESSION; IN-VIVO; LIPODYSTROPHY; MOUSE AB Fatty liver is a common feature of both obesity and lipodystrophy, reflecting compromised adipose tissue function. The lipin-deficient fatty liver dystrophy (fld) mouse is an exception, as there is lipodystrophy without a fatty liver. Using a combination of indirect calorimetry and stable-isotope flux phenotyping, we determined that fld mice exhibit abnormal fuel utilization throughout the diurnal cycle, with increased glucose oxidation near the end of the fasting period and increased fatty acid oxidation during the feeding period. The mechanisms underlying these alterations include a twofold increase compared with wild-type mice in tissue glycogen storage during the fed state, a 40% reduction in hepatic glucose production in the fasted state, and a 27-fold increase in de novo fatty acid synthesis in liver during the fed state. Thus, the inability to store energy in adipose tissue in the fld mouse leads to a compensatory increase in glycogen storage for use during the fasting period and reliance upon hepatic fatty acid synthesis to provide fuel for peripheral tissues during the fed state. The increase in hepatic fatty acid synthesis and peripheral utilization provides a potential mechanism to ameliorate fatty liver in the fld that would otherwise occur as a consequence of adipose tissue dysfunction. C1 SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA. Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. SUNY Stony Brook, Dept Physiol & Biophys, Stony Brook, NY 11794 USA. RP Kurland, IJ (reprint author), SUNY Stony Brook, Dept Med, HSC T-15 Room 060, Stony Brook, NY 11794 USA. EM irwin.kurland@stonybrook.edu FU NHLBI NIH HHS [HL28481]; NIDDK NIH HHS [R01 DK058132-07, DK58132] NR 44 TC 23 Z9 23 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2006 VL 55 IS 12 BP 3429 EP 3438 DI 10.2337/db06-0260 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 111JG UT WOS:000242446800028 PM 17130489 ER PT J AU van Genugten, RE Utzschneider, KM Tong, J Gerchman, F Zraika, S Udayasankar, J Boyko, EJ Fujimoto, WY Kahn, SE AF van Genugten, Renate E. Utzschneider, Kristina M. Tong, Jenny Gerchman, Fernando Zraika, Sakeneh Udayasankar, Jayalakshmi Boyko, Edward J. Fujimoto, Wilfred Y. Kahn, Steven E. CA Amer Diabet Assoc GENNID Study Grp TI Effects of sex and hormone replacement therapy use on the prevalence of isolated impaired fasting glucose and isolated impaired glucose tolerance in subjects with a family history of type 2 diabetes SO DIABETES LA English DT Article ID HEALTHY POSTMENOPAUSAL WOMEN; PLACEBO-CONTROLLED TRIAL; CORONARY-HEART-DISEASE; INSULIN SENSITIVITY; DOUBLE-BLIND; RISK-FACTORS; ESTROGEN; METABOLISM; RESISTANCE; SECRETION AB Impaired fasting glucose (IFG) is more prevalent in men and impaired glucose tolerance (IGT) more prevalent in women. To explore whether this sex difference is related to female sex hormones, we performed a cross-sectional analysis of data from 2,164 (1,329 women and 835 men) first-degree relatives of individuals with type 2 diabetes. Subjects were categorized based on a 75-g oral glucose tolerance test. Sex and hormone replacement therapy (HRT) effects on the distribution of glucose tolerance were assessed using multinomial logistic regression corrected for familial clustering. Compared with men, women were more likely to have isolated IGT (relative risk 1.8 [95% CI 1.3-2.5]) and less likely to have isolated IFG (0.5 [0.3-0.7]) adjusted for ethnicity, age, waist, fasting insulin, and early insulin release (Delta I0-30/Delta G(0-30)). To evaluate HRT effects, postmenopausal women using (n = 238) or not using (n = 378) HRT were compared. HRT users were more likely to have isolated IGT (2.2 [1.2-4.0]) after adjustment, but the prevalence of isolated IFG did not differ by HRT status. Based on the influence of sex and HRT on the prevalence of isolated IFG and isolated IGT, we conclude that female sex hormones may play an important role in the pathogenesis of IFG and IGT. C1 VA Puget Sound Hlth Care Syst 151, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Dept Med, Div Gen Internal Med, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. RP Utzschneider, KM (reprint author), VA Puget Sound Hlth Care Syst 151, Dept Med, Div Metab Endocrinol & Nutr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM kutzschn@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 NR 37 TC 21 Z9 22 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2006 VL 55 IS 12 BP 3529 EP 3535 DI 10.2337/db06-0577 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 111JG UT WOS:000242446800040 PM 17130501 ER PT J AU Cleary, PA Orchard, TJ Genuth, S Wong, ND Detrano, R Backlund, JYC Zinman, B Jacobson, A Sun, WJ Lachin, JM Nathan, DM AF Cleary, Patricia A. Orchard, Trevor J. Genuth, Saul Wong, Nathan D. Detrano, Robert Backlund, Jye-Yu C. Zinman, Bernard Jacobson, Alan Sun, Wanjie Lachin, John M. Nathan, David M. CA DCCT EDIC Research Group TI The effect of intensive glycemic treatment on coronary artery calcification in type 1 diabetic participants of the diabetes control and complications Trial/Epidemiology of diabetes interventions and complications (DCCT/EDIC) study SO DIABETES LA English DT Article ID BEAM COMPUTED-TOMOGRAPHY; INTIMA-MEDIA THICKNESS; CARDIOVASCULAR-DISEASE; HEART-DISEASE; RISK-FACTORS; FOLLOW-UP; MELLITUS; EPIDEMIOLOGY; IDDM; ATHEROSCLEROSIS AB The Epidemiology of Diabetes Interventions and Complications (EDIC) study, an observational follow-up of the Diabetes Control and Complications Trial (DCCT) type 1 diabetes cohort, measured coronary artery calcification (CAC), an index of atherosclerosis, with computed tomography (CT) in 1,205 EDIC patients at similar to 7-9 years after the end of the DCCT. We examined the influence of the 6.5 years of prior conventional versus intensive diabetes treatment during the DCCT, as well as the effects of cardiovascular disease risk factors, on CAC. The prevalences of CAC > 0 and > 200 Agatston units were 31.0 and 8.5%, respectively. Compared with the conventional treatment group, the intensive group had significantly lower geometric mean CAC scores and a lower prevalence of CAC > 0 in the primary retinopathy prevention cohort, but not in the secondary intervention cohort, and a lower prevalence of CAC > 200 in the combined cohorts. Waist-to-hip ratio, smoking, hypertension, and hypercholesterolemia, before or at the time of CT, were significantly associated with CAC in univariate and multivariate analyses. CAC was associated with mean HbA(1c) (A1C) levels before enrollment, during the DCCT, and during the EDIC study. Prior intensive diabetes treatment during the DCCT was associated with less atherosclerosis, largely because of reduced levels of A1C during the DCCT. C1 George Washington Univ, Ctr Biostat, Rockville, MD USA. Univ Pittsburgh, Pittsburgh, PA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Calif Irvine, Irvine, CA USA. Harbor UCLA Med Ctr, Torrance, CA 90509 USA. Univ Toronto, Toronto, ON, Canada. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Nathan, DM (reprint author), Massachusetts Gen Hosp, Diabet Unit, 32 Fruit St, Boston, MA 02114 USA. EM dnathan@partners.org RI Zinman, Bernard/E-7266-2013; Hegele, Robert/G-3301-2011; OI orchard, trevor/0000-0001-9552-3215; Lachin, John/0000-0001-9838-2841 FU NIDDK NIH HHS [N01 DK062204, N01 DK062204-007] NR 52 TC 134 Z9 141 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD DEC PY 2006 VL 55 IS 12 BP 3556 EP 3565 DI 10.2337/db06-0653 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 111JG UT WOS:000242446800043 PM 17130504 ER PT J AU Florez, JC Saxena, R Winckler, W Burtt, NP Almgren, P Bostrom, KB Tuomi, T Gaudet, D Ardlie, KG Daly, MJ Altshuler, D Hirschhorn, JN Groop, L AF Florez, Jose C. Saxena, Richa Winckler, Wendy Burtt, Noel P. Almgren, Peter Bostrom, Kristina Bengtsson Tuomi, Tiinamaija Gaudet, Daniel Ardlie, Kristin G. Daly, Mark J. Altshuler, David Hirschhorn, Joel N. Groop, Leif TI The Kruppel-like factor 11 (KLF11) Q62R polymorphism is not associated with type 2 diabetes in 8,676 people SO DIABETES LA English DT Article ID TRANSCRIPTION-FACTOR-7-LIKE-2 TCF7L2 GENE; RISK; VARIANTS; REPLICATION; POPULATION; SUSCEPTIBILITY; RECEPTOR; DISEASE; LINKAGE; REGION AB Kruppel-like factor 11 is a pancreatic transcription factor whose activity induces the insulin gene. A common glutamine-to-arginine change at codon 62 (Q62R) in its gene KLF11 has been recently associated with type 2 diabetes in two independent samples. Q62R and two other rare missense variants (A347S and T220M) were also shown to affect the function of KLF11 in vitro, and insulin levels were lower in carriers of the minor allele at Q62R. We therefore examined their impact on common type 2 diabetes in several family-based and case-control samples of northern-European ancestry, totaling 8,676 individuals. We did not detect the rare A347S and T220M variants in our samples. With respect to Q62R, despite > 99% power to detect an association of the previously published magnitude, Q62R was not associated with type 2 diabetes (pooled odds ratio 0.97 [95% Cl 0.88-1.08], P = 0.63). In a subset of normoglycemic individuals, we did not observe significant differences in various insulin traits according to genotype at KLF11 Q62R. We conclude that the KLF11 A347S and T220M mutations do not contribute to increased risk of diabetes in European-derived populations and that the Q62R polymorphism has, at best, a minor effect on diabetes risk. C1 Massachusetts Gen Hosp, Diabet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Med & Populat Genet Program, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Broad Inst, Canc Biol Program, Cambridge, MA 02138 USA. Lund Univ, Dept Endocrinol, Univ Hosp MAS, Malmo, Sweden. Lund Univ, Dept Clin Sci, Univ Hosp MAS, Malmo, Sweden. Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland. Univ Helsinki, Res Program Mol Med, Helsinki, Finland. Folkhalsan Res Ctr, Folkhalsan Genet Inst, Helsinki, Finland. Univ Montreal, Chicoutimi Hosp, Community Genon Ctr, Chicoutimi, PQ, Canada. SeraCare LifeSci, Genom Collaborat Div, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Diabet Unit, Ctr Human Genet Res, Simches Res Bldg,CPZN 6820, Boston, MA 02114 USA. EM jcflorez@paitners.org RI Altshuler, David/A-4476-2009; OI Altshuler, David/0000-0002-7250-4107; Tuomi, Tiinamaija/0000-0002-8306-6202 FU NIDDK NIH HHS [R01 DK072041, 1 K23 DK65978-03] NR 28 TC 11 Z9 11 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2006 VL 55 IS 12 BP 3620 EP 3624 DI 10.2337/db.06-0867 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 111JG UT WOS:000242446800051 PM 17130512 ER PT J AU Munoz, J Lok, KH Gower, BA Fernandez, JR Hunter, GR Lara-Castro, C De Luca, M Garvey, WT AF Munoz, Julian Lok, Kerry H. Gower, Barbara A. Fernandez, Jose R. Hunter, Gary R. Lara-Castro, Cristina De Luca, Maria Garvey, W. Timothy TI Polymorphism in the transcription factor 7-like 2 (TCF7L2) gene is associated with reduced insulin secretion in nondiabetic women SO DIABETES LA English DT Article ID BETA-CELL FUNCTION; GLUCOSE-TOLERANCE; INTRAVENOUS GLUCOSE; DIABETES-MELLITUS; RESISTANCE; SENSITIVITY; ONSET; RISK AB Recently, the transcription factor 7-like 2 (TCF7L2) gene on chromosome 10q25.2 has been linked with type 2 diabetes among Caucasians, with disease associations noted for single nucleotide polymorphisms.(SNPs) rs12255372 and rs7903146. To investigate mechanisms by which TCF7L2 could contribute to type 2 diabetes, we examined the effects of these SNPs on clinical and metabolic traits affecting glucose homeostasis in 256 nondiabetic female subjects (138 European Americans and 118 African Americans) aged 7-57 years. Outcomes included BMI, percent body fat, insulin sensitivity (S-i), acute insulin response to glucose (AIR(g)), and the disposition index (DI). Homozygosity for the minor allele (TT) of SNP rs12255372 occurred in 9% of individuals and was associated with a 31% reduction in DI values in a recessive model. The at-risk allele TT was also associated with lower AIR(g) adjusted for S-i in both ethnic groups, whereas rs12255372 genotype was not associated with measures of adiposity or with S-i. The T allele of rs12255372 was also associated with increased prevalence of impaired fasting glucose. Genotypes at rs7903146 were not associated with any metabolic trait. Lower S-i and higher AIR(g) observed in the African-American compared with the European-American subgroup could not be explained by the TCF7L2 genotype. Our data suggest that the TCF7L2 gene is an important factor regulating insulin secretion, which could explain its association with type 2 diabetes. C1 Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. Univ Alabama, Dept Human Studies, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Munoz, J (reprint author), Univ Alabama, Dept Nutr Sci, 1675 Webb Nutr Sci Bldg,Room 241, Birmingham, AL 35294 USA. EM munozj@uab.edu OI De Luca, Maria/0000-0001-6345-7508 FU NCRR NIH HHS [M01 RR00032]; NIDDK NIH HHS [R01 DK067426, R01 DK49779, R01 DK58278, P30 DK56336] NR 18 TC 70 Z9 72 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2006 VL 55 IS 12 BP 3630 EP 3634 DI 10.2337/db06-0574 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 111JG UT WOS:000242446800053 PM 17130514 ER PT J AU Levin, BE Kang, L Sanders, NM Dunn-Meynell, AA AF Levin, Barry E. Kang, Ling Sanders, Nicole M. Dunn-Meynell, Ambrose A. TI Role of neuronal glucosensing in the regulation of energy homeostasis SO DIABETES LA English DT Article; Proceedings Paper CT 7th Servier-IGIS Symposium CY MAR 30-APR 02, 2006 CL St Jean Cap Ferrat, FRANCE ID VENTROMEDIAL HYPOTHALAMIC NUCLEUS; SENSITIVE K+ CHANNELS; INSULIN-INDUCED HYPOGLYCEMIA; MELANIN-CONCENTRATING HORMONE; CONTROLLING FOOD-INTAKE; DIET-INDUCED OBESITY; ATP CHANNELS; EXTRACELLULAR GLUCOSE; ARCUATE NUCLEUS; RAT-BRAIN AB Glucosensing is a property of specialized neurons in, the brain that regulate their membrane potential and firing rate as a function of ambient glucose levels. These neurons have several similarities to beta- and alpha-cells in the pancreas, which are also responsive to ambient glucose levels. Many use glucokinase as a rate-limiting step in the production of ATP and its effects on membrane potential and ion channel function to sense glucose. Glucosensing neurons are organized in an interconnected distributed network throughout the brain that also receives afferent neural input from glucosensors in the liver, carotid body, and small intestines. In addition to glucose, glucosensing neurons can use other metabolic substrates, hormones, and peptides to regulate their firing rate. Consequently, the output of these "metabolic sensing" neurons represents their integrated response to all of these simultaneous inputs. The efferents of these neurons regulate feeding, neuroendocrine and autonomic function, and thereby energy expenditure and storage. Thus, glucosensing neurons play a critical role in the regulation of energy homeostasis. Defects in the ability to sense glucose and regulatory hormones like leptin and insulin may underlie the predisposition of some individuals to develop diet-induced obesity. C1 Dept Vet Affairs New Jersey Hlth Care Syst, Neurol Serv, E Orange, NJ USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol & Neurosci, Newark, NJ 07103 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Div Endocrinol & Metab, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Levin, BE (reprint author), VA Med Ctr, Neurol Serv, 127C,385 Tremont Ave, E Orange, NJ 07018 USA. EM levin@umdnj.edu NR 107 TC 21 Z9 21 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2006 VL 55 SU 2 BP S122 EP S130 DI 10.2337/db06-S016 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 113MM UT WOS:000242602000018 ER PT J AU Grant, RW Lester, WT Meigs, JB Chueh, HC AF Grant, Richard W. Lester, William T. Meigs, James B. Chueh, Henry C. TI New models of population management for patients with diabetes - using informatics tools to support primary care SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article; Proceedings Paper CT International Symposium on New Technologies for Insulin Replacement CY APR 28-MAY 01, 2005 CL Assisi, ITALY SP Lifescan Italia, Aventis Pharma, Medtronic, Novo Nordisk, Abbott, Bayer, Bayer Diagnostici, Boheringer Ingelheim, Fondaz Cassa Risparmio Perugia, GlaxoSmithKline, Lab Guidotti, Living Cell Technologies, Menarini, Merck Farma, Pfizer, Roche, Servier Italia, SPA, Takeda Europe R&D Ctr Ltd, Banca Popolare Spoleto, Becton Dickinson Italia, Eli Lilly Italia, Merck Sharp & Dome, Novartis Pharma, Schwartz Pharma, Sigma Tau, Wyeth Lederle DE diabetes; medication adherence; clinical inertia; population management; evidence-based care; clinical practice ID CONTROLLED-TRIAL AB Diabetes management continues to fall short of evidence-based goals of care. Population management represents a new approach to diabetes care for large numbers of patients with diabetes cared for within a single clinical system. This method is information intensive and generally requires an advanced informatics infrastructure. While Information Processing is a critical first step in population management, to have a significant impact on disease control population-based intervention must also employ potent Clinical Action tools that lower barriers to effective care. In this review we present two recent population management interventions within our health system that illustrate the principles of Information Processing and Clinical Action in diabetes care. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Gen Med Unit, Boston, MA USA. Massachusetts Gen Hosp, Lab Comp Sci, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Grant, RW (reprint author), 50-9 Staniford St, Boston, MA 02114 USA. EM Rgrant@partners.org OI Grant, Richard/0000-0002-6164-8025 FU NIDDK NIH HHS [DK067452] NR 6 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD DEC PY 2006 VL 74 SU 2 BP S220 EP S224 DI 10.1016/S0168-8227(06)70036-5 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 126LC UT WOS:000243513400035 PM 17182326 ER PT J AU Holmkvist, J Cervin, C Lyssenko, V Winckler, W Anevski, D Cilio, C Almgren, P Berglund, G Nilsson, P Tuomi, T Lindgren, CM Altshuler, D Groop, L AF Holmkvist, J. Cervin, C. Lyssenko, V. Winckler, W. Anevski, D. Cilio, C. Almgren, P. Berglund, G. Nilsson, P. Tuomi, T. Lindgren, C. M. Altshuler, D. Groop, L. TI Common variants in HNF-1 alpha and risk of type 2 diabetes SO DIABETOLOGIA LA English DT Article DE association study; case-control studies; glucose; hepatocyte nuclear factor 1-alpha; insulin; MODY3; prospective studies; type 2 diabetes mellitus ID HEPATIC NUCLEAR FACTOR-1-ALPHA; AMINO-ACID POLYMORPHISM; LARGE-SCALE ASSOCIATION; BETA-CELL FUNCTION; INSULIN SENSITIVITY; SUSCEPTIBILITY GENE; GENOMEWIDE SEARCH; FINNISH FAMILIES; HNF1-ALPHA GENE; SECRETION AB Mutations in the hepatocyte nuclear factor 1-alpha gene (HNF-1 alpha, now known as the transcription factor 1 gene [TCF1]) cause the most common monogenic form of diabetes, MODY3, but it is not known if common variants in HNF-1a are associated with decreased transcriptional activity or phenotypes related to type 2 diabetes, or whether they predict future type 2 diabetes. We studied the effect of four common polymorphisms (rs1920792, I27L, A98V and S487N) in and upstream of the HNF-1 alpha gene on transcriptional activity in vitro, and their possible association with type 2 diabetes and insulin secretion in vivo. Certain combinations of the I27L and A98V polymorphisms in the HNF-1 alpha gene showed decreased transcriptional activity on the target promoters glucose transporter 2 (now known as solute carrier family 2 [facilitated glucose transporter], member 2) and albumin in both HeLa and INS-1 cells. In vivo, these polymorphisms were associated with a modest but significant impairment in insulin secretion in response to oral glucose. Insulin secretion deteriorated over time in individuals carrying the V allele of the A98V polymorphism (n=2,293; p=0.003). In a new case-control (=1,511 and n=2,225 respectively) data set, the I27L polymorphism was associated with increased risk of type 2 diabetes, odds ratio (OR)=1.5 (p=0.002; multiple logistic regression), particularly in elderly (age > 60 years) and overweight (BMI > 25 kg/m(2)) patients (OR=2.3, p=0.002). This study provides in vitro and in vivo evidence that common variants in the MODY3 gene, HNF-1 alpha, influence transcriptional activity and insulin secretion in vivo. These variants are associated with a modestly increased risk of late-onset type 2 diabetes in subsets of elderly overweight individuals. C1 Lund Univ, Dept Clin Sci Diabet & Endocrinol, Clin Res Ctr, Malmo Univ Hosp, S-20502 Malmo, Sweden. Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. Massachusetts Gen Hosp, Dept Mol Biol, Ctr Human Genet, Res & Diabet Unit, Boston, MA 02114 USA. Chalmers, Sch Math Sci, S-41296 Gothenburg, Sweden. Lund Univ, Dept Med, Malmo Univ Hosp, S-20502 Malmo, Sweden. Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland. Univ Helsinki, Res Program Mol Med, Helsinki, Finland. Folkhalsan Res Ctr, Helsinki, Finland. Karolinska Inst, Dept Biosci, Novum, Huddinge, Sweden. Karolinska Univ Hosp, Clin Res Ctr, Huddinge, Sweden. RP Groop, L (reprint author), Lund Univ, Dept Clin Sci Diabet & Endocrinol, Clin Res Ctr, Malmo Univ Hosp, S-20502 Malmo, Sweden. EM leif.groop@med.lu.se RI Altshuler, David/A-4476-2009; OI Altshuler, David/0000-0002-7250-4107; Tuomi, Tiinamaija/0000-0002-8306-6202 FU Wellcome Trust [090532] NR 38 TC 48 Z9 54 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD DEC PY 2006 VL 49 IS 12 BP 2882 EP 2891 DI 10.1007/s00125-006-0450-x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 104GZ UT WOS:000241948200011 PM 17033837 ER PT J AU Martin, SI Sepehr, A Fishman, JA AF Martin, Stanley I. Sepehr, Alireza Fishman, Jay A. TI Primary infection with cytomegalovirus in ulcerative colitis SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE cytomegalovirus; CMV colitis; ulcerative colitis; inflammatory bowel disease; primary infection; antiviral therapy ID INFLAMMATORY-BOWEL-DISEASE; TUMOR-NECROSIS-FACTOR; TRANSPLANT RECIPIENTS; CLINICAL-SIGNIFICANCE; PREVALENCE; PATIENT; ADULT; ONSET; CMV C1 Harvard Univ, Sch Med, Transplant Infect Dis & Compromised Host Program, Div Infect Dis,Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Harvard Univ, Sch Med, Transplant Infect Dis & Compromised Host Program, Div Infect Dis,Massachusetts Gen Hosp, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM jfishman@partners.org RI Martin, Stanley/E-3600-2011 NR 31 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD DEC PY 2006 VL 51 IS 12 BP 2184 EP 2187 DI 10.1007/s10620-006-9474-9 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 121WV UT WOS:000243188600012 PM 17120145 ER PT J AU Malo, MS Biswas, S Abedrapo, MA Yeh, L Chen, A Hodin, RA AF Malo, Madhu S. Biswas, Shaluk Abedrapo, Mario A. Yeh, Lisa Chen, Alexander Hodin, Richard A. TI The pro-inflammatory cytokines, IL-1 beta and TNF-alpha, inhibit intestinal alkaline phosphatase gene expression SO DNA AND CELL BIOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; CHAIN FATTY-ACIDS; DISTAL ULCERATIVE-COLITIS; CULTURED RAT ENTEROCYTES; KRUPPEL-LIKE FACTOR; MESSENGER-RNA; BUTYRATE ENEMAS; CROHNS-DISEASE; CELIAC-DISEASE AB High levels of the pro-inflammatory cytokines, interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), are present in the gut mucosa of patients suffering form various diseases, most notably inflammatory bowel diseases (IBD). Since the inflammatory milieu can cause important alterations in epithelial cell function, we examined the cytokine effects on the expression of the enterocyte differentiation marker, intestinal alkaline phosphatase (IAP), a protein that detoxifies bacterial lipopolysaccharides (LPS) and limits fat absorption. Sodium butyrate (NaBu), a short-chain fatty acid and histone deacetylase (HDAC) inhibitor, was used to induce IAP expression in HT-29 cells and the cells were also treated +/- the cytokines. Northern blots confirmed IAP induction by NaBu, however, pretreatment (6 h) with either cytokine showed a dose-dependent inhibition of IAP expression. IAP Western analyses and alkaline phosphatase enzyme assays corroborated the Northern data and confirmed that the cytokines inhibit IAP induction. Transient transfections with a reporter plasmid carrying the human IAP promoter showed significant inhibition of NaBu-induced IAP gene activation by the cytokines (100 and 60% inhibition with IL-1 beta and TNF-alpha, respectively). Western analyses showed that NaBu induced H4 and H3 histone acetylation, and pretreatment with IL-1 beta or TNF-alpha did not change this global acetylation pattern. In contrast, chromatin immunoprecipitation showed that local histone acetylation of the IAP promoter region was specifically inhibited by either cytokine. We conclude that IL-1 beta and TNF-alpha inhibit NaBu-induced IAP gene expression, likely by blocking the histone acetylation within its promoter. Cytokine-mediated IAP gene silencing may have important implications for gut epithelial function in the setting of intestinal inflammatory conditions. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hodin, RA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,Gray Bigelow 504, Boston, MA 02114 USA. EM rhodin@partners.org FU NIDDK NIH HHS [R01DK47186, R01DK50623] NR 82 TC 32 Z9 34 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD DEC PY 2006 VL 25 IS 12 BP 684 EP 695 DI 10.1089/dna.2006.25.684 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 120VY UT WOS:000243115700005 PM 17233117 ER PT J AU Guinan, JJ AF Guinan, John J., Jr. TI Olivocochlear efferents: Anatomy, physiology, function, and the measurement of efferent effects in humans SO EAR AND HEARING LA English DT Review ID EVOKED OTOACOUSTIC EMISSIONS; GUINEA-PIG COCHLEA; OUTER HAIR-CELLS; CONTRALATERAL ACOUSTIC STIMULATION; ACTIVE MICROMECHANICAL PROPERTIES; COMPOUND ACTION-POTENTIALS; AUDITORY-NERVE RESPONSES; BROAD-BAND NOISE; ELECTRICAL-STIMULATION; INFERIOR COLLICULUS AB This review covers the basic anatomy and physiology of the olivocochlear reflexes and the use of otoacoustic emissions (OAEs) in humans to monitor the effects of one group, the medial olivocochlear (MOO efferents. MOC fibers synapse on outer hair cells (OHCs), and activation of these fibers inhibits basilar membrane responses to low-level sounds. This MOC-induced decrease in the gain of the cochlear amplifier is reflected in changes in OAEs. Any OAE can be used to monitor MOC effects on the cochlear amplifier. Each OAE type has its own advantages and disadvantages. The most straightforward technique for monitoring MOC effects is to elicit MOC activity with an elicitor sound contralateral to the OAE test ear. MOC effects can also be monitored using an ipsilateral elicitor of MOC activity, but the ipsilateral elicitor brings additional problems caused by suppression and cochlear slow intrinsic effects. To measure MOC effects accurately, one must ensure that there are no middle-ear-muscle contractions. Although standard clinical middle-ear-muscle tests are not adequate for this, adequate tests can usually be done with OAE-measuring instruments. An additional complication is that most probe sounds also elicit MOC activity, although this does not prevent the probe from showing MOC effects elicited by contralateral sound. A variety of data indicate that MOC efferents help to reduce acoustic trauma and lessen the masking of transients by background noise; for instance, they aid in speech comprehension in noise. However, much remains to be learned about the role of efferents in auditory function. Monitoring MOC effects in humans using OAEs should continue to provide valuable insights into the role of MOC efferents and may also provide clinical benefits. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Speech & Hearing Biosci & Technol Program,Harvard, Cambridge, MA 02138 USA. RP Guinan, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM jjg@epl.meei.harvard.edu FU NIDCD NIH HHS [R01 DC005977, R01-DC000235, R01-DC005977] NR 139 TC 249 Z9 257 U1 3 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0196-0202 EI 1538-4667 J9 EAR HEARING JI Ear Hear. PD DEC PY 2006 VL 27 IS 6 BP 589 EP 607 DI 10.1097/01.aud.0000240507.83072.e7 PG 19 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 104AF UT WOS:000241927600001 PM 17086072 ER PT J AU Pierie, JPEN Betensky, RA Choudry, U Willett, CG Souba, WW Ott, MJ AF Pierie, J. -P. E. N. Betensky, R. A. Choudry, U. Willett, C. G. Souba, W. W. Ott, M. J. TI Outcomes in a series of 103 retroperitoneal sarcomas SO EJSO LA English DT Article DE surgery; intra-operative radiation therapy ID SOFT-TISSUE SARCOMAS; RADIATION-THERAPY; INTRAOPERATIVE RADIOTHERAPY; PROGNOSTIC FACTORS; SURVIVAL; MANAGEMENT; EXPERIENCE; SURGERY AB Aims: To report the effect on outcome of selection in patients receiving intra-operative electron beam radiation (IOERT) and external beam radiation therapy (EBRT). Methods: One hundred and three patients treated for primary RS were studied. Median follow-up was 27 months. Clinical presentation, tumor characteristics, and treatment methods were analyzed to determine impact on survival and recurrence and if selection was occurring. Results: Mean age was 55 +/- 17 years. Mean tumor size was 15 +/- 6 cm and 88 were high-grade. Complete gross tumor resection (CR) occurred in 62 patients and improved survival vs. both debulking (p=0.0005) and biopsy (p < 0.0001). The 5- and 10-year survival rates were 62% and 52% for those with CR vs. 29% and 20% after incomplete resection. Among the 62 CR patients, there was selection to receive additional EBRT IOERT in patients with high-grade tumors (p=0.005) and/or microscopically positive margins (p=0.011). In these high-risk patients there was a trend for IOERT to further augment survival vs. EBRT alone and to increase the time to both local and distant recurrences (p=0.036). Conclusions: Complete gross resection is the primary form of curative treatment for retroperitoneal sarcomas. Selection led to patients with high-risk tumors receiving additional radiation therapy. There appears to be a beneficial effect of IOERT plus EBRT in these high-risk patients after complete tumor resection. (c) 2006 Published by Elsevier Ltd. C1 Med Ctr Leeuwarden, Dept Surg, NL-8901 BR Leeuwarden, Netherlands. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Penn State Geisinger Hlth Syst, Dept Surg, Hershey, PA USA. RP Pierie, JPEN (reprint author), Med Ctr Leeuwarden, Dept Surg, Henri Dunantweg 2,POB 888, NL-8901 BR Leeuwarden, Netherlands. EM j.pierie@znb.nl NR 26 TC 26 Z9 29 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0748-7983 J9 EJSO-EUR J SURG ONC JI EJSO PD DEC PY 2006 VL 32 IS 10 BP 1235 EP 1241 DI 10.1016/j.ejso.2006.07.002 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 121CW UT WOS:000243136700034 PM 16919908 ER PT J AU Handschin, C Spiegelman, BM AF Handschin, Christoph Spiegelman, Bruce M. TI Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy hemeostasis, and metabolism SO ENDOCRINE REVIEWS LA English DT Review ID TRANSCRIPTIONAL COACTIVATOR; MITOCHONDRIAL BIOGENESIS; HEPATIC GLUCONEOGENESIS; SKELETAL-MUSCLE; INSULIN-RESISTANCE; GENE-EXPRESSION; PROTEIN-KINASE; OXIDATIVE-PHOSPHORYLATION; ADAPTIVE THERMOGENESIS; PGC-1-ALPHA EXPRESSION AB Many biological programs are regulated at the transcriptional level. This is generally achieved by the concerted actions of several transcription factors. Recent findings have shown that, in many cases, transcriptional coactivators coordinate the overall regulation of the biological programs. One of the best-studied examples of coactivator control of metabolic pathways is the peroxisome proliferator-activated receptor coactivator 1 (PGC-1) family. These proteins are strong activators of mitochondrial function and are thus dominant regulators of oxidative metabolism in a variety of tissues. The PGC-1 coactivators themselves are subject to powerful regulation at the transcriptional and posttranslational levels. Recent studies have elucidated the function of the PGC-1 coactivators in different tissues and have highlighted the implications of PGC-1 dysregulation in diseases such as diabetes, obesity, cardiomyopathy, or neurodegeneration. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, One Jimmy Fund Way, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu RI Handschin, Christoph/E-6886-2015 OI Handschin, Christoph/0000-0003-0603-1097 FU NIDDK NIH HHS [DK54477, DK61562] NR 86 TC 560 Z9 570 U1 3 U2 36 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD DEC PY 2006 VL 27 IS 7 BP 728 EP 735 DI 10.1210/er.2006-0037 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 116VJ UT WOS:000242831300005 PM 17018837 ER PT J AU Ao, Y Go, VLW Toy, N Li, T Wang, Y Song, MK Reeve, JR Liu, YY Yang, H AF Ao, Yan Go, Vay Liang W. Toy, Natalie Li, Tei Wang, Yu Song, Moon K. Reeve, Joseph R., Jr. Liu, Yanyun Yang, Hong TI Brainstem thyrotropin-releasing hormone regulates food intake through vagal-dependent cholinergic stimulation of ghrelin secretion SO ENDOCRINOLOGY LA English DT Article ID GASTRIC-ACID-SECRETION; DORSAL MOTOR NUCLEUS; CAUDAL RAPHE NUCLEI; GENE-EXPRESSION; INTRACISTERNAL TRH; MEDULLARY RAPHE; FOS EXPRESSION; SUBSTANCE-P; RATS; COMPLEX AB The brainstem is essential for mediating energetic response to starvation. Brain stem TRH is synthesized in caudal raphe nuclei innervating brainstem and spinal vagal and sympathetic motor neurons. Intracisternal injection (ic) of a stable TRH analog RX77368 (7.5-25 ng) dose-dependently stimulated solid food intake by 2.4- to 3-fold in freely fed rats, an effect that lasted for 3 h. By contrast, RX77368 at 25 ng injected into the lateral ventricle induced a delayed and insignificant orexigenic effect only in the first hour. In pentobarbital-anesthetized rats, RX77368 (50 ng) ic induced a significant bipeak increase in serum total ghrelin levels from the basal of 8.7 +/- 1.7 ng/ml to 13.4 +/- 2.4 ng/ml at 30 min and 14.5 +/- 2.0 ng/ml at 90 min, which was prevented by either bilateral vagotomy (-60 min) or atropine pretreatment (2 mg/kg, -30 min) but magnified by bilateral adrenalectomy (-60 min). TRH analog ic-induced food intake in freely fed rats was abolished by either peripheral atropine or ghrelin receptor antagonist (D-Lys-3)-GHRP-6 (10 mu mol/kg) or ic Y1 receptor antagonist 122PU91 (10 nmol/5 mu l). Brain stem TRH mRNA and TRH receptor 1 mRNA increased by 57-58 and 33-35% in 24- and 48-h fasted rats and returned to the fed levels after a 3-h refeeding. Natural food intake in overnight fasted rats was significantly reduced by ic TRH antibody, ic Y1 antagonist, and peripheral atropine. These data establish a physiological role of brainstem TRH in vagal-ghrelin-mediated stimulation of food intake, which involves interaction with brainstem Y1 receptors. C1 Vet Affairs Greater Los Angeles Healthcare Syst, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Ulcer Res & Educ, Digest Dis Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Div Digest Dis, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA USA. RP Yang, H (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, CURE, Digest Dis Res Ctr, Bldg 115,Room 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM hoyang@ucla.edu FU NIDDK NIH HHS [DK-41301] NR 51 TC 31 Z9 32 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2006 VL 147 IS 12 BP 6004 EP 6010 DI 10.1210/en.2006-0820 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 105QK UT WOS:000242047200056 PM 16959836 ER PT J AU Kuo, T Christensen, R Gelberg, L Rubenstein, L Burke, A AF Kuo, T Christensen, R Gelberg, L Rubenstein, L Burke, A TI Community-research collaboration between researchers and acupuncturists: Integrating a participatory research approach in a statewide survey of licensed acupuncturists in California SO ETHNICITY & DISEASE LA English DT Article DE acupuncture; community participation; mistrust; Oriental Medicine ID UNITED-STATES; COMPLEMENTARY; MEDICINE AB The Licensed Acupuncture Collaborative Study, a job analysis of licensed acupuncturists in California, provides a model for building community-research partnerships between university researchers and communities of non-physician clinicians. The study design used a project-management approach based on the core principles of community-based participatory research: 1) mobilizing shared expertise and resources to address issues of concern; 2) sharing power in the decision-making process; and 3) promoting mutual ownerships of resources and products derived from the collaboration. A project infrastructure involving the sharing of study responsibilities across university researchers, individual acupuncturists, and state community organizations was developed and cultivated over a three-year project period. Essential factors in the success of this project included shared objectives, addressing the concerns about collaboration among academic and community partners, inclusion of nontraditional viewpoints about healthcare policy, and participation by the acupuncturist community in performing the research. These activities helped to overcome mistrust and perceived power differences between researchers and the acupuncturist community. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, Los Angeles, CA 90024 USA. Amer Assoc Oriental Med, Los Angeles, CA USA. VA Greater Los Angeles Med Ctr, VAGLAHS Ctr Excellence Study Healthcare Provider, Sepulveda, CA USA. San Francisco State Univ, Dept Hlth Educ, Inst Holist Healing Studies, San Francisco, CA 94132 USA. RP Kuo, T (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, 10880 Wilshire Blvd,Suite 1800, Los Angeles, CA 90024 USA. EM tkuo@mednet.ucla.edu NR 30 TC 0 Z9 0 U1 1 U2 2 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD WIN PY 2006 VL 16 IS 1 SU 1 BP 98 EP 106 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 010EW UT WOS:000235170700010 ER PT J AU Katznelson, L Robinson, MW Coyle, CL Lee, H Farrell, CE AF Katznelson, Laurence Robinson, Mara W. Coyle, Caryn L. Lee, Hang Farrell, Christina E. TI Effects of modest testosterone supplementation and exercise for 12 weeks on body composition and quality of life in elderly men SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID MUSCLE STRENGTH; OLDER MEN; ACQUIRED HYPOGONADISM; ANDROGEN DEFICIENCY; SKELETAL-MUSCLE; HEALTH; MALES; AGE; SERUM; PHARMACOKINETICS AB Objective: One of the factors that may promote deterioration in quality of life and body composition in elderly men is the relative decline in serum testosterone levels with aging. In this study, we assessed the effects of modest doses of testosterone and a home-based strengthening program on quality of life and body composition in elderly men with relative testosterone insufficiency. Design: Double-blind, placebo-controlled randomized study (testosterone), and additional randomization to a resistance exercise program or no additional exercise for 12 weeks in men between ages of 65 and 85 years with relative testosterone insufficiency. Methods: Seventy sedentary, community dwelling men were randomized to a 5 mg testoderm transdermal system applied daily vs placebo system, and additionally randomized to a home-based resistance exercise program. Subjects were randomized to Group 1 (testosterone plus exercise), Group 2 (testosterone plus no exercise), Group 3 (placebo plus exercise), and Group 4 (placebo plus no exercise). Endpoints included quality of life (assessed by the short form-36 questionnaire) and body composition (measured by dual x-ray absorptiometry scan). Results: Serum testosterone increased by a mean of 10.0 +/- 1.9, 6.6 +/- 1.6, 0.52 +/- 0.6, and 0.5 +/- 0.6 nmol/l in Groups 1, 2, 3, and 4 respectively. There was a significant interaction of testosterone and exercise on quality of life in the domains of physical functioning (P=0.03), role physical (P=0.01), general health (P=0.049), and social functioning (P=0.04). There were no effects of testosterone or exercise on quality of life alone, nor in body composition parameters. Conclusions: Modest testosterone supplementation to elderly men with relative testosterone insufficiency improved quality of life when accompanied by an exercise program. The combination of testosterone and exercise may be an important strategy in the elderly, though further studies are necessary to determine the long-term impact on body composition and function and for analysis of risk/benefit ratios as well. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Phys Therapy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Katznelson, L (reprint author), Stanford Univ, Sch Med, 875 Blake Wilbur Dr, Stanford, CA 94305 USA. EM lkatznelson@stanford.edu FU NCRR NIH HHS [M01-RR-01066]; NIA NIH HHS [R29 AG15882-04] NR 42 TC 27 Z9 28 U1 0 U2 6 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 EI 1479-683X J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD DEC PY 2006 VL 155 IS 6 BP 867 EP 875 DI 10.1530/eje.1.02291 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 124GW UT WOS:000243357300014 PM 17132757 ER PT J AU Chiappelli, F Navarro, AM Moradi, DR Manfrini, E Prolo, P AF Chiappelli, Francesco Navarro, Audrey M. Moradi, David R. Manfrini, Ercolano Prolo, Paolo TI Evidence-based research in complementary and alternative medicine III: Treatment of patients with Alzheimer's disease SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article DE Alzheimer's disease; evidence-based medicine; systematic review; treatment interventions ID RANDOMIZED CONTROLLED-TRIAL; AMYLOID PRECURSOR PROTEIN; DOUBLE-BLIND; GINKGO-BILOBA; APOLIPOPROTEIN-E; SENILE DEMENTIA; UNITED-STATES; RATING-SCALE; MODERATE; BETA AB This paper presents the novel domain of evidence-based research (EBR) in the treatment of patients with Alzheimer's disease (AD) from the perspective of traditional medicine and of complementary and alternative medicine. In earlier lectures we have described the process of evidence-based medicine as a methodological approach to clinical practice that is directed to aid clinical decision-making. Here, we present a practical example of this approach with respect to traditional pharmacological interventions and to complementary and alternative treatments for patients with AD. C1 Univ Calif Los Angeles, Sch Dent, Div Oral Biol & Med, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. Univ Ancona, Neurol Sect Hlth Dist Urbino, Ancona, Italy. RP Chiappelli, F (reprint author), Univ Calif Los Angeles, Sch Dent, Div Oral Biol & Med, CHS 63-090, Los Angeles, CA 90095 USA. EM chiappelli@dent.ucla.edu NR 74 TC 3 Z9 3 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1741-427X J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PD DEC PY 2006 VL 3 IS 4 BP 411 EP 424 DI 10.1093/ecam/nel072 PG 14 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 120GL UT WOS:000243072400003 PM 17173104 ER PT J AU Yerly, D Di Giammarino, L Bihl, F Cerny, A AF Yerly, Daniel Di Giammarino, Loriana Bihl, Florian Cerny, Andreas TI Targets of emerging therapies for viral hepatitis B and C SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE gene therapy; hepatitis B virus; hepatitis C virus; immune therapy; nucleoside analogue; nucleotide analogue; polymerase inhibitor; protease inhibitor; therapeutic vaccine ID VIRUS SERINE-PROTEASE; ANTISENSE OLIGONUCLEOTIDE INHIBITION; HUMAN-IMMUNODEFICIENCY-VIRUS; DEPENDENT RNA-POLYMERASE; BLOOD MONONUCLEAR-CELLS; SMALL INTERFERING RNAS; RIBOSOME ENTRY SITE; IN-VITRO; ADEFOVIR DIPIVOXIL; ANTIVIRAL ACTIVITY AB Viral hepatitis B and C, structurally two completely different viruses, commonly infect human hepatocytes and cause similar clinical manifestations. Since their discovery, IFN has been a pillar in the treatment. However, because of the different natures of the viruses, therapeutic approaches diverge and new treatment targets are tailored specifically for each virus. Herein, the authors analyse therapeutic approaches for hepatitis B virus (HBV) and hepatitis C virus (HCV) and focus on emerging concepts that are under clinical evaluation. In particular, promising viral inhibitors for HBV and HCV are reviewed and the current status of research for gene therapy for HCV is described. Immune therapy is a fast-moving field with fascinating results which include therapeutic vaccines and toll-like receptor agonists that could improve tomorrow's treatment approaches. C1 Univ Bern, Clin Rheumatol & Clin Immunol Allergol, CH-3010 Bern, Switzerland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Partners AIDS Res Ctr, Boston, MA 02114 USA. Osped Reg Lugano, Dept Med, CH-6903 Lugano, Switzerland. RP Cerny, A (reprint author), Univ Bern, Clin Rheumatol & Clin Immunol Allergol, CH-3010 Bern, Switzerland. EM andreas.cerny@bluewin.ch NR 144 TC 6 Z9 6 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD DEC PY 2006 VL 10 IS 6 BP 833 EP 850 DI 10.1517/14728222.10.6.833 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 108XW UT WOS:000242273500007 PM 17105371 ER PT J AU Carpenter, BD Lee, M Ruckdeschel, K Van Haitsma, KS Feldman, PH AF Carpenter, Brian D. Lee, Monica Ruckdeschel, Katy Van Haitsma, Kimberly S. Feldman, Penny H. TI Adult children as informants about parent's psychosocial preferences SO FAMILY RELATIONS LA English DT Article DE adult children; family gerontology; intergenerational relations; psychosocial preferences; long-term care planning ID OLDER-ADULTS; CIRCUMPLEX MODEL; CARE; DEPRESSION; DECISIONS; SCALE AB Utilizing data from 80 adult children-older parent dyads, this study examined the degree to which adult children could predict the psychosocial preferences of their older parents. Overall, children demonstrated good knowledge about parent preferences, although there was wide variability within the sample and across preference domains. Children underestimated how important parents considered continued enrichment and personal growth. Knowledge was associated with parents' functional status and mood. Parent, but not child, perceptions of family flexibility and cohesion were related to children's knowledge. Findings suggest that family life education and intervention programs need to address contextual factors as a means to improve intergenerational knowledge and enhance the likelihood that parent preferences are considered in care planning. C1 Washington Univ, Dept Psychol, St Louis, MO 63130 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Madlyn & Leonard Abramson Ctr Jewish Life, Polisher Res Inst, N Wales, PA 19454 USA. Visiting Nurse Serv New York, Ctr Home Care Policy & Res, New York, NY 10021 USA. RP Carpenter, BD (reprint author), Washington Univ, Dept Psychol, Campus Box 1125, St Louis, MO 63130 USA. EM bcarpenter@wustl.edu; mmlee@artsci.wustl.edu; ruckdesc@mail.med.upenn.edu; kvanhaitsma@abramsoncenter.org; Penny.Feldman@vnsny.org NR 35 TC 17 Z9 17 U1 2 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0197-6664 J9 FAM RELAT JI Fam. Relat. PD DEC PY 2006 VL 55 IS 5 BP 552 EP 563 DI 10.1111/j.1741-3729.2006.00425.x PG 12 WC Family Studies; Social Work SC Family Studies; Social Work GA 119GC UT WOS:000242999800005 ER PT J AU Yorgason, JB Almeida, D Neupert, SD Spiro, A Hoffman, L AF Yorgason, Jeremy B. Almeida, David Neupert, Shevaun D. Spiro, Avron, III Hoffman, Lesa TI A dyadic examination of daily health symptoms and emotional well-being in late-life couples SO FAMILY RELATIONS LA English DT Article DE health; aging; dyads; marriage; daily diary; longitudinal ID MARITAL QUALITY; GENDER-DIFFERENCES; ADJUSTMENT SCALE; MENTAL-HEALTH; NONDISTRESSED COUPLES; PHYSICAL SYMPTOMS; CAREGIVER BURDEN; NEGATIVE AFFECT; OLDER-ADULTS; DAILY LIVES AB This study investigated the link between daily health symptoms and spousal emotional well-being in a sample of 96 older dyads. Higher negative mood and lower positive mood were associated with spousal symptoms in couples wherein husbands or wives reported higher average levels of symptoms. For wives, partner effects were moderated by husbands' marital satisfaction and illness severity. Specifically, higher husband marital satisfaction and illness severity were associated with higher negative mood and lower positive mood for wives on days where husbands reported higher symptom levels. In their work with later-life families, practitioners and educators should address long-term and daily health-related relationship stressors. C1 Brigham Young Univ, Sch Family Life, Provo, UT 84602 USA. Penn State Univ, Dept Human Dev & Family Studies, University Pk, PA 16802 USA. N Carolina State Univ, Dept Psychol, Raleigh, NC 27695 USA. VA Boston Healthcare Syst, Boston, MA 02130 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02130 USA. Univ Nebraska, Dept Psychol, Lincoln, NE 68588 USA. RP Yorgason, JB (reprint author), Brigham Young Univ, Sch Family Life, Provo, UT 84602 USA. EM jeremy_yorgason@byu.edu; dma18@psu.edu; shevaun_neupert@ncsu.edu; aspiro3@bu.edu; lhoffman@unlnotes.unl.edu NR 56 TC 16 Z9 16 U1 2 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0197-6664 J9 FAM RELAT JI Fam. Relat. PD DEC PY 2006 VL 55 IS 5 BP 613 EP 624 DI 10.1111/j.1741-3729.2006.00430.x PG 12 WC Family Studies; Social Work SC Family Studies; Social Work GA 119GC UT WOS:000242999800010 ER PT J AU Nahmias, Y Kramvis, Y Barbe, L Casali, M Berthiaume, F Yarmush, ML AF Nahmias, Yaakov Kramvis, Yiannos Barbe, Laurent Casali, Monica Berthiaume, Francois Yarmush, Martin L. TI A novel formulation of oxygen-carrying matrix enhances liver-specific function of cultured hepatocytes SO FASEB JOURNAL LA English DT Article DE cytochrome P450; fluorocarbon ID LONG-TERM CULTURE; BLOOD SUBSTITUTES; PERFLUOROCARBON EMULSIONS; SANDWICH CONFIGURATION; RAT HEPATOCYTES; CELL-CULTURE; IN-VITRO; HEMOGLOBIN; GRADIENTS; GROWTH AB Oxygen is an important component of the cellular microenvironment, mediating cell survival, differentiation, and function. Oxygen supply is a limiting factor during culture of highly metabolic cells such as hepatocytes. Here we present a simple formulation of a fluorocarbon-based oxygen carrier embedded in collagen gel that increases oxygen concentration in culture 6-fold. Rat hepatocytes cultured on oxygen carrier-collagen showed a significant increase in viability and function. Cytochrome P450IA1 activity was increased by 140% in serum-free cultures and by 820% in serum-containing cultures. The significantly higher hepatocellular function on oxygen carrier-collagen matrix persisted and increased during long-term culture. Long-term albumin secretion was increased by 350% in serum-free cultures and by 166% in serum-containing culture. Long-term urea secretion was increased by 79% in serum-free cultures and by 76% in serum-containing cultures. We conclude that oxygen supply may limit hepatocyte function in vitro. This limitation can be overcome by addition of an oxygen carrier to the extracellular matrix. Culture of hepatocytes on oxygen-carrying matrix mimics the oxygen-rich environment of the liver and provides a simple method for enhanced long-term function.-Nahmias, Y., Kramvis, Y., Barbe, L., Casali, M., Berthiaume, F., Yarmush, M. L. A novel formulation of oxygen-carrying matrix enhances liver-specific function of cultured hepatocytes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Burns Hosp,Dept Surg,Ctr Engn Med, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Burns Hosp,Dept Surg,Ctr Engn Med, Boston, MA 02114 USA. EM ireis@sbi.org RI Nahmias, Yaakov/H-4725-2013; OI Nahmias, Yaakov/0000-0002-6051-616X; Barbe, Laurent/0000-0003-4475-6478 NR 45 TC 45 Z9 47 U1 1 U2 13 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD DEC PY 2006 VL 20 IS 14 BP 2531 EP + DI 10.1096/fj.06-6192fje PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 111YB UT WOS:000242490700013 PM 17077286 ER PT J AU Valencia, A Rajadurai, A Carle, AB Kochevar, IE AF Valencia, Antonio Rajadurai, Anpuchchelvi Carle, A. Bjorn Kochevar, Irene E. TI 7-Dehydrocholesterol enhances ultraviolet A-induced oxidative stress in keratinocytes: Roles of NADPH oxidase, mitochondria, and lipid rafts SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE oxidative stress; ultraviolet radiation; reactive oxygen species; Smith-Lemli-Opitz syndrome; NADPH oxidase; lipid rafts; keratinocytes ID LEMLI-OPITZ-SYNDROME; PROTEIN-TYROSINE PHOSPHATASES; GROWTH-FACTOR RECEPTOR; UVA RADIATION; PLASMA-MEMBRANE; OUTER LEAFLET; IN-VITRO; ACTIVATION; CHOLESTEROL; DOMAINS AB Long wavelength solar UVA radiation stimulates formation of reactive oxygen species (ROS) and prostaglandin E-2 (PGE(2)), which are involved in skin photosensitivity and tumor promotion. High levels of 7-dehydrocholesterol (7-DHC), the precursor to cholesterol, cause exaggerated photosensitivity to UVA in patients with Smith-Lemli-Opitz syndrome (SLOS). Partially replacing cholesterol with 7-DHC in keratinocytes rapidly (< 5 min) increased UVA-induced ROS, intracellular calcium, phospholipase A(2) activity, PGE(2), and NADPH oxidase activity. UVA-induced ROS and PGE(2) production were inhibited in these cells by depleting the Nox1 subunit of NADPH oxidase using siRNA or using a mitochondrial radical quencher, MitoQ Partial replacement of cholesterol with 7-DHC also disrupted membrane lipid raft domains, although depletion of cholesterol, which also disrupts lipid rafts, did not affect UVA-induced increases in ROS and PGE(2). Phospholipid liposomes containing 7-DHC were more rapidly oxidized by a free radical mechanism than those containing cholesterol. These results indicate that 7-DHC enhances rapid UVA-induced ROS and PGE(2) formation by enhancing free radical-mediated membrane lipid oxidation and suggests that this mechanism might underlie the UVA photosensitivity in SLOS. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kochevar, IE (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Thier 224,55 Fruit St, Boston, MA 02114 USA. EM kochevar@helix.mgh.harvard.edu FU NIGMS NIH HHS [GM 30955, R01 GM030755, R01 GM030755-22] NR 66 TC 29 Z9 31 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC 1 PY 2006 VL 41 IS 11 BP 1704 EP 1718 DI 10.1016/j.freeradbiomed.2006.09.006 PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 103EU UT WOS:000241869300011 PM 17145559 ER PT J AU Leaf, A AF Leaf, Alexander TI Prevention of sudden cardiac death by n-3 polyunsaturated fatty acids SO FUNDAMENTAL & CLINICAL PHARMACOLOGY LA English DT Review DE cardiac arrhythmias; fish oil; fish oil fatty acids; prevention of cardiac deaths; sudden cardiac death ID RAT VENTRICULAR MYOCYTES; LONG-CHAIN; FISH-OIL; MYOCARDIAL-INFARCTION; CONTROLLED-TRIAL; NA+ CHANNELS; ARRHYTHMIAS; RISK; FIBRILLATION; OMEGA-3-FATTY-ACIDS AB There were already several epidemiologic studies that showed eating fish frequently seemed to reduce deaths from coronary heart disease. There were also observational and clinical trials, which more specifically showed that the reduction in cardiovascular deaths from eating fish were largely the result of n-3 polyunsaturated fatty acids in fish oil for the prevention of sudden cardiac death (SCD). This led me to perform a clinical trial in which all subjects had an implanted cardioverter-defibrillator and were at very high risk of SCD. The results of this study and the mechanisms by which the n-3 fish oil fatty acids prevent fatal cardiac arrhythmias will be the subject of this review. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Leaf, A (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM aleaf@partners.org NR 34 TC 20 Z9 22 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0767-3981 J9 FUND CLIN PHARMACOL JI Fundam. Clin. Pharmacol. PD DEC PY 2006 VL 20 IS 6 BP 525 EP 538 DI 10.1111/j.1472-8206.2006.00438.x PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 117YL UT WOS:000242909100003 PM 17109646 ER PT J AU Weisberg, E Wright, RD Jiang, JR Ray, A Moreno, D Manley, PW Fabbro, D Hall-Meyers, E Catley, L Podar, K Kung, AL Griffin, JD AF Weisberg, Ellen Wright, Renee D. Jiang, Jingrui Ray, Arghya Moreno, Daisy Manley, Paul W. Fabbro, Doriano Hall-Meyers, Elizabeth Catley, Laurie Podar, Klaus Kung, Andrew L. Griffin, James D. TI Effects of PKC412, nilotinib, and imatinib against GIST-associated PDGFRA mutants with differential imatinib sensitivity SO GASTROENTEROLOGY LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; KINASE INHIBITOR PKC412; IN-VITRO SENSITIVITY; TYROSINE KINASE; SELECTIVE INHIBITOR; PROTEIN-KINASE; BCR-ABL; MUTATIONS; AMN107; CELLS AB Background & Aims: Activating mutations in platelet-derived growth factor receptor alpha (PDGFRA) have been reported in a subset of gastrointestinal stromal tumor (GIST) patients who do not express the mutant stem cell factor receptor c-kit. The responsiveness of mutant PDGFRA-positive GIST to imatinib depends on the location of the PDGFRA mutation; for example, the V561D juxtamembrane domain mutation is more sensitive to imatinib than the D842V kinase domain mutation. In this study, we compare the effects of 3 tyrosine kinase inhibitors, PKC412 and nilotinib, and imatinib, on 2 GIST-related PDGFRA mutants, V561D and D842V, which possess differential sensitivity to imatinib. Methods: The effects of PKC412, nilotinib, and imatinib, alone and in combination, were evaluated via in vitro proliferation studies performed with V561D- or D842V-PDGFRA mutants. The effects of nilotinib and PKC412, alone and combined, were investigated in vivo. Results: PKC412 potently inhibited the V561D-PDGFRA mutant in vitro and the D842V-PDGFRA mutant in vitro and in vivo. Both imatinib and nilotinib displayed potent activity in vitro against the V561D-PDGFRA mutant but were significantly less efficacious against D842V-PDGFRA. However, when combined with either imatinib or PKC412, nilotinib showed no evidence for antagonism and acted in a cooperative fashion against D842V-PDGFRA. Conclusions: Our findings support the clinical testing of PKC412 for treatment of mutant PDGFRA-GIST. The data also support the use of nilotinib as a treatment option for V561D-PDGFRA-associated GIST, although the reduced sensitivity of D842V-PDGFRA probably limits the potential of nilotinib monotherapy for D842V-PDGFRA-associated GIST. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Novartis Inst Biomed Res, Basel, Switzerland. RP Weisberg, E (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Ellen_Weisberg@dfci.harvard.edu RI Catley, Laurence/E-5313-2013; OI Kung, Andrew/0000-0002-9091-488X FU NCI NIH HHS [CA36167, P01 CA066996-05, CA66996, R37 CA036167, P01 CA066996, R01 CA036167]; NIDDK NIH HHS [P01 DK050654, DK50654] NR 21 TC 61 Z9 66 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2006 VL 131 IS 6 BP 1734 EP 1742 DI 10.1053/j.gastro.2006.09.017 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 119RP UT WOS:000243031100017 PM 17087936 ER PT J AU Van Bodegraven, AA Curley, CR Hunt, KA Monsuur, AJ Linskens, RK Onnie, CM Crusius, JBA Annese, V Latiano, A Silverberg, MS Bitton, A Fisher, SA Steinhart, AH Forbes, A Sanderson, J Prescott, NJ Strachan, DP Playford, RJ Mathew, CG Wijmenga, C Daly, MJ Rioux, JD van Heel, DA AF Van Bodegraven, Adriaan A. Curley, Christine R. Hunt, Karen A. Monsuur, Alienke J. Linskens, Ronald K. Onnie, Clive M. Crusius, J. Bart A. Annese, Vito Latiano, Anna Silverberg, Mark S. Bitton, Alain Fisher, Sheila A. Steinhart, A. Hilary Forbes, Alastair Sanderson, Jeremy Prescott, Natalie J. Strachan, David P. Playford, Raymond J. Mathew, Christopher G. Wijmenga, Cisca Daly, Mark J. Rioux, John D. van Heel, David A. TI Genetic variation in myosin IXB is associated with ulcerative colitis SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; GTPASE-ACTIVATING PROTEIN; SUSCEPTIBILITY LOCI; CELIAC-DISEASE; CROHN-DISEASE; HUMAN GENOME; RHO; POLYMORPHISM; VARIANTS; MOTOR AB Background & Aims: Common germline genetic variation in the 3' region of myosin IXB (MYO9B) has been associated recently with susceptibility to celiac disease, with a hypothesis that MYO9B variants might influence intestinal permeability. These findings suggested the current study investigating a possible further role for MYO9B variation in inflammatory bowel disease. Methods: Eight single-nucleotide polymorphisms (SNPs) were selected to tag common haplotypes from the 35-kb 3' region of MYO9B. These included the strongest celiac disease-associated variants reported in a Dutch cohort. These SNPs were studied in 3 independently collected and genotyped case-control cohorts of European descent (UK, Dutch, and Canadian/Italian), comprising in total 2717 inflammatory bowel disease patients (1197 with Crohn's disease, 1520 with ulcerative colitis) and 4440 controls. Results: Common variation in MYO9B was associated with susceptibility to inflammatory bowel disease in all 3 cohorts examined (most associated SNP, rs1545620; meta-analysis P=1.9 X 10(-6); odds ratio, 1.2), with the same alleles showing association as reported for celiac disease. Conclusions: MYO9B genetic variants predispose to inflammatory bowel disease. Interestingly, rs1545620 is a nonsynonymous variant leading to an amino acid change (Ala1011Ser) in the third calmodulin binding IQ domain of MYO9B. Unlike previous variants (in other genes) reported to predispose to inflammatory bowel disease, the association at MY09B was considerably stronger with ulcerative colitis, although weaker association with Crohn's disease also was observed. These data imply shared causal mechanisms underlying intestinal inflammatory diseases. C1 Queens Marys Sch Med & Dent, Ctr Gastroenterol, Inst Cell & Mol Sci, London E1 2AD, England. Harvard Univ, Cambridge, MA 02138 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Vrije Univ Amsterdam, Med Ctr, Dept Gastroenterol, NL-1081 HV Amsterdam, Netherlands. Univ Utrecht, Med Ctr, CG Utrecht, DBG Dept Med Genet, Utrecht, Netherlands. St Anna Ziekenhuis, Dept Gastroenterol & Internal Med, Geldrop, Netherlands. Kings Coll London, Sch Med, Guys Hosp, Dept Med & Mol Genet, London WC2R 2LS, England. Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Immunogenet Lab, NL-1081 HV Amsterdam, Netherlands. IRCCS Hosp, CSS, San Giovanni Rotondo, Italy. Univ Toronto, Sinai Hosp Inflammatory Bowel Dis Ctr, Toronto, ON, Canada. McGill Univ, Ctr Hlth, Royal Victoria Hosp, Dept Gastroenterol, Montreal, PQ, Canada. Kings Coll Hosp London, Dept Gastroenterol, London, England. Guys Hosp, Dept Gastroenterol, London SE1 9RT, England. Univ London St Georges Hosp, Sch Med, Div Community Hlth Sci, London SW17 0RE, England. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. RP van Heel, DA (reprint author), Queens Marys Sch Med & Dent, Ctr Gastroenterol, Inst Cell & Mol Sci, Turner St, London E1 2AD, England. EM d.vanheel@qmul.ac.uk RI van Heel, David/A-8005-2011; Prescott, Natalie/F-6490-2011; Silverberg, Mark/B-4183-2008; Wijmenga, Cisca/D-2173-2009; Rioux, John/A-9599-2015; Mathew, Christopher/G-3434-2015; Latiano, Anna/R-1965-2016; OI Wijmenga, Cisca/0000-0002-5635-1614; Prescott, Natalie/0000-0002-5901-7371; Rioux, John/0000-0001-7560-8326; Mathew, Christopher/0000-0003-4178-1838; Latiano, Anna/0000-0003-3719-2061; van Heel, David/0000-0002-0637-2265 FU Medical Research Council [G0000934]; Wellcome Trust [GR068094MA, 068545/Z/02] NR 28 TC 69 Z9 73 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2006 VL 131 IS 6 BP 1768 EP 1774 DI 10.1053/j.gastro.2006.09.011 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 119RP UT WOS:000243031100021 PM 17087940 ER PT J AU Mayer, EA Naliboff, BD Craig, ADB AF Mayer, Emeran A. Naliboff, Bruce D. Craig, A. D. Bud TI Neuroimaging of the brain-gut axis: From basic understanding to treatment of functional G1 disorders SO GASTROENTEROLOGY LA English DT Review ID IRRITABLE-BOWEL-SYNDROME; LAMINA-I NEURONS; POSITRON-EMISSION-TOMOGRAPHY; 5-HT3 RECEPTOR ANTAGONIST; ANTERIOR CINGULATE CORTEX; VISCERAL STIMULI; CUTANEOUS PAIN; COGNITIVE MODULATION; CEREBRAL ACTIVATION; GENDER-DIFFERENCES AB We are enthusiastic in the introduction of a new monthly review article series, entitled "Reviews in Basic and Clinical Gastroenterology." Written by authorities in their respective fields, the objective of each review article is to provide an overview of a particular theme or topic for the broad scientific and clinical readership. Within a given topic, both basic and clinical aspects will be covered, accompanied by key figures and relevant references, The reader will also appreciate that topics will be interwoven from month to month as well. We hope you enjoy this section. C1 Univ Calif Los Angeles, Neuroimaging Program, Ctr Neurovisceral Sci & Womens Hlth, VAGLAHS,David Geffen Sch Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, CURE, Digest Dis Res Ctr, David Geffen Sch Med, Los Angeles, CA 90073 USA. Barrow Neurol Inst, Phoenix, AZ 85013 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Mayer, EA (reprint author), Univ Calif Los Angeles, Neuroimaging Program, Ctr Neurovisceral Sci & Womens Hlth, VAGLAHS,David Geffen Sch Med, Bldg 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM emayer@ucla.edu FU NCCIH NIH HHS [R24 AT002681]; NIDDK NIH HHS [P50 DK64539, R01 DK48351]; NINDS NIH HHS [R01 NS40413]; NINR NIH HHS [R01 NR007768] NR 143 TC 199 Z9 204 U1 5 U2 26 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2006 VL 131 IS 6 BP 1925 EP 1942 DI 10.1053/j.gastro.2006.10.026 PG 18 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 119RP UT WOS:000243031100036 PM 17188960 ER PT J AU Sanyal, AJ Fontana, RJ Di Bisceglie, AM Everhart, JE Doherty, MC Everson, GT Donovan, JA Mallet, PF Mehta, S Sheikh, MY Reid, AE Ghany, MG Gretch, DR AF Sanyal, Arun J. Fontana, Robert J. Di Bisceglie, Adrian M. Everhart, James E. Doherty, Michael C. Everson, Gregory T. Donovan, John A. Mallet, Peter F. Mehta, Savant Sheikh, Muhammad Y. Reid, Andrea E. Ghany, Marc G. Gretch, David R. CA HALT-C Trial Grp TI The prevalence and risk factors associated with esophageal varices in subjects with hepatitis C and advanced fibrosis SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 24-28, 2003 CL BOSTON, MA SP Amer Assoc Study Liver Dis ID CIRRHOTIC-PATIENTS; NATURAL-HISTORY; PORTAL-HYPERTENSION; LIVER-CIRRHOSIS; GASTROINTESTINAL-TRACT; PROGNOSTIC INDICATORS; RANDOMIZED-TRIAL; VIRUS-INFECTION; PREVENTION; HEMORRHAGE AB Background: The factors predictive of the presence or the absence of esophageal varices in hepatitis C virus (HCV) and advanced fibrosis have not been defined. Objectives: To define the prevalence of esophageal varices and the factors that are positively and negatively with such varices in hepatitis C and advanced fibrosis. Design: A prospective study of esophageal varices and associated risk factors in subjects with hepatitis C and advanced fibrosis. Setting: Prerandomization data from the HALT-C (hepatitis C long-term antiviral treatment against cirrhosis) clinical trial. Patients and Intervention: Subjects with bridging fibrosis or cirrhosis, who were virologic nonresponders to treatment with pegylated interferon alpha 2a and ribavirin, underwent encloscopy Results: Sixteen percent of subjects with bridging fibrosis (95/598) and 39% of subjects with cirrhosis (164/418) had varices (P < .0001); 2% of subjects with bridging fibrosis (13/598) and 11% of those with cirrhosis (48/418) had medium or large varices. Subjects with bridging fibrosis and varices had a significantly lower platelet count and higher bilirubin and international normalized ratio (INR) compared with those without varices, suggesting that the biopsy may have underestimated the severity of fibrosis. A platelet count > 150,000/mm(3) was associated with a negative predictive value of 99% for esophageal varices. By logistic regression modeling, African American race and female sex were protective, whereas a lower platelet count and higher bilirubin and INR predicted varices (c statistic, 0.758). Conclusions: The risk of having varices increases with decreasing platelet counts, increasing bilirubin, and INR. The probability of having medium or large varices at platelet counts > 150,000/mm(3) is negligible in this population. C1 Virginia Commonwealth Univ, Med Ctr, Dept Internal Med, Div Gastroenterol,Hlth Syst, Richmond, VA 23298 USA. Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI 48109 USA. St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. New England Res Inst, Watertown, MA 02172 USA. Univ Colorado, Sch Med, Sect Hepatol, Div Gastroenterol & Hepatol, Denver, CO 80202 USA. Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90089 USA. Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dallas, TX 75230 USA. Univ Massachusetts, Med Ctr, Div Gastroenterol, Worcester, MA 01605 USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA 92717 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. NIDDK, Liver Dis Branch, Div Digest Dis & Nutr, NIH,Dept Hlth & Human Serv, Bethesda, MD USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Sanyal, AJ (reprint author), Virginia Commonwealth Univ, Med Ctr, Dept Internal Med, Div Gastroenterol,Hlth Syst, Box 980341, Richmond, VA 23298 USA. FU NCRR NIH HHS [M01RR-00633, M01RR-01066, M01RR-00827, M01RR-00051, M01RR-06192, M01RR-00043, M01RR-00042, M01RR-00065]; NIDDK NIH HHS [N01-DK-9-2326, N01-DK-9-2323, N01-DK-9-2327, N01-DK-9-2322, N01-DK-9-2324, N01-DK-9-2320, N01-DK-9-2325, N01-DK-9-2328, N01-DK-9-2319, N01-DK-9-2321, N01-DK-9-2318] NR 33 TC 55 Z9 57 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD DEC PY 2006 VL 64 IS 6 BP 855 EP 864 DI 10.1016/j.gie.2006.03.007 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 116AM UT WOS:000242774900002 PM 17140886 ER PT J AU Lieberman, D AF Lieberman, David TI Organizing and designing a research study: a 12-step approach SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT ASGE 2nd Workshop on Achieving Academic Success CY JUL 22-23, 2006 CL Washington, DC SP Amer Soc Gastrointestinal Endoscopy C1 Oregon Hlth Sci Univ, Div Gastroenterol, Portland VA Med Ctr, Portland, OR 97201 USA. RP Lieberman, D (reprint author), Oregon Hlth Sci Univ, Div Gastroenterol, Portland VA Med Ctr, P3-G1, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD DEC PY 2006 VL 64 IS 6 SU S BP S2 EP S3 DI 10.1016/j.gie.2006.10.036 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 117GP UT WOS:000242861400002 PM 17113849 ER PT J AU Walker, JA Tchoudakova, AV McKenney, PT Brill, S Wu, DY Cowley, GS Hariharan, IK Bernards, A AF Walker, James A. Tchoudakova, Anna V. McKenney, Peter T. Brill, Suzanne Wu, Dongyun Cowley, Glenn S. Hariharan, Iswar K. Bernards, Andre TI Reduced growth of Drosophila neurofibromatosis 1 mutants reflects a non-cell-autonomous requirement for GTPase-activating protein activity in larval neurons SO GENES & DEVELOPMENT LA English DT Article DE neurofibromatosis type 1; organismal growth control; non-cell autonomy; Ras signal transduction; Drosophila melanogaster ID GAP-RELATED DOMAIN; ADENYLYL-CYCLASE; PHOSPHOINOSITIDE 3-KINASE; SEROTONIN NEURONS; PROTHORACIC GLAND; INSULIN-RECEPTOR; GENE-EXPRESSION; SENSORY NEURONS; CRITICAL WEIGHT; TYPE-1 NF1 AB Neurofibromatosis type 1 (NF1) is among the most common genetic disorders of humans and is caused by loss of neurofibromin, a large and highly conserved protein whose only known function is to serve as a GTPase-Activating Protein (GAP) for Ras. However, most Drosophila NF1 mutant phenotypes, including an overall growth deficiency, are not readily modified by manipulating Ras signaling strength, but are rescued by increasing signaling through the cAMP-dependent protein kinase A pathway. This has led to suggestions that NF1 has distinct Ras-and cAMP-related functions. Here we report that the Drosophila NF1 growth defect reflects a non-cell-autonomous requirement for NF1 in larval neurons that express the R-Ras ortholog Ras2, that NF1 is a GAP for Ras1 and Ras2, and that a functional NF1-GAP catalytic domain is both necessary and sufficient for rescue. Moreover, a Drosophila p120RasGAP ortholog, when expressed in the appropriate cells, can substitute for NF1 in growth regulation. Our results show that loss of NF1 can give rise to non-cell-autonomous developmental defects, implicate aberrant Ras-mediated signaling in larval neurons as the primary cause of the NF1 growth deficiency, and argue against the notion that neurofibromin has separable Ras-and cAMP-related functions. C1 Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Bernards, A (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. EM abernard@partners.org NR 64 TC 20 Z9 21 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC 1 PY 2006 VL 20 IS 23 BP 3311 EP 3323 DI 10.1101/gad.1466806 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 112LJ UT WOS:000242527100011 PM 17114577 ER PT J AU Shannon, KM Muzikansky, A Chan-Smutko, G Niendorf, KB Ryan, PD AF Shannon, Kristen Mahoney Muzikansky, Alona Chan-Smutko, Gayun Niendorf, Kristen Baker Ryan, Paula D. TI Uptake of BRCA1 rearrangement panel testing: In individuals previously tested for BRCA1/2 mutations SO GENETICS IN MEDICINE LA English DT Article DE BRCA1/2 testing; genetic testing uptake; decliners of genetic testing; BRCA1 rearrangement panel ID BREAST-CANCER PATIENTS; OVARIAN-CANCER; HEREDITARY BREAST; FAMILIES; SUSCEPTIBILITY; GENE; RELATIVES; DELETION AB Purpose: Individuals undergoing genetic testing for BRCA1/2 mutations are routinely counseled about the sensitivity and specificity of testing. In August 2002, testing for 5 large genomic rearrangements in the BRCA1 gene that would not have been detected with full gene sequence analysis became commercially available. We present our data on uptake of the BRCA1 rearrangement panel testing in our clinical cancer genetics program. Methods: Women who participated in our clinical genetic testing program and had previously received an uninformative negative or variant of uncertain significance result from BRCA-1/2 full gene sequencing were invited to consider BRCA1 rearrangement panel testing. Results: Overall, 18/72 individuals underwent BRCA1 rearrangement panel testing. No significant differences were found in the levels of BRCAPRO scores (P = 0.406), age at testing (P = 0.986), number of children (P = 0.35) or number of siblings (P = 0.4) between individuals who chose to pursue additional testing with the rearrangement panel and those who declined. Fisher's Exact Test analysis showed that there is a negative association between having breast or ovarian cancer and being inclined to undergo rearrangement panel testing (P = 0.013). Conclusion: Individuals who undergo genetic testing will not consistently pursue additional or enhanced genetic testing. Future research is needed to clearly elucidate the factors associated with uptake of additional genetic testing. C1 Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Risk Anal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02115 USA. RP Shannon, KM (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Risk Anal, 55 Fruit St YAW 9800, Boston, MA 02115 USA. NR 26 TC 2 Z9 2 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD DEC PY 2006 VL 8 IS 12 BP 740 EP 745 DI 10.1097/01.gim.000250202.06200.6d PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 121MX UT WOS:000243162800002 PM 17172936 ER PT J AU Vartanian, JG Carvalho, AL Yueh, B Furia, CLB Toyota, J McDowell, JA Weymuller, EA Kowalski, LP AF Vartanian, Jose Guilherme Carvalho, Andre Lopes Yueh, Bevan Furia, Cristina Lemos B. Toyota, Julia McDowell, Jennifer A. Weymuller, Ernest A., Jr. Kowalski, Luiz Paulo TI Brazilian-Portuguese validation of the University of Washington Quality of Life questionnaire for patients with head and neck cancer SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE quality of life; head and neck cancer; questionnaires; validity; reliability ID CROSS-CULTURAL ADAPTATION; ORGAN PRESERVATION; HEALTH-STATUS; SCALE; CHEMOTHERAPY; RADIOTHERAPY; LARYNGECTOMY; GUIDELINES; DISABILITY; ANXIETY AB Background. The University of Washington Quality of Life (UW-QOL) questionnaire is an English-language survey instrument used worldwide to assess the quality of life of patients with head and neck cancer. To be used in other cultures, such instruments require careful translation and psychometric validation in other languages. Methods. The translation and cultural adaptation of the questionnaire were performed following accepted international guidelines. The psychometric validation was performed on a consecutive series of patients with at least 1 year of disease-free survival after treatment for squamous cell carcinoma of the upper aerodigestive tract, recruited from October 2004 to January 2005 from a tertiary cancer center hospital. Eligible subjects were invited to complete the Portuguese version of the UW-QOL questionnaire during routine clinical consultation and complete it again within 15 days. They also completed a validated Portuguese version of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and a questionnaire to evaluate anxiety and depression symptoms (Hospital Anxiety and Depression Scale [HADS]). Results. A Portuguese version of the questionnaire was developed in iterative fashion. In the psychometric validation process, a total of 109 patients were analyzed. Reliability was excellent, including both internal consistency (Cronleach's alpha [U] of 0.744) and test retest reliability (intraclass correlation coefficient [ICC] of 0.882). Construct validity was supported by statistically significant relationships between the SF-36 and HAD questionnaires and the translated UW-QOL questionnaire. Conclusions. The Brazilian-Portuguese version of the UW-QOL questionnaire appears to be culturally appropriate and psychometrically valid. This version is a valuable tool to evaluate accurately the quality of life of Brazilian patients with head and neck cancer. (c) 2006 Wiley Periodicals, Inc. C1 Ctr Tratamento & Pesquisa Hosp Canc AC Camargo, Dept Otorhinolaryngol Head & Neck Surg, BR-01509900 Sao Paulo, Brazil. Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. RP Kowalski, LP (reprint author), Ctr Tratamento & Pesquisa Hosp Canc AC Camargo, Dept Otorhinolaryngol Head & Neck Surg, Rua Prof Antonio Prudente,211, BR-01509900 Sao Paulo, Brazil. EM lp_kowalski@uol.com.br RI Francisco, Suely/D-9065-2014; Kowalski, Luiz/D-1701-2012; Carvalho, Andre/C-1185-2011; Vartanian, Jose/B-4470-2015; Carvalho, Andre/S-7053-2016; OI Kowalski, Luiz/0000-0001-5865-9308; Carvalho, Andre/0000-0001-7214-6402; Carvalho, Andre/0000-0001-7214-6402; Yueh, Bevan/0000-0003-1380-1053; Kowalski, Luiz Paulo/0000-0002-0481-156X NR 24 TC 21 Z9 26 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD DEC PY 2006 VL 28 IS 12 BP 1115 EP 1121 DI 10.1002/hed.20464 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 111LD UT WOS:000242452200009 PM 16823873 ER PT J AU Mroz, EA Rocco, JW AF Mroz, Edmund A. Rocco, James W. TI RNA interference: Natural, experimental, and clinical roles in cancer biology SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Review DE head and neck oncology; RNA interference; microRNA; shRNA; gene knockout ID SQUAMOUS-CELL CARCINOMA; DOUBLE-STRANDED-RNA; SHORT HAIRPIN RNAS; ANTI-SENSE RNA; SMALL INHIBITORY RNA; MAMMALIAN-CELLS; GENE-THERAPY; MICROPROCESSOR COMPLEX; CAENORHABDITIS-ELEGANS; LENTIVIRAL VECTORS AB The old idea of using antisense RNA to block messenger RNA has recently led to powerful new techniques for knocking down expression of individual protein-coding genes. The simplicity and general applicability of these new methods for RNA interference (RNAi) have turned them into fundamental tools in molecular and cellular biology, with more than 5000 publications using them during the few years since they were developed. These experimental methods are now known to exploit fundamental cellular processes that regulate differentiation via genomically encoded RNAi sequences known as microRNAs (miRNAs); changes in endogenous microRNA regulation have now been implicated in oncogenesis. Clinical trials based on local delivery of interfering RNA have already begun. More general methods for safe and effective delivery of interfering RNA to intact organisms are being developed, which could open the way to widespread clinical applications. Because RNAi can provide selective knockdown of almost any protein, it may soon provide an approach to individualized cancer therapy. (c) 2006 Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Rocco, JW (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, 55 Fruit St, Boston, MA 02114 USA. EM jrocco@partners.org NR 75 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 EI 1097-0347 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD DEC PY 2006 VL 28 IS 12 BP 1132 EP 1141 DI 10.1002/hed.20439 PG 10 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 111LD UT WOS:000242452200011 PM 16823868 ER PT J AU Baggish, AL Smith, RN Palacios, I Vlahakes, GJ Yoerger, DM Picard, MH Lowry, PA Jang, IK Fifer, MA AF Baggish, A. L. Smith, R. N. Palacios, I. Vlahakes, G. J. Yoerger, D. M. Picard, M. H. Lowry, P. A. Jang, I-K Fifer, M. A. TI Pathological effects of alcohol septal ablation for hypertrophic obstructive cardiomyopathy SO HEART LA English DT Article ID VENTRICULAR-TACHYCARDIA; CHEMICAL ABLATION; ETHANOL; INJECTION; INFUSION; MYOCARDIUM; REDUCTION; CARCINOMA; STENOSIS; CATHETER AB Background: The pathological effects and the mechanisms of action of intracoronary administration of ethanol for alcohol septal ablation (ASA) for the management of hypertrophic obstructive cardiomyopathy (HOCM) are unknown. Methods: We examined surgical specimens and, in one case, autopsy specimens from four patients who underwent surgical septal myectomy 2 days to 14 months after unsuccessful ASA. Results: Pathological examination early after ASA showed coagulative necrosis of both the myocardium and the septal perforator arteries. Affected arteries were distended and occluded by necrotic intraluminal debris, without platelet-fibrin thrombi. Late after unsuccessful ASA, excised septal tissue was heterogeneous, containing a region of dense scar, and adjacent tissue containing viable myocytes and interspersed scar. Conclusions: Intracoronary administration of ethanol in patients with HOCM causes acute myocardial infarction with vascular necrosis. The coagulative necrosis of the arteries, their distension by necrotic debris and the absence of platelet-fibrin thrombi distinguish ethanol-induced infarction from that caused by atherosclerotic coronary artery disease. The direct vascular toxicity of ethanol may be an important aspect of the mechanism of successful ASA. C1 Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Fifer, MA (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, 55 Fruit St,Gray Bigelow Bldg,Suite 800,Mailstop, Boston, MA 02114 USA. EM mfifer@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 23 TC 28 Z9 32 U1 1 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD DEC PY 2006 VL 92 IS 12 BP 1773 EP 1778 DI 10.1136/hrt.2006.092007 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 105QU UT WOS:000242048200014 PM 16807273 ER PT J AU Batchelor, TT Byrne, TN AF Batchelor, Tracy T. Byrne, Thomas N. TI Supportive care of brain tumor patients SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID MOLECULAR-WEIGHT HEPARIN; PNEUMOCYSTIS-CARINII PNEUMONIA; DEEP-VEIN THROMBOSIS; GLUCOCORTICOID-INDUCED OSTEOPOROSIS; CEREBROSPINAL-FLUID PRESSURE; VASCULAR-PERMEABILITY FACTOR; SPINAL EPIDURAL LIPOMATOSIS; PLACEBO-CONTROLLED TRIAL; HIGH-GRADE GLIOMAS; VENA-CAVA FILTER AB The supportive care of patients who have brain tumors consists mainly. of the treatment of brain edema, seizures, venous thromboembolism, and cognitive dysfunction. Each of these complications may occur in patients who have primary or metastatic brain tumors. The development of any of these complications significantly increases the morbidity and mortality associated with brain tumors. Effective treatment is usually possible, however, and can result in an improved quality of life for these patients. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Stephen E & Catherine Pappas Ctr Neur, Boston, MA 02114 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Batchelor, TT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Stephen E & Catherine Pappas Ctr Neur, 55 Fruit St, Boston, MA 02114 USA. EM tbatchelor@partners.org NR 171 TC 30 Z9 30 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 2006 VL 20 IS 6 BP 1337 EP + DI 10.1016/j.hoc.2006.09.013 PG 26 WC Oncology; Hematology SC Oncology; Hematology GA 116NY UT WOS:000242810800011 PM 17113467 ER PT J AU Everson, GT Hoefs, JC Seeff, LB Bonkovsky, HL Naishadham, D Shiffinan, ML Kahn, JA Lok, ASF Di Bisceglie, AM Lee, WM Dienstag, JL Ghany, MG Morishima, C AF Everson, Gregory T. Hoefs, John C. Seeff, Leonard B. Bonkovsky, Herbert L. Naishadham, Deepa Shiffinan, Mitchell L. Kahn, Jeffrey A. Lok, Anna S. F. Di Bisceglie, Adrian M. Lee, William M. Dienstag, Jules L. Ghany, Marc G. Morishima, Chihiro CA HALT-C Trial Grp TI Impact of disease severity on outcome of antiviral therapy for chronic hepatitis C: Lessons from the HALT-C trial SO HEPATOLOGY LA English DT Article ID VIRUS-INFECTION; UNITED-STATES; PEGINTERFERON ALPHA-2A; LIVER-TRANSPLANTATION; COMBINATION THERAPY; PLUS RIBAVIRIN; CIRRHOSIS; PREVALENCE; MANAGEMENT; MORBIDITY AB In patients with chronic hepatitis C, advanced fibrosis and cirrhosis are associated with lower rates of sustained virologic response (SVR) to interferon (IFN)-based therapy. In this study, we assessed virologic response to retreatment with peginterferon alfa-2a and ribavirin (RBV), as a function of the baseline fibrosis score (Ishak staging) and platelet count, in 1,046 patients enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. All patients had failed prior treatment with IFN or peginterferon +/- RBV and had Ishak fibrosis scores >= 3. Four groups of patients with increasingly severe liver disease were compared: (A) bridging fibrosis (Ishak 3 and 4) with platelet counts > 125,000/mm(3) (n = 559); (B) bridging fibrosis with platelet counts <= 125,000/mm(3) (n = 96); (C) cirrhosis (Ishak 5 and 6) with platelet counts > 125,000/mm3 (n = 198); and (D) cirrhosis with platelet counts 5125,000/mm3 (n = 193). SVR rates were 23%, 17%, 10%, and 9% in groups A, B, C, and D, respectively (P < .0001 for trend). Reduction in SVR as a function of increasingly severe disease was independent of age, percent African American, HCV genotype, HCV level, and type of prior therapy. Dose reduction lowered SVR frequencies, but to a lesser extent than disease severity. By logistic regression, cirrhosis (P < .0001) was the major determinant that impaired virologic response, independent of dose reduction or platelet count. In conclusion, disease severity is a major independent determinant of rate of SVR in patients with advanced chronic hepatitis C. New strategies are needed to optimize antiviral therapy in these "difficult-to-cure" patients. C1 Univ Colorado, Sch Med, Hlth Sci Ctr, Div Gastroenterol & Hepatol,Sect Hepatol, Denver, CO 80262 USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA 92717 USA. NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Dept Biol Mol & Struct, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Liver Biliary Pancret Ctr, Farmington, CT USA. New England Res Inst, Watertown, MA 02172 USA. Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA 23284 USA. Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90089 USA. Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. St Louis Univ, Sch Med, St Louis, MO 63103 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. NIDDK, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. RP Everson, GT (reprint author), Univ Colorado, Sch Med, Hlth Sci Ctr, Div Gastroenterol & Hepatol,Sect Hepatol, 4200 E 9th Ave,B-154, Denver, CO 80262 USA. EM greg.everson@uchsc.edu RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU NCRR NIH HHS [M01RR-00042, M01RR-00043, M01RR-00051, M01RR-00065, M01RR-00633, M01RR-00827, M01RR-01066, M01RR-06192]; NIDDK NIH HHS [N01-DK-9-2326, N01-DK-9-2318, N01-DK-9-2319, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2322, N01-DK-9-2323, N01-DK-9-2324, N01-DK-9-2325, N01-DK-9-2327, N01-DK-9-2328] NR 27 TC 109 Z9 111 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2006 VL 44 IS 6 BP 1675 EP 1684 DI 10.1002/hep.21440 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 112QC UT WOS:000242540700038 PM 17133499 ER PT J AU Bruder, ED Raff, H Goodfriend, TL AF Bruder, E. D. Raff, H. Goodfriend, T. L. CA Aurora St Lukes Med Ctr TI An oxidized derivative of linoleic acid stimulates dehydroepiandrosterone production by human adrenal cells SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE adrenal cortex; steroidogenesis; androgens; fatty acids ID POLYCYSTIC-OVARY-SYNDROME; ARACHIDONIC-ACID; ALDOSTERONE SECRETION; ANDROGEN PRODUCTION; FATTY-ACIDS; IN-VITRO; STEROIDOGENESIS; EXCESS; RAT; AXIS AB We previously reported that an oxidized derivative of linoleic acid stimulated steroidogenesis in rat adrenal cells. This derivative was also detected in human plasma, and was positively correlated with visceral adiposity and plasma DHEA-S. The present study sought to characterize the effects of this derivative, 12,13-epoxy-9-keto-(10-trans)-octadecenoic acid (EKODE), on steroid production by normal human adrenocortical cells obtained during clinically-indicated adrenalectomy. Cell suspensions were incubated in the presence of varying concentrations of EKODE and ACTH. EKODE (16 mu M) significantly increased DHEA production by 28% under basal conditions and by 25% in the presence of a low concentration of ACTH (0.2 ng/ml). The effect on DHEA was absent at a higher ACTH concentration (2.0 ng/ml). EKODE decreased cortisol production by 16% (low ACTH) and 25% (high ACTH), but was without effect on cortisol under basal conditions. The results suggest that EKODE affects adrenal DHEA production in the human, possibly by modulating steroidogenic enzyme activity. We postulate that excess visceral fat delivers fatty acids to the liver, where oxidized derivatives are formed that modulate adrenal steroidogenesis. This may be an important phenomenon in the genesis of changes in adrenal function associated with syndromes of obesity, especially those that include androgen excess. C1 Aurora St Lukes Med Ctr, Endocrine Res Lab, Milwaukee, WI 53215 USA. Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. Univ Wisconsin, Dept Pharmacol, Madison, WI 53706 USA. RP Raff, H (reprint author), Aurora St Lukes Med Ctr, Endocrine Res Lab, Phys Off Bldg,2801 W KK River Pky,Suite 245, Milwaukee, WI 53215 USA. EM hraff@mcw.edu FU NHLBI NIH HHS [HL076238] NR 20 TC 6 Z9 6 U1 1 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD DEC PY 2006 VL 38 IS 12 BP 803 EP 806 DI 10.1055/s-2006-956182 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 124GR UT WOS:000243356800005 PM 17163354 ER PT J AU Fukuoka, Y Oostendorp, TF Sherman, DA Armoundas, AA AF Fukuoka, Yutaka Oostendorp, Thom F. Sherman, Derin A. Armoundas, Antonis A. TI Applicability of the single equivalent moving dipole model in an infinite homogeneous medium to identify cardiac electrical sources: A computer simulation study in a realistic anatomic geometry torso model SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE body surface potentials; equivalent dipole; inverse problem; simulation study ID RADIOFREQUENCY CATHETER ABLATION; VENTRICULAR-TACHYCARDIA; BODY-SURFACE; MYOCARDIAL-INFARCTION; REPOLARIZATION POTENTIALS; VOLUME CONDUCTORS; INVERSE SOLUTION; ACTIVATION; SITES; LOCALIZATION AB We have previously proposed an inverse algorithm for fitting potentials due to an arbitrary bio-electrical source to a single equivalent moving dipole (SEMD) model. The algorithm achieves fast identification of the SEMD parameters by employing a SEMD model embedded in an infinite homogeneous volume conductor. However, this may lead to systematic error in the identification of the SEMD parameters. In this paper, we investigate the accuracy of the algorithm in a realistic anatomic geometry torso model (forward problem). Specifically, we investigate the effect of measurement noise, dipole position and electrode configuration in the accuracy of the algorithm. The boundary element method was used to calculate the forward potential distribution at multiple electrode positions on the body surface due to a point dipole in the heart. We have found that the position and not the number of electrodes as well as the site of the origin of the arrhythmia in the heart have a significant effect on the accuracy of the inverse algorithm, while the measurement noise does not. Finally, we have shown that the inverse algorithm preserves the topology of the source distribution in the heart, thus potentially allowing the cardiac electrophysiologist to efficiently and accurately guide the tip of the catheter to the ablation site. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Tokyo Med & Dent Univ, Sch Biomed Sci, Tokyo 1138510, Japan. Radboud Univ Med Ctr, NL-6500 HB Nijmegen, Netherlands. Cornell Coll, Mt Vernon, IA 52314 USA. RP Armoundas, AA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM fukuoka.bsm@tmd.ac.jp; aarmoundas@partners.org RI Oostendorp, Thom/B-9648-2013 NR 31 TC 13 Z9 13 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD DEC PY 2006 VL 53 IS 12 BP 2436 EP 2444 DI 10.1109/TBME.2006.880882 PN 1 PG 9 WC Engineering, Biomedical SC Engineering GA 110FJ UT WOS:000242363400003 PM 17153200 ER PT J AU Cooper, RA Boninger, ML Spaeth, DM Ding, D Guo, SF Koontz, AM Fitzgerald, SG Cooper, R Kelleher, A Collins, DM AF Cooper, Rory A. Boninger, Michael L. Spaeth, Donald M. Ding, Dan Guo, Songfeng Koontz, Alicia M. Fitzgerald, Shirley G. Cooper, Rosemarie Kelleher, Annmarie Collins, Diane M. TI Engineering better wheelchairs to enhance community participation SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Review DE biomechanics; controls; human-machine interfaces; rehabilitation engineering; wheelchair ID SPINAL-CORD-INJURY; POWER-ASSISTED WHEELCHAIR; BEARING UPPER EXTREMITY; LONG-TERM PARAPLEGIA; LOW-LEVEL PARAPLEGIA; PAIN INDEX WUSPI; MULTIPLE-SCLEROSIS; SHOULDER PAIN; USERS SHOULDER; ELECTROMYOGRAPHIC ANALYSIS AB With about 2.2 million Americans currently using wheeled mobility devices, wheelchairs are frequently provided to people with impaired mobility to provide accessibility to the community. Individuals with spinal cord injuries, arthritis, balance disorders, and other conditions or diseases are typical users of wheelchairs. However, secondary injuries and wheelchair-related accidents are risks introduced by wheelchairs. Research is underway to advance wheelchair design to prevent or accommodate secondary injuries related to propulsion and transfer biomechanics, while improving safe, functional performance and accessibility to the community. This paper summarizes research and development underway aimed at enhancing safety and optimizing wheelchair design. C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15206 USA. RP Cooper, RA (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu OI Boninger, Michael/0000-0001-6966-919X FU PHS HHS [H133E990001, H133N000019] NR 192 TC 35 Z9 35 U1 4 U2 18 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1534-4320 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD DEC PY 2006 VL 14 IS 4 BP 438 EP 455 DI 10.1109/TNSRE.2006.888382 PG 18 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 118OJ UT WOS:000242951300005 PM 17190036 ER PT J AU Burns, CE Zon, LI AF Burns, Caroline Erter Zon, Leonard I. TI Homing sweet homing: Odyssey of hematopoietic stem cells SO IMMUNITY LA English DT Editorial Material ID EMBRYO C1 Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Stem Cell Inst, Boston, MA 02115 USA. RP Burns, CE (reprint author), Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. NR 9 TC 12 Z9 14 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2006 VL 25 IS 6 BP 859 EP 862 DI 10.1016/j.immuni.2006.11.005 PG 4 WC Immunology SC Immunology GA 120LY UT WOS:000243087500003 PM 17174927 ER PT J AU Zerria, K Jerbi, E Hammami, S Maaroufi, A Boubaker, S Xiong, JP Arnaout, MA Fathallah, DM AF Zerria, K. Jerbi, E. Hammami, S. Maaroufi, A. Boubaker, S. Xiong, J. P. Arnaout, M. A. Fathallah, D. M. TI Recombinant integrin CD11b A-domain blocks polymorphonuclear cells recruitment and protects against skeletal muscle inflammatory injury in the rat SO IMMUNOLOGY LA English DT Article DE adhesion molecules; inflammation; integrins; ischaemia-reperfusion; muscle trauma ID LEUKOCYTE ADHESION MOLECULES; MONOCLONAL-ANTIBODIES; INFARCT SIZE; IN-VIVO; NEUTROPHIL DEPLETION; TRANSPLANT REJECTION; CR3 CD11B/CD18; BINDING-SITE; RECEPTOR; ACTIVATION AB The beta 2 integrin CD11b/CD18 (CR3) is a major adhesion receptor of neutrophils, normally utilized to fend off infections. This receptor contributes, however, to multiple forms of non-infectious inflammatory injury when dysregulated as shown in gene knock-outs and through the use of blocking monoclonal antibodies. The major ligand recognition site of CR3 has been mapped to the A-domain in the CD11b subunit (CD11bA). The recombinant form of this domain exhibits a ligand binding profile similar to that of the holoreceptor. To assess the potential anti-inflammatory activity of CD11bA as a competitive antagonist of CR3 in vivo, we assessed its effects on a developed animal model of traumatic skeletal muscle injury in the rat. Recombinant soluble rat CD11bA-domain fused to glutathione-S-transferase (GST) was administered intravenously in a single dose at 1 mg/kg to nine groups of Wistar rats, five in each group, 30 min before inducing traumatic skeletal muscle injury. Control animals received either a function-blocking anti-CD11b/CD18 monoclonal antibody (1 mg/kg), non-functional mutant forms of the CD11bA (D140GS/AGA, T209/A, D242/A), recombinant GST or buffer alone. In control animals, the wounded muscle showed oedema, erythrocyte extravasation and myonecrosis both within and outside the immediate wounded area (5-10 mm zone) and influx of neutrophils was detected 30 min post-wound, followed by a second wave 3 hr later. Wild-type CD11bA- or anti-CD11b monoclonal antibody (mAb)-treated rats showed a comparable and significant decrease in the number of infiltrating PMN (78 + 4%, n = 70 and 86 +/- 2%, n = 50, respectively) and preservation of the muscular fibres outside the immediate zone of necrosis (75 + 4%, n = 70, 84 +/- 1%, n = 50, respectively), compared to controls. These data demonstrate that CD11bA can be an effective tissue-preserving agent in acute inflammatory muscular injury. C1 Inst Pasteur, Mol Biotechnol Grp, Tunis 1002, Tunisia. Inst Pasteur, Anatomopathol Lab, Tunis 1002, Tunisia. A Mami Hosp, Dept Thorac & Cardiovasc Surg, Ariana, Tunisia. Massachusetts Gen Hosp, Div Nephrol, Leukocyte Biol & Inflammat Program, Struct Biol Program, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Fathallah, DM (reprint author), Inst Pasteur, Mol Biotechnol Grp, BP 74, Tunis 1002, Tunisia. EM dahmani.fathallah@pasteur.rns.tn NR 45 TC 11 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2006 VL 119 IS 4 BP 431 EP 440 DI 10.1111/j.1365-2567.2006.02454.x PG 10 WC Immunology SC Immunology GA 103VS UT WOS:000241915600001 PM 17026721 ER PT J AU Stratidis, JG Lee, SA AF Stratidis, John G. Lee, Samuel A. TI Ocular candidiasis: Update on diagnosis and management SO INFECTIONS IN MEDICINE LA English DT Article DE Candida albicans; chorioretinitis; endophthalmitis; antifungal therapy ID POLYMERASE-CHAIN-REACTION; ENDOGENOUS FUNGAL ENDOPHTHALMITIS; HOSPITAL-ACQUIRED CANDIDEMIA; ALBICANS ENDOPHTHALMITIS; ATTRIBUTABLE MORTALITY; SPECIES INFECTIONS; UNITED-STATES; EPIDEMIOLOGY; VORICONAZOLE; PENETRATION AB Ocular candidiasis has become an increasingly important complication in patients with candidemia. It presents most commonly as chorioretinitis, but endophthalmitis may also occur. Diagnosis requires a high degree of clinical suspicion, and ocular screening is advocated up to 2 weeks after negative findings on initial ophthalmologic examination. Based on available data, monotherapy with fluconazole is reasonable first-line therapy, with or without vitrectomy, Fluconazole has superior vitreal penetration and less toxicity compared with amphotericin B. Voriconazole has good ocular tissue penetration and may prove useful in treatment of ocular candidiasis requiring a broader spectrum of antifungal activity. Increasing awareness and screening for ocular candidiasis in the clinical setting and comparative data on treatment options are urgently needed to define optimal management. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 33 TC 0 Z9 0 U1 0 U2 0 PU SCP COMMUNICATIONS INC PI NEW YORK PA 134 W 29TH ST, NEW YORK, NY 10001-5304 USA SN 0749-6524 J9 INFECT MED JI Infect. Med. PD DEC PY 2006 VL 23 IS 12 BP 579 EP + PG 5 WC Infectious Diseases SC Infectious Diseases GA 116DO UT WOS:000242782900007 ER PT J AU Balenci, L Deloulme, JC Saoudi, Y Bernards, A Baudier, J AF Balenci, L. Deloulme, J. C. Saoudi, Y. Bernards, A. Baudier, J. TI IQGAPI is a key protein in VEGF-triggered neural progenitor cells migration SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Meeting Abstract CT 16th Biennial Meeting of the International-Society-for-Developmental-Neuroscience CY AUG 24-28, 2006 CL Banff, CANADA SP Int Soc Dev Neurosci DE adult neurogenesis; neural progenitors; IQGAP1; VEGF; migration C1 INSERM, EMI 0104, F-75654 Paris 13, France. INSERM, U366, F-75654 Paris, France. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD DEC PY 2006 VL 24 IS 8 BP 499 EP 499 DI 10.1016/j.ijdevneu.2006.09.074 PG 1 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 128NE UT WOS:000243663700071 ER PT J AU Vasudevan, A Bhide, PG AF Vasudevan, A. Bhide, P. G. TI Co-ordinate regulation of angiogenesis and neurogenesis in the embryonic telencephalon SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Meeting Abstract CT 16th Biennial Meeting of the International-Society-for-Developmental-Neuroscience CY AUG 24-28, 2006 CL Banff, CANADA SP Int Soc Dev Neurosci DE angiogenesis; neurogenesis; embryonic; telencephalon C1 Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD DEC PY 2006 VL 24 IS 8 BP 535 EP 536 DI 10.1016/j.ijdevneu.2006.09.155 PG 2 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 128NE UT WOS:000243663700152 ER PT J AU Zhang, QH Cao, HH Astrakas, LG Mintzopoulos, D Mindrinos, MN Schulz, J Tompkins, RG Rahme, LG Tzika, AA AF Zhang, Qunhao Cao, Haihui Astrakas, Loukas G. Mintzopoulos, Dionyssios Mindrinos, Michael N. Schulz, John, III Tompkins, Ronald G. Rahme, Laurence G. Tzika, A. Aria TI Uncoupling protein 3 expression and intramyocellular lipid accumulation by NMR following local burn trauma SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE nuclear magnetic resonance; skeletal muscle; burn; trauma; uncoupling protein 3; intramyocellular lipids ID MAGNETIC-RESONANCE-SPECTROSCOPY; MITOCHONDRIAL ENERGY-METABOLISM; MESSENGER-RNA EXPRESSION; FREE FATTY-ACIDS; SKELETAL-MUSCLE; INSULIN-RESISTANCE; THERMAL-INJURY; TIME-COURSE; IN-VIVO; UCP3 AB Burn trauma is a clinical condition accompanied by muscle wasting that severely impedes rehabilitation in burn survivors. Mitochondrial uncoupling protein 3 (UCP3) is uniformly expressed in myoskeletal mitochondria and its expression has been found to increase in other clinical syndromes that, like burn trauma, are associated with muscle wasting (e.g., starvation, fasting, cancer, sepsis). The aim of this study was to explore the effects of burn trauma on UCP3 expression, intramyocellular lipids, and plasma-free fatty acids. Mice were studied at 6 h, 1 d and 3 d after nonlethal hindlimb burn trauma. Intramyocellular lipids in hindlimb skeletal muscle samples collected from burned and normal mice were measured using (1)H NMR spectroscopy on a Bruker 14.1 Tesla spectrometer at 4 degrees C. UCP3 mRNA and protein levels were also measured in these samples. Plasma-free fatty acids were measured in burned and normal mice. Local burn trauma was found to result in: 1) upregulation of UCP3 mRNA and protein expression in hindlimb myoskeletal mitochondria by 6 h postburn; 2) increased intramyocellular lipids; and 3) increased plasma-free fatty acids. Our findings show that the increase in UCP3 after burn trauma may be linked to burn-induced alterations in lipid metabolism. Such a link could reveal novel insights into how processes related to energy metabolism are controlled in burn and suggest that induction of UCP3 by burn in skeletal muscle is protective by either activating cellular redox signaling and/or mitochondrial uncoupling. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,NMR Surg Lab,Shriners Burn Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02114 USA. Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. RP Tzika, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,NMR Surg Lab,Shriners Burn Inst, 51 Blossom St,Room 261, Boston, MA 02114 USA. EM atzika@partners.org RI Astrakas, Loukas/F-5918-2011 FU NIGMS NIH HHS [P50GM0217000] NR 45 TC 8 Z9 8 U1 0 U2 1 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD DEC PY 2006 VL 18 IS 6 BP 1223 EP 1229 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 109MZ UT WOS:000242313700028 PM 17089030 ER PT J AU Chien, W Ashland, J Haver, K Hardy, SC Curren, P Hartnick, CJ AF Chien, Wade Ashland, Jean Haver, Kenan Hardy, Stephen C. Curren, Paula Hartnick, Christopher J. TI Type 1 laryngeal cleft: Establishing a functional diagnostic and management algorithm SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE laryngeal cleft; aspiration; cough; laryngoplasty; functional endoscopic evaluation of swallow; modified barium swallow ID LARYNGOTRACHEOESOPHAGEAL CLEFTS; POSTERIOR LARYNGEAL; ENDOSCOPIC REPAIR AB Objectives: To report our experience with all patients diagnosed with type 1 laryngeal cleft over a period of 3 years in our referral practice and to describe a functional diagnostic and management algorithm for children with this disorder. Methods: A prospective longitudinal study in a tertiary care referral center. Twenty pediatric patients diagnosed with type I laryngeal cleft in a 3-year period (5/1 /2002-5/1/2005) were included in this study. The incidence, presenting symptoms, diagnostic procedures, medical and surgical interventions performed, and clinical outcomes were evaluated. Results: The incidence of type 1 laryngeal cleft was 7.6%. Among the 20 patients in this study, aspiration with thin liquids was the most common presenting symptom (18 patients, 90%). Three patients underwent modified barium swallow (MBS) alone, 3 patients underwent functional endoscopic evaluation of swallow (FEES) alone, and 11 patients underwent both MBS and FEES prior to intraoperative endoscopic evaluation. Four patients (20%) were successfully treated with conservative therapy. Sixteen patients (80%) required endoscopic surgical repair after failing a course of conservative measures. The success rate of surgical repair was 94% (15 out of 16 patients). Conclusions: Type 1 laryngeal cleft can be challenging diagnostically. We propose a functional diagnostic and management algorithm that includes MBS, FEES, suspension laryngoscopy with bimanual interarytenoid palpation, and a trial of conservative therapy, as a way to diagnose and manage type 1 laryngeal cleft prior to consideration of surgical repair. If conservative therapy fails, then surgical intervention is indicated. (C) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Speech Language Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp Children, Sch Med, Boston, MA USA. Massachusetts Eye & Ear Infirm, Pediat Airway Voice & Swallowing Ctr, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM wadechien@hotmail.com NR 19 TC 45 Z9 49 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD DEC PY 2006 VL 70 IS 12 BP 2073 EP 2079 DI 10.1016/j.ijporl.2006.07.021 PG 7 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 115AW UT WOS:000242707900009 PM 16959329 ER PT J AU Srinivasan, VJ Ko, TH Wojtkowski, M Carvalho, M Clermont, A Bursell, SE Song, QH Lem, J Duker, JS Schuman, JS Fujimoto, JG AF Srinivasan, Vivek J. Ko, Tony H. Wojtkowski, Maciej Carvalho, Mariana Clermont, Allen Bursell, Sven-Erik Song, Qin Hui Lem, Janis Duker, Jay S. Schuman, Joel S. Fujimoto, James G. TI Noninvasive volumetric Imaging and morphometry of the rodent retina with high-speed, ultrahigh-resolution optical coherence tomography SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT SPIE BIOS Biomedical Optics Conference 2006 CY JAN, 2006 CL San Jose, CA SP SPIE BIOS ID MACULAR DISEASES; DEGENERATION; MICROSCOPY; PATHOLOGY AB PURPOSE. To demonstrate high-speed, ultrahigh-resolution optical coherence tomography (OCT) for noninvasive, in vivo, three-dimensional imaging of the retina in rat and mouse models. METHODS. A high-speed, ultrahigh-resolution OCT system using spectral, or Fourier domain, detection has been developed for small animal retinal imaging. Imaging is performed with a contact lens and postobjective scanning. An axial image resolution of 2.8 mu m is achieved with a spectrally broadband superluminescent diode light source with a bandwidth of similar to 150 nm at similar to 900-nm center wavelength. Imaging can be performed at 24,000 axial scans per second, which is similar to 100 times faster than previous ultrahigh-resolution OCT systems. High-definition and three-dimensional retinal imaging is performed in vivo in mouse and rat models. RESULTS. High-speed, ultrahigh-resolution OCT enabled high-definition, high transverse pixel density imaging of the murine retina and visualization of all major intraretinal layers. Raster scan protocols enabled three-dimensional volumetric imagingand comprehensive retinal segmentation algorithms allowed measurement of retinal layers. An OCT fundus image, akin to a fundus photograph was generated by axial summation of three-dimensional OCT data, thus enabling precise registration of OCT measurements to retinal fundus features. CONCLUSIONS. High-speed, ultrahigh-resolution OCT enables imaging of retinal architectural morphology in small animal models. OCT fundus images allow precise registration of OCT images and repeated measurements with respect to retinal fundus features. Three-dimensional OCT imaging enables visualization and quantification of retinal structure, which promises to allow repeated, noninvasive measurements to track disease progression, thereby reducing the need for killing the animal for histology. This capability can accelerate basic research studies in rats and mice and their translation into clinical patient care. C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Tufts Univ, New England Eye Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. Tufts Univ, New England Eye Ctr, Ctr Vis Res, Boston, MA 02111 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02115 USA. Univ Pittsburgh, Sch Med, Ctr Eye, Dept Ophthalmol, Pittsburgh, PA 15260 USA. RP Fujimoto, JG (reprint author), MIT, Dept Elect Engn & Comp Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM jgfuji@mit.edu RI Schuman, Joel/K-7304-2012; Wojtkowski, Maciej/D-6822-2014; Carvalho, Mariana/J-7610-2012 OI Schuman, Joel/0000-0002-8885-3766; Carvalho, Mariana/0000-0002-4281-5799 FU NEI NIH HHS [R01 EY012008-04, R01 EY011289, R01 EY011289-20, R01 EY011289-21, R01 EY012008, R01 EY013178, R01 EY013178-06, R01 EY013178-07, R01-EY11289-20, R01-EY12008-04, R01-EY13178-06] NR 33 TC 116 Z9 119 U1 1 U2 9 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2006 VL 47 IS 12 BP 5522 EP 5528 DI 10.1167/iovs.06-0195 PG 7 WC Ophthalmology SC Ophthalmology GA 110TW UT WOS:000242404900053 PM 17122144 ER PT J AU Freedberg, KA Hirschhorn, LR Schackman, BR Wolf, LL Martin, LA Weinstein, MC Goldin, S Paltiel, AD Katz, C Goldie, SJ Losina, E AF Freedberg, Kenneth A. Hirschhorn, Lisa R. Schackman, Bruce R. Wolf, Lindsey L. Martin, Lindsay A. Weinstein, Milton C. Goldin, Susan Paltiel, A. David Katz, Carol Goldie, Sue J. Losina, Elena TI Cost-effectiveness of an intervention to improve adherence to antiretroviral therapy in HIV-infected patients SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT Proceedings of the State of the Science Meeting on Intervention Research to Improve ARV Adherence CY NOV, 2005 CL Yale Univ, New Haven, CT SP Natl Inst Drug Abuse HO Yale Univ DE adherence; AIDS; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; PLASMA VIRAL LOAD; CONTROLLED-TRIAL; CLINICAL-TRIALS; PLUS INDINAVIR; EFFICACY; PROGRAM; MEDICATION; IMPACT; ERA AB Adherence to antiretroviral medications has been shown to be an important factor in predicting viral suppression and clinical outcomes. The objective of this analysis was to assess the cost-effectiveness of a nursing intervention on antiretroviral adherence using data from a randomized controlled clinical trial as input to a computer-based simulation model of HIV disease. For a cohort of HIV-infected patients similar to those in the clinical trial (mean initial CD4 count of 319 cells/mm(3)), implementing the nursing intervention in addition to standard care yielded a 63% increase in virologic suppression at 48 weeks. This produced increases in expected survival (from 94.5 to 100.9 quality-adjusted life months) and estimated discounted direct lifetime medical costs ($253,800 to $261,300). The incremental cost-effectiveness ratio for the intervention was $14,100 per quality-adjusted life year gained compared with standard care. Adherence interventions with modest effectiveness are likely to provide long-term survival benefit to patients and to be cost-effective compared with other uses of HIV care funds. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr AIDS Res, Div AIDS, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Risk Anal, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. JSI Res & Training Inst, Boston, MA USA. Cornell Univ, Weill Med Coll, Dept Publ Hlth, New York, NY USA. Inst Healthcare Improvement, Cambridge, MA USA. Yale Univ, Sch Med, New Haven, CT USA. Cambridge Hlth Alliance, Zinberg Clin, Cambridge, MA USA. RP Freedberg, KA (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM kfreedberg@partners.org FU NIAID NIH HHS [P30 AI042851, R01AI42006, K25AI50436, R01 AI042006, K24 AI062476, K24AI062476, K25 AI050436, P30AI42851]; NIDA NIH HHS [K01 DA017179, K01DA17179]; NIMH NIH HHS [R01 MH065869, R01MH65869]; PHS HHS [6 H97 HA 00128, I H97 HA 00176] NR 51 TC 27 Z9 28 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 1 PY 2006 VL 43 SU 1 BP S113 EP S118 DI 10.1097/01.qai.0000248334.52072.25 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 110AX UT WOS:000242351800015 PM 17133193 ER PT J AU Chen, LX Vivino, F AF Chen, Lan X. Vivino, Frederick TI Puzzling crystals in the synovial fluid SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Editorial Material C1 Penn Presbyterian Med Ctr, Div Rheumatol, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Div Rheumatol, Philadelphia, PA 19104 USA. RP Chen, LX (reprint author), Penn Presbyterian Med Ctr, Div Rheumatol, Philadelphia, PA 19104 USA. EM chenxl@mail.med.upenn.edu 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 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD DEC PY 2006 VL 12 IS 6 BP 306 EP 306 DI 10.1097/01.rhu.0000252405.68057.eb PG 1 WC Rheumatology SC Rheumatology GA 115SH UT WOS:000242753600012 PM 17149065 ER PT J AU Koukopoulos, A Sani, G Koukopoulos, AE Albert, MJ Girardi, P Tatarelli, R AF Koukopoulos, Athanasios Sani, Gabriele Koukopoulos, Alexia E. Albert, Matthew J. Girardi, Paolo Tatarelli, Roberto TI Endogenous and exogenous cyclicity and temperament in bipolar disorder: Review, new data and hypotheses SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Review DE cyclicity; triggering factors; bipolarity; temperament ID LITHIUM TREATMENT; AFFECTIVE-ILLNESS; ANTI-DEPRESSANTS; UNIPOLAR; SPECTRUM; SEQUENCE; DISCONTINUATION; RECURRENCE; SAMPLE; MANIA AB In this special issue dedicated to Falret and the French contributions to the concept of cyclicity in manic depressive illness, we begin with a historical overview of the development of the concept of cyclicity and its fundamental significance in manic-depressive illness and we underscore how the concept fell into neglect only to reemerge in recent years. We then look at the intimate relationship between mania and depression. The hypothesis of the primacy of mania is discussed. The thesis is presented, supported by the examination of 100 consecutive index manias, that in most cases mania is triggered by external factors acting upon hyperthymic patients, determining an exogenous cyclicity. On the other hand, in BPII patients the temperamental mood instability (cyclothymia) is an inherent and decisive factor in determining the cyclic autonomous course of the disorder. Finally, a new distinction of Bipolar Disorders, based on premorbid temperament and course of the illness, is considered. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Roma La Sapienza, St Andrea Hosp, Dept Psychiat, Rome, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. RP Koukopoulos, A (reprint author), Ctr Lucio Bini, 42,Via Crescenzio, I-00193 Rome, Italy. EM a.koukopoulos@fastwebnet.it OI Tatarelli, Roberto/0000-0003-4396-2632 NR 82 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD DEC PY 2006 VL 96 IS 3 BP 165 EP 175 DI 10.1016/j.jad.2006.08.031 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 122FW UT WOS:000243212100004 PM 16997381 ER PT J AU Hammerschlag, R Lao, LX Napadow, V Schnyer, RN Sherman, KJ Broderick, M Doyle, H Hansen, L Ly, H Stegall, J Milley, R Scholten, R Bain, P Langevin, HM Glick, R Mao, J Coeytaux, RR Paterson, C Harris, R Longhurst, J Chen, KW Ballen, K AF Hammerschlag, Richard Lao, Lixing Napadow, Vitaly Schnyer, Rosa N. Sherman, Karen J. Broderick, Maris Doyle, Hudson Hansen, Laura Ly, Helen Stegall, Jonathan Milley, Ryan Scholten, Robert Bain, Paul Langevin, Helene M. Glick, RonalD Mao, Jun Coeytaux, Remy R. Paterson, Charlotte Harris, Richard Longhurst, John Chen, Kevin W. Ballen, Karen TI Controversies in acupuncture research: Selection of controls and outcome measures in acupuncture clinical trials SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Editorial Material ID HUMAN BRAIN; RAT MODEL; ELECTROACUPUNCTURE; PAIN; FMRI; STIMULATION; ANALGESIA; PLACEBO; FIBROMYALGIA; EXPECTANCY AB This paper summarizes the scientific session and round-table discussion on acupuncture research held during the North American Research Conference on Complementary and Integrative Medicine, sponsored by the Consortium of Academic Health Centers for Integrative Medicine (CAHCIM), at Edmonton, Alberta, Canada, May 24-27, 2006. The session. panelists, co-sponsored by the Society for Acupuncture Research, focused on two main challenges in the design of acupuncture clinical trials: selection of appropriate controls and outcome measures. What follows are highlights of each presentation, as provided by the panelist, as well as an edited transcript of the discussion. C1 Mary Ann Liebert Inc, New Rochelle, NY 10801 USA. Univ Vermont, Dept Orthopaed, Burlington, VT USA. Univ Vermont, Dept Orthopaed & Rehabil, Burlington, VT 05405 USA. Oregon Coll Oriental Med, Dept Res, Portland, OR USA. Univ Maryland, Sch Med, Ctr Integrat Med, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Osher Inst, Boston, MA USA. New England Sch Acupuncture, Watertown, MA USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Univ Bristol, Bristol BS8 1TH, Avon, England. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Calif Irvine, Irvine, CA 92717 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Univ Vermont, Dept Neurol, Burlington, VT USA. RP Ballen, K (reprint author), Mary Ann Liebert Inc, 140 Hugenot St,3rd Floor, New Rochelle, NY 10801 USA. EM kballen@liebertpub.com RI Harris, Richard/F-1307-2011; Mao, Jun/F-5009-2012; Lao, Lixing/I-7979-2013; OI Lao, Lixing/0000-0003-0198-9714 NR 21 TC 28 Z9 28 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD DEC PY 2006 VL 12 IS 10 BP 943 EP 953 PG 11 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 123BK UT WOS:000243271100002 ER PT J AU Hsiao, AF Wong, MD Goldstein, MS Becerra, LS Cheng, EM Wenger, NS AF Hsiao, An-Fu Wong, Mitchell D. Goldstein, Michael S. Becerra, Lida S. Cheng, Eric M. Wenger, Neil S. TI Complementary and alternative medicine use among Asian-American subgroups: Prevalence, predictors, and lack of relationship to acculturation and access to conventional health care SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID ETHNIC-DIFFERENCES; BREAST-CANCER; UNITED-STATES; SERVICES; THERAPY; CHINESE; WOMEN AB Objectives: Acculturation and access to conventional health care have been found to be predictors of complementary and alternative medicine (CAM) use in the general population. We hypothesized that these factors would be predictors of CAM use in Asian-American subgroups. Because of differences in health and cultural beliefs, we also hypothesized that patterns and predictors of CAM use would vary among Asian-American subgroups. Methods: Cross-sectional survey of a sample of 9187 adults representative of the California population. Results: Nearly three quarters of Asian-Americans used at least one type of CAM in the past 12 months, which was significantly higher than the national prevalence rate. Chinese Americans had the highest prevalence of any CAM use, whereas South Asians had the lowest prevalence (86% vs. 67%, respectively). Acculturation and access to conventional medical care was unrelated to any CAM use for most Asian-American subgroups. Spirituality was the strongest predictor of any CAM use for most Asian-American subgroups. Conclusions: CAM use varies across Asian-American subgroups. Acculturation and access to conventional medical care is unrelated to any CAM use for most Asian-American subgroups. C1 Univ Calif Irvine, Ctr Hlth Policy Res, Irvine, CA 92697 USA. VA Long Beach Healthcare Syst, Long Beach, CA USA. Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Community Hlth Sci, Los Angeles, CA USA. Univ Calif Los Angeles, Ctr Hlth Policy & Res, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Hsiao, AF (reprint author), Univ Calif Irvine, Ctr Hlth Policy Res, 111 Acad,Suite 220, Irvine, CA 92697 USA. EM anfu.hsiao@va.gov OI Wong, Mitchell/0000-0002-4800-8410 FU NCCIH NIH HHS [R21 AT002248-01] NR 31 TC 27 Z9 27 U1 2 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD DEC PY 2006 VL 12 IS 10 BP 1003 EP 1010 DI 10.1089/acm.2006.12.1003 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 123BK UT WOS:000243271100008 PM 17212572 ER PT J AU Riekse, RG Li, G Petrie, EC Leverenz, JB Vavrek, D Vuletic, S Albers, JJ Montine, TJ Lee, VMY Lee, M Seubert, P Galasko, D Schellenberg, GD Hazzard, WR Peskind, ER AF Riekse, Robert G. Li, Ge Petrie, Eric C. Leverenz, James B. Vavrek, Darcy Vuletic, Simona Albers, John J. Montine, Thomas J. Lee, Virginia M. -Y. Lee, Michael Seubert, Peter Galasko, Douglas Schellenberg, Gerard D. Hazzard, William R. Peskind, Elaine R. TI Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; statins; tau; clinical trial; CSF ID MILD COGNITIVE IMPAIRMENT; AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN-E; TAU PHOSPHORYLATION; CHOLESTEROL-METABOLISM; REDUCTASE INHIBITORS; INCIDENT DEMENTIA; EPSILON-4 ALLELE; BETA PROTEIN; MAP KINASE AB Background: Treatment with HMG-CoA reductase inhibitors ("statins") has been variably associated with a reduced risk of Alzheimer's disease (AD) in epidemiologic studies and reduced amyloid-beta (A beta) deposition in animal models of AD. Putative neuroprotective effects of statins may vary in relation to their ability to penetrate into the central nervous system, (CNS). Methods: We measured levels of cerebrospinal fluid (CSF) AD biomarkers following 14 weeks of treatment with simvastatin (a CNS permeant statin; n = 10) at 40 mg/day or pravastatin (a CNS impermeant statin; a = 13) at 80 mg/day in hypercholesterolenlic subjects without dementia. Results: Simvastatin, but not pravastatin, reduced CSF levels of phospho-tau-181 (p-tau(181)) in all subjects. There were no differences in CSF levels of total tau, A beta(42), A beta(40), soluble amyloid 0 protein precuisor (sA beta PP) a or beta, or F-2-isoprostanes. Conclusions: Statins may modulate the phosphorylation of tau in humans and this effect may depend oil the CNS availability of the statin. These results suggest another mechanism by which statins may act to reduce, the risk of AD. C1 VA Puget Sound Hlth Care Syst, Geriatr & Extended Care, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. Washington Univ, Sch Med, Dept Med, Div Geriatr Med, St Louis, MO 63130 USA. Washington Univ, Sch Med, Dept Psychiat & Behav Sci, St Louis, MO 63130 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63130 USA. Washington Univ, Sch Med, Dept Pathol, Div Neuropathol, St Louis, MO 63130 USA. Washington Univ, Sch Med, NW Lipid Metab & Diabet Res Labs, St Louis, MO 63130 USA. VA Puget Sound Hlth Care Syst, NW Network VISN Mental Illness Res 20, Educ & Clin Ctr, Seattle, WA USA. RP Li, G (reprint author), VA Puget Sound Hlth Care Syst, Geriatr & Extended Care, S-116 MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM gli@u.washington.edu FU NHLBI NIH HHS [HL30086]; NIA NIH HHS [P50 AG05136, K08 AG023670, K23 AG20020] NR 57 TC 55 Z9 58 U1 3 U2 9 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PD DEC PY 2006 VL 10 IS 4 BP 399 EP 406 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 134YP UT WOS:000244120900008 PM 17183151 ER PT J AU Qin, WP Chachich, M Lane, M Roth, G Bryant, M de Cabo, R Ottinger, MA Mattison, J Ingram, D Gandy, S Pasinetti, GM AF Qin, Weiping Chachich, Mark Lane, Mark Roth, George Bryant, Mark de Cabo, Rafael Ottinger, Mary Ann Mattison, Julie Ingram, Donald Gandy, Samuel Pasinetti, Giulio Maria TI Calorie restriction attenuates Alzheimer's disease type brain amyloidosis in Squirrel monkeys (Saimiri sciureus) SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE calorie restriction; Alzheimer's disease; amyloid; Squirrel monkeys ID RHESUS-MONKEYS; FAMILY; LONGEVITY; DEACETYLASES; MECHANISM; INSULIN; SIRT1; RISK AB Recent studies from our laboratories and others suggest that calorie restriction (CR) may benefit Alzheimer's disease (AD) by preventing amyloid-beta (A beta) neuropathology in the mouse models of AD. Moreover, we found that promotion of the NAD+-dependent SIRT1 mediated deacetylase activity, a key regulator in CR extension of life span, may be a mechanism by which CR influences AD-type neuropathology. In this study we continued to explore the role of CR in AD-type brain amyloidosis in Squirrel monkeys (Saimiri sciureus). Monkeys were maintained on the normal and CR diets throughout the entire lifespan until they died of natural causes. We found that 30% CR resulted in reduced contents of A beta(1-40) and beta(1-42) peptides in the temporal cortex of Squirrel monkeys, relative to control (CON) fed monkeys. The decreased contents of cortical A beta peptide inversely correlated with SIRT1 protein concentrations in the same brain region; no detectable change in total full-lengthamyloid-beta protein precursor (AOPP) level was found. Most interestingly, we found that 30% CR resulted in a select elevation of alpha- but not beta- or gamma- secretase activity which coincided with decreased ROCK1 protein content in the same brain region, relative to CON group. Collectively, the study suggests that investigation of the role of CR in non-human primates may provide a valuable approach for further clarifying the role of CR in AD. C1 CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Geriatr Res & Clin Ctr, Bronx, NY 10468 USA. Off Res Serv, Div Vet Resources, Bethesda, MD USA. Thomas Jefferson Univ, Farber Inst Neurosci, Philadelphia, PA 19107 USA. RP Pasinetti, GM (reprint author), CUNY Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1668, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu RI de Cabo, Rafael/E-7996-2010; de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU NCCIH NIH HHS [AT002602]; NIA NIH HHS [P01 AG010491-14, AG02219, P01 AG010491] NR 25 TC 95 Z9 100 U1 1 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PD DEC PY 2006 VL 10 IS 4 BP 417 EP 422 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 134YP UT WOS:000244120900011 PM 17183154 ER PT J AU King, DW Taft, C King, LA Hammond, C Stone, ER AF King, Daniel W. Taft, Casey King, Lynda A. Hammond, Charity Stone, Erika R. TI Directionality of the association between social support and posttraumatic stress disorder: A longitudinal investigation SO JOURNAL OF APPLIED SOCIAL PSYCHOLOGY LA English DT Article ID MALE VIETNAM VETERANS; GULF-WAR VETERANS; MISSING DATA; COVARIANCE-STRUCTURES; COMBAT STRESS; MODEL; SAMPLE; SYMPTOMS; INDEXES; FEMALE AB This study examined the nature of the association between social support and posttraumatic stress disorder (PTSD) symptomatology among 2,249 male veterans of the 1990-1991 Gulf War. Using structural equation modeling, a cross-lagged panel analysis indicated a strong negative relationship between PTSD at Time 1 and social support at Time 2, while social support at Time 1 did not predict PTSD at Time 2. Findings suggest that, over time, interpersonal problems associated with PTSD may have a detrimental influence on the quality and quantity of available social support resources. It is recommended that greater focus be placed on the interpersonal skills of those suffering from PTSD. C1 Boston Univ, VA Boston Healthcare Syst, Natl Ctr PTSD, Dept Psychol, Boston, MA 02130 USA. Boston Univ, VA Boston Healthcare Syst, Natl Ctr PTSD, Dept Psychiat, Boston, MA 02130 USA. Boston Univ, VA Boston Healthcare Syst, Natl Ctr PTSD, Sch Med, Boston, MA 02130 USA. RP King, DW (reprint author), Boston Univ, VA Boston Healthcare Syst, Natl Ctr PTSD, Dept Psychol, 116B-5,150 S Huntington Ave, Boston, MA 02130 USA. EM danking@bu.edu NR 44 TC 70 Z9 71 U1 4 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0021-9029 J9 J APPL SOC PSYCHOL JI J. Appl. Soc. Psychol. PD DEC PY 2006 VL 36 IS 12 BP 2980 EP 2992 DI 10.1111/j.0021-9029.2006.00138.x PG 13 WC Psychology, Social SC Psychology GA 104IH UT WOS:000241951600008 ER PT J AU Kitatani, K Idkowiak-Baldys, J Bielawski, J Taha, TA Jenkins, RW Senkal, CE Ogretmen, B Obeid, LM Hannun, YA AF Kitatani, Kazuyuki Idkowiak-Baldys, Jolanta Bielawski, Jacek Taha, Tarek A. Jenkins, Russell W. Senkal, Can E. Ogretmen, Besim Obeid, Lina M. Hannun, Yusuf A. TI Protein kinase C-induced activation of a ceramide/protein phosphatase 1 pathway leading to dephosphorylation of p38 MAPK SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NOVO SPHINGOLIPID BIOSYNTHESIS; SIGNAL-REGULATED KINASE-1/2; STRESS-INDUCED APOPTOSIS; CELL-PERMEABLE CERAMIDE; NECROSIS-FACTOR-ALPHA; SERINE PALMITOYLTRANSFERASE; SPHINGOMYELIN CYCLE; MITOCHONDRIAL POOL; PROMOTES APOPTOSIS; EPITHELIAL-CELLS AB Recently we showed that, in human breast cancer cells, activation of protein kinase C by 4 beta-phorbol 12-myristate 13-acetate (PMA) produced ceramide formed from the salvage pathway ( Becker, K. P., Kitatani, K., Idkowiak-Baldys, J., Bielawski, J., and Hannun, Y.A. (2005) J. Biol. Chem. 280, 2606-2612). In this study, we investigated intracellular signaling events mediated by this novel activated pathway of ceramide generation. PMA treatment resulted in transient activation of mitogen-activated protein kinases (ERK1/2, JNK1/2, and p38) followed by dephosphorylation/inactivation. Interestingly, fumonisin B1 (FB1), an inhibitor of the salvage pathway, attenuated loss of phosphorylation of p38, suggesting a role for ceramide in p38 dephosphorylation. This was confirmed by knock-down of longevity-assurance homologue 5, which partially suppressed the formation of C16-ceramide induced by PMA and increased the phosphorylation of p38. These results demonstrate a role for the salvage pathway in feedback inhibition of p38. To determine which protein phosphatases act in this pathway, specific knock-down of serine/threonine protein phosphatases was performed, and it was observed that knock-down of protein phosphatase 1 (PP1) catalytic subunits significantly increased p38 phosphorylation, suggesting activation of PP1 results in an inhibitory effect on p38. Moreover, PMA recruited PP1 catalytic subunits to mitochondria, and this was significantly suppressed by FB1. In addition, phospho-p38 resided in PMA-stimulated mitochondria. Upon PMA treatment, a mitochondria-enriched/purified fraction exhibited significant increases in C16-ceramide, a major ceramide specie, which was suppressed by FB1. Taken together, these data suggest that accumulation of C16-ceramide in mitochondria formed from the protein kinase C-dependent salvage pathway results at least in part from the action of longevity-assurance homologue 5, and the generated ceramide modulates the p38 cascade via PP1. C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Div Gen Internal Med, Charleston, SC 29401 USA. RP Hannun, YA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, 173 Ashley Ave,POB 250509, Charleston, SC 29425 USA. EM hannun@musc.edu OI Kitatani, Kazuyuki/0000-0002-8516-6135; obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [CA87584, CA88932]; NIA NIH HHS [AG16583]; NIGMS NIH HHS [GM08716] NR 71 TC 42 Z9 42 U1 1 U2 2 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 DEC 1 PY 2006 VL 281 IS 48 BP 36793 EP 36802 DI 10.1074/jbc.M608137200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 108DP UT WOS:000242220800037 PM 17030510 ER PT J AU Xu, CQ Call, ME Wucherpfennig, KW AF Xu, Chenqi Call, Matthew E. Wucherpfennig, Kai W. TI A membrane-proximal tetracysteine motif contributes to assembly of CD3 delta epsilon and CD3 gamma epsilon dimers with the T cell receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANTIGEN RECEPTOR; TCR/CD3 COMPLEX; CD3-EPSILON-GAMMA HETERODIMER; GLUCOCORTICOID RECEPTOR; MOLECULAR-CLONING; CRYSTAL-STRUCTURE; T3-GAMMA SUBUNIT; CD3 COMPLEX; ALPHA-CHAIN; ZETA-CHAIN AB Assembly of the T cell receptor (TCR) with its dimeric signaling modules, CD3 delta epsilon, CD3 gamma epsilon, and zeta zeta, is organized by transmembrane (TM) interactions. Each of the three assembly steps requires formation of a three-helix interface involving one particular basic TCR TM residue and two acidic TM residues of the respective signaling dimer. The extracellular domains of CD3 delta epsilon and CD3 gamma epsilon contribute to assembly, but TCR interaction sites on CD3 dimers have not been defined. The structures of the extracellular domains of CD3 delta epsilon and CD3 gamma epsilon demonstrated parallel beta-strands ending at the first cysteine in the CXXCXEXXX motif present in the stalk segment of each CD3 chain. Mutation of the membrane-proximal cysteines impaired assembly of either CD3 dimer with TCR, and little complex was isolated when all four membrane-proximal cysteines were mutated to alanine. These mutations had, however, no discernable effect on CD3 delta epsilon or CD3 gamma epsilon dimerization. CD3 delta epsilon assembled with a TCR alpha mutant that lacked both immunoglobulin domains, but shortening of the TCR alpha connecting peptide reduced assembly, consistent with membrane-proximal TCR alpha-CD3 delta epsilon interactions. Chelation of divalent cations did not affect assembly, indicating that coordination of a cation by the tetracysteine motif was not required. The membrane-proximal cysteines were within close proximity but only formed covalent CD3 dimers when one cysteine was mutated. The four cysteines may thus form two intrachain disulfide bonds integral to the secondary structure of CD3 stalk regions. The three-chain interaction theme first established for the TM domains thus extends into the membrane-proximal domains of TCR alpha-CD3 delta epsilon and TCR alpha-CD3 delta epsilon. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. EM Kai_Wucherpfennig@dfci.harvard.edu FU NIAID NIH HHS [R01 AI054520] NR 41 TC 30 Z9 31 U1 1 U2 6 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 DEC 1 PY 2006 VL 281 IS 48 BP 36977 EP 36984 DI 10.1074/jbc.M607164200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 108DP UT WOS:000242220800058 PM 17023417 ER PT J AU Oh, KJ Barbuto, S Pitter, K Morash, J Walensky, LD Korsmeyer, SJ AF Oh, Kyoung Joon Barbuto, Scott Pitter, Kenneth Morash, Joel Walensky, Loren D. Korsmeyer, Stanley J. TI A membrane-targeted BID BCL-2 homology 3 peptide is sufficient for high potency activation of BAX in vitro SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYTOCHROME-C RELEASE; OUTER MITOCHONDRIAL-MEMBRANE; CONFORMATIONAL-CHANGE; PROAPOPTOTIC BAX; CONTACT SITES; FAMILY-MEMBER; TUMOR-CELLS; BH3 DOMAINS; X-L; APOPTOSIS AB The multidomain pro-apoptotic proteins BAX and BAK constitute an essential gateway to mitochondrial dysfunction and programmed cell death. Among the "BCL-2 homology (BH) 3-only" members of pro-apoptotic proteins, truncated BID (tBID) has been implicated in direct BAX activation, although an explicit molecular mechanism remains elusive. We find that BID BH3 peptide alone at submicromolar concentrations cannot activate BAX or complement BID BH3 mutant-tBID in mitochondrial and liposomal release assays. Because tBID contains structurally defined membrane association domains, we investigated whether membrane targeting of BID BH3 peptide would be sufficient to restore its pro-apoptotic activity. We developed a Ni2+-nitrilotriacetic acid liposomal assay system that efficiently conjugates histidine-tagged peptides to a simulated outer mitochondrial membrane surface. Strikingly, nanomolar concentrations of a synthetic BID BH3 peptide that is chemically tethered to the liposomal membrane activated BAX almost as efficiently as tBID itself. These results highlight the importance of membrane targeting of the BID BH3 domain in tBID-mediated BAX activation and support a model in which tBID engages BAX to trigger its pro-apoptotic activity. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol & Med,Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. RP Oh, KJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol & Med,Howard Hughes Med Inst, 1 Jimmy Fund Way,Smith Bldg 758, Boston, MA 02115 USA. EM kyoung_joon_oh@dfci.harvard.edu FU NCI NIH HHS [P01 CA68484, R01 CA50239]; NHLBI NIH HHS [K08 HL074049] NR 58 TC 53 Z9 54 U1 1 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 DEC 1 PY 2006 VL 281 IS 48 BP 36999 EP 37008 DI 10.1074/jbc.M602341200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 108DP UT WOS:000242220800061 PM 16987815 ER PT J AU Weinberg, MS Wall, C Robertsson, J O'Neil, E Sienko, K Fields, R AF Weinberg, Marc. S. Wall, Conrad Robertsson, Jimmy O'Neil, Edward Sienko, Kathleen Fields, Robert TI Tilt determination in MEMS inertial vestibular prosthesis SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID ATTITUDE DETERMINATION; VECTOR OBSERVATIONS; POSTURAL CONTROL; SENSORS; ACCELEROMETERS; REHABILITATION; ELECTROTACTILE; DEFICITS; SYSTEMS; SUPPORT AB Background: There is a clear need for a prosthesis that improves postural stability in the balance impaired. Such a device would be used as a temporary aid during recovery from ablative inner-ear surgery, a postural monitor during rehabilitation (for example, hip surgery), and as a permanent prosthesis for those elderly prone to falls. Method of approach: Recently developed, small instruments have enabled wearable prostheses to augment or replace vestibular functions. The current prosthesis communicates by vibrators mounted on the subject's trunk. In this paper we emphasize the unique algorithms that enable tilt indication with modestly performing micromachined gyroscopes and accelerometers. Results: For large angles and multiple axes, gyro drift and unwanted lateral accelerations are successfully rejected. In single-axis tests, the most dramatic results were obtained in standard operating tests where balance-impaired subjects were deprived of vision and proprioceptive inputs. Balance-impaired subjects who fell (into safety restraints) when not aided were able to stand with the prosthesis. Initial multiaxis tests with healthy subjects have shown that sway is reduced in both forward-back and sideward directions. Conclusions: Positive results in initial testing and a sound theoretical basis for the hardware warrant continued development and testing, which is being conducted at three sites. C1 Draper Lab, Cambridge, MA 02139 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. MIT, Cambridge, MA 02139 USA. RP Weinberg, MS (reprint author), Draper Lab, Mail Stop 37,555 Technol Sq, Cambridge, MA 02139 USA. EM mweinberg@draper.com FU NIDCD NIH HHS [R01 DC06201-01] NR 53 TC 13 Z9 13 U1 2 U2 6 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD DEC PY 2006 VL 128 IS 6 BP 943 EP 956 DI 10.1115/1.2378922 PG 14 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 119BT UT WOS:000242987900019 PM 17154697 ER PT J AU Lozano-Calderon, S Blazar, P Zurakowski, D Lee, SG Ring, D AF Lozano-Calderon, Santiago Blazar, Philip Zurakowski, David Lee, Sang-Gil Ring, David TI Diagnosis of scaphoid fracture displacement with radiography and computed tomography SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID NATURAL-HISTORY; IMMOBILIZATION; NONUNIONS; DEFORMITY; PATTERNS; WRIST; THUMB; WAIST; NEED; MRI AB Background: Displacement is an important risk factor for nonunion of scaphoid wrist fractures. We compared computed tomography with radiographs with regard to their ability to detect displacement. Methods: Six blinded observers rated thirty scaphoid fractures (ten displaced and twenty nondisplaced) with use of radiographs and computed tomography. The radiographs were evaluated separately from the computed tomography scans and then, in a third evaluation, the two imaging studies were reviewed simultaneously. The evaluations were repeated four weeks later. Observers were asked to evaluate specific measures of fracture displacement and then to judge the fracture as being displaced or nondisplaced. Results: Intraobserver reliability was better for computed tomography alone and the combination of radiographs and computed tomography than it was for radiographs alone (kappa values, 0.65, 0.63, and 0.54, respectively; all p < 0.001). The interobserver reliability was also better for computed tomography alone and the combination of radiographs and computed tomography than it was for radiographs alone (kappa values, 0.43, 0.48, and 0.27, respectively; all p < 0.001). The average sensitivity was 75% for radiographs alone, 72% for computed tomography alone, and 80% for both; the average specificity was 64%, 80%, and 73%, respectively; the average accuracy was 68%, 77%, and 75%, respectively. The positive predictive values (assuming a 5% prevalence of fracture displacement) were low (0.10, 0.13, and 0.16) and the negative predictive values were high (0.97, 0.98, and 0.99) for the radiographs, computed tomography, and combined modality. Conclusions: Computed tomography improves the reliability of detecting scaphoid fracture displacement but has a more limited effect on accuracy, which remains <80%. The utility of computed tomography scans for diagnosing scaphoid fracture displacement is affected by the low prevalence of fracture displacement. This study suggests that computed tomography scans are useful for ruling out displacement but not for diagnosing it. We recommend that all scaphoid fractures be evaluated with computed tomography in order to rule out displacement. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. RP Lozano-Calderon, S (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 31 TC 38 Z9 38 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 DEC PY 2006 VL 88A IS 12 BP 2695 EP 2703 DI 10.2106/JBJS.E.01211 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 114AW UT WOS:000242640100017 PM 17142420 ER PT J AU Jawa, A Lieberman, AE Alexieva, CCN Jupiter, JB AF Jawa, Andrew Lieberman, Avidov E. Alexieva, Constanza C. N. Jupiter, Jesse B. TI Primary intra-articular non-Hodgkin's lymphoma of the elbow - A case report SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID LIMB-SPARING THERAPY; T-CELL LYMPHOMA; RHEUMATOID-ARTHRITIS; MONOARTHRITIS; SYNOVIUM; PATIENT; SARCOMA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jawa, A (reprint author), 88 Hancock St 15, Cambridge, MA 02139 USA. EM ajawa@partners.org NR 19 TC 4 Z9 4 U1 0 U2 0 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 DEC PY 2006 VL 88A IS 12 BP 2730 EP 2734 DI 10.2106/JBJS.E.00094 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 114AW UT WOS:000242640100023 PM 17142425 ER PT J AU Okike, K Bhattacharyya, T AF Okike, Kanu Bhattacharyya, Timothy TI Trends in the management of open fractures - A critical analysis SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Review ID OPEN TIBIAL FRACTURES; PRESSURE PULSATILE LAVAGE; VACUUM-ASSISTED CLOSURE; BONE MORPHOGENETIC PROTEIN-2; LOCAL ANTIBIOTIC-THERAPY; OPEN EXTREMITY FRACTURES; SOFT-TISSUE COVERAGE; INTRAMEDULLARY NAILS; EXTERNAL FIXATION; FEMORAL-SHAFT C1 Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Okike, K (reprint author), Harvard Univ, 64 Linnaean St, Cambridge, MA 02138 USA. OI Okike, Kanu/0000-0001-9310-9969 NR 102 TC 58 Z9 70 U1 0 U2 2 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 DEC PY 2006 VL 88A IS 12 BP 2739 EP 2748 DI 10.2106/JBJS.F.00146 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 114AW UT WOS:000242640100025 PM 17142427 ER PT J AU Hansen, MF Seton, M Merchant, A AF Hansen, Marc F. Seton, Margaret Merchant, Anand TI Osteosarcoma in Paget's disease of bone SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT Conference on Pagets Disease of Bone/Fibrous Dysplasia - Advances and Challenges CY JAN 12-14, 2006 CL Ft Landerdale, FL DE Paget's disease of bone; osteosarcoma; bone remodeling; genetics ID VALOSIN-CONTAINING PROTEIN; OSTEOGENIC-SARCOMA; OSTEITIS DEFORMANS; MET/HGF RECEPTOR; LONG SURVIVAL; UBA DOMAIN; EXPRESSION; MUTATIONS; SQSTM1; CELLS AB Paget's disease of bone (PDB) is a focal disorder of bone metabolism first described by Sir James Paget in 1876. It is presumed benign in nature and mediated by abnormal osteoclast function. The incidence of osteosarcomas complicating PDB is estimated at < 1%. These cancers occur mostly in persons with long-standing, polyostotic disease and affect patients in their seventh decade or when osteosarcoma is remarkably rare in the general population. Epidemiological studies suggest that this late peak of osteosarcomas is absent in regions where Paget's is infrequently reported. Whereas PDB has a predilection for the axial skeleton, skull, femurs, and tibias, pagetic osteosarcoma tend to spare the spine, and are reported more commonly in the pelvis, femur, humerus, and skull. A molecular basis for the association of osteosarcoma with Paget's disease is unclear. These osteosarcomas are osteogenic in origin, consistently arise in sites of pagetic bone, and may present as metachronous, multifocal lesions. On histopathology, the lesions are usually osteoblastic, and the tumor phenotype is sometimes characterized as an exaggerated, chaotic form of the accelerated bone remodeling that characterizes PDB. New insights from the biology of adolescent osteosarcomas, VCP and SQSTM1 mutations now defined in patients with Paget's disease, and emerging evidence that stromal lesions are present in patients with Paget's disease are changing the way we think about the pathogenesis of PDB and the rare complication of pagetic osteosarcomas. C1 Univ Connecticut, Ctr Hlth, Ctr Mol Med, Farmington, CT 06030 USA. Massachusetts Gen Hosp, New England Registry Pagets Dis Bone, Boston, MA 02114 USA. RP Hansen, MF (reprint author), Univ Connecticut, Ctr Hlth, Ctr Mol Med, 263 Farmington Ave, Farmington, CT 06030 USA. EM mhansen@nso2.uchc.edu RI Merchant, Anand/B-3467-2010 NR 74 TC 33 Z9 37 U1 0 U2 1 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 DEC PY 2006 VL 21 SU 2 BP P58 EP P63 DI 10.1359/JBMR.06S211 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 129ME UT WOS:000243732800012 PM 17229010 ER PT J AU Kurihara, N Zhou, H Reddy, SV Palacios, VG Subler, MA Dempster, DW Windle, JJ Roodman, GD AF Kurihara, Noriyoshi Zhou, Hua Reddy, Sakamuri V. Palacios, Veronica Garcia Subler, Mark A. Dempster, David W. Windle, Jolene J. Roodman, G. David TI Experimental models of Paget's disease SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT Conference on Pagets Disease of Bone/Fibrous Dysplasia - Advances and Challenges CY JAN 12-14, 2006 CL Ft Landerdale, FL DE Paget's disease; osteoclast; TAF(II)-17; IL-6; measles virus nucleocapsid ID 1,25-DIHYDROXYVITAMIN D-3; OSTEOCLAST PRECURSORS; BONE; VIRUS; CELLS; EXPRESSION; ETIOLOGY; SEQUENCE; PROTEIN; MICE AB We targeted the MVNP gene to the OCL lineage in transgenic mice. These mice developed abnormal OCLs and bone lesions similar to those found in Paget's patients. These results show that persistent expression of MVNP in OCLs can induce pagetic-like bone lesions in vivo. C1 VA Pittsburgh Healthcare Syst, Dept Med Hematol Oncol, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Dept Med Hematol Oncol, Pittsburgh, PA USA. Helen Hayes Hosp, Reg Bone Ctr, W Haverstraw, NY USA. Childrens Res Inst, Dept Pediat, Charleston, SC USA. Virginia Commonwealth Univ, Richmond, VA USA. Columbia Univ Coll Phys & Surg, New York, NY USA. RP Roodman, GD (reprint author), VA Pittsburgh Healthcare Syst, Dept Med Hematol Oncol, R&D 151-U,Univ Dr, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu OI Windle, Jolene/0000-0001-6690-385X FU NCATS NIH HHS [UL1 TR000005]; NCI NIH HHS [P30-CA16059]; NIAMS NIH HHS [P01-AR049363] NR 17 TC 3 Z9 3 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 DEC PY 2006 VL 21 SU 2 BP P55 EP P57 DI 10.1359/JBMR.06S210 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 129ME UT WOS:000243732800011 PM 17229020 ER PT J AU Jassal, DS Desai, SC Neilan, TG Avery, E Vlahakes, GJ Agnihotri, AK AF Jassal, Davinder S. Desai, Shaun C. Neilan, Tomas G. Avery, Edwin Vlahakes, Gus J. Agnihotri, Arvind K. TI The impact of spontaneous echocardiographic contrast in patients with left atrial enlargement undergoing cardiac valvular surgery SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE spontaneous echocardiographic contrast; left atrium; aorta; transesophageal echocardiography; surgical outcomes ID SPONTANEOUS ECHO CONTRAST; BLOOD-FLOW VELOCITY; DESCENDING AORTA; THORACIC AORTA; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; MITRAL REGURGITATION; NATURAL-HISTORY; SINUS RHYTHM; HIGH-RISK; FIBRILLATION AB Objective: The aim of this study was to evaluate the impact of either left atrial or aortic spontaneous echocardiographic contrast (SEC), as identified on intraoperative transesophageal echocardiography, on short-term morbidity and mortality in patients with left atrial enlargement undergoing cardiac valvular surgery. Design: Retrospective and observational. Setting: Single-center, university teaching hospital. Participants: The authors identified 197 patients (105 males and 92 females; mean age, 68 +/- 14 years) with left atrial enlargement who underwent surgical intervention for valvular heart disease from January 1, 2004 to January 1, 2005. Main Results: Of the total population, 40 patients (20.3%) showed left atrial SEC, and 10 patients (5.1%) showed aortic SEC. On multivariate analysis, increasing left atrial size and the absence of mitral regurgitation were independent predictors for the presence of left atrial SEC. On multivariate analysis, the presence of atrial fibrillation and a dilated descending aorta were predictive of aortic SEC. Although the identification of left atrial SEC was an echocardiographic marker of an increased risk for thromboembolic events postoperatively, this finding did not hold true for the presence of aortic SEC. Conclusions: Intraoperative identification of left atrial dilatation or aortic dilatation is predictive of SEC in the left atrium or descending aorta, respectively. The identification of left atrial SEC is an echocardiographic marker of an increased risk for thromboembolic events in this high-risk population. (C) 2006 Elsevier Inc. All rights reserved. C1 St Boniface Gen Hosp, Dept Cardiac Sci, Div Cardiol, Inst Cardiovasc Sci, Winnipeg, MB R2H 2A6, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiol,Cardiac Ultrasound Lab, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Anesthesiol, Boston, MA USA. RP Jassal, DS (reprint author), St Boniface Gen Hosp, Dept Cardiac Sci, Div Cardiol, Inst Cardiovasc Sci, 409 Tache Ave, Winnipeg, MB R2H 2A6, Canada. EM djassal@sbgh.mb.ca NR 27 TC 1 Z9 1 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 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD DEC PY 2006 VL 20 IS 6 BP 772 EP 776 DI 10.1053/j.jvca.2006.07.009 PG 5 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 114PP UT WOS:000242678400003 PM 17138078 ER PT J AU Fitzsimons, MG Walker, J Inglessis, I Boucher, C AF Fitzsimons, Michael G. Walker, Jennifer Inglessis, Ignacio Boucher, Charles TI Left main coronary artery spasm: Medical versus surgical management SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE vasospasm; cardiopulmonary bypass grafting; ischemia; left main coronary artery ID INTRAVASCULAR ULTRASOUND; MYOCARDIAL-INFARCTION; ANGINA; ANGIOPLASTY; VASOSPASM; STENOSIS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Cardiac Anesthesia, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiac Surg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiol, Boston, MA USA. RP Fitzsimons, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Cardiac Anesthesia, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM mfitzsimons@partners.org NR 22 TC 4 Z9 4 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 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD DEC PY 2006 VL 20 IS 6 BP 834 EP 836 DI 10.1053/j.jvca.2006.04.002 PG 3 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 114PP UT WOS:000242678400014 PM 17138089 ER PT J AU Chitilian, HV Alston, TA Avery, EG AF Chitilian, Hovig V. Alston, Theodore A. Avery, Edwin G. TI Transesophageal echocardiographic bull's eye - Diagnosis: Spinal cord SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE transesophageal ultrasonography ID INJECTIONS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Cardiac Anesthesia Grp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Avery, EG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Cardiac Anesthesia Grp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM eavery@partners.org NR 7 TC 4 Z9 4 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 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD DEC PY 2006 VL 20 IS 6 BP 894 EP 895 DI 10.1053/j.jvca.2005.09.007 PG 2 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 114PP UT WOS:000242678400028 PM 17138103 ER PT J AU Nguyen, LT Taravella, MJ Pelak, VS AF Nguyen, Ly T. Taravella, Michael J. Pelak, Victoria S. TI Determining whether delayed nonarteritic ischemic optic neuropathy associated with cataract extraction is a true entity SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Cataract-and-Refractive-Surgery CY MAR 22, 2006 CL San Francisco, CA SP Amer Soc Cataract & Refract Surg ID SURGERY AB PURPOSE: To evaluate cases of delayed nonarteritic anterior and posterior ischemic optic neuropathy after cataract extraction and to evaluate the need for centralized prospective reporting of nonarteritic ischemic optic neuropathy after cataract extraction. SETTING: Neuro-ophthalmology Clinics, University of Colorado Health Sciences Center and Denver Veterans Affairs Medical Center, Denver, Colorado, USA. METHODS: A retrospective review of all patients referred to the Neuro-ophthalmology Divisions, University of Colorado Health Sciences Center and Denver Veterans Affairs Medical Center, from January 2001 to October 2005 was performed. All patients with a diagnosis of nonarteritic anterior or posterior ischemic optic neuropathy were identified. Patients with ischemic optic neuropathy that occurred between 2 months and 12 months after cataract extraction were selected for evaluation. RESULTS: Six eyes with nonarteritic ischemic optic neuropathy that occurred 2 to 6 months after cataract extraction in 4 patients (2 bilateral nonarteritic ischemic optic neuropathy) and I eye with nonarteritic ischemic optic neuropathy that occurred after 6 months in 1 patient were identified. One patient had nonarteritic ischemic optic neuropathy in 1 eye 3 months after cataract extraction and 4 years later had nonarteritic ischemic optic neuropathy in the fellow eye 5 months after cataract extraction. Follow-up after the last cataract extraction was 1 to 3 years for all patients. CONCLUSIONS: Although an association between cataract extraction and delayed nonarteritic anterior and posterior ischemic optic neuropathy has been suggested, current data do not support a causal relationship. In addition, the window of postoperative susceptibility for delayed ischemic optic neuropathy after cataract extraction is unclear. C1 Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Rocky Mt Lions Eye Inst,Dept Neurol, Aurora, CO 80045 USA. Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Rocky Mt Lions Eye Inst,Dept Ophthalmol, Aurora, CO 80045 USA. RP Pelak, VS (reprint author), Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Rocky Mt Lions Eye Inst,Dept Neurol, POB 6510,Mail Stop F727, Aurora, CO 80045 USA. EM victoria.pelak@uchsc.edu NR 17 TC 7 Z9 8 U1 0 U2 0 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 DEC PY 2006 VL 32 IS 12 BP 2105 EP 2109 DI 10.1016/j.jcrs.2006.08.028 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 116RL UT WOS:000242819900032 PM 17137991 ER PT J AU Pardee, AB AF Pardee, Arthur B. TI Tumor progression - Targets for differential therapy SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID S-PHASE ENTRY; BETA-LAPACHONE; GENE-EXPRESSION; BREAST-CANCER; CELL-GROWTH; PROTEIN; ACTIVATION; APOPTOSIS; INHIBITION; LEADS AB Differential killing of the patient's cancer cells versus normal cells is a necessity for chemotherapy. Advantage can betaken of close regulations of gene expression and of enzyme activity that are essential for normal cell functioning, and that are altered during tumor progression. Summarized here is our research on four such progression changes of cancer cells; some deregulate proliferation control and others decrease programmed death (apoptosis). These processes will be illustrated with examples of potential chemotherapies based on them. Methods for discovery of such changes include Differential Display and microarrays. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Pardee, AB (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Smith 936,44 Binney St, Boston, MA 02115 USA. EM arthur_pardee@dfci.harvard.edu NR 27 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 2006 VL 209 IS 3 BP 589 EP 591 DI 10.1002/jcp.20728 PG 3 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 101QD UT WOS:000241754600002 PM 17001691 ER PT J AU Biswas, DK Iglehart, JD AF Biswas, Debajit K. Iglehart, J. Dirk TI Linkage between EGFR family receptors and nuclear factor kappaB (NF-kappa B) signaling in breast cancer SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID BASAL-LIKE SUBTYPE; ESTROGEN-RECEPTOR; THERAPEUTIC TARGET; GENE-EXPRESSION; ACTIVATION; INHIBITION; CARCINOMA; PATHWAY; GROWTH; TUMORS AB In the United States there are 225,000 new cases of invasive breast cancer annually, and at least 50,000 women are diagnosed with ductal carcinoma in situ (DCIS). Breast cancer is a collection of disorders of mammary epithelial cells with distinct pathological characteristics and diverse clinical manifestations. Breast cancers are divided broadly into four classes by the level of the biomarkers HER2 (erbB2/neu) and the estrogen receptor (ER). Histologic grade is also an important modifier of breast cancer taxonomy and behavior. Broadly speaking, breast cancer can be divided into those that are HER2-positive, containing cancers that are both ER-positive and negative, cancers that are ER-positive and divided into high-grade and low-grade tumors, and the remaining but important class of cancers that are both ER-negative and HER2-negative. These last cancers are called basal-like and were first recognized as a distinct group by gene expression arrays. Nuclear factor kappaB (NF-kappa B) is family of multifunctional transcription factors that when activated generate pleotrophic changes in target cells. Elevated levels of active NF-kappa B are detected in many human diseases including breast cancers. High-level active NF-kappa B is detected in specific subclasses of breast cancers briefly described above, predominantly in ER-negative and epidermal growth factor family receptor (EGFR) overexpressing breast cancers (predominantly HER2 amplified cancers). This article is focused on the role of NF-kappa B activation initiated by the EGFR family receptors in subclasses of breast cancer. The combined influence of EGFR family receptors and NF-kappa B signaling on the transformation of ER-negative human mammary epithelial cell is illustrated. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Biswas, DK (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Smith 1054,44 Binney St, Boston, MA 02115 USA. EM Debajit_Biswas@dfci.harvard.edu NR 38 TC 81 Z9 88 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 2006 VL 209 IS 3 BP 645 EP 652 DI 10.1002/jcp.20785 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 101QD UT WOS:000241754600011 PM 17001676 ER PT J AU Poloyac, SM Zhang, YQ Bies, RR Kochanek, PM Graham, SH AF Poloyac, Samuel M. Zhang, Yuqing Bies, Robert R. Kochanek, Patrick M. Graham, Steven H. TI Protective effect of the 20-HETE inhibitor HET0016 on brain damage after temporary focal ischemia SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE arachidonic acid; cytochrome P450; hydroxyeicosatetraenoic acid; middle cerebral artery occlusion; N-hydroxy-N-4-butyl-2-methylphenylformamidine; stroke ID CEREBRAL-BLOOD-FLOW; ENDOTHELIAL GROWTH-FACTOR; 20-HYDROXYEICOSATETRAENOIC ACID; SUBARACHNOID HEMORRHAGE; ARACHIDONIC-ACID; ACTIVATED CHANNELS; GLOBAL-ISCHEMIA; NITRIC-OXIDE; RAT-LIVER; EXPRESSION AB Cytochrome P450 metabolism of arachidonic acid produces the potent vasoconstrictive metabolite, 20-hydroxyeicosatetraenoic acid (20-HETE). Recent studies have implicated 20-HETE as a vasoconstrictive mediator in hemorrhagic stroke. The purpose of this study was to determine the effect of the 20-HETE inhibitor, HET0016, on lesion volume and cerebral blood flow (CBF) after temporary middle cerebral artery occlusion (MCAO) in rats. Plasma pharmacokinetics and tissue concentrations of HET0016 were determined after a 10 mg/kg intraperitoneal dose. Separate rats were treated with HET0016 or vehicle before 90 mins of MCAO. Lesion volume was assessed by 2,3,5-triphenyl-tetrazolium-chloride and cerebral flow was determined using laser Doppler flow. The effect of MCAO on in vitro microsomal formation of mono-oxygenated arachidonic acid metabolites was also determined. Results show that HET0016 has a short biologic half-life, distributes into the brain, and is associated with a 79.6% reduction in 20-HETE concentration in the cortex. Lesion volume was greatly reduced in HET0016-treated (9.1%+/- 4.9%) versus vehicle-treated (57.4%+/- 9.8%; n=6; P < 0.001) rats. An attenuation of the observed decrease in CBF was observed in HET0016-treated (180 mins 89.2%+/- 6.2%; 240 mins 88.1%+/- 5.7% of baseline flow) versus vehicle control (180 mins 57.6%+/- 09.0%; 240 mins 53.8%+/- 20.0% of baseline flow; n=6; P < 0.05). Brain cortical microsomal formation rate of 20-HETE was also reduced at 24 dh in the ipsilateral hemisphere after MCAO. These data support a significant role for 20-HETE in the pathogenesis of ischemic stroke. C1 Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Safar Ctr Resuscitat Res, Dept Crit Care Med, Pittsburgh, PA 15261 USA. VA Pittsburgh Healthcare Syst, Geriat Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Poloyac, SM (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, 808A Salk Hall, Pittsburgh, PA 15261 USA. EM poloyac@pitt.edu RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X FU NIBIB NIH HHS [EB001975-06]; NINDS NIH HHS [1R01NS052315-01] NR 45 TC 36 Z9 36 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD DEC PY 2006 VL 26 IS 12 BP 1551 EP 1561 DI 10.1038/sj.jcbfm.9600309 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 111HJ UT WOS:000242441700009 PM 16570075 ER PT J AU Adler, LA Spencer, TJ Levine, LR Tamura, R Ramsey, J Kelsey, DK Ball, S Allen, AJ Biederman, J AF Adler, Lenard A. Spencer, Thomas J. Levine, Louise R. Tamura, Roy Ramsey, Janet Kelsey, Douglas K. Ball, Susan Allen, Albert J. Biederman, Joseph TI Conducting long-term studies: Observations from a functional outcome study for adult attention-deficit/hyperactivity disorder (ADHD) SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT Conference on New Clinical Drug Evaluation Unit Meeting CY JUN 12-15, 2006 CL Boca Raton, FL SP Natl Inst Mental Hlth C1 NYU, Med Ctr, New York, NY 10016 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Lilly Res Labs, Indianapolis, IN USA. Medfocus, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD DEC PY 2006 VL 16 IS 6 BP 657 EP 657 PG 1 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 127RZ UT WOS:000243605300017 ER PT J AU Wilens, T Hammerness, P Spencer, TJ Whitley, J Traina, S Santry, A Biederman, J AF Wilens, Timothy Hammerness, Paul Spencer, Thomas J. Whitley, Julia Traina, Stephanie Santry, Alison Biederman, Joseph TI Combined OROS MPH and atomoxetine in ADHD treatment in children SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT Conference on New Clinical Drug Evaluation Unit Meeting CY JUN 12-15, 2006 CL Boca Raton, FL SP Natl Inst Mental Hlth C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD DEC PY 2006 VL 16 IS 6 BP 660 EP 661 PG 2 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 127RZ UT WOS:000243605300022 ER PT J AU Utzschneider, KM Kahn, SE AF Utzschneider, Kristina M. Kahn, Steven E. TI Review: The role of insulin resistance in nonalcoholic fatty liver disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID TYPE-2 DIABETIC-PATIENTS; ACTIVATED PROTEIN-KINASE; METABOLIC RISK-FACTORS; NECROSIS-FACTOR-ALPHA; C-REACTIVE PROTEIN; ADIPOSE-TISSUE; HEPATIC STEATOSIS; WEIGHT-LOSS; NONDIABETIC PATIENTS; GENE-EXPRESSION AB Context: Insulin resistance is an almost universal finding in nonalcoholic fatty liver disease (NAFLD). This review outlines the evidence linking insulin resistance and NAFLD, explores whether liver fat is a cause or consequence of insulin resistance, and reviews the current evidence for treatment of NAFLD. Evidence Acquisition: Evidence from epidemiological, experimental, and clinical research studies investigating NAFLD and insulin resistance was reviewed. Evidence Synthesis: Insulin resistance in NAFLD is characterized by reductions in whole-body, hepatic, and adipose tissue insulin sensitivity. The mechanisms underlying the accumulation of fat in the liver may include excess dietary fat, increased delivery of free fatty acids to the liver, inadequate fatty acid oxidation, and increased de novo lipogenesis. Insulin resistance may enhance hepatic fat accumulation by increasing free fatty acid delivery and by the effect of hyperinsulinemia to stimulate anabolic processes. The impact of weight loss, metformin, and thiazolidinediones, all treatments aimed at improving insulin sensitivity, as well as other agents such as vitamin E, have been evaluated in patients with NAFLD and have shown some benefit. However, most intervention studies have been small and uncontrolled. Conclusion: Insulin resistance is a major feature of NAFLD that, in some patients, can progress to steatohepatitis. Treatments aimed at reducing insulin resistance have had some success, but larger placebo-controlled studies are needed to fully establish the efficacy of these interventions and possibly others in reducing the deleterious effects of fat accumulation in the liver. C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98108 USA. RP Utzschneider, KM (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM kutzschn@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 NR 118 TC 295 Z9 315 U1 4 U2 31 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 DEC PY 2006 VL 91 IS 12 BP 4753 EP 4761 DI 10.1210/jc.2006-0587 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 113EN UT WOS:000242581300005 PM 16968800 ER PT J AU Fonseca, VA Kahn, SE AF Fonseca, Vivian A. Kahn, Steven E. TI Commentary: Of hopes and DREAMS: The quest to prevent type 2 diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE; MELLITUS; RAMIPRIL C1 Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA. Univ Washington, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Fonseca, VA (reprint author), Tulane Univ, Med Ctr, Diabet Program, 1430 Tulane Ave,SL 53, New Orleans, LA 70112 USA. EM vfonseca@tulane.edu OI Kahn, Steven/0000-0001-7307-9002 NR 11 TC 1 Z9 1 U1 0 U2 2 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 DEC PY 2006 VL 91 IS 12 BP 4762 EP 4763 DI 10.1210/jc.2006-2164 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 113EN UT WOS:000242581300006 PM 17062761 ER PT J AU Welt, CK Gudmundsson, JA Arason, G Adams, J Palsdottir, H Gudlaugsdottir, G Ingadottir, G Crowley, WF AF Welt, C. K. Gudmundsson, J. A. Arason, G. Adams, J. Palsdottir, H. Gudlaugsdottir, G. Ingadottir, G. Crowley, W. F. TI Characterizing discrete subsets of polycystic ovary syndrome as defined by the Rotterdam criteria: The impact of weight on phenotype and metabolic features SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; HYPERANDROGENIC WOMEN; INSULIN-RESISTANCE; MENSTRUAL-CYCLE; ENDOCRINE; DIAGNOSIS; DYSLIPIDEMIA; ASSOCIATION; SECRETION; SISTERS AB Context: The Rotterdam criteria for polycystic ovary syndrome (PCOS) defines discrete subgroups whose phenotypes are not yet clear. Objective: The phenotypic characteristics of women in the PCOS subgroups defined by the Rotterdam criteria were compared. Design: The study was observational. Setting: Subjects were studied in an outpatient setting in Boston and Reykjavik. Patients: Four subgroups of subjects with PCOS defined by 1) irregular menses (IM), hyperandrogenism (HA), and polycystic ovary morphology (PCOM, n = 298); 2) IM/HA(n = 7); 3) HA/PCOM(n = 77); and 4) IM/PCOM (n = 36) and a group of controls (n = 64), aged 18-45 yr, were examined. Intervention: Subjects underwent a physical exam; fasting blood samples for androgens, gonadotropins, and metabolic parameters; and a transvaginal ultrasound. Main Outcome Measures: The phenotype was compared between groups. Results: Ninety-seven percent of women with IM/HA had PCOM. Therefore, the groups with and without PCOM were combined. The Ferriman-Gallwey score and androgen levels were highest in the hyperandrogenic groups (IM/HA and HA/PCOM), whereas ovarian volume was higher in all PCOS subgroups compared with controls, as expected based on the definitions of the PCOS subgroups. Body mass index and insulin levels were highest in the IM/HA subgroup. Conclusions: Subjects with PCOS defined by IM/HA are the most severely affected women on the basis of androgen levels, ovarian volumes, and insulin levels. Their higher body mass index partially accounts for the increased insulin levels, suggesting that weight gain exacerbates the symptoms of PCOS. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. JONUSTUMIiDSTOD RANNSOKNAVERKEFNA, IS-105 Reykjavik, Iceland. Landspitali Univ Hosp, Dept Obstet & Gynecol, IS-101 Reykjavik, Iceland. ARTmed IVF, IS-101 Reykjavik, Iceland. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, BHX 511,55 Fruit St, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [M01-RR-01066]; NICHD NIH HHS [U01 HD 4417] NR 37 TC 128 Z9 136 U1 0 U2 4 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 DEC PY 2006 VL 91 IS 12 BP 4842 EP 4848 DI 10.1210/jc.2006-1327 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 113EN UT WOS:000242581300020 PM 17003085 ER PT J AU Johnsen, S Dolan, SE Fitch, KV Kanter, JR Hemphill, LC Connelly, JM Lees, RS Lee, H Grinspoon, S AF Johnsen, Stine Dolan, Sara E. Fitch, Kathleen V. Kanter, Jenna R. Hemphill, Linda C. Connelly, Jean M. Lees, Robert S. Lee, Hang Grinspoon, Steve TI Carotid intimal medial thickness in human immunodeficiency virus-infected women: Effects of protease inhibitor use, cardiac risk factors, and the metabolic syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORONARY-HEART-DISEASE; MYOCARDIAL-INFARCTION; HIV-INFECTION; ANTIRETROVIRAL THERAPY; ENDOTHELIAL FUNCTION; CARDIOVASCULAR RISK; ARTERY-DISEASE; BONE-DENSITY; ATHEROSCLEROSIS; ADULTS AB Context: Little is known regarding carotid intimal medial thickness (IMT) in HIV-infected women and the risk factors for subclinical atherosclerosis in this population, including antiretroviral therapy and the metabolic syndrome. Objective: Our objective was to assess carotid IMT in relationship to HIV status and antiretroviral therapy in HIV-infected women in comparison with healthy age- and body mass index (BMI)-matched control subjects. Setting and Subjects: The study took place at an academic medical center and included 97 HIV-infected women compared with 86 age- and BMI-matched healthy control subjects. Main Outcome Measures: We assessed carotid IMT, metabolic syndrome, and risk factors for increased IMT. Results: Carotid IMT was not increased in HIV-infected women [0.62 mm (0.57-0.68); median (IQR)] compared with non-HIV-infected women [0.61mm(0.55-0.68)] matched for age and BMI (P = 0.07) but was increased significantly among HIV patients receiving a protease inhibitor (PI) [0.65 (0.59-0.71) mm] vs. non-PI-treated patients [0.61 (0.57-0.66) mm] (P < 0.05) and vs. control subjects [0.61 (0.55-0.68) mm] (P < 0.05). The prevalence of metabolic syndrome was significantly increased among the HIV-infected women compared with control subjects and particularly in PI- vs. non- PI- treated HIV patients (45 vs. 19%, P = 0.001). Metabolic syndrome score correlated with IMT among non-HIV patients but not among the HIV group. Individual risk factors most strongly associated with IMT in multivariate regression modeling in the control group were age and waist-to-hip ratio, and among the HIV group age and waist circumference. Conclusions: These data demonstrate increased carotid IMT in HIV-infected women receiving PI therapy, which may be due to associated metabolic abnormalities related to PI therapy or more direct effects of this medication class on the vasculature. Additional studies of the mechanisms by which PI uses results in subclinical atherosclerosis are needed. C1 Massachusetts Gen Hosp, Program Nutrit Metab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Biostat Ctr, Boston Heart Fdn, Boston, MA 02114 USA. Skejby Hosp, Dept Infect Dis, DK-8200 Aarhus, Denmark. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutrit Metab, Boston, MA 02114 USA. EM Sgrinspoon@partners.org FU NCRR NIH HHS [M01 RR001066, M01-RR-01066]; NIDDK NIH HHS [R01 DK59535, P30 DK040561, P30 DK040561-11, R01 DK059535] NR 39 TC 56 Z9 56 U1 0 U2 0 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 DEC PY 2006 VL 91 IS 12 BP 4916 EP 4924 DI 10.1210/jc.2006-1140 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 113EN UT WOS:000242581300031 PM 17003092 ER PT J AU Eriksson, AL Lorentzon, M Mellstrom, D Vandenput, L Swanson, C Andersson, N Hammond, GL Jakobsson, J Rane, A Orwoll, ES Ljunggren, O Johnell, O Labrie, F Windahl, SH Ohlsson, C AF Eriksson, A. L. Lorentzon, M. Mellstrom, D. Vandenput, L. Swanson, C. Andersson, N. Hammond, G. L. Jakobsson, J. Rane, A. Orwoll, E. S. Ljunggren, O. Johnell, O. Labrie, F. Windahl, S. H. Ohlsson, C. TI SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ELDERLY-MEN; FREE TESTOSTERONE; POSTMENOPAUSAL WOMEN; SWEDISH MEN; STEROIDS; REPEAT; STANDARDIZATION; PREDICTOR; FRACTURES; ESTRADIOL AB Context: SHBG regulates free sex steroid levels, which in turn regulate skeletal homeostasis. Twin studies have demonstrated that genetic factors largely account for interindividual variation in SHBG levels. Glucuronidated androgen metabolites have been proposed as markers of androgenic activity. Objective: Our objective was to investigate whether polymorphisms in the SHBG gene promoter [(TAAAA)(n) microsatellite and rs1799941 single-nucleotide polymorphism] are associated with serum levels of SHBG, sex steroids, or bone mineral density (BMD) in men. Design and Study Subjects: We conducted a population-based study of two cohorts of Swedish men: elderly men (MrOS Sweden; n congruent to 3000; average age, 75.4 yr) and young adult men ( GOOD study; n = 1068; average age, 18.9 yr). Main Outcome Measures: We measured serum levels of SHBG, testosterone, estradiol, dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol glucuronides, androsterone glucuronide, and BMD determined by dual-energy x-ray absorptiometry. Results: In both cohorts, (TAAAA)(n) and rs1799941 genotypes were associated with serum levels of SHBG (P < 0.001), dihydrotestosterone (P < 0.05), and 5 alpha-androstane-3 alpha,17 beta- diol glucuronides (P < 0.05). In the elderly men, they were also associated with testosterone and BMD at all hip bone sites. The genotype associated with high levels of SHBG was also associated with high BMD. Interestingly, male mice overexpressing human SHBG had increased cortical bone mineral content in the femur, suggesting that elevated SHBG levels may cause increased bone mass. Conclusions: Our findings demonstrate that polymorphisms in the SHBG promoter predict serum levels of SHBG, androgens, and glucuronidated androgen metabolites, and hip BMD in men. C1 Div Endocrinol, Dept Internal Med, S-41345 Gothenburg, Sweden. Univ Gothenburg, Sahlgrenska Acad, Ctr Bone Res, SE-41345 Gothenburg, Sweden. Univ Gothenburg, Dept Internal Med, SE-41345 Gothenburg, Sweden. Univ Gothenburg, Dept Geriatr, SE-41345 Gothenburg, Sweden. Univ British Columbia, Dept Obstet & Gynaecol, Vancouver, BC V5Z 4H4, Canada. Family Res Inst, Vancouver, BC V5Z 4H4, Canada. Karolinska Univ Hosp, Karolinska Inst, Div Clin Pharmacol, SE-14186 Stockholm, Sweden. Oregon Hlth Sci Univ, Bone & Mineral Res Unit, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97207 USA. Uppsala Univ, Dept Med Sci, SE-75185 Uppsala, Sweden. Malmo Gen Hosp, Dept Orthopaed, SE-20502 Malmo, Sweden. Univ Laval Hosp, Res Ctr, Laval, PQ G1V 4G2, Canada. Univ Laval, Laval, PQ G1V 4G2, Canada. RP Ohlsson, C (reprint author), Div Endocrinol, Dept Internal Med, Grona Straket 8, S-41345 Gothenburg, Sweden. EM claes.ohlsson@medic.gu.se RI Perez , Claudio Alejandro/F-8310-2010; Schulze, Jenny/J-2909-2012; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Orwoll, Eric/0000-0002-8520-7355; Vandenput, Liesbeth/0000-0002-1712-6131 NR 32 TC 54 Z9 55 U1 0 U2 4 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 DEC PY 2006 VL 91 IS 12 BP 5029 EP 5037 DI 10.1210/jc.2006-0679 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 113EN UT WOS:000242581300050 PM 16926255 ER PT J AU Holman, JB Brendel, DH AF Holman, Julieta Bleichmar Brendel, David H. TI The ethics of palliative care in psychiatry SO JOURNAL OF CLINICAL ETHICS LA English DT Article ID OF-LIFE CARE; DEMENTIA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. McLean Hosp, Inst Review Board, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Holman, JB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jholman@partners.org; dbrendel@partners.org NR 4 TC 4 Z9 4 U1 1 U2 3 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD WIN PY 2006 VL 17 IS 4 BP 333 EP 338 PG 6 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 137VX UT WOS:000244321900008 PM 17330725 ER PT J AU Purtilo, RB AF Purtilo, Ruth B. TI Attention to caregivers and hope: Overlooked aspects of ethics consultation SO JOURNAL OF CLINICAL ETHICS LA English DT Article C1 Massachusetts Gen Hosp, Eth Initiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Purtilo, RB (reprint author), Massachusetts Gen Hosp, Eth Initiat, Boston, MA 02114 USA. EM rpurtilo@mghihp.edu NR 12 TC 0 Z9 0 U1 0 U2 1 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD WIN PY 2006 VL 17 IS 4 BP 358 EP 363 PG 6 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 137VX UT WOS:000244321900013 PM 17330730 ER PT J AU Ghannoum, MA Arthington-Skaggs, B Chaturvedi, V Espinel-Ingroff, A Pfaller, MA Rennie, R Rinaldi, MG Walsh, TJ AF Ghannoum, M. A. Arthington-Skaggs, B. Chaturvedi, V. Espinel-Ingroff, A. Pfaller, M. A. Rennie, R. Rinaldi, M. G. Walsh, T. J. TI Interlaboratory study of quality control isolates for a broth microdilution method (modified CLSI M38-A) for testing susceptibilities of dermatophytes to antifungals SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article AB The Clinical and Laboratory Standards Institute (CLSI; formerly National Committee for Clinical Laboratory Standards, or NCCLS) M38-A standard for the susceptibility testing of filamentous fungi does not specifically address the testing of dermatophytes. In 2003, a multicenter study investigated the reproducibility of the microdilution method developed at the Center for Medical Mycology, Cleveland, Ohio, for testing the susceptibility of dermatophytes. Data from that study supported the introduction of this method for testing dermatophytes in the future version of the CLSI M38-A standard. In order for the method to be accepted by CLSI, appropriate quality control isolates needed to be identified. To that end, an interlaboratory study, involving the original six laboratories plus two additional sites, was conducted to evaluate potential candidates for quality control isolates. These candidate strains included five Trichophyton rubrum strains known to have elevated MICs to terbinafine and five Trichophyton mentagrophytes strains. Antifungal agents tested included ciclopirox, fluconazole, griseofulvin, itraconazole, posaconazole, terbinafine, and voriconazole. Based on the data generated, two quality control isolates, one T. rubrum isolate and one T. mentagrophytes isolate, were identified and submitted to the American Type Culture Collection (ATCC) for inclusion as reference strains. Ranges encompassing 95.2 to 97.9% of all data points for all seven drugs were established. C1 Case Western Reserve Univ Hosp, Ctr Med Mycol, EMBA, Cleveland, OH 44106 USA. Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA USA. Dept Hlth, Albany, NY USA. VCU Med Ctr, Richmond, VA USA. Univ Iowa, Coll Med, Dept Pathol, Iowa City, IA 52242 USA. Univ Alberta Hosp, Natl Ctr Mycol, Edmonton, AB T6G 2B7, Canada. Univ Texas, Hlth Sci Ctr, Audie L Murphy Mem Vet Hosp, Lab Serv, San Antonio, TX USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Ghannoum, MA (reprint author), Case Western Reserve Univ Hosp, Ctr Med Mycol, EMBA, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM mag3@case.edu NR 6 TC 22 Z9 22 U1 0 U2 1 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 DEC PY 2006 VL 44 IS 12 BP 4353 EP 4356 DI 10.1128/JCM.00688-06 PG 4 WC Microbiology SC Microbiology GA 117MC UT WOS:000242876300009 PM 17050812 ER PT J AU Jones, KL Glickstein, LJ Damle, N Sikand, VK McHugh, G Steere, AC AF Jones, Kathryn L. Glickstein, Lisa J. Damle, Nitin Sikand, Vijay K. McHugh, Gail Steere, Allen C. TI Borrelia burgdorferi genetic markers and disseminated disease in patients with early Lyme disease SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LENGTH POLYMORPHISM ANALYSIS; SENSU-STRICTO; LINEAR PLASMID-25; MAMMALIAN HOST; DIVERSITY; INFECTION; VLSE; OSPC; PCR; SPIROCHETE AB Three genetic markers of Borrelia burgdorferi have been associated with disseminated disease: the OspC type, the 16S-23S rRNA intergenic spacer type (RST), and vlsE. Here, we modified previous methods so as to identify the three markers by PCR and restriction fragment length polymorphism in parallel, analyzed B. burgdorferi isolates from erythema migrans (EM) skin lesions in 91 patients, and correlated the results with evidence of dissemination. OspC type A was found approximately twice as frequently in patients with disseminated disease, whereas type K was identified approximately twice as often in those without evidence of dissemination, but these trends were not statistically significant. The remaining seven types identified were found nearly equally in patients with or without evidence of dissemination. RST 1 strains were significantly associated with dissemination (P = 0.03), whereas RST 2 and RST 3 strains tended to have an inverse association with this outcome. The vlsE gene was identified in all 91 cases, using primer sets specific for an N-terminal sequence of B. burgdorferi strain B31 (vlsE(B31)) or strain 297 (vlsE(297)), but neither marker was associated with dissemination. Specific combinations of the three genetic markers usually occurred together. OspC type A was always found with RST 1 and vlsE(B31), type K was always identified with RST 2 and more often with vlsE(297), and types E and I were almost always found with RST 3 and equally often with vlsE(B31) and vlsE(297). We conclude that B. burgdorferi strains vary in their capacity to disseminate, but almost all strains isolated from EM lesions sometimes caused disseminated disease. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Jones, KL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, 55 Fruit St,CNY 149-8301, Boston, MA 02114 USA. EM KLJones@partners.org FU NIAMS NIH HHS [AR-20358, R01 AR020358]; PHS HHS [CCU110 291] NR 40 TC 50 Z9 50 U1 1 U2 5 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 DEC PY 2006 VL 44 IS 12 BP 4407 EP 4413 DI 10.1128/JCM.01077-06 PG 7 WC Microbiology SC Microbiology GA 117MC UT WOS:000242876300018 PM 17035489 ER PT J AU Garcia, LS Garcia, JP AF Garcia, Lynne S. Garcia, John Paul TI Detection of Giardia lamblia antigens in human fecal specimens by a solid-phase qualitative immunochromatographic assay SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CRYPTOSPORIDIUM-PARVUM ANTIGENS; LINKED-IMMUNOSORBENT-ASSAY; ENZYME-IMMUNOASSAY; DIRECT FLUORESCENCE; MICROPLATE ASSAY; STOOL SPECIMENS AB The SIMPLE-READ Giardia rapid assay (Medical Chemical Corporation) is a solid-phase qualitative immunochromatographic assay that detects Giardia lamblia in aqueous extracts of human fecal specimens. Testing 106 Giardia-positive and 104 Giardia-negative stool specimens yielded a sensitivity of 97.2% and a speciticity of 100% for the SIMPLE-READ Giardia rapid assay. C1 LSG & Associates, Santa Monica, CA 90402 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Garcia, LS (reprint author), LSG & Associates, 512 12th St, Santa Monica, CA 90402 USA. EM Lynnegarcia12@earthlink.net NR 15 TC 9 Z9 12 U1 0 U2 0 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 DEC PY 2006 VL 44 IS 12 BP 4587 EP 4588 DI 10.1128/JCM.01458-06 PG 2 WC Microbiology SC Microbiology GA 117MC UT WOS:000242876300050 PM 17065273 ER PT J AU Karayiannis, NB Xiong, YH Frost, JD Wise, MS Hrachovy, RA Mizrahi, EM AF Karayiannis, Nicolaos B. Xiong, Yaohua Frost, James D., Jr. Wise, Merrill S. Hrachovy, Richard A. Mizrahi, Eli M. TI Automated detection of videotaped neonatal seizures based on motion tracking methods SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article DE motion tracking; motion trajectory signal; motor activity signal; neonatal seizure; neural network; seizure detection; video recording ID MOTOR-ACTIVITY SIGNALS; QUANTUM NEURAL-NETWORKS; QUANTIFYING MOTION; RECORDINGS; EEG; EXTRACTION; NEWBORN AB This study was carried out during the second phase of the project "Video Technologies for Neonatal Seizures" and aimed at the development of a seizure detection system by training neural networks, using quantitative motion information extracted by motion tracking methods from short video segments of infants monitored for seizures. The motion of the infants' body parts was quantified by temporal motion trajectory signals extracted from video recordings by robust motion trackers, based on block motion models. These motion trackers were developed to autonomously adjust to illumination and contrast changes that may occur during the video frame sequence. The computational tools and procedures developed for automated seizure detection were evaluated on short video segments selected and labeled by physicians from a set of 240 video recordings of 54 patients exhibiting myoclonic seizures (80 segments), focal clonic seizures (80 segments), and random infant movements (80 segments). This evaluation provided the basis for selecting the most effective strategy for training neural networks to detect neonatal seizures as well as the decision scheme used for interpreting the responses of the trained neural networks. The best neural networks exhibited sensitivity and specificity above 90%. The best among the motion trackers developed in this study produced quantitative features that constitute a reliable basis for detecting myoclonic and focal clonic neonatal seizures. The performance targets of the second phase of the project may be achieved by combining the quantitative features described in this paper with those obtained by analyzing motion strength signals produced by motion segmentation methods. C1 Baylor Coll Med, Peter Kellaway Sect Neurophysiol, Dept Neurol, Houston, TX 77030 USA. Baylor Coll Med, Peter Kellaway Sect Neurophysiol, Dept Pediat, Houston, TX 77030 USA. Univ Houston, Dept Elect & Comp Engn, Houston, TX USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Frost, JD (reprint author), Baylor Coll Med, Peter Kellaway Sect Neurophysiol, Dept Neurol, NB302,1 Baylor Plaza, Houston, TX 77030 USA. FU NIBIB NIH HHS [1 R01 EB00183]; NINDS NIH HHS [N01-NS-2316] NR 32 TC 8 Z9 8 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD DEC PY 2006 VL 23 IS 6 BP 521 EP 531 DI 10.1097/00004691-200612000-00004 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 115UD UT WOS:000242758400004 PM 17143140 ER PT J AU Taplin, ME Xie, WL Bubley, GJ Ernstoff, MS Walsh, W Morganstern, DE Regan, MM AF Taplin, Mary-Ellen Xie, Wanling Bubley, Glenn J. Ernstoff, Marc S. Walsh, William Morganstern, Daniel E. Regan, Meredith M. TI Docetaxel, estramustine, and 15-month androgen deprivation for men with prostate-specific antigen progression after definitive local therapy for prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RADICAL PROSTATECTOMY; SALVAGE RADIOTHERAPY; RADIATION-THERAPY; ADJUVANT; CHEMOTHERAPY; MITOXANTRONE; PREDNISONE; MORTALITY AB Purpose Androgen-deprivation therapy (ADT) is effective for relapsed prostate cancer, but is rarely curative. The purpose of this trial was to determine the feasibility, toxicity, and prostate-specific antigen (PSA) response of chemotherapy and limited ADT for men with PSA relapse. Patients and Methods Eligible men had an increasing PSA and no metastases after prostatectomy and/or radiation for localized disease. Treatment consisted of four cycles of docetaxel (70 mg/m(2)) every 21 days and estramustine 280 mg tid on days 1 through 5. After chemotherapy, goserelin acetate and bicalutamide were prescribed for 15 months. Results Sixty-two patients were enrolled. A complete PSA response (CB) was defined as PSA at or below the assay-specific lower limit. The proportion of patients with CR after chemotherapy, after ADT, and at 1 year after completion of ADT was 53%, 63%, and 36%, respectively. Testosterone was more than 100 ng/dL (median, 250 ng/dL) 1 year after completion of ADT in 97% of patients. Patients with a PSA less than 3.0 ng/mL at enrollment had a significantly longer time to progression (TTP; P =.0004). Of 56 patients who were observed at least 1 year after completion of ADT, 23 (41%) have not experienced progression as of their last follow-up. The median TTP is 34 months from treatment initiation (maximum, 74 months free from progression). Conclusion Chemotherapy plus ADT was feasible for early prostate cancer relapse. Forty-one percent of men who are at least 1 year after completion of ADT with recovered testosterone have not experienced progression. This approach is being tested in a randomized trial with investigation of predictors of response. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Taplin, ME (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM mtaplin@partners.org NR 18 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2006 VL 24 IS 34 BP 5408 EP 5413 DI 10.1200/JCO.2006.06.6589 PG 6 WC Oncology SC Oncology GA 112OJ UT WOS:000242535400010 PM 17135641 ER PT J AU Woods, DW Flessner, CA Franklin, ME Keuthen, NJ Goodwin, RD Stein, DJ Walther, MR AF Woods, Douglas W. Flessner, Christopher A. Franklin, Martin E. Keuthen, Nancy J. Goodwin, Renee D. Stein, Dan J. Walther, Michael R. CA Trichotillomania Learning Ctr Sci TI The Trichotillomania Impact Project (TIP): Exploring phenomenology, functional impairment, and treatment utilization SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID NATIONAL EPIDEMIOLOGIC SURVEY; ANXIETY STRESS SCALES; MGH HAIRPULLING SCALE; HAIR PULLERS; PSYCHOMETRIC PROPERTIES; BEHAVIORAL-THERAPY; SAMPLES; COMORBIDITY; PREVALENCE; DISORDERS AB Background: Trichotillomania (TTM) occurs in 0.6% to 3.4% of adults. Questions remain about phenomenological features of the disorder, its impact on functioning, and treatment utilization. The current study (i.e., The Trichotillomania Impact Project) was designed to provide initial information regarding these issues. Method: An Internet-based survey was completed by 1697 individuals who self-reported symptoms consistent with a diagnosis of TTM (DSM-IV-TR). The survey assessed phenomenological experiences; social, occupational, academic, and psychological impact; as well as treatment-seeking experiences. The survey link operated from April 2005 through May 2005. Results: Survey results suggest considerable variability in TTM phenomenology. Individuals with more severe TTM symptoms endorsed more frequent phenomenological experiences of physical or mental anxiety prior to pulling and relief, pleasure, or gratification after pulling. Mild to moderate life impairment in social, occupational, academic, and psychological functioning was reported for the entire study sample. These impairments were more pronounced as TTM symptoms became more severe. A summary of treatment seeking in the sample suggests that pharmacotherapy was the most commonly received treatment, followed by behavior therapy. Unfortunately, treatment in general was perceived as relatively ineffective. Conclusion: This study underscores the clinical significance of severe hair pulling and highlights the need for research on its pathogenesis and treatment. C1 Univ Wisconsin, Dept Psychol, Milwaukee, WI 53211 USA. Univ Penn, Sch Med, Ctr Treatment & Study Anxiety, Philadelphia, PA 19104 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Columbia Univ, Dept Epidemiol, New York, NY USA. Univ Cape Town, Dept Psychiat, ZA-7925 Cape Town, South Africa. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. TLC SAB, Santa Cruz, CA USA. RP Woods, DW (reprint author), Univ Wisconsin, Dept Psychol, 2441 E Hartford Ave,211 Garland Hall, Milwaukee, WI 53211 USA. EM dwoods@uwm.edu RI Citations, TLC SAB/C-4006-2011; Flessner, Christopher/K-1483-2015; Stein, Dan/A-1752-2008 OI Stein, Dan/0000-0001-7218-7810 NR 43 TC 127 Z9 127 U1 5 U2 13 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 DEC PY 2006 VL 67 IS 12 BP 1877 EP 1888 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 120LI UT WOS:000243085800006 PM 17194265 ER PT J AU Ostacher, MJ Nierenberg, AA Perlis, RH Eidelman, P Borrelli, DJ Tran, TB Ericson, GM Weiss, RD Sachs, GS AF Ostacher, Michael J. Nierenberg, Andrew A. Perlis, Roy H. Eidelman, Polina Borrelli, David J. Tran, Tanya B. Ericson, Gianna Marzilli Weiss, Roger D. Sachs, Gary S. TI The relationship between smoking and suicidal behavior, comorbidity, and course of illness in bipolar disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID TREATMENT-ENHANCEMENT-PROGRAM; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; NICOTINE DEPENDENCE; STEP-BD; DSM-IV; PARTICIPANTS; DEPRESSION; MINI AB Objectives: The rate of smoking in people with bipolar disorder is much greater than in the general population, but the implications of smoking for the course of bipolar disorder have not been well studied. The purpose of this retrospective study was to examine the relationship between smoking, severity of bipolar disorder, suicidal behavior, and psychiatric and substance use disorder comorbidity. Method: We evaluated 399 outpatients with bipolar disorder who were treated in a bipolar specialty clinic from December 1999 to October 2004. Diagnosis, mood state, course of illness, functioning, and psychiatric comorbidities were assessed using the Affective Disorders Evaluation and the Mini-International Neuropsychiatric Interview. Results: Of the 399 patients evaluated, 155 (38.8%) had a history of daily smoking. Having ever smoked was associated with earlier age at onset of first depressive or manic episode, lower Global Assessment of Functioning scores, higher Clinical Global Impressions-Bipolar Disorder scale scores, lifetime history of a suicide attempt (47% for smokers vs. 25% for those who had never smoked), and lifetime comorbid disorders: anxiety disorders, alcohol abuse and dependence, and substance abuse and dependence. In a logistic regression model including these factors, suicide attempts and substance dependence were significantly associated with smoking in patients with bipolar disorder. Conclusions: Bipolar patients with lifetime smoking were more likely to have earlier age at onset of mood disorder, greater severity of symptoms, poorer functioning, history of a suicide attempt, and a lifetime history of comorbid anxiety and substance use disorders. Smoking may be independently associated with suicidal behavior in bipolar disorder. C1 Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. McLean Hosp, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Ostacher, MJ (reprint author), Massachusetts Gen Hosp, Bipolar Clin & Res Program, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM mostacher@partners.org OI Ostacher, Michael/0000-0003-0353-7535 FU NIDA NIH HHS [R01 DA00326, R01 DA15968] NR 19 TC 67 Z9 68 U1 5 U2 8 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 DEC PY 2006 VL 67 IS 12 BP 1907 EP 1911 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 120LI UT WOS:000243085800009 PM 17194268 ER PT J AU Freeman, MP Hibbeln, JR Wisner, KL Davis, JM Mischoulon, D Peet, M Keck, PE Mayangell, LB Richardson, AJ Lake, J Stoll, AL AF Freeman, Marlene P. Hibbeln, Joseph R. Wisner, Katherine L. Davis, John M. Mischoulon, David Peet, Malcolm Keck, Paul E., Jr. Mayangell, Lauren B. Richardson, Alexandra J. Lake, James Stoll, Andrew L. TI Omega-3 fatty acids: Evidence basis for treatment and future research in psychiatry SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID POLYUNSATURATED FATTY-ACIDS; PLACEBO-CONTROLLED TRIAL; ETHYL-EICOSAPENTAENOIC ACID; RANDOMIZED DOUBLE-BLIND; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; DEPENDENT DIABETES-MELLITUS; BLOOD-CELL MEMBRANES; DOSE FISH-OIL; DOCOSAHEXAENOIC ACID AB Objective: To determine if the available data support the use of omega-3 essential fatty acids (EFA) for clinical use in the prevention and/or treatment of psychiatric disorders. Participants: The authors of this article were invited participants in the Omega-3 Fatty Acids Subcommittee, assembled by the Committee on Research on Psychiatric Treatments of the American Psychiatric Association (APA). Evidence: Published literature and data presented at scientific meetings were reviewed. Specific disorders reviewed included major depressive disorder, bipolar disorder, schizophrenia, dementia, borderline personality disorder and impulsivity, and attention-deficit/hyperactivity disorder. Meta-analyses were conducted in major depressive and bipolar disorders and schizophrenia, as sufficient data were available to conduct such analyses in these areas of interest. Consensus Process: The subcommittee prepared the manuscript, which was reviewed and approved by the following APA committees: the Committee on Research on Psychiatric Treatments, the Council on Research, and the Joint Reference Committee. Conclusions: The preponderance of epidemiologic and tissue compositional studies supports a protective effect of omega-3 EFA intake, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in mood disorders. Meta-analyses of randomized controlled trials demonstrate a statistically significant benefit in unipolar and bipolar depression (p = .02). The results were highly heterogeneous, indicating that it is important to examine the characteristics of each individual study to note the differences in design and execution. There is less evidence of benefit in schizophrenia. EPA and DHA appear to have negligible risks and some potential benefit in major depressive disorder and bipolar disorder, but results remain inconclusive in most areas of interest in psychiatry. Treatment recommendations and directions for future research are described. Health benefits of omega-3 EFA may be especially important in patients with psychiatric disorders, due to high prevalence rates of smoking and obesity and the metabolic side effects of some psychotropic medications. C1 Univ Arizona, Coll Med, Womens Mental Hlth Program, Dept Psychiat, Tucson, AZ 85724 USA. Univ Arizona, Coll Med, Womens Mental Hlth Program, Dept Obstet & Gynecol, Tucson, AZ 85724 USA. Univ Arizona, Coll Med, Womens Mental Hlth Program, Dept Nutr Sci, Tucson, AZ 85724 USA. NIAAA, Bethesda, MD USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Sheffield, Sch Hlth & Related Res, Sheffield, S Yorkshire, England. Univ Cincinnati, Coll Med, Psychopharmacol Res Program, Dept Psychiat, Cincinnati, OH USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. Dept Vet Affairs, VISN Mental Illness Res Educ & Clin Core 16, Houston, TX USA. Univ Oxford, Dept Physiol Human Anat & Genet, Oxford, England. Stanford Univ, Dept Psychiat, Palo Alto, CA 94304 USA. Stanford Univ, Ctr Integrative Med, Palo Alto, CA 94304 USA. Harvard Univ, Sch Med, Dept Psychiat, McLean Hosp, Boston, MA USA. RP Freeman, MP (reprint author), Univ Arizona, Coll Med, Womens Mental Hlth Program, Dept Psychiat, 1501 N Campbell Ave,POB 245002, Tucson, AZ 85724 USA. EM marlenef@email.arizona.edu FU NCCIH NIH HHS [5 K23 AT001129-05]; NIMH NIH HHS [5K23MH066265] NR 133 TC 383 Z9 396 U1 5 U2 95 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 DEC PY 2006 VL 67 IS 12 BP 1954 EP 1967 PG 16 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 120LI UT WOS:000243085800016 PM 17194275 ER PT J AU Gershuny, BS Keuthen, NJ Gentes, EL Russo, AR Emmott, EC Jameson, M Dougherty, DD Loh, R Jenike, MA AF Gershuny, Beth S. Keuthen, Nancy J. Gentes, Emily L. Russo, Amanda R. Emmott, Elizabeth C. Jameson, Mariko Dougherty, Darin D. Loh, Rebecca Jenike, Michael A. TI Current posttraumatic stress disorder and history of trauma in trichotillomania SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE trichotillomania; posttraumatic stress disorder; trauma ID OBSESSIVE-COMPULSIVE DISORDER; MGH HAIRPULLING SCALE; POPULATION; EVENTS AB Though some researchers and clinicians postulate that trauma and post-traumatic stress disorder (PTSD) may be implicated in the etiologic underpinnings of trichotillomania (TTM), very little research to date has examined such postulations. To address this gap in the literature, the current study assessed the prevalence of trauma and PTSD in 42 individuals seeking treatment for TTM. Relations between symptoms of PTSD and TTM also were examined, as were differences in TTM symptoms between those with and without PTSD. Findings revealed that approximately 76% reported a history of at least one traumatic event, and 19% met criteria for PTSD. Furthermore, negative correlations were demonstrated between symptoms of PTSD and characteristics of TTK and the PTSD group reported less severe TTM characteristics. Findings suggest that the prevalence of PTSD in TTM may be higher than in the general population and that a history of greater number of types of traumas is associated with a longer duration of hair pulling as well as the scalp as the primary pulling site. The authors also speculate that in traumatized individuals, TTM may represent a form of coping vis-a-vis self-soothing or self-harm. (c) 2006 Wiley Periodicals, Inc. C1 Skidmore Coll, Dept Psychol, Saratoga Springs, NY 12866 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gershuny, BS (reprint author), Skidmore Coll, Dept Psychol, 815 N Broadway, Saratoga Springs, NY 12866 USA. EM gershuny@skidmore.edu RI Citations, TLC SAB/C-4006-2011 NR 25 TC 18 Z9 18 U1 3 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD DEC PY 2006 VL 62 IS 12 BP 1521 EP 1529 DI 10.1002/jclp.20303 PG 9 WC Psychology, Clinical SC Psychology GA 108HW UT WOS:000242231900005 PM 16897695 ER PT J AU Acharya, N Rosen, AS Polzer, JP D'Souza, DN Perahia, DG Cavazzoni, PA Baldessarini, RJ AF Acharya, Nayan Rosen, Amy S. Polzer, John P. D'Souza, Deborah N. Perahia, David G. Cavazzoni, Patrizia A. Baldessarini, Ross J. TI Duloxetine - Meta-analyses of suicidal behaviors and ideation in clinical trials for major depressive disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; RANDOMIZED CONTROLLED-TRIALS; FLUOXETINE TREATMENT; FOLLOW-UP; RISK; PLACEBO; ANTIDEPRESSANTS; REDUCTION; CLOZAPINE; DATABASE AB Background: Uncertainty regarding relationships of antidepressant treatment and suicidality encouraged systematic review of data on suicidal behaviors and ideation from Phase II and III clinical trials of duloxetine for major depressive disorder (MDD). Methods: We evaluated all completed duloxetine trials in MDD with data lock by February 2, 2004. We compared incidence of suicide-related events with duloxetine versus placebo in controlled trials, using Mantel-Haenszel incidence difference (MHID) and exposure time-adjusted rate difference (MHRD) methods, and analyzed changes in Hamilton Depression Scale (HAMD) Item-3 (suicidality) scores. Results: There were no significant differences in the incidence of suicide-related events with duloxetine versus placebo in 12 placebo-controlled trials (duloxetine, 1812; placebo, 1814 patients). The MHID for suicide-related behaviors was -0.03% (95% confidence interval [CI], -0.48 to 0.42) and MHRD -0.002 (95% CI, -0.02 to 0.02). Changes in HAMD Item-3 suicidality scores showed more improvement with duloxetine (MHID, 9.56%; 95% CI, 4.50 to 14.6; P < 0.001) and less worsening of suicidal ideation with duloxetine (MHID, -4.25%; 95% CI, -6.55 to -1.95; P < 0.001). Other Item-3 findings showed no consistent pattern; a slightly higher proportion of duloxetine-treated patients with a change from 0 (absent) to 3 was balanced against a higher proportion of placebo-treated patients changing from 0 to 2. Conclusions: We found no evidence of an increased risk of suicidal behaviors or ideation during treatment with duloxetine compared with placebo in MDD patients. HAMD Item-3 suicidality scores had more improvement and less worsening of suicidal ideation with duloxetine than placebo. C1 Eli Lilly Res Ctr, Indianapolis, IN USA. Eli Lilly Res Ctr, Windlesham, Surrey, England. Gordon Hosp, London, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,McLean Div, Belmont, MA USA. RP Acharya, N (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. EM acharya_nayan@lilly.com NR 52 TC 33 Z9 33 U1 5 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD DEC PY 2006 VL 26 IS 6 BP 587 EP 594 DI 10.1097/01.jcp.0000246216.26400.db PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 108RI UT WOS:000242256500007 PM 17110815 ER PT J AU Pettinati, HM O'Brien, CP Rabinowitz, AR Wortman, SM Oslin, DW Kampman, KM Dackis, CA AF Pettinati, Helen M. O'Brien, Charles P. Rabinowitz, Amanda R. Wortman, Shoshana M. Oslin, David W. Kampman, Kyle M. Dackis, Charles A. TI The status of naltrexone in the treatment of alcohol dependence - Specific effects on heavy drinking SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Review ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; DOUBLE-BLIND; RELAPSE PREVENTION; OPIOID DEPENDENCE; PROBLEM DRINKERS; ORAL NALMEFENE; CLINICAL-TRIAL; LOW-RISK AB Background: In almost 2 decades of naltrexone research for treating alcoholism, there have been 29 published randomized placebo-controlled trials of opioid antagonists, primarily naltrexone, for the treatment of alcohol dependence. The present review builds on prior systematic reviews while maximizing the number of included studies to date, for the purpose of resolving inconsistencies in naltrexone's reported efficacy across trials. Clinical trial results in this article are evaluated by the type of outcome measure used to determine naltrexone's treatment advantage, that is, measures related to reducing heavy drinking versus those related to increasing abstinence. Methods: We conducted a Medline search to identify double-blind studies from 1990 to the present (2006) that evaluated the use of an opiate antagonist for the treatment of alcohol dependence. There were 29 studies identified, representing 5997 alcohol-dependent patients, which met our study inclusion criteria for this review. Studies were evaluated in this review on 4 prespecified drinking outcomes-2 related to "any drinking" and 2 related to "heavy or excessive drinking." Results: In the treatment of alcohol dependence, we found that 19 (70%) of 27 clinical trials that measured reductions in "heavy or excessive drinking" demonstrated an advantage for prescribing naltrexone over placebo, whereas only 9 (36%) of 25 clinical trials that measured abstinence or "any drinking" found an advantage for medication over placebo. Conclusion: The majority of double-blind clinical trials in the literature favored prescribing naltrexone for alcohol dependence to reduce heavy drinking. This finding is consistent with our understanding of naltrexone's mechanism of action of decreasing excessive drinking by reducing the reward associated with drinking alcohol. Thus, we conclude that outcome measures related to heavy or excessive drinking are most relevant to defining naltrexone's therapeutic effects. Factors influencing naltrexone response (treatment adherence and distinct patient subgroups) are also discussed. C1 Univ Penn, Dept Psychiat, Treatment Res Ctr, Sch Med,Ctr Study Addict, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Pettinati, HM (reprint author), Univ Penn, Dept Psychiat, Treatment Res Ctr, Sch Med,Ctr Study Addict, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM Pettinati_H@mail.trc.upenn.edu FU NIAAA NIH HHS [R01-AA014851, R01-AA09544]; NIDA NIH HHS [P50 DA12756]; NIMH NIH HHS [K08-MH01599-01A1] NR 103 TC 101 Z9 102 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD DEC PY 2006 VL 26 IS 6 BP 610 EP 625 DI 10.1097/01.jcp.0000245566.52401.20 PG 16 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 108RI UT WOS:000242256500010 PM 17110818 ER PT J AU Rosowski, JJ Ravicz, ME Songer, JE AF Rosowski, John J. Ravicz, Michael E. Songer, Jocelyn E. TI Structures that contribute to middle-ear admittance in chinchilla SO JOURNAL OF COMPARATIVE PHYSIOLOGY A-NEUROETHOLOGY SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY LA English DT Article DE middle-ear structure-function; comparative auditory function ID GUINEA-PIG; INPUT IMPEDANCE; CAT; HEARING; MODEL; TRANSMISSION; FREQUENCY; MOUSE; DEPENDENCE; ACOUSTICS AB We describe measurements of middle-ear input admittance in chinchillas (Chinchilla lanigera) before and after various manipulations that define the contributions of different middle-ear components to function. The chinchilla's middle-ear air spaces have a large effect on the low-frequency compliance of the middle ear, and removing the influences of these spaces reveals a highly admittant tympanic membrane and ossicular chain. Measurements of the admittance of the air spaces reveal that the high-degree of segmentation of these spaces has only a small effect on the admittance. Draining the cochlea further increases the middle-ear admittance at low frequencies and removes a low-frequency (less than 300 Hz) level dependence in the admittance. Spontaneous or sound-driven contractions of the middle-ear muscles in deeply anesthetized animals were associated with significant changes in middle-ear admittance. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM John_Rosowski@meei.harvard.edu FU NIDCD NIH HHS [R01 DC000194, R01 DC000194-24] NR 78 TC 38 Z9 38 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-7594 J9 J COMP PHYSIOL A JI J. Comp. Physiol. A -Neuroethol. Sens. Neural Behav. Physiol. PD DEC PY 2006 VL 192 IS 12 BP 1287 EP 1311 DI 10.1007/s00359-006-0159-9 PG 25 WC Behavioral Sciences; Neurosciences; Physiology; Zoology SC Behavioral Sciences; Neurosciences & Neurology; Physiology; Zoology GA 120HH UT WOS:000243074600005 PM 16944166 ER PT J AU Dietrich, T Kaye, EK Nunn, ME Van Dyke, T Garcia, RI AF Dietrich, T. Kaye, E. Krall Nunn, M. E. Van Dyke, T. Garcia, R. I. TI Gingivitis susceptibility and its relation to periodontitis in men SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE gingivitis; pathogenesis; periodontitis; susceptibility ID PLAQUE-INDUCED GINGIVITIS; CLINICAL EXPRESSION; CIGARETTE-SMOKING; DISEASE; INFLAMMATION; MODULATION; REPRODUCIBILITY; DIABETICS; HEALTH AB The objective of this cross-sectional study was to evaluate whether gingivitis susceptibility is associated with periodontitis. We analyzed data of 462 men in the VA Dental Longitudinal Study aged 47 to 92 years who had never smoked or had quit smoking 5+ years previously. Multiple logistic regression models, with tooth-level bleeding on probing at sites with attachment loss <= 2 mm as the dependent variable, were derived with adjustment for plaque, calculus, crown coverage, age, income, education, marital status, body mass index, diabetes, and vitamin C intake, and stratification by age (< 65, 65+ years). Periodontitis and mean attachment loss were positively associated with bleeding on probing, with stronger associations among men < 65 years old ( for periodontitis, OR 2.1; 95% CI 1.5, 3.1) than men 65+ years of age ( OR 1.2; 95% CI 0.9, 1.6). Our results suggest that among never and former smokers, gingivitis susceptibility is higher among men with periodontitis compared with that in men without periodontitis. C1 Univ Goldman, Dept Hlth Pol & Hlth Serv Res, Sch Dent Med, Boston, MA 02118 USA. Univ Goldman, Dept Periodontol & Oral Biol, Sch Dent Med, Boston, MA USA. VA Boston Healthcare Syst, Boston, MA USA. RP Dietrich, T (reprint author), Univ Goldman, Dept Hlth Pol & Hlth Serv Res, Sch Dent Med, 715 Albany St,560, Boston, MA 02118 USA. EM tdietric@bu.edu OI Dietrich, Thomas/0000-0002-2557-7645 FU NIDCR NIH HHS [K24 DE000419-01, K24 DE000419, K24 DE00419] NR 28 TC 8 Z9 9 U1 0 U2 3 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2006 VL 85 IS 12 BP 1134 EP 1137 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 108JG UT WOS:000242235500014 PM 17122168 ER PT J AU Chuang, SK Cai, T AF Chuang, S. -K. Cai, T. TI Predicting clustered dental implant survival using frailty methods SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE clustered data; survival predictions; frailty; correlated survival analysis; proportional hazards model; dental implants ID FAILURE TIME DATA; PROSPECTIVE MULTICENTER; REGRESSION-ANALYSIS; MARGINAL APPROACH; ITI-IMPLANTS; MODELS; RATES AB The purpose of this study was to predict future implant survival using information on risk factors and on the survival status of an individual's existing implant( s). We considered a retrospective cohort study with 677 individuals having 2349 implants placed. We proposed to predict the survival probabilities using the Cox proportional hazards frailty model, with three important risk factors: smoking status, timing of placement, and implant staging. For a non-smoking individual with 2 implants placed, an immediate implant and in one stage, the marginal probability that 1 implant would survive 12 months was 85.8% ( 95% CI: 77%, 91.7%), and the predicted joint probability of surviving for 12 months was 75.1% ( 95% CI: 62.1%, 84.7%). If 1 implant was placed earlier and had survived for 12 months, then the second implant had an 87.5% ( 95% CI: 80.3%, 92.4%) chance of surviving 12 months. Such conditional and joint predictions can assist in clinical decision-making for individuals. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Chuang, SK (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM schuang@hsph.harvard.edu FU NIAID NIH HHS [R37 AI024643]; NIDCR NIH HHS [R03 DE016919, R03 DE016919-01] NR 32 TC 13 Z9 13 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2006 VL 85 IS 12 BP 1147 EP 1151 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 108JG UT WOS:000242235500017 PM 17122171 ER PT J AU Duda, SH Bosiers, M Lammer, J Scheinert, D Zeller, T Oliva, V Tielbeek, A Anderson, J Wiesinger, B Tepe, G Lansky, A Jaff, MR Mudde, C Tielemans, H Beregi, JP AF Duda, Stephan H. Bosiers, Marc Lammer, Johannes Scheinert, Dierk Zeller, Thomas Oliva, Vincent Tielbeek, Alexander Anderson, John Wiesinger, Benjamin Tepe, Gunnar Lansky, Alexandra Jaff, Michael R. Mudde, Catharina Tielemans, Hans Beregi, Jean-Paul TI Drug-eluting and bare nitinol stents for the treatment of atherosclerotic lesions in the superficial femoral artery: Long-term results from the SIROCCO trial SO JOURNAL OF ENDOVASCULAR THERAPY LA English DT Article DE drug-eluting stent; femoral artery; peripheral vascular disease; restenosis ID POPLITEAL ARTERIES; DISEASE; ANGIOPLASTY; OCCLUSIONS AB Purpose: To review clinical outcomes of patients with chronic limb ischemia and TASC type C lesions treated with sirolimus-eluting versus bare SMART nitinol self-expanding stents. Methods: Data were obtained from a randomized, multicenter, double-blinded study conducted in 2 phases. All 93 patients had chronic limb ischemia and superficial femoral artery (SFA) occlusions or stenoses (average lesion length 8.3 cm). In total, 47 patients (31 men; mean age 66.3 +/- 9.1 years, range 50-84) received the sirolimus-eluting SMART stent and 46 patients (36 men; mean age 65.9 +/- 10.8 years, range 38-83) received a bare SMART nitinol stent. Both groups were followed for a mean 24 months. Results: Both the sirolimus-eluting and the bare SMART stents were effective in revascularizing the diseased SFA and in sustaining freedom from restenosis. For both types of stents, improvements in ankle-brachial indices (ABI) and symptoms of claudication were maintained over 24 months (median 24-month ABI 0.96 for the sirolimus group versus 0.87 for the bare stent group, p>0.05). At 24 months, the restenosis rate in the sirolimus group was 22.9% versus 21.1% in the bare stent group (p>0.05). The cumulative in-stent restenosis rates according to duplex ultrasound were 4.7%, 9.0%, 15.6%, and 21.9%, respectively, at 6, 9, 18, and 24 months; the rates did not differ significantly between the treatment groups. The TLR rate for the sirolimus group was 6% and for the bare stent group 13%; the TVR rates were somewhat higher: 13% and 22%, respectively. Mortality rates did not differ significantly between the groups. Conclusion: These data demonstrate that the sirolimus-eluting and the bare SMART stent are effective, safe, and free from restenosis in a majority of patients for up to 24 months. Because the restenosis rate in the bare stent group is unexpectedly low, no significant difference could be found between the sirolimus-eluting and the bare SMART stents. C1 Jewish Hosp Berlin, Ctr Diagnost Radiol & Minimally Invas Therapy, D-13347 Berlin, Germany. Univ Tubingen, Dept Radiol, Tubingen, Germany. St Blasius Ziekenhuis, Dendermonde, Belgium. AKH Univ Clin Vienna, Dept Angiog & Intervent Radiol, Vienna, Austria. Herzzentrum Leipzig, Leipzig, Germany. Herzzentrum Bad Krozingen, Bad Krozingen, Germany. Univ Montreal, Ctr Hosp, Dept Radiol, Montreal, PQ, Canada. Catharina Hosp, Eindhoven, Netherlands. Ashford Specialist Ctr, Ashford, SA, Australia. Cardiovasc Res Fdn, Angio Core Lab, New York, NY USA. Massachusetts Gen Hosp, Vasc Ultrasound Core Lab, Boston, MA 02114 USA. Clin Trial Operat, Oss, Netherlands. Cordis, Waterloo, Belgium. Hop Cardiol, CHRU Lille, Serv Radiol, F-59037 Lille, France. RP Duda, SH (reprint author), Jewish Hosp Berlin, Ctr Diagnost Radiol & Minimally Invas Therapy, Heinz Galinski Str 1, D-13347 Berlin, Germany. EM stephan.duda@t-online.de NR 17 TC 273 Z9 285 U1 1 U2 16 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1526-6028 J9 J ENDOVASC THER JI J. Endovascular Ther. PD DEC PY 2006 VL 13 IS 6 BP 701 EP 710 DI 10.1583/05-1704.1 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 116GT UT WOS:000242791200001 PM 17154704 ER PT J AU Taft, CT O'Farrell, TJ Torres, SE Panuzio, J Monson, CM Murphy, M Murphy, CM AF Taft, Casey T. O'Farrell, Timothy J. Torres, Sandra E. Panuzio, Jillian Monson, Candice M. Murphy, Marie Murphy, Christopher M. TI Examining the correlates of psychological aggression among a community sample of couples SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE psychological aggression; physical aggression; anger; relationship adjustment ID INTIMATE PARTNER VIOLENCE; PHYSICAL AGGRESSION; DOMESTIC VIOLENCE; EARLY MARRIAGE; SPOUSE ABUSE; WOMEN; POWER; CONSEQUENCES; ASSOCIATION; BEHAVIORS AB In this study, the authors examined the correlates of psychological aggression victimization and perpetration among a community sample of 145 heterosexual couples. For both women and men, psychological aggression victimization was associated with greater psychological distress, anxiety, and physical health symptoms beyond the effects of physical aggression. Psychological aggression victimization was also uniquely associated with higher levels of depression for women. Trait anger and poor relationship adjustment were the strongest correlates of psychological aggression perpetration across genders. Childhood father-to-child and father-to-mother aggressions were associated with psychological aggression perpetration for men only, suggesting possible distinct etiologies across genders. These data highlight the importance of the further development of models for psychological aggression in both women and men. C1 Natl Ctr Posttraumat Stress Disorder, VA Boston Healthcare Syst, Womens Hlth Sci Div, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dept Psychiat, Families & Addict Program, Cambridge, MA 02138 USA. Natl Ctr Posttraumat Stress Disorder, Behav Sci Div, Boston, MA 02130 USA. Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21228 USA. RP Taft, CT (reprint author), Natl Ctr Posttraumat Stress Disorder, VA Boston Healthcare Syst, Womens Hlth Sci Div, 116B-2,150 S Huntington Ave, Boston, MA 02130 USA. EM casey.taft@va.gov FU NIAAA NIH HHS [K02AA00234, R01AA10356] NR 43 TC 71 Z9 72 U1 4 U2 16 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD DEC PY 2006 VL 20 IS 4 BP 581 EP 588 DI 10.1037/0893-3200.20.4.581 PG 8 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 116DD UT WOS:000242781800006 PM 17176192 ER PT J AU Sinha, S Goldstein, M Penrod, J Hochman, T Kamran, M Tenner, C Cohen, G Schwartz, MD AF Sinha, Sanjai Goldstein, Matthew Penrod, Joan Hochman, Tsivia Kamran, Mohammad Tenner, Craig Cohen, Gabriela Schwartz, Mark D. TI beta-blocker use among veterans with systolic heart failure SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 29, 2006 CL Los Angeles, CA SP Soc Gen Internal Med DE heart failure; beta-blockers; utilization; prescription rates; guideline adherence ID MORTALITY; OUTCOMES; DISEASE; TRIAL; CARDIOLOGISTS; TOLERABILITY; CARVEDILOL; EXPERIENCE; MANAGEMENT; MORBIDITY AB beta-Blockers reduce mortality in patients with systolic chronic heart failure (CHF), yet prescription rates have remained low among primary care providers. To determine the beta-blocker prescription rate among patients with systolic CHF at primary care Veterans Affairs (VA) clinics, its change over time; and to determine factors associated with nonprescription. Retrospective chart review. Seven hundred and forty-five patients with diagnostic codes for CHF followed in primary care clinics at 3 urban VA Medical Centers. Rate of beta-blocker prescription and comparison of patient characteristics between those prescribed versus those not prescribed beta-blockers. Only 368 (49%) had documented systolic CHF. Eighty-two percent (303/368) of these patients were prescribed a beta-blocker. The prescription rate rose steadily over 3 consecutive 2-year time periods. Patients with more severely depressed ejection fractions were more likely to be on a beta-blocker than patients with less severe disease. Independent predictors of nonprescription included chronic obstructive pulmonary disease, asthma, depression, and age. Patients under 65 years old were 12 times more likely to receive beta-blockers than those over 85. Primary care providers at VA Medical Centers achieved high rates of beta-blocker prescription for CHF patients. Subgroups with relative contraindications had lower prescription rates and should be targeted for quality improvement initiatives. C1 Bronx Vet Adm Med Ctr, Dept Med, Bronx, NY USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. VA New York Harbor Healthcare Syst, Dept Med, New York, NY USA. NYU, Sch Med, New York, NY USA. RP Sinha, S (reprint author), 1st Floor,Suite D,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM sanjai.sinha@med.va.gov NR 21 TC 10 Z9 12 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2006 VL 21 IS 12 BP 1306 EP 1309 DI 10.1111/j.1525-1497.2006.00601.x PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 100NI UT WOS:000241675400019 PM 17105526 ER PT J AU Cha, SS Ross, JS Lurie, P Sacajiu, G AF Cha, Stephen S. Ross, Joseph S. Lurie, Peter Sacajiu, Galit TI Description of a research-based health activism curriculum for medical students SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med DE medical education; professionalism; health care reform; curriculum evaluation ID MANAGED CARE; PROFESSIONALISM; EDUCATION; ETHICS; SYSTEM AB Few curricula train medical students to engage in health system reform. To develop physician activists by teaching medical students the skills necessary to advocate for socially equitable health policies in the U.S. health system. Montefiore Medical Center, the University Hospital of the Albert Einstein College of Medicine, Bronx, NY. We designed a 1-month curriculum in research-based health activism to develop physician activists. The annual curriculum includes a student project and 4 course sections; health policy, research methods, advocacy, and physician activists as role models; taught by core faculty and volunteers from academic institutions, government, and nongovernmental organizations. From 2002 to 2005, 47 students from across the country have participated. Students reported improved capabilities to generate a research question, design a research proposal, and create an advocacy plan. Our curriculum demonstrates a model for training physician activists to engage in health systems reform. C1 VA Connecticut Healthcare Syst, West Haven, CT USA. Yale Univ, Dept Internal Med, New Haven, CT 06520 USA. CUNY Mt Sinai Sch Med, Brookdale Dept Geriat & Adult Dev, New York, NY 10029 USA. James J Peters Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. Publ Citizens Hlth Res Grp, Washington, DC USA. Montefiore Med Ctr, Dept Internal Med, Bronx, NY 10467 USA. RP Cha, SS (reprint author), US House Representatives, Comm Govt Reform, 511 Ford House Off Bldg, Washington, DC 20515 USA. EM stephen.cha@yale.edu NR 19 TC 11 Z9 11 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2006 VL 21 IS 12 BP 1325 EP 1328 DI 10.1111/j.1525-1497.2006.00608.x PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 100NI UT WOS:000241675400023 PM 16961754 ER PT J AU Aryana, A Esterbrooks, DJ Morris, PC AF Aryana, Arash Esterbrooks, Dennis J. Morris, Peter C. TI Nonbacterial thrombotic endocarditis with recurrent embolic events as manifestation of ovarian neoplasm SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE nonbacterial thrombotic endocarditis; valvular vegetations; ovarian adenocarcinoma; malignancy C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Creighton Univ, Sch Med, Cardiac Ctr, Omaha, NE 68178 USA. Creighton Univ, Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Omaha, NE 68178 USA. RP Aryana, A (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM aaryana@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2006 VL 21 IS 12 BP 1338 EP 1338 DI 10.1111/j.1525-1497.2006.00614.x PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 100NI UT WOS:000241675400028 ER PT J AU Aryana, A Esterbrooks, DJ Morris, PC AF Aryana, Arash Esterbrooks, Dennis J. Morris, Peter C. TI Nonbacterial thrombotic endocarditis with recurrent embolic events as manifestation of ovarian neoplasm SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE nonbacterial thrombotic endocarditis; valvular vegetations; ovarian adenocarcinoma; malignancy ID CANCER-PATIENTS; ADENOCARCINOMA; TROUSSEAU; DISEASE; STROKE AB We describe the case of a 43-year-old woman with transient ischemic neurologic deficits and recurrent systemic and pulmonary emboli in whom infectious work-up and extensive thrombophilic evaluation were unremarkable. Transesophageal echocardiography (TEE) established the diagnosis of nonbacterial thrombotic endocarditis (NBTE). This is a rare condition often associated with hypercoagulable states or advanced malignancy such as adenocarcinomas, characterized by cardiac vegetations along valvular coaptation lines without destruction of leaflets. In our patient, we diagnosed an ovarian clear cell adenocarcinoma, a malignant disorder that has been rarely reported in association with NBTE. This case illustrates that NBTE can present as an atypical manifestation of malignancy and must be distinguished from infective endocarditis, which implies a different therapeutic strategy. When confronted with findings of NBTE without a clear etiology, an occult neoplasm must be excluded. Anticoagulant therapy is the mainstay of treatment. However, cardiac vegetations may require surgical intervention in rare instances. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Creighton Univ, Sch Med, Cardiac Ctr, Omaha, NE USA. Creighton Univ, Med Ctr, Dept OB GYN, Div Gynecol Oncol, Omaha, NE USA. RP Aryana, A (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St GRB 109, Boston, MA 02114 USA. EM aaryana@partners.org NR 20 TC 10 Z9 12 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 DEC PY 2006 VL 21 IS 12 BP C12 EP C15 DI 10.1111/j.1525-1497.2006.00614.x PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 100NI UT WOS:000241675400004 PM 16965557 ER PT J AU Cotton, S Tsevat, J Szaflarski, M Kudel, I Sherman, SN Feinberg, J Leonard, AC Holmes, WC AF Cotton, Sian Tsevat, Joel Szaflarski, Magdalena Kudel, Ian Sherman, Susan N. Feinberg, Judith Leonard, Anthony C. Holmes, William C. TI Changes in religiousness and spirituality attributed to HIV/AIDS - Are there sex and race differences? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE HIV/AIDS; religion; spirituality; coping; chronic illness ID QUALITY-OF-LIFE; HIV; END; CARE; CANCER; HEALTH AB Having a serious illness such as HIV/AIDS raises existential issues, which are potentially manifested as changes in religiousness and spirituality. The objective of this study was (1) to describe changes in religiousness and spirituality of people with HIV/AIDS, and (2) to determine if these changes differed by sex and race. Three-hundred and forty-seven adults with HIV/AIDS from 4 sites were asked demographic, clinical, and religious/spiritual questions. Six religious/spiritual questions assessed personal and social domains of religiousness and spirituality. Eighty-eight participants (25%) reported being "more religious" and 142 (41%) reported being "more spiritual" since being diagnosed with HIV/AIDS. Approximately 1 in 4 participants also reported that they felt more alienated by a religious group since their HIV/AIDS diagnosis and approximately 1 in 10 reported changing their place of religious worship because of HIV/AIDS. A total of 174 participants (50%) believed that their religiousness/spirituality helped them live longer. Fewer Caucasians than African Americans reported becoming more spiritual since their HIV/AIDS diagnosis (37% vs 52%, respectively; P <.015), more Caucasians than African Americans felt alienated from religious communities (44% vs 21%, respectively; P <.001), and fewer Caucasians than African Americans believed that their religiousness/spirituality helped them live longer (41% vs 68% respectively; P <.001). There were no significantly different reported changes in religious and spiritual experiences by sex. Many participants report having become more spiritual or religious since contracting HIV/AIDS, though many have felt alienated by a religious group-some to the point of changing their place of worship. Clinicians conducting spiritual assessments should be aware that changes in religious and spiritual experiences attributed to HIV/AIDS might differ between Caucasian and African Americans. C1 Univ Cincinnati, Med Ctr, Inst Study Hlth, Cincinnati, OH 45267 USA. Univ Cincinnati, Med Ctr, Dept Family Med, Cincinnati, OH 45267 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. Univ Cincinnati, Med Ctr, Dept Internal Med, Div Gen Internal Med, Cincinnati, OH 45221 USA. Univ Cincinnati, Med Ctr, Inst Study Hlth, Cincinnati, OH 45221 USA. Vet Adm Med Ctr, Hlth Serv Res & Dev, Cincinnati, OH 45220 USA. RP Cotton, S (reprint author), Univ Cincinnati, Med Ctr, Dept Family Med, POB 670840, Cincinnati, OH 45267 USA. FU NCCIH NIH HHS [R01 AT01147, K24 AT001676, R01 AT001147]; NIAID NIH HHS [U01 AI 25897] NR 23 TC 27 Z9 27 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2006 VL 21 SU 5 BP S14 EP S20 DI 10.1111/j.1525-1497.2006.00641.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 100TY UT WOS:000241693100004 PM 17083495 ER PT J AU Tsuang, D Simpson, K Larson, EB Peskind, E Kukull, W Bowen, JB McCormick, W Teri, L Montine, T Thompson, ML Leverenz, JB AF Tsuang, Debby Simpson, Kate Larson, Eric B. Peskind, Elaine Kukull, Walter Bowen, James B. McCormick, Wayne Teri, Linda Montine, Thomas Thompson, Mary Lou Leverenz, James B. TI Predicting Lewy body pathology in a community-based sample with clinical diagnosis of Alzheimer's disease SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article; Proceedings Paper CT 130th Annual Meeting of the American-Neurological-Association CY SEP 25-28, 2005 CL San Diego, CA SP Amer Neurol Assoc, AstraZeneca DE clinical-neuropathological; dementia; Alzheimer's disease; Lewy bodies; prediction ID INTERNATIONAL WORKSHOP; CASE SERIES; DEMENTIA; BODIES; CRITERIA; SENSITIVITY; VALIDATION; CONSORTIUM; ACCURACY; VALIDITY AB Accurate antemortem prediction of Lewy body pathology in patients with dementia is problematic. This study generates a model that better predicts Lewy body pathology in community-based patients with clinical Alzheimer's disease. Lewy body pathology was detected in 80 of 152 participants (52.6%) with an initial diagnosis of probable Alzheimer's disease. In a stepwise logistic regression model, female gender, lower education, being married, bradykinesia, hallucinations, and absence of irritability predicted the greatest likelihood of Lewy body pathology. The predictive model correctly diagnosed Lewy body pathology with an estimated sensitivity of 75%, specificity of 68%, and accuracy of 72%; the area under the receiver operating characteristic curve was 0.75. In a community-based autopsy sample, this predictive model confirmed parkinsonism and hallucinations as important predictors of Lewy body pathology in patients with clinical Alzheimer's disease. The model also identified other demographic and clinical characteristics that might enhance the prediction of Lewy body pathology. C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Internal Med, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Sch Nursing, Seattle, WA 98195 USA. Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. RP Tsuang, D (reprint author), VAPSHCS 116,1660 S Columbian Way, Seattle, WA 98108 USA. EM dwt1@u.washington.edu RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Kukull, Walter/0000-0001-8761-9014 FU NIA NIH HHS [R01-AG10845, AG05136, AG06781, U01AG06781] NR 35 TC 10 Z9 10 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD DEC PY 2006 VL 19 IS 4 BP 195 EP 201 DI 10.1177/0891988706292755 PG 7 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 107FO UT WOS:000242156300001 PM 17085757 ER PT J AU Ring, D AF Ring, David TI Fractures of the coronoid process of the ulna SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Review DE coronoid fractures; traumatic elbow instability; elbow dislocation; internal fixation ID RADIAL HEAD; ELBOW JOINT; DISLOCATION; STABILITY; ADULTS; INJURIES; FIXATION; END AB The coronoid process is critical to elbow stability and is vulnerable during injury. Traumatic elbow injures are relatively uncommon, so it is important for surgeons to be mindful of the importance of specialized treatment of the coronoid for optimal elbow function. Optimal coronoid fracture fixation is determined by fracture morphology, which can usually be predicted based on the overall pattern of injury. There is evidence that improved understanding of coronoid fractures and their management is improving the results of treatment. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, 55 Fruit St,YAW 2, Boston, MA 02114 USA. EM dring@partners.org NR 34 TC 39 Z9 48 U1 1 U2 6 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 DEC PY 2006 VL 31A IS 10 BP 1679 EP 1689 DI 10.1016/j.jhsa.2006.08.020 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 117LB UT WOS:000242873500017 PM 17145391 ER PT J AU Chan, JSD Brezniceanu, ML Liu, F Zhang, SL Guo, DF Filep, JG Ingelfinger, JR AF Chan, John S. D. Brezniceanu, Marie-Luise Liu, Fang Zhang, Shao-Ling Guo, Deng-Fu Filep, Janos G. Ingelfinger, Julie R. TI Attenuation of hypertension, angiotensinogen (Ang) gene expression, and renal injury in db/d13 transgenic mice overexpressing catalase in renal proximal tubular cells. SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 21sth Scientific Meeting of the International-Society-of-Hypertension/5th Asian-Pacific Congress of Hypertension/29th Annual Scientific Meeting of the Japanese-Society-of-Hypertension CY OCT 15-19, 2006 CL Fukuoka, JAPAN SP Int Soc Hypertens, Japanese Soc Hypertens C1 Hop Maison Neuve Rosemont, Res Ctr, Montreal, PQ H1T 2M4, Canada. Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. EM john.chan@umontreal.ca 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 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD DEC PY 2006 VL 24 SU 6 BP 113 EP 114 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 116AD UT WOS:000242774000386 ER PT J AU Zhang, JH Kawashima, S Yokoyama, M Huang, P Hill, CE AF Zhang, Jian Hong Kawashima, Seinosuke Yokoyama, Mitsuhiro Huang, Paul Hill, Caryl E. TI Increased eNOS accounts for changes in connexin expression in renal arterioles during diabetes SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 21sth Scientific Meeting of the International-Society-of-Hypertension/5th Asian-Pacific Congress of Hypertension/29th Annual Scientific Meeting of the Japanese-Society-of-Hypertension CY OCT 15-19, 2006 CL Fukuoka, JAPAN SP Int Soc Hypertens, Japanese Soc Hypertens C1 Kobe Univ, Sch Med, Dept Internal Med 1, Kobe, Hyogo, Japan. Harvard Univ, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Sch Med, Charlestown, MA USA. EM caryl.hill@anu.edu.au NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD DEC PY 2006 VL 24 SU 6 BP 114 EP 114 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 116AD UT WOS:000242774000387 ER PT J AU Ota, H Kaneki, M Kobayashi, T Iijima, K Eto, M Kozaki, K Akishita, M Ouchi, Y AF Ota, Hidetaka Kaneki, Masao Kobayashi, Takashi Iijima, Katsuya Eto, Masato Kozaki, Koichi Akishita, Masahiro Ouchi, Yasuyoshi TI Sirt1,a longevity gene,regulates senescence-like phenotype in human endothelial cells. SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 21sth Scientific Meeting of the International-Society-of-Hypertension/5th Asian-Pacific Congress of Hypertension/29th Annual Scientific Meeting of the Japanese-Society-of-Hypertension CY OCT 15-19, 2006 CL Fukuoka, JAPAN SP Int Soc Hypertens, Japanese Soc Hypertens C1 Univ Tokyo, Grad Sch Med, Tokyo, Japan. Kyorin Univ, Sch Med, Tokyo, Japan. Massachusetts Gen Hosp, Harvard Med Sch, Dept Anesthesia & Crit Care, Harvard, MA USA. EM hidetaka217@hotmail.com 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 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD DEC PY 2006 VL 24 SU 6 BP 131 EP 131 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 116AD UT WOS:000242774000458 ER PT J AU Hayashi, T Sato, KK Izumotani, KS Nishizawa, Y Okamoto, T Fujimoto, WY Boyko, EJ AF Hayashi, Tomoshige Sato, Kyoko K. Izumotani, Kyoko S. Nishizawa, Yoshiki Okamoto, Teruo Fujimoto, Wilfred Y. Boyko, Edward J. TI Optimal waist circumference cut points and the metabolic syndrome in Japanese SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 21sth Scientific Meeting of the International-Society-of-Hypertension/5th Asian-Pacific Congress of Hypertension/29th Annual Scientific Meeting of the Japanese-Society-of-Hypertension CY OCT 15-19, 2006 CL Fukuoka, JAPAN SP Int Soc Hypertens, Japanese Soc Hypertens C1 Osaka City Univ, Grad Sch Med, Dept Prevent Med & Environm Hlth, Osaka 558, Japan. Osaka City Univ, Grad Sch Med, Osaka 558, Japan. Washington Univ, Dept Med, Seattle, WA USA. Epidemiol Res & Informat CTr, Vet Affairs Puget Sound Hlth care Syst, Seattle, WA 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 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD DEC PY 2006 VL 24 SU 6 BP 150 EP 150 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 116AD UT WOS:000242774001040 ER PT J AU Tuck, ML Abedi, K Smutko, V Nyby, MD AF Tuck, Michael L. Abedi, Karolin Smutko, Victoria Nyby, Michael D. TI Rosiglitazone reduces hypertension in fructose-fed rats by increasing nitric oxide bioavailability SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 21sth Scientific Meeting of the International-Society-of-Hypertension/5th Asian-Pacific Congress of Hypertension/29th Annual Scientific Meeting of the Japanese-Society-of-Hypertension CY OCT 15-19, 2006 CL Fukuoka, JAPAN SP Int Soc Hypertens, Japanese Soc Hypertens C1 Univ Calif Los Angeles, Va Greater Los Angeles Health Syst, Los Angeles, CA 90024 USA. EM mnyby@ucla.edu 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 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD DEC PY 2006 VL 24 SU 6 BP 161 EP 161 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 116AD UT WOS:000242774001083 ER PT J AU Tuck, ML Nyby, MD Douglas, K Abedi, K Makino, H AF Tuck, Michael L. Nyby, Michael D. Douglas, Kyle Abedi, Karolin Makino, Hirofumi TI Telmisartan and insulin affect angiotensin II type 1 and type 2 receptor expression in vascular smooth muscle and vascular endothelial cells SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 21sth Scientific Meeting of the International-Society-of-Hypertension/5th Asian-Pacific Congress of Hypertension/29th Annual Scientific Meeting of the Japanese-Society-of-Hypertension CY OCT 15-19, 2006 CL Fukuoka, JAPAN SP Int Soc Hypertens, Japanese Soc Hypertens C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. EM mnyby@ucla.edu 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 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD DEC PY 2006 VL 24 SU 6 BP 301 EP 301 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 116AD UT WOS:000242774002090 ER PT J AU Rosendorff, C Atlas, SA Almendral, JL AF Rosendorff, Clive Atlas, Steven A. Almendral, Jesus L. TI Angiotensin receptor blockade and cardiovascular hypertrophy, results from the echocardiographic study of the effect on cardiovascular hypertrophy of olmesartan (the ECHO study) SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 21sth Scientific Meeting of the International-Society-of-Hypertension/5th Asian-Pacific Congress of Hypertension/29th Annual Scientific Meeting of the Japanese-Society-of-Hypertension CY OCT 15-19, 2006 CL Fukuoka, JAPAN SP Int Soc Hypertens, Japanese Soc Hypertens C1 Mt Sinai Sch Med, James J Peters VA Med Ctr, New York, NY USA. 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 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD DEC PY 2006 VL 24 SU 6 BP 373 EP 373 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 116AD UT WOS:000242774002392 ER PT J AU Chan, RK Ibrahim, SI Takahashi, K Kwon, E McCormack, M Ezekowitz, A Carroll, MC Moore, FD Austen, WG AF Chan, Rodney K. Ibrahim, Shahrul I. Takahashi, Kazue Kwon, Edwin McCormack, Michael Ezekowitz, Alan Carroll, Michael C. Moore, Francis D., Jr. Austen, William G., Jr. TI The differing roles of the classical and mannose-binding lectin complement pathways in the events following skeletal muscle ischemia-reperfusion SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL ANTIBODY; INJURY; ACTIVATION; MICE; IGM; NEUTROPHILS; FICOLIN; C1Q AB Complement is an important mediator of the injuries observed after skeletal muscle ischemia and subsequent reperfusion. Although the classical pathway had been assumed to be the major pathway of activation leading to injury, the mannose-binding lectin (MBL) pathway might also play a contributing role. In this study, we found that MBL-deficient mice had significant protection after skeletal muscle reperfusion injury compared with wild-type, classical pathway-specific C1q-deficient mice, or MBL-deficient mice reconstituted with recombinant human MBL. MBL-deficient mice, however, were not protected from permeability edema or secondary lung injury after ischemia-reperfusion. These data indicate that blockade of the classical pathway alone (C1q) is protective against permeability edema and remote pulmonary injury but not protective against histologic muscle injury. In contrast, blocking the MBL pathway alone protects against histological injury but is not protective against permeability edema or lung injury. Thus, the activation of both pathways is likely responsible for the full spectrum of injuries observed after skeletal muscle reperfusion injury. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Plast Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg & Pediat, Boston, MA 02115 USA. RP Austen, WG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Plast Surg, 10 Fruit St, Boston, MA 02115 USA. EM wausten@partners.org FU NIGMS NIH HHS [P50 GM 52585] NR 25 TC 52 Z9 53 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 DEC 1 PY 2006 VL 177 IS 11 BP 8080 EP 8085 PG 6 WC Immunology SC Immunology GA 108TJ UT WOS:000242261800069 PM 17114482 ER PT J AU Mathias, JR Perrin, BJ Liu, TX Kanki, J Look, AT Huttenlocher, A AF Mathias, Jonathan R. Perrin, Benjamin J. Liu, Ting-Xi Kanki, John Look, A. Thomas Huttenlocher, Anna TI Resolution of inflammation by retrograde chemotaxis of neutrophils in transgenic zebrafish SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE GFP; leukocyte ID IN-VIVO; MIGRATION; MACROPHAGES; IMMUNITY; EMBRYOS; CELLS; MODEL AB Neutrophil chemotaxis to sites of inflammation is a critical process during normal immune responses to tissue injury and infection and pathological immune responses leading to chronic inflammation. Although progress has been made in understanding the mechanisms that promote nentrophil recruitment to inflamed tissue, the mechanisms that regulate the resolution phase of the inflammatory response have remained relatively elusive. To define the mechanisms that regulate neutrophil-mediated inflammation in vivo, we have developed a novel transgenic zebrafish in which the neutrophils express GFP under control of the myeloperoxidase promoter (zMPO:GFP). Tissue injury induces a robust, inflammatory response, which is characterized by the rapid chemotaxis of neutrophils to the wound site. In vivo time-lapse imaging shows that neutrophils subsequently display directed retrograde chemotaxis back toward the vasculature. These findings implicate retrograde chemotaxis as a novel mechanism that regulates the resolution phase of the inflammatory response. The zMPO:GFP zebrafish provides unique insight into the mechanisms of nentrophil-mediated inflammation and thereby offers opportunities to identify new regulators of the inflammatory response in vivo. C1 Univ Wisconsin, Dept Pharmacol, Madison, WI 53706 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Huttenlocher, A (reprint author), Univ Wisconsin, Dept Pharmacol, 2715 Med Sci Ctr,1300 Univ Ave, Madison, WI 53706 USA. EM huttenlocher@wisc.edu FU NCI NIH HHS [CA93152]; NCRR NIH HHS [P40 RR12546]; NHLBI NIH HHS [T32 HL07899-07]; NIGMS NIH HHS [R01 GM074827] NR 34 TC 201 Z9 206 U1 5 U2 22 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 2006 VL 80 IS 6 BP 1281 EP 1288 DI 10.1189/jlb.0506346 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 111VT UT WOS:000242484100012 PM 16963624 ER PT J AU Nesathurai, S Graham, WA Edell, DJ Rosene, DL Mansfield, K Sehgal, P Magill, D Sledge, JB AF Nesathurai, Shanker Graham, W. Andrew Edell, David J. Rosene, Doug L. Mansfield, Keith Sehgal, Prabhat Magill, David Sledge, John B. TI Electromyographic telemetry in the development of humane primate model of spinal cord injury SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE telemetry; electromyogram; neurophysiology; non-human primate C1 Harvard Univ, Spaulding Rehabil Hosp, Sch Med, Boston, MA 02138 USA. InnerSea Technol Inc, Bedford, MA USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA. NYU, Sch Med, New York, NY USA. N Shore Med Ctr, Peabody, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Nesathurai, S (reprint author), Harvard Univ, Spaulding Rehabil Hosp, Sch Med, Boston, MA 02138 USA. EM snesathurai@partners.org RI Rosene, Douglas/G-1973-2015; OI Rosene, Douglas/0000-0001-8719-1441 NR 5 TC 1 Z9 1 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD DEC PY 2006 VL 35 IS 6 BP 397 EP 400 DI 10.1111/j.1600-0684.2006.00161.x PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 101JI UT WOS:000241736700011 PM 17214669 ER PT J AU Nesathurai, S Graham, WA Mansfield, K Magill, D Sehgal, P Westmoreland, SV Prusty, S Rosene, DL Sledge, JB AF Nesathurai, Shanker Graham, W. Andrew Mansfield, Keith Magill, David Sehgal, Prabhat Westmoreland, Susan V. Prusty, Somnath Rosene, Doug L. Sledge, John B. TI Model of traumatic spinal cord injury in Macaca fascicularis: similarity of experimental lesions created by epidural catheter to human spinal cord injury SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE histology; neurophysiology; non-human primate; spinal cord injury ID PRIMATE; GRAFTS C1 Harvard Univ, Spaulding Rehabil Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA. NYU, Med Ctr, New York, NY 10016 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. N Shore Med Ctr, Peabody, MA USA. RP Nesathurai, S (reprint author), Harvard Univ, Spaulding Rehabil Hosp, Sch Med, Boston, MA 02115 USA. EM snesathurai@partners.org RI Rosene, Douglas/G-1973-2015; OI Rosene, Douglas/0000-0001-8719-1441 FU NCRR NIH HHS [P51RR00168] NR 14 TC 8 Z9 8 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD DEC PY 2006 VL 35 IS 6 BP 401 EP 404 DI 10.1111/j.1600-0684.2006.00162.x PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 101JI UT WOS:000241736700012 PM 17214670 ER PT J AU Jaffer, FA Sosnovik, DE Nahrendorf, M Weissleder, R AF Jaffer, Farouc A. Sosnovik, David E. Nahrendorf, Matthias Weissleder, Ralph TI Molecular imaging of myocardial infarction SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Review DE molecular imaging; myocardial infarction; remodeling; protease; angiogenesis; apoptosis; MRI; optical imaging; nuclear imaging ID POSITRON-EMISSION-TOMOGRAPHY; MATRIX-METALLOPROTEINASE INHIBITION; ENDOTHELIAL GROWTH-FACTOR; LEFT-VENTRICULAR ENLARGEMENT; REPORTER GENE-EXPRESSION; IN-VIVO VISUALIZATION; MAGNETIC-RESONANCE; FACTOR-XIII; HEART-FAILURE; CARDIOMYOCYTE APOPTOSIS AB Molecular tools are rapidly elucidating the molecular and cellular processes underlying myocardial infarction. To further understand these biological processes in vivo, investigators are embracing the burgeoning field of molecular imaging. Here we review important aspects of molecular imaging technology and then devote the majority of the text to studies that shed light on the in vivo pathogenesis of myocardial infarction. In particular, we focus on post-infarction healing and remodeling and discuss molecular imaging of proteolytic activity, angiogenesis, transglutaminase activity, and apoptosis. In the future, novel reporter agents and high-resolution cardiac imaging systems should enable imaging of emerging targets such as activated macrophages and myeloperoxidase activity, as well as stem cell-based and gene therapy-based myocardial regenerative strategies, in both experimental and clinical subjects. (C) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, MGH, CMIR, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiol Div, Boston, MA 02114 USA. RP Jaffer, FA (reprint author), Harvard Univ, Sch Med, MGH, CMIR, 149 13th St,Rm 5406, Boston, MA 02129 USA. EM fjaffer@partners.org OI Jaffer, Farouc/0000-0001-7980-384X NR 125 TC 24 Z9 25 U1 1 U2 13 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 DEC PY 2006 VL 41 IS 6 BP 921 EP 933 DI 10.1016/j.yjmcc.2006.09.008 PG 13 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 120MT UT WOS:000243089700001 PM 17067633 ER PT J AU Simon, NM Weiss, AM Kradin, R Evans, KC Reese, HE Otto, MW Oppenheimer, JE Smoller, JW Zalta, A Worthington, JJ Pollack, MH AF Simon, Naomi M. Weiss, Alexander M. Kradin, Richard Evans, Karleyton C. Reese, Hannah E. Otto, Michael W. Oppenheimer, Julia E. Smoller, Jordan W. Zalta, Alyson Worthington, John J., III Pollack, Mark H. TI The relationship of anxiety disorders, anxiety sensitivity and pulmonary dysfunction with dyspnea-related distress and avoidance SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article; Proceedings Paper CT 24th Annual Conference of Anxiety-Disorders-Association-of-America CY MAR 11-14, 2004 CL Miami, FL SP Anxiety Disorders Assoc Amer DE anxiety; anxiety sensitivity; avoidance; COPD; dyspnea; pulmonary dysfunction ID PANIC DISORDER; PSYCHIATRIC-DISORDERS; TRAIT ANXIETY; PRIMARY-CARE; DISEASE; ASTHMA; FEAR; DEPRESSION; COPD; HYPERVENTILATION AB Little is known about factors that mediate the relationship between anxiety and respiratory-related distress and disability. We hypothesized that elevations in anxiety sensitivity would be associated with greater severity of dyspnea, greater dyspnea-related avoidance, and poorer subjective assessment of health in patients with dyspnea referred for pulmonary function testing, regardless of objective evidence of pulmonary dysfunction. A total of 182 consecutive patients receiving pulmonary function tests to evaluate dyspnea were screened with a patient-rated Primary Care Evaluation of Mental Disorders and completed the Anxiety Sensitivity Index and questionnaires assessing symptom severity and avoidance. Anxiety Sensitivity Index score predicted more severe subjective dyspnea and greater dyspnea-related avoidance, even after adjustment for anxiety disorders and pulmonary dysfunction. Despite some limitations, these data provide preliminary support that strategies to identify, measure, and address high levels of anxiety sensitivity should be examined to reduce subjective distress and improve functioning for patients with dyspnea. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Simches Res Bldg,Suite 2200,185 Cambridge St, Boston, MA 02114 USA. EM nsimon@partners.org OI Zalta, Alyson/0000-0002-5159-8431 FU NIMH NIH HHS [MH-01831] NR 60 TC 19 Z9 20 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD DEC PY 2006 VL 194 IS 12 BP 951 EP 957 DI 10.1097/01.nmd.0000249062.25829.53 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 116FO UT WOS:000242788100011 PM 17164635 ER PT J AU Hoge, EA Tamrakar, SM Christian, KM Mahara, N Nepal, MK Pollack, MH Simon, NM AF Hoge, Elizabeth A. Tamrakar, Sharad M. Christian, Kelly M. Mahara, Namrata Nepal, Mahendra K. Pollack, Mark H. Simon, Naomi M. TI Cross-cultural differences in somatic presentation in patients with generalized anxiety disorder SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE cross-cultural comparison; anxiety disorders; transcultural studies ID PSYCHOMETRIC PROPERTIES; DEPRESSION; INVENTORY; SOMATIZATION AB Little is known about cultural differences in the. expression of distress in anxiety disorders. Previous cross-cultural studies of depression have found a greater somatic focus in Asian populations. We examined anxiety symptoms in patients with generalized anxiety disorder (GAD) in urban mental health settings in Nepal (N = 30) and in the United States (N = 23). Participants completed the Beck Anxiety Inventory (BAI). The overall BAI score and somatic and psychological subscales were compared. While there was no difference in total BAI scores, the Nepali group scored higher on the somatic subscale (i.e. "dizziness" and "indigestion," t[df] = -2.63[50], p < 0.05), while the American group scored higher on the psychological subscale (i.e. "scared" and "nervous," f[df] = 3.27[50], p < 0.01). Nepali patients with GAD had higher levels of somatic symptoms and lower levels of psychological symptoms than American patients with GAD. Possible explanations include differences in cultural traditions of describing distress and the mind-body dichotomy. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tribhuvan Univ Teaching Hosp, Kathmandu, Nepal. RP Hoge, EA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Simches Res Bldg,185 Cambridge St,Suite 2200, Boston, MA 02114 USA. EM ehoge@partners.org RI Hoge, Elizabeth/H-5879-2012 OI Hoge, Elizabeth/0000-0002-5513-2292 NR 18 TC 24 Z9 24 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD DEC PY 2006 VL 194 IS 12 BP 962 EP 966 DI 10.1097/01.nmd.0000243813.59385.75 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 116FO UT WOS:000242788100013 PM 17164637 ER PT J AU Wen, PY Schiff, D Kesari, S Drappatz, J Gigas, DC Doherty, L AF Wen, Patrick Y. Schiff, David Kesari, Santosh Drappatz, Jan Gigas, Debra C. Doherty, Lisa TI Medical management of patients with brain tumors SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE anticonvulsants; corticosteroids; pneumocystis pneumonitis; venous thromboembolic disease; fatigue ID MOLECULAR-WEIGHT HEPARIN; DEEP-VEIN THROMBOSIS; PNEUMOCYSTIS-CARINII-PNEUMONIA; QUALITY-OF-LIFE; RECURRENT MALIGNANT GLIOMA; HIGH-GRADE GLIOMA; POSTOPERATIVE VENOUS THROMBOEMBOLISM; RECEIVING CRANIAL IRRADIATION; STEVENS-JOHNSON SYNDROME; HIV-NEGATIVE PATIENTS AB The most common medical problems in brain tumor patients include the management of seizures, peritumoral edema, medication side effects, venous thromboembolism (VTE), fatigue and cognitive dysfunction. Despite their importance, there are relatively few studies specifically addressing these issues. There is increasing evidence that brain tumor patients who have not had a seizure do not benefit from prophylactic antiepileptic medications. Patients on corticosteroids are at greater risk of Pneumocystis jerovecii pneumonia and may benefit from prophylactic therapy. There is also growing evidence suggesting that anticoagulation may be more effective than inferior vena cava IVC) filtration devices for treating VTE in brain tumor patients and the risk of hemorrhage with anticoagulation is relatively small. Low-molecular weight heparin may be more effective than coumadin. Medications such as modafinil and methylphenidate have assumed an increasing role in the treatment of fatigue, while donepezil and memantine may be helpful with memory loss. C1 Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. Univ Virginia, Hlth Sci Ctr, Neurooncol Ctr, Charlottesville, VA 22908 USA. RP Wen, PY (reprint author), Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, SW430D,44 Binney St, Boston, MA 02115 USA. EM pwen@partners.org RI Kesari, Santosh/E-8461-2013 NR 207 TC 72 Z9 72 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD DEC PY 2006 VL 80 IS 3 BP 313 EP 332 DI 10.1007/s11060-006-9193-2 PG 20 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 119HE UT WOS:000243002600013 PM 16807780 ER PT J AU Singh, I Pannu, R Singh, AK AF Singh, I. Pannu, R. Singh, A. K. TI Role of lactosylceramide in regulation of inflammatory response and astrogliosis: Implications for neuroinflammatory diseases SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 2nd ISN Special Neurochemistry Conference CY DEC 01-05, 2006 CL ANTIGUA & BARBU SP ISN C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2006 VL 99 SU 1 MA 81 BP 27 EP 28 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 121ZA UT WOS:000243194300083 ER PT J AU Berman, JW Carson, MJ Chang, L Cox, BM Fox, HS Gonzalez, RG Hanson, GR Hauser, KF Ho, WZ Hong, JS Major, EO Maragos, WF Masliah, E McArthur, JC Miller, DB Nath, A O'Callaghan, JP Persidsky, Y Power, C Rogers, TJ Royal, W AF Berman, Joan W. Carson, Monica J. Chang, Linda Cox, Brian M. Fox, Howard S. Gonzalez, R. Gilberto Hanson, Glen R. Hauser, Kurt F. Ho, Wen-Zhe Hong, Jau-Shyong Major, Eugene O. Maragos, William F. Masliah, Eliezer McArthur, Justin C. Miller, Diane B. Nath, Avindra O'Callaghan, James P. Persidsky, Yuri Power, Christopher Rogers, Thomas J. Royal, Walter, III TI NeuroAIDS, Drug Abuse, and Inflammation: Building Collaborative Research Activities SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Review DE NeuroAIDS; drug abuse; HIV; SIV; inflammation; brain AB Neurological complications of human immunodeficiency virus (HIV) infection are a public health problem despite the availability of active antiretroviral therapies. The neuropathogenesis of HIV infection revolves around a complex cascade of events that include viral infection and glial immune activation, monocyte-macrophage brain infiltration, and secretion of a host of viral and cellular inflammatory and neurotoxic molecules. Although there is evidence that HIV-infected drug abusers experience more severe neurological disease, the biological basis for this finding is unknown. A scientific workshop organized by the National Institute on Drug Abuse (NIDA) was held on March 23-24, 2006 to address this question. The goal of the meeting was to bring together basic science and clinical researchers who are experts in NeuroAIDS, glial immunity, drugs of abuse, and/or pharmacology in order to find new approaches to understanding interactions between drug abuse and neuroAIDS. The format of the meeting was designed to stimulate open discussion and forge new multidisciplinary research collaborations. This report includes transcripts of active discussions and short presentations from invited participants. The presentations were separated into sections that included: Glial Biology, Inflammation, and HIV; Pharmacology, Neurotoxicology, and Neuroprotection; NeuroAIDS and Virology; and Virus-Drug and Immune-Drug Interactions. Research priorities were identified. Additional information about this meeting is available through links from the NIDA AIDS Research Program website (http://www.nida.nih.gov/about/organization/arp/arp-websites.htm). C1 [Berman, Joan W.] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. [Carson, Monica J.] Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA. [Chang, Linda] Univ Hawaii, Med Ctr, John A Burns Sch Med, Honolulu, HI 96816 USA. [Cox, Brian M.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. [Fox, Howard S.] Scripps Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hanson, Glen R.] Univ Utah, Med Ctr, Dept Pharmacol & Toxicol, Salt Lake City, UT 84132 USA. [Fox, Howard S.] La Jolla Canc Res Fdn, La Jolla, CA 92037 USA. [Hauser, Kurt F.] Univ Kentucky, Coll Med, Dept Anat & Neurobiol, Lexington, KY 40536 USA. [Hauser, Kurt F.] Univ Kentucky, Coll Med, Lucille P Markey Canc Ctr, Lexington, KY 40536 USA. [Ho, Wen-Zhe] Univ Penn, Med Ctr, Dept Pediat, Philadelphia, PA 19104 USA. [Hong, Jau-Shyong] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. [Major, Eugene O.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. [Maragos, William F.] Univ Kentucky, Coll Med, Dept Neurol, Lexington, KY 41287 USA. [Masliah, Eliezer] Univ Calif San Diego, Med Ctr, Dept Neurosci, La Jolla, CA 92093 USA. [McArthur, Justin C.; Nath, Avindra] Johns Hopkins Sch Med, Dept Neurol, Bethesda, MD 20205 USA. [Miller, Diane B.] Ctr Dis Control NIOSH, Toxicol & Mol Biol Branch, Morgantown, WV 30333 USA. [O'Callaghan, James P.] Ctr Dis Control NIOSH, Mol Neurotoxicol Lab, Morgantown, WV USA. [Persidsky, Yuri] Univ Nebraska, Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE 68198 USA. [Power, Christopher] Univ Alberta, Dept Med, Edmonton, AB T2N 4N1, Canada. [Rogers, Thomas J.] Temple Univ, Sch Med, Fels Inst, Philadelphia, PA 19104 USA. [Royal, Walter, III] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. RP Berman, JW (reprint author), Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. EM berman@aecom.yu.edu; monica.carson@ucr.edu; lchang@hawaii.edu; bcox@usuhs.mil; hsfox@scripps.edu; rggonzalez@partners.org; glen.hanson@hsc.utah.edu; khauser@uky.edu; ho@email.chop.edu; hong3@niehs.nih.gov; majorg@ninds.nih.gov; Maragos@uky.edu; emasliah@ucsd.edu; jm@welchlink.welch.jhu.edu; dum6@cdc.gov; anath1@jhmi.edu; jdo5@cdc.gov; ypersids@unmc.edu; chris.power@ualberta.ca; rogerst@temple.edu; wroyal@som.umaryland.edu RI Power, Christopher/C-7181-2013; O'Callaghan, James/O-2958-2013; OI Fox, Howard/0000-0003-2032-374X FU NINDS NIH HHS [R01 NS039508, R01 NS045735] NR 126 TC 16 Z9 16 U1 3 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD DEC PY 2006 VL 1 IS 4 BP 351 EP 399 DI 10.1007/s11481-006-9048-9 PG 49 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA V04MX UT WOS:000207063600001 PM 18040811 ER PT J AU Rousseau, A Nutt, CL Betensky, RA Iafrate, AJ Han, M Ligon, KL Rowitch, DH Louis, DN AF Rousseau, Audrey Nutt, Catherine L. Betensky, Rebecca A. Iafrate, A. John Han, Moonjoo Ligon, Keith L. Rowitch, David H. Louis, David N. TI Expression of oligodendroglial and astrocytic lineage markers in diffuse gliomas: Use of YKL-40, ApoE, ASCL1, and NKX2-2 SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE ApoE; astrocytoma; ASCL1; immunohistochemistry; NKX2-2; oligodendroglioma; YKL-40 ID TRANSCRIPTION FACTOR SOX10; CENTRAL-NERVOUS-SYSTEM; APOLIPOPROTEIN-E; GENE-EXPRESSION; SERUM YKL-40; TERMINAL DIFFERENTIATION; BREAST-CANCER; BRAIN-TUMORS; CELLS; OLIG2 AB The phenotypic heterogeneity of astrocytic and oligodendroglial tumor cells complicates establishing accurate diagnostic criteria, and lineage-specific markers would facilitate diagnosis of glioma subtypes. Based on data from the literature and from expression microarrays, we selected molecules relevant to gliogenesis and glial lineage specificity and then used immunohistochemistry to assess expression of these molecules in 55 diffuse gliomas, including 8 biphasic oligoastrocytomas, 21 oligodendrogliomas (all with 1p/19qloss), 21 astrocytomas, and 5 glioblastomas. For the astrocytic lineage markers (GFAP, YKL-40, and ApoE), GFAP expression was significantly higher in the astrocytic component of oligoastrocytomas compared with the oligodendroglial part; similar patterns were detected for YKL-40 and ApoE, although the differences were not significant. GFAP, YKL-40, and ApoE reliably distinguished grade II-III oligodendrogliomas from grade II-IV astrocytomas (p < 0.0001, p = 0.002, and p < 0.0001, respectively). Among the oligodendroglial lineage markers (Olig2, Sox10, ASCL1, and NKX2-2), ASCL1 and NKX2-2 displayed significantly different immunostaining between oligodendrogliomas and astrocytomas (p = 0.017 and 0.004, respectively), but none clearly differentiated between the 2 glial populations of oligoastrocytomas. In addition to GFAP, therefore, YKL-40, ApoE, ASCL1, and NKX2-2 represent promising tumor cell markers to distinguish oligodendrogliomas from astrocytomas. C1 Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02139 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Grp Hosp Pitie Salpetriere, INSERM, U711, Neurooncol Unit, F-75634 Paris, France. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, CNY7,149 13th St, Charlestown, MA 02139 USA. EM dlouis@partners.org RI Nutt, Catherine/K-8794-2012; Rousseau, Audrey/L-3193-2015 FU NCI NIH HHS [CA 95616, CA 57683] NR 51 TC 40 Z9 41 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD DEC PY 2006 VL 65 IS 12 BP 1149 EP 1156 DI 10.1097/01.jnen.0000248543.90304.2b PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 126MM UT WOS:000243517000007 PM 17146289 ER PT J AU Takahashi, M Uchikado, H Caprotti, D Weidenheim, KM Dickson, DW Ksiezak-Reding, H Pasinetti, GM AF Takahashi, Makio Uchikado, Hirotake Caprotti, Domenico Weidenheim, Karen M. Dickson, Dennis W. Ksiezak-Reding, Hanna Pasinetti, Giulio M. TI Identification of G-protein coupled receptor kinase 2 in paired helical filaments and neurofibrillary tangles SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; corticobasal degeneration; Lewy body disease; Pick disease; progressive supranuclear palsy; tau ID PROGRESSIVE SUPRANUCLEAR PALSY; ALZHEIMERS-DISEASE PATHOLOGY; SPORADIC PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; LEWY BODIES; PICKS-DISEASE; BETA(2)-ADRENERGIC RECEPTOR; NEURODEGENERATIVE DISEASES; PHOSPHORYLATION SITES; TAU FILAMENTS AB G-protein coupled receptor kinases (GRKs) constitute a serine/ threonine kinase family playing a major role in agonist-induced phosphorylation and desensitization of G-protein coupled receptors. Recently, GRK2 and GRX5 have been demonstrated to phosphorylate alpha-synuclein (Ser129) and other synuclein isoforms. We studied colocalization of GRK2, GRK5, alpha-synuclein, and tau in neurodegenerative disorders characterized by fibrillary tau inclusions and/or alpha-synuclein-enriched Lewy bodies. We found that Lewy bodies were negative for both GRK2 and GRK5 in Lewy body disease (LBD) and LBD mixed with Alzheimer disease (AD + LBD). Instead, GRK2 but not GRK5 colocalized with 40% to 50% of neurofibrillary tangles in AD + LBD and AD brains. In disorders with less prominent alpha-synucleinopathy, neuronal and glial fibrillary tau deposits known to contain distinct subsets of tau isoforms were also positive for GRK2. These deposits included tufted astrocytes and coiled bodies in progressive supranuclear palsy, astrocytic plaques in corticobasal degeneration, and Pick bodies in Pick disease. In addition, paired helical filaments isolated from AD and AD + LBD brains were found to immunogold-label for GRK2, suggesting that GRK2 could be a potential tau kinase associated with fibrillary tau. Our studies indicate that GRK2 is a novel component of neuronal and glial fibrillary tau deposits with no preference in tau isoform binding. GRK2 may play a role in hyperphosphory lation of tau in tauopathies. C1 James J Peters VA Med Ctr, Dept Psychiat, Neuroinflammat Res Labs, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, Neuroinflammat Res Labs, Bronx, NY USA. Mayo Clin, Dept Neuropathol & Neurosci, Jacksonville, FL 32224 USA. Montefiore Med Ctr, Dept Pathol, Bronx, NY 10467 USA. RP Ksiezak-Reding, H (reprint author), James J Peters VA Med Ctr, Dept Psychiat, Neuroinflammat Res Labs, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM hanna.reding@mssm.edu OI Dickson, Dennis W/0000-0001-7189-7917 NR 58 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD DEC PY 2006 VL 65 IS 12 BP 1157 EP 1169 DI 10.1097/01.jnen.0000248542.82681.12 PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 126MM UT WOS:000243517000008 PM 17146290 ER PT J AU Mizoguchi, M Betensky, RA Batchelor, TT Bernay, DC Louis, DN Nutt, CL AF Mizoguchi, Masahiro Betensky, Rebecca A. Batchelor, Tracy T. Bernay, Derek C. Louis, David N. Nutt, Catherine L. TI Activation of STAT3, MAPK, and AKT in malignant astrocytic gliomas: Correlation with EGFR status, tumor grade, and survival SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE AKT; EGFR; glioma; MAPK; phosphorylation; STAT3 ID GROWTH-FACTOR-RECEPTOR; PROSTATE-CANCER CELLS; GLIOBLASTOMA-MULTIFORME CELLS; PROTEIN-KINASE B; CONSTITUTIVE ACTIVATION; SIGNAL TRANSDUCER; PATHWAY ACTIVATION; GENE AMPLIFICATION; CROSS-TALK; KAPPA-B AB Diffuse astrocytic gliomas are the most common human glial tumors with glioblastoma being the most malignant form. Epidermal growth factor receptor (EGFR) gene amplification is one of the most common genetic changes in glioblastoma and can lead to the activation of various downstream signaling molecules, including STAT3, MAPK, and AKT. In this study, we investigated the activation status of these 3 signaling molecules as well as wild-type (EGFRwt) and mutant (EGFRvIII) EGFR in 82 malignant astrocytic gliomas (55 glioblastomas and 27 anaplastic astrocytomas) using immunohistochemistry. The presence of EGFRwt, but not EGFRvIII, immunopositivity correlated significantly with prevalent EGFR gene amplification in glioblastomas. STAT3 and AKT activation correlated significantly with EGFR status, although the correlation for p-STAT3 was attributed exclusively to EGFRvIII. The distribution of these 3 activated molecules varied significantly with tumor grade; although activation of STAT3 was essentially identical between anaplastic astrocytomas and glioblastomas, an increase in the activation of MAPK and AKT appeared to correlate with the progression of anaplastic astrocytoma to glioblastoma. Finally, activated STAT3 and AKT were marginally predictive of improved and worse prognosis, respectively. Taken together, these findings begin to elucidate the interrelationship between these signaling pathways in astrocytic gliomas in vivo. C1 Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02139 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Dept Pathol, Canc Ctr & Neurol Serv, Charlestown, MA 02139 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Dept Neurol, Boston, MA 02114 USA. RP Nutt, CL (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, CNY7,149 13th St, Charlestown, MA 02139 USA. EM cnutt@partners.org FU NCI NIH HHS [CA 95616, CA 57683] NR 50 TC 92 Z9 96 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD DEC PY 2006 VL 65 IS 12 BP 1181 EP 1188 DI 10.1097/01.jnen.0000248549.14962.b2 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 126MM UT WOS:000243517000010 PM 17146292 ER PT J AU Vincent, JL Snyder, AZ Fox, MD Shannon, BJ Andrews, JR Raichle, ME Buckner, RL AF Vincent, Justin L. Snyder, Abraham Z. Fox, Michael D. Shannon, Benjamin J. Andrews, Jessica R. Raichle, Marcus E. Buckner, Randy L. TI Coherent spontaneous activity identifies a hippocampal-parietal memory network SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; MEDIAL PREFRONTAL CORTEX; CONSCIOUS RESTING STATE; EMOTION-INDUCED CHANGES; VISUAL AREA MT; EPISODIC MEMORY; RECOGNITION MEMORY; DEFAULT-MODE; FUNCTIONAL CONNECTIVITY; CEREBRAL-CORTEX AB Despite traditional theories emphasizing parietal contributions to spatial attention and sensory-motor integration, functional MRI (fMRI) experiments in normal subjects suggest that specific regions within parietal cortex may also participate in episodic memory. Here we examined correlations in spontaneous blood-oxygenation-level-dependent (BOLD) signal fluctuations in a resting state to identify the network associated with the hippocampal formation (HF) and determine whether parietal regions were elements of that network. In the absence of task, stimuli, or explicit mnemonic demands, robust correlations were observed between activity in the HF and several parietal regions (including precuneus, posterior cingulate, retrosplenial cortex, and bilateral inferior parietal lobule). These HF-correlated regions in parietal cortex were spatially distinct from those correlated with the motion-sensitive MT+ complex. Reanalysis of event-related fMRI studies of recognition memory showed that the regions spontaneously correlated with the HF (but not MT+) were also modulated during directed recollection. These regions showed greater activity to successfully recollected items as compared with other trial types. Together, these results associate specific regions of parietal cortex that are sensitive to successful recollection with the HF. C1 Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Psychol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Biomed Engn, St Louis, MO 63110 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Raichle, ME (reprint author), Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, 4525 Scott Ave, St Louis, MO 63110 USA. EM marc@npg.wustl.edu RI Vincent, Justin/B-5033-2012 FU NIA NIH HHS [P50 AG 05681, P01 AG 03991]; NINDS NIH HHS [NS 06833] NR 120 TC 524 Z9 529 U1 5 U2 47 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 2006 VL 96 IS 6 BP 3517 EP 3531 DI 10.1152/jn.00048.2006 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 107NH UT WOS:000242177800067 PM 16899645 ER PT J AU Mendez, MF Chen, AK Shapira, JS Lu, PH Miller, BL AF Mendez, MF Chen, AK Shapira, JS Lu, PH Miller, BL TI Acquired extroversion associated with bitemporal variant of frontotemporal dementia SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID FRONTAL-LOBE DEGENERATION; NON-ALZHEIMER TYPE; TEMPORAL VARIANTS; SOCIAL-BEHAVIOR; WILLIAMS-SYNDROME; BLOOD-FLOW; DISEASE; EMOTION; COGNITION; NEUROBIOLOGY AB Frontotemporal dementia (FTD) is characterized by alterations in personality. The nature of the personality changes depend on the localization of the pathology. The authors present three patients with acquired extroversion who met criteria for FTD. All three patients exhibited predominant bilateral temporal involvement as determined with functional neuroimaging. Possible mechanisms for acquired extroversion in bitemporal FTD include bilateral amygdalar damage with decreased interpersonal fear or sense of threat, orbitofrontal-ventromedial damage with social disinhibition, and relative sparing of dorsolateral frontal and anterior cingulate regions with preserved interpersonal agency. FTD can be a vehicle for unraveling the basis of personality characteristics such as the introversion/extroversion dimension. C1 VA Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@ucla.edu FU NIA NIH HHS [P01 AG019724, AG-19724-01] NR 46 TC 12 Z9 12 U1 2 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 2006 VL 18 IS 1 BP 100 EP 107 DI 10.1176/appi.neuropsych.18.1.100 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 014YU UT WOS:000235519900014 PM 16525077 ER PT J AU Wang, JB Gabuzda, D AF Wang, Jianbin Gabuzda, Dana TI Reconstitution of human immunodeficiency virus-induced neurodegeneration using isolated populations of human neurons, astrocytes, and microglia and neuroprotection mediated by insulin-like growth factors SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE astrocyte; HIV; IGF; microglia; neurodegeneration; neuron ID MONOCYTE-DERIVED MACROPHAGES; CHEMOKINE RECEPTOR CXCR4; FACTOR-BINDING PROTEIN-2; HIV-ASSOCIATED DEMENTIA; CENTRAL-NERVOUS-SYSTEM; GENE-EXPRESSION; TYPE-1 INFECTION; IN-VIVO; IGF-I; HIV-1-INFECTED INDIVIDUALS AB Primary human neuron cultures are an important in vitro model system for studies on mechanisms involved in human immunodeficiency virus (HIV)-associated dementia (HAD) and other neurological disorders. Here, more than 80 cell surface antigens were screened to identify a marker that could readily distinguish between neurons and astrocytes and found that neurons lack CD44 surface expression, whereas astrocytes and other cell types in brain are CD44(+). Neurons and astrocytes were isolated from human fetal brain based on differential expression of CD44. Using purified neurons cocultured with astrocytes and/or microglia, it was demonstrated that HIV infection of microglia induces cellular activation and production of soluble factors that activate uninfected microglia and astrocytes and induce neuronal cell death. Activated astrocytes promoted HIV replication in microglia, thereby amplifying HIV-induced neurotoxicity. A screen for 120 cytokine/proteins detected upregulation of insulin-like growth factor (IGF)-binding protein (IGFBP)-2, interleukin (IL)-6, and CCL8/MCP-2 (monocyte chemoattractant protein 2) in supernatants of HIV-infected brain cell cultures. IGF-1 and -2 increased neuronal survival in HIV-infected brain cell cultures, whereas IGFBP-2 inhibited prosurvival effects of these growth factors. These findings identify CD44 as a marker that can be used to sort neurons from other cell types in brain, suggest the importance of microglia-astrocyte interactions in neurodegenerative mechanisms associated with HIV infection, and indicate a role for insulin-like growth factors in neuroprotection from HIV-induced neurodegeneration. The ability to reconstitute brain cultures using isolated populations of neurons, astrocytes, and microglia will be valuable for studies on pathogenic mechanisms in HAD and other neurological disorders, and will also facilitate neuroactive drug discovery. C1 Harvard Univ, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dept Pathol, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dept Neurol, Sch Med, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Harvard Univ, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Sch Med, JF 816,44 Binney St, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu FU NINDS NIH HHS [NS37277, NS35734] NR 100 TC 15 Z9 15 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 2006 VL 12 IS 6 BP 472 EP 491 DI 10.1080/13550280601039659 PG 20 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 115CK UT WOS:000242712200007 PM 17162663 ER PT J AU Tanvetyanon, T Choudhury, AM AF Tanvetyanon, Tawee Choudhury, Abdul M. TI Physician practice in the discontinuation of statins among patients with advanced lung cancer SO JOURNAL OF PALLIATIVE CARE LA English DT Article ID CORONARY-HEART-DISEASE; CONTROLLED-TRIAL; CHOLESTEROL; PREVENTION; CHEMOTHERAPY; PRAVASTATIN; SURVIVAL; EVENTS; DEATH AB Background. Statins are effective in reducing events from coronary heart disease and can prolong survival. However, this benefit is controversial when other concurrent serious health problems greatly limit the patient's longevity. Methods: We conducted a retrospective chart review of patients with advanced lung cancer who were receiving statins and had lived for at least one month since diagnosis. Findings: Forty-seven patients with median age of 71 years were included. Discontinuation of statins occurred in 25 patients (53.2%) before the date of death. Median survival was 370 days. Statins were discontinued at a median of 244 days after cancer diagnosis. Discontinuations were more prevalent in patients who received chemotherapy or had a history of cerebrovascular diseases. Lipid monitoring was observed in 25 patients (53.2%). Interpretation: About half of patients with advanced lung cancer who were prescribed statins did not have this drug discontinued until the time of death. Lipid monitoring was suboptimal and, when it occurred, indicated the lipid goal was rarely achieved. C1 Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. RP Tanvetyanon, T (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA. NR 21 TC 12 Z9 12 U1 0 U2 0 PU CENTER BIOETHICS CLIN RES INST MONTREAL PI MONTREAL PA 110 PINE AVE W, MONTREAL, QUEBEC H2W 1R7, CANADA SN 0825-8597 J9 J PALLIATIVE CARE JI J. Palliative Care PD WIN PY 2006 VL 22 IS 4 BP 281 EP 285 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 120KK UT WOS:000243083400006 PM 17263055 ER PT J AU Fenix, JB Cherlin, EJ Prigerson, HG Johnson-Hurzeler, R Kasl, SV Bradley, EH AF Fenix, J. B. Cherlin, Emily J. Prigerson, Holly G. Johnson-Hurzeler, Rosemary Kasl, Stanislav V. Bradley, Elizabeth H. TI Religiousness and major depression among bereaved family caregivers: a 13-month follow-up study SO JOURNAL OF PALLIATIVE CARE LA English DT Article ID HOSPICE ENROLLMENT; UNITED-STATES; BURDEN; CANCER; SYMPTOMS; LIFE; PEOPLE; EPIDEMIOLOGY; POPULATION; DISABILITY AB Objective: To examine the association between a multi-item measure of religiousness and major depressive disorder (MDD) in bereaved family caregivers of patients with cancer. Design: A prospective longitudinal study of primary caregivers of consecutive patients (n=175) with cancer enrolled in the largest hospice in Connecticut. Results: Caregivers with a high religiousness summary score were significantly less likely to have MDD at the 13-month follow-up interview (OR=0.79, 95% Cl: 0.68-0.91). This finding remained significant (OR=0.74, 95% Cl: 0.59-0.91) after adjustment for caregiver MDD at baseline, caregiver age, caregiver burden, and number of activities restricted due to caregiving roles. Conclusions: Family caregivers who reported greater religiousness at baseline had lower rates of depression in the 13-month follow up after their loss. Collaboration with religious support groups or community groups during bereavement could offer an effective mechanism for speeding the process of recovery for some caregivers. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06519 USA. Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat, Boston, MA USA. Connecticut Hospice, Branford, CT 06405 USA. John D Thompson Hospice Inst Educ Training & Res, Branford, CT 06405 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06520 USA. RP Fenix, JB (reprint author), 40233 Arroyo Dr, Irvine, CA 92617 USA. FU NCI NIH HHS [R01 CA106370, CA106370]; NIA NIH HHS [P30AG21342]; NIMH NIH HHS [MH63892] NR 46 TC 17 Z9 18 U1 6 U2 11 PU CENTER BIOETHICS CLIN RES INST MONTREAL PI MONTREAL PA 110 PINE AVE W, MONTREAL, QUEBEC H2W 1R7, CANADA SN 0825-8597 J9 J PALLIATIVE CARE JI J. Palliative Care PD WIN PY 2006 VL 22 IS 4 BP 286 EP 292 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 120KK UT WOS:000243083400007 PM 17263056 ER PT J AU Ray, A Block, SD Friedlander, RJ Zhang, BH Maciejewski, PK Prigerson, HG AF Ray, Alaka Block, Susan D. Friedlander, Robert J. Zhang, Baohui Maciejewski, Paul K. Prigerson, Holly G. TI Peaceful awareness in patients with advanced cancer SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID COMPLICATED GRIEF; TRAUMATIC GRIEF; PROGNOSIS; CAREGIVERS; COMMUNICATION; LIFE; BEREAVEMENT; PREFERENCES; DISCLOSURE; DISORDERS AB Background: Previous studies have shown that prognostic awareness may be harmful to mental health yet beneficial for end of life care planning. The effects of prognostic awareness coupled with a sense of inner peace are unknown. Methods: In the multisite, longitudinal Coping with Cancer Study, 280 patients with advanced cancer were interviewed at baseline. Patients defining themselves as "terminally ill" and/or "at peace" most days were paired with others on sociodemographic, mental health and advance care planning. Primary caregivers of deceased patients were interviewed 6 months postloss and compared on their physical and mental health and their perceptions of patients' end-of-life care and death. Results: Overall, 17.5% of patients reported being both peaceful and aware. Peacefully aware patients had lower rates of psychological distress and higher rates of advance care planning (e.g., completing do-not-resuscitate [DNR] orders, advance care planning discussions with physicians) than those who were not peacefully aware. Additionally, peacefully aware patients had the highest overall quality of death as reported by their caretakers in a postmortem evaluation. Surviving caregivers of peacefully aware patients were more physically and mentally healthy 6 months postloss than caregivers of patients who were "aware" but not peaceful. Conclusions: Patients with advanced cancer who are peacefully aware have better mental health and quality of death outcomes, and their surviving caregivers have better bereavement outcomes. Peaceful awareness is associated with modifiable aspects of medical care (e.g., discussions about terminal treatment preferences). C1 Harvard Univ, Sch Med, Ctr Psychooncol & Palliat Care Res, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Psychosocial Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Med Sch Ctr Palliat Care, Boston, MA USA. New Hampshire Oncolhematol PA, Hooksett, NH USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Ray, A (reprint author), Harvard Univ, Sch Med, Ctr Psychooncol & Palliat Care Res, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM alaka_ray@dfci.harvard.edu FU NCI NIH HHS [CA106370, R01 CA106370]; NIMH NIH HHS [MH63892] NR 23 TC 49 Z9 50 U1 2 U2 14 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 DEC PY 2006 VL 9 IS 6 BP 1359 EP 1368 DI 10.1089/jpm.2006.9.1359 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 120PD UT WOS:000243096200021 PM 17187544 ER PT J AU Misra, M Miller, KK Tsai, P Stewart, V End, A Freed, N Herzog, DB Goldstein, M Riggs, S Klibanski, A AF Misra, Madhusmita Miller, Karen K. Tsai, Patrika Stewart, Victoria End, Alison Freed, Natalie Herzog, David B. Goldstein, Mark Riggs, Suzanne Klibanski, Anne TI Uncoupling of cardiovascular risk markers in adolescent girls with anorexia nervosa SO JOURNAL OF PEDIATRICS LA English DT Article ID C-REACTIVE PROTEIN; NUTRITION EXAMINATION SURVEY; DENSITY LIPOPROTEIN-CHOLESTEROL; APPARENTLY HEALTHY-MEN; NECROSIS-FACTOR-ALPHA; NON-HDL CHOLESTEROL; APOLIPOPROTEIN-B; SECRETORY DYNAMICS; INSULIN-RESISTANCE; BONE METABOLISM AB Objective: Cardiovascular (CV) risk begins in childhood, and low body weight should result in a favorable risk profile. However, adolescents with anorexia nervosa (AN) have alterations in many hormonal factors that mediate CV risk. We hypothesized that in AN, growth hormone (GH) resistance and hypereortisolemia would increase CV risk through effects on pro-inflammatory cytokines and lipid status despite low weight. Study design: We examined CV risk markers (high sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], apolipoprotein-B [Apo-B], and lipid profile) in 23 subjects with AN and in 20 control subjects 12 to 18 years of age, in whom GH, cortisol, leptin, and triiodothyronine (T3) had been previously determined. Results: Subjects with AN had higher Apo-B (P < .0001), IL-6 (P = .03), Apo-B/high-density lipoprotien (HDL) (P = .01), and Apo-B/low-density lipoprotein (LDL) (P < .0001) and lover hsCRP (P = .01) than controls. Triglycerides were lower and HDL higher in subjects with AN. IGF-I predicted hsCRP in controls but not in AN. Log hsCRP correlated positively with GH and inversely with leptin. On regression modeling, the roost significant predictor of log hsCRP was leptin; T3 predicted log IL-6, log Apo-B, log Apo-B/HDL, and Apo-B/hDL; and cortisol independently predicted log Apo-B. IL-6 decreased with weight gain. Conclusion: CV risk markers are uncoupled in AN, with increased Apo-B and IL-6 and decreased hsCRP, related to hormonal alterations. IL-6 normalizes with weight gain. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457, Boston, MA 02114 USA. Massachusetts Gen Hosp, Eating Disorders Unit, Child Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Adolescent Med, Boston, MA 02114 USA. Hasbro Childrens Hosp, Adolescent Med Unit, Providence, RI USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457, 55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org FU NCRR NIH HHS [M01-RR-01066, K23 RR018851]; NIDDK NIH HHS [DK 062249] NR 50 TC 18 Z9 18 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD DEC PY 2006 VL 149 IS 6 BP 763 EP 769 DI 10.1016/j.jpeds.2006.08.043 PG 7 WC Pediatrics SC Pediatrics GA 122QW UT WOS:000243242500009 PM 17137889 ER PT J AU Joffe, S Fernandez, CV Pentz, RD Ungar, DR Mathew, NA Turner, CW Alessandri, AJ Woodman, CL Singer, DA Kodish, E AF Joffe, Steven Fernandez, Conrad V. Pentz, Rebecca D. Ungar, David R. Mathew, N. Ajoy Turner, Curtis W. Alessandri, Angela J. Woodman, Catherine L. Singer, Dale A. Kodish, Eric TI Involving children with cancer in decision-making about research participation SO JOURNAL OF PEDIATRICS LA English DT Article ID INFORMED-CONSENT; CLINICAL-TRIALS; ASSENT; ADOLESCENTS; AUTONOMY; PERMISSION; STANDARDS; ABILITY; AGE C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Dalhousie Univ, Dept Pediat, Halifax, NS, Canada. Dalhousie Univ, Dept Bioeth, Halifax, NS, Canada. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Penn State Childrens Hosp, Dept Pediat, Hershey, PA USA. CureSearch Natl Childhood Canc Fdn, Bethesda, MD USA. Texas Tech Univ, Hlth Sci Ctr, Dept Pediat, Amarillo, TX USA. Princess Margaret Hosp Children, Dept Paediat Hematol Oncol, Perth, WA, Australia. Univ Iowa, Coll Med, Dept Psychiat, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Dept Family Med, Iowa City, IA 52242 USA. Childrens Hosp, Phoenix, AZ USA. Cleveland Clin Fdn, Lerner Coll Med, Dept Bioeth, Cleveland, OH 44195 USA. RP Joffe, S (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM steven_joffe@dfci.harvard.edu OI Joffe, Steven/0000-0002-0667-7384 FU NCI NIH HHS [CA096872, CA98413, CA083267, CA98543] NR 35 TC 40 Z9 40 U1 2 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD DEC PY 2006 VL 149 IS 6 BP 862 EP 868 DI 10.1016/j.jpeds.2006.08.027 PG 7 WC Pediatrics SC Pediatrics GA 122QW UT WOS:000243242500028 PM 17137908 ER PT J AU Thureen, P Reece, M Rodden, D Barbour, L Chappell, J Leitner, JW Jones, RO Draznin, B AF Thureen, Patti Reece, Melanie Rodden, Donna Barbour, Lynn Chappell, James Leitner, J. Wayne Jones, Richard O. Draznin, Boris TI Increased farnesylation of p21-Ras and neonatal macrosomia in women with gestational diabetes SO JOURNAL OF PEDIATRICS LA English DT Article ID GROWTH-FACTOR; INSULIN; HYPERINSULINEMIA; TISSUES AB Sit of 22 mothers with gestational diabetes mellitus had infants with macrosomia, cord blood hyperinsulinemia, and increased amounts of a key mitogenic intermediate, farnesylated p21-Ras. The ability of fetal hyperinsulinemia to increase the availability of farnesylated p21-Ras may represent one mechanism of the growth-promoting action of insulin during fetal development. C1 Univ Colorado, Hlth Sci Ctr, Dept Pediat, Res Sev,Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Obstet & Gynecol, Res Sev,Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Res Sev,Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. Denver Hlth & Hosp Author, Denver, CO USA. RP Thureen, P (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pediat, Res Sev,Denver Vet Affairs Med Ctr, 4200 E 9th Ave,B-195, Denver, CO 80262 USA. EM patti.thureen@uchsc.edu FU NCRR NIH HHS [M01 RR00069] NR 12 TC 6 Z9 6 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD DEC PY 2006 VL 149 IS 6 BP 871 EP 873 DI 10.1016/j.jpeds.2006.08.071 PG 3 WC Pediatrics SC Pediatrics GA 122QW UT WOS:000243242500030 PM 17137910 ER PT J AU Paris, JJ Billinngs, JA Cummings, B Moreland, MP AF Paris, J. J. Billinngs, J. A. Cummings, B. Moreland, M. P. TI Howe v. MGH and Hudson v. Texas Children's Hospital: two approaches to resolving family-physician disputes in end-of-life care SO JOURNAL OF PERINATOLOGY LA English DT Editorial Material ID FUTILITY C1 Boston Coll, Dept Theol, Chestnut Hill, MA 02167 USA. Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Villanova Law Sch, Villanova, PA USA. RP Paris, JJ (reprint author), Boston Coll, Dept Theol, Chestnut Hill, MA 02167 USA. EM john.paris@bc.edu NR 11 TC 3 Z9 3 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0743-8346 J9 J PERINATOL JI J. Perinatol. PD DEC PY 2006 VL 26 IS 12 BP 726 EP 729 DI 10.1038/sj.jp.7211591 PG 4 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 108NH UT WOS:000242246000002 PM 17122785 ER PT J AU Lin, CR Amaya, F Barrett, L Wang, HB Takada, J Samad, TA Woolf, CJ AF Lin, Chung-Ren Amaya, Fumimasa Barrett, Lee Wang, Haibin Takada, Junji Samad, Tarek A. Woolf, Clifford J. TI Prostaglandin E-2 receptor EP4 contributes to inflammatory pain hypersensitivity SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DEPENDENT PROTEIN-KINASE; DOUBLE-STRANDED-RNA; PROSTANOID RECEPTOR; PROSTACYCLIN RECEPTOR; MAMMALIAN-CELLS; GENE-EXPRESSION; SENSORY NEURONS; MESSENGER-RNA; SPINAL-CORD; HYPERALGESIA AB Prostaglandin E-2 (PGE(2)) is both an inflammatory mediator released at the site of tissue inflammation and a neuromodulator that alters neuronal excitability and synaptic processing. The effects of PGE(2) are mediated by four G-protein-coupled EP receptors (EP1-EP4). Here we show that the EP4 receptor subtype is expressed by a subset of primary sensory dorsal root ganglion (DRG) neurons, and that its levels, but not that of the other EP1-3 subtypes, increase in the DRG after complete Freund' adjuvant-induced peripheral inflammation. Administration of both an EP4 antagonist [AH23848, (4Z)-7-[(rel-1S,2S,5R)-5-((1,1 '-biphenyl-4-yl)methoxy)-2-(4-morpholinyl)-3oxocyclopentyl]-4-heptenoic acid] and EP4 knockdown with intrathecally delivered short hairpin RNA attenuates inflammation-induced thermal and mechanical behavioral hypersensitivity, without changing basal pain sensitivity. AH23848 also reduces the PGE(2)-mediated sensitization of capsaicin-evoked currents in DRG neurons in vitro. These data suggest that EP4 is a potential target for the pharmacological treatment of inflammatory pain. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plastic Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Pfizer Global Res & Dev, Discovery Biol Res, Aichi, Japan. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plastic Res Grp, 149 13th St,Room 4309, Charlestown, MA 02129 USA. EM cjwoolf@partners.org NR 39 TC 115 Z9 117 U1 1 U2 9 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 DEC PY 2006 VL 319 IS 3 BP 1096 EP 1103 DI 10.1124/jpet.106.105569 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 105QX UT WOS:000242048500012 PM 16966471 ER PT J AU Wang, HS Oh, DS Ohning, GV Pisegna, JR AF Wang, Hank S. Oh, David S. Ohning, Gordon V. Pisegna, Joseph R. TI Cyto-reduction of neuroendocrine tumours using Sandostatin LAR (R) in combination with Infergen (R): results of a case series SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Article ID ACTING SOMATOSTATIN ANALOG; MIDGUT CARCINOID-TUMORS; ENDOCRINE GASTROENTEROPANCREATIC TUMORS; INTERFERON-ALPHA; OCTREOTIDE ACETATE; CANCER CELLS; EXPRESSION; LANREOTIDE; THERAPY; GROWTH AB Historically, limited trials evaluating biotherapy in treating metastatic neuroenclocrine tumours have yielded mixed results. In this study, the efficacy of a novel combination therapy featuring longacting Sandostatin LAR (R) plus-interferon was evaluated. In a prospective case series, 12 patients with unresectable metastatic neuroendocrine tumours refractory to treatment initiated therapy with Infergen (R) and Sandostatin LAR (R). Radiological response was followed serially at 3-month intervals. A biochemical response was considered significant if marker levels decreased by >= 50% compared with baseline. Inhibition of tumour growth lasting for greater than 3 months (mean response 22.6 +/- 17.7 months) was seen in eight patients. Complete tumour regression was observed in one patient, lasting for 40 months; three patients exhibited partial tumour regression (mean response 29.3 +/- 24.0 months), and four patients maintained a stable tumour response (mean response 13.3 +/- 9.2 months). Four patients showed no response to therapy (mean response 5.0 +/- 6.0 months). All enrolled patients are alive currently. The biochemical response seen in seven patients did not correlate with the radiological response. These results suggest that the novel combination of longacting Sanclostatin LAR (R) with an a-interferon may be at least as effective as either combination therapy with short-acting octreotide or monotherapy with Sandostatin LAR (R). C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. Vet Adm Greater Los Angeles Healthcare Syst, Dept Gastroenterol & Hepatol, Los Angeles, CA USA. RP Pisegna, JR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Bldg 115,Room 316,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jpisegna@ucla.edu NR 33 TC 1 Z9 1 U1 0 U2 0 PU PHARMACEUTICAL PRESS-ROYAL PHARMACEUTICAL SOC GREAT BRITIAN PI LONDON PA 1 LAMBETH HIGH ST, LONDON SE1 7JN, ENGLAND SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD DEC PY 2006 VL 58 IS 12 BP 1623 EP 1628 DI 10.1211/jpp.58.12.0009 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 126BY UT WOS:000243488400009 PM 17331326 ER PT J AU Bowers, HA Tomas, C Tengs, T Kempton, JW Lewitus, AJ Oldach, DW AF Bowers, Holly A. Tomas, Carmelo Tengs, Torstein Kempton, Jason W. Lewitus, Alan J. Oldach, David W. TI Raphidophyceae [Chadefaud ex Silva] systematics and rapid identification: Sequence analyses and real-time PCR assays SO JOURNAL OF PHYCOLOGY LA English DT Article DE Chattonella; Fibrocapsa; Heterosigma; PCR; Raphidophyceae; Taqman ID FIBROCAPSA-JAPONICA RAPHIDOPHYCEAE; INTERNAL TRANSCRIBED SPACER; ALGA HETEROSIGMA-AKASHIWO; RIBOSOMAL-RNA; RED TIDE; OLIGONUCLEOTIDE PROBES; PFIESTERIA-PISCICIDA; NUCLEOTIDE-SEQUENCES; GENETIC-VARIATION; DNA AB Species within the class Raphidophyceae were associated with fish kill events in Japanese, European, Canadian, and U. S. coastal waters. Fish mortality was attributable to gill damage with exposure to reactive oxygen species (peroxide, superoxide, and hydroxide radicals), neurotoxins, physical clogging, and hemolytic substances. Morphological identification of these organisms in environmental water samples is difficult, particularly when fixatives are used. Because of this difficulty and the continued global emergence of these species in coastal estuarine waters, we initiated the development and validation of a suite of real-time polymerase chain reaction (PCR) assays. Sequencing was used to generate complete data sets for nuclear encoded small-subunit ribosomal RNA (SSU rRNA; 18S); internal transcribed spacers 1 and 2, 5.8S; and plastid encoded SSU rRNA (16S) for confirmed raphidophyte cultures from various geographic locations. Sequences for several Chattonella species (C. antiqua, C. marina, C. ovata, C. subsalsa, and C. verruculosa), Heterosigma akashiwo, and Fibrocapsa japonica were generated and used to design rapid and specific PCR assays for several species including C. verruculosa Hara et Chihara, C. subsalsa Biecheler, the complex comprised of C. marina Hara et Chihara, C. antiqua Ono and C. ovata, H. akashiwo Ono, and F. japonica Toriumi et Takano using appropriate loci. With this comprehensive data set, we were also able to perform phylogenetic analyses to determine the relationship between these species. C1 Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. Univ N Carolina, Wilmington, NC 28409 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Marine Resources Res Inst, S Carolina Dept Nat Resources, Charleston, SC 29422 USA. Univ S Carolina, Belle W Baruch Inst Marine & Coastal Sci, Georgetown, SC 29442 USA. Marine Resources Res Inst, Hollings Marine Lab, S Carolina Dept Nat Resources, Charleston, SC 29412 USA. RP Oldach, DW (reprint author), Univ Maryland, Inst Human Virol, 725 W Lombard St, Baltimore, MD 21201 USA. EM oldach@umbi.umd.edu OI Oldach, David/0000-0002-8811-2562 FU NIEHS NIH HHS [P01 ES010594, P01 ES010594-06A1] NR 77 TC 57 Z9 57 U1 0 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3646 J9 J PHYCOL JI J. Phycol. PD DEC PY 2006 VL 42 IS 6 BP 1333 EP 1348 DI 10.1111/j.1529-8817.2006.00285.x PG 16 WC Plant Sciences; Marine & Freshwater Biology SC Plant Sciences; Marine & Freshwater Biology GA 116WR UT WOS:000242835000017 PM 20411032 ER PT J AU Wang, PW Sachs, GS Zarate, CA Marangell, LB Calabrese, JR Goldberg, JF Sagduyu, K Miyahara, S Ketter, TA AF Wang, Po W. Sachs, Gary S. Zarate, Carlos A. Marangell, Lauren B. Calabrese, Joseph R. Goldberg, Joseph F. Sagduyu, Kemal Miyahara, Sachiko Ketter, Terence A. TI Overweight and obesity in bipolar disorders SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE anticonvulsants; antipsychotics; bipolar disorders; mood stabilizers; obesity; overweight ID PREVALENCE C1 Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Baylor Coll Med, Houston, TX 77030 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Zucker Hillside Hosp, N Shore Long Isl Jewish Hlth Syst, Glen Oaks, NY USA. Univ Missouri, Kansas City, MO 64110 USA. Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Wang, PW (reprint author), Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, 401 Quarry Rd,Room 2117, Stanford, CA 94305 USA. EM wangp0@stanford.edu FU NIMH NIH HHS [N01MH80001] NR 6 TC 40 Z9 42 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD DEC PY 2006 VL 40 IS 8 BP 762 EP 764 DI 10.1016/j.jpyschires.2006.01.007 PG 3 WC Psychiatry SC Psychiatry GA 103VR UT WOS:000241915500010 PM 16516926 ER PT J AU Ang-Lee, K Oreskovich, MR Saxon, AJ Jaffe, C Meredith, C Ellis, MLK Malte, CA Knox, PC AF Ang-Lee, Kathleen Oreskovich, Michael R. Saxon, Andrew J. Jaffe, Craig Meredith, Charles Ellis, Mei Ling K. Malte, Carol A. Knox, Patricia C. TI Single dose of 24 milligrams of buprenorphine for heroin detoxification: An open-label study of five inpatients SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE buprenorphine; clinical trial; detoxification; opioid dependence; opioid withdrawal ID OPIOID DETOXIFICATION; OPIATE DETOXIFICATION; WITHDRAWAL SYMPTOMS; DOUBLE-BLIND; FOLLOW-UP; ADDICTS; CLONIDINE AB Previous studies indicate that buprenorphine has efficacy in medically supervised opioid withdrawal, but the optimal dosing for maximum tolerability and case of administration remains undetermined. Five heroin-dependent individuals entered this open-label study of inpatient detoxification with a single 24mg dose of buprenorphine. The mean Clinical Opiate Withdrawal Scale (COWS) score prior to buprenorphine administration was 17.6 (SD = 3.36). COWS scores declined significantly thereafter. There was one episode of precipitated withdrawal that resolved within four hours. Use of ancillary medications was minimal. This study suggests that a single high dose of buprenorphine can be used safely and effectively for inpatient detoxification. C1 Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Washington Phys Hlth Program, Seattle, WA USA. Univ Washington, Sch Med, Mental Illness Res Educ & Clin Ctr, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Recovery Ctr King Cty, Seattle, WA USA. VA Puget Sound Healthcare Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. RP Ang-Lee, K (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, 1959 NE Pacific St,Box 356560, Seattle, WA 98195 USA. EM kanglee@u.washington.edu NR 24 TC 1 Z9 1 U1 2 U2 3 PU HAIGHT-ASHBURY PUBL PI SAN FRANCISCO PA 409 CLAYTON ST, SAN FRANCISCO, CA 94117 USA SN 0279-1072 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD DEC PY 2006 VL 38 IS 4 BP 505 EP 512 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 139PA UT WOS:000244443100008 PM 17373566 ER PT J AU Johnson, JG Vanderwerker, LC Bornstein, RF Zhang, BH Prigerson, HG AF Johnson, Jeffrey G. Vanderwerker, Lauren C. Bornstein, Robert F. Zhang, Baohui Prigerson, Holly G. TI Development and validation of an instrument for the assessment of dependency among bereaved persons SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE dependency; bereavement; complicated grief; depression; risk assessment ID HEALTH-SERVICE USE; TRAUMATIC GRIEF; COMPLICATED GRIEF; INTERPERSONAL DEPENDENCY; PRELIMINARY EXPLORATIONS; PSYCHIATRIC-DISORDERS; CONJUGAL BEREAVEMENT; DYADIC ADJUSTMENT; PHYSICAL ILLNESS; MARITAL QUALITY AB Dependency among bereaved individuals has been hypothesized to be an important predictor of severe and enduring grief reactions. However, although there are a number of instruments that assess interpersonal dependency as a personality trait or style, no scales are available to assess bereavement-related dependency. Data from 170 widowed participants in a community-based longitudinal investigation, who had been bereaved for an average of 10.8 months, were used to investigate the reliability and validity of the Bereavement Dependency Scale (BDS), an instrument that was developed to assess dependency on the deceased among bereaved persons. Results indicated that the BDS demonstrated acceptable internal reliability and satisfactory convergent, discriminant, and construct validity. The BDS may be a clinically useful predictor of enduring and complicated grief reactions, major depressive disorder, and suicidality among recently bereaved individuals. C1 Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Gettysburg Coll, Dept Psychol, Gettysburg, PA 17325 USA. Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA 02115 USA. RP Prigerson, HG (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, 44 Binney St SW G440A, Boston, MA 02115 USA. EM holly_prigerson@dfci.harvard.edu NR 54 TC 10 Z9 10 U1 3 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD DEC PY 2006 VL 28 IS 4 BP 263 EP 272 DI 10.1007/s10862-005-9016-3 PG 10 WC Psychology, Clinical SC Psychology GA 102VO UT WOS:000241841600006 ER PT J AU Griffin, PW Mroczek, DK Spiro, A AF Griffin, Paul W. Mroczek, Daniel K. Spiro, Avron, III TI Variability in affective change among aging men: Longitudinal findings from the VA Normative Aging Study SO JOURNAL OF RESEARCH IN PERSONALITY LA English DT Article DE personality development; subjective well-being; emotional well-being; positive and negative affect; growth curve models ID NEGATIVE AFFECT; EMOTIONAL EXPERIENCE; POSITIVE PSYCHOLOGY; PERSONALITY-CHANGE; LIFE-SPAN; HAPPINESS; HEALTH; AGE; EXTRAVERSION; OPTIMIZATION AB We examined change in both positive and negative affect over ages 45 to 97 among 1534 men (mean age=69 years). Positive affect demonstrated a linear decline with age, while negative affect declined until approximately 70 years, and thereafter showed a gradual increase. Results indicated significant individual differences in rates of change for both positive and negative affect. We then examined whether personality, health, and work status might account for individual differences in levels and rates of change in affect. Higher extraversion was associated with higher levels of positive affect, but not with rate of change. Higher neuroticism predicted higher levels of negative affect, as well as an attenuated decline in middle-adulthood, and a steeper increase in later adulthood. Better health was associated with higher levels of positive affect and lower levels of negative, but was also found to predict less decline in negative affect. Work predicted lower levels of positive affect and higher levels of negative affect, as well as greater declines in positive affect. These findings indicate that individuals differ in the manner in which they change in affect over time. (c) 2005 Elsevier Inc. All rights reserved. C1 Pace Univ, Dept Psychol, Pleasantville, NY 10570 USA. Fordham Univ, Dept Psychol, Bronx, NY 10458 USA. Boston Univ, Sch Publ Hlth, Boston VA Healthcare Syst, Boston, MA 02215 USA. RP Griffin, PW (reprint author), Pace Univ, Dept Psychol, 861 Bedford Rd,32 Marks Hall, Pleasantville, NY 10570 USA. EM pgriffin@pace.edu NR 77 TC 30 Z9 30 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0092-6566 J9 J RES PERS JI J. Res. Pers. PD DEC PY 2006 VL 40 IS 6 BP 942 EP 965 DI 10.1016/j.jrp.2005.09.011 PG 24 WC Psychology, Social SC Psychology GA 116QD UT WOS:000242816500005 ER PT J AU Tsao, JCI Dobalian, A Wiens, BA Gylys, JA Evans, GD AF Tsao, JCI Dobalian, A Wiens, BA Gylys, JA Evans, GD TI Posttraumatic stress disorder in rural primary care: Improving care for mental health following bioterrorism SO JOURNAL OF RURAL HEALTH LA English DT Article ID MAJOR DEPRESSION; TERRORISM; DISASTER; SEEKING AB Context. Recent bioterrorist attacks have highlighted the critical need for health care organizations to prepare for future threats. Yet, relatively little attention has been paid to the mental health needs of rural communities in the wake of such events. A critical aspect of bioterrorism is emphasis on generating fear and uncertainty, thereby contributing to increased needs for mental health care, particularly for posttraumatic stress disorder, which has been estimated to occur in 28% of terrorism survivors. Purpose: Prior experience with natural disasters suggests that first responders typically focus on immediate medical trauma or injury, leaving rural communities to struggle with the burden of unmet mental health needs both in the immediate aftermath and over the longer term. The purpose of the present article is to draw attention to the greater need to educate rural primary care providers who will be the frontline providers of mental health services following bioterrorism, given the limited availability of tertiary mental health care in. rural communities. Methods: We reviewed the literature related to bioterrorist events and mental health with an emphasis on rural communities. Findings and Conclusions: Public health agencies should work with rural primary care providers and mental health professionals to develop educational interventions focused on posttraumatic stress disorder and other mental disorders, as well as algorithms for assessment, referral, and treatment of postevent psychological disorders and somatic complaints to ensure the availability, continuity, and delivery of quality mental health care for rural residents following bioterrorism and other public health emergencies. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Pediat Pain Program, Los Angeles, CA 90024 USA. VA Greater Los Angles Healthcare Syst, HSR&D Ctr Excellence Study Healthcare Provider Be, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. Univ Florida, Dept Clin & Hlth Psychol, Natl Rural Behav Hlth Ctr, Gainesville, FL USA. Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL USA. N Florida S Georgia Vet Hlth Syst, Psychol Serv, Gainesville, FL USA. RP Tsao, JCI (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Pediat Pain Program, 10940 Wilshire Blvd,Suite 1450, Los Angeles, CA 90024 USA. EM jtsao@mednet.ucla.edu FU AHRQ HHS [U01HS14355-01]; PHS HHS [R04RH01310-01] NR 36 TC 9 Z9 9 U1 2 U2 5 PU NATL RURAL HEALTH ASSOC PI KANSAS CITY PA ONE WEST ARMOUR BLVD, STE 301, KANSAS CITY, MO 64111 USA SN 0890-765X J9 J RURAL HEALTH JI J. Rural Health PD WIN PY 2006 VL 22 IS 1 BP 78 EP 82 DI 10.1111/j.1748-0361.2006.00006.x PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 007HH UT WOS:000234959100011 PM 16441340 ER PT J AU Fresco, DM Alloy, LB Reilly-Harrington, N AF Fresco, David M. Alloy, Lauren B. Reilly-Harrington, Noreen TI Association of attributional style for negative and positive events and the occurrence of life events with depression and anxiety SO JOURNAL OF SOCIAL AND CLINICAL PSYCHOLOGY LA English DT Article ID CAUSAL MEDIATION COMPONENTS; LOW COGNITIVE RISK; LEARNED HELPLESSNESS; DIATHESIS-STRESS; TRIPARTITE MODEL; PSYCHIATRIC-INPATIENTS; HOPELESSNESS THEORY; DISORDERS; VULNERABILITY; SPECIFICITY AB This study examined the relationship of attributional styles for negative and positive events with depression and anxiety. A sample of 239 college students underwent structured diagnostic interviews and completed self-report measures of attributional style and major life events at two time points separated by approximately four weeks. Using cross-sectional methodology, attributional styles for negative and positive events were compared across current diagnoses of unipolar depression and/or anxiety. A current mood disorder, when comorbid with an anxiety disorder, was associated with a tendency to see negative events as arising from internal, stable, and global causes. A depression diagnosis was distinguished from no depression diagnosis by the tendency to assign external, unstable, and specific causes for positive events. Using a prospective design, Time I attributional styles for negative and positive events were assessed as moderators of the relationships between negative and positive life events and levels of subsequent depression symptoms. The tendency to see negative events arising from internal, stable, and global causes and positive events arising from external, unstable, and specific causes, was associated with higher levels of clinician-assessed depression symptoms, particularly when confronted with negative life events or the absence of positive events. Findings indicate that attributional style for positive events contributes to our understanding of cognitive vulnerability to emotional disorders. C1 Kent State Univ, Dept Psychol, Kent, OH 44242 USA. Temple Univ, Philadelphia, PA 19122 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Fresco, DM (reprint author), Kent State Univ, Dept Psychol, 118 Kent Hall, Kent, OH 44242 USA. EM fresco@kent.edu RI Fresco, David/F-6522-2013; OI Fresco, David/0000-0001-6736-3912 NR 48 TC 21 Z9 25 U1 2 U2 6 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0736-7236 J9 J SOC CLIN PSYCHOL JI J. Soc. Clin. Psychol. PD DEC PY 2006 VL 25 IS 10 BP 1140 EP 1159 DI 10.1521/jscp.2006.25.10.1140 PG 20 WC Psychology, Clinical; Psychology, Social SC Psychology GA 121SK UT WOS:000243177100005 ER PT J AU Freeman, AL Derincek, A Beaubien, BP Buttermann, GR Lew, WD Wood, KB AF Freeman, Andrew L. Derincek, Alihan Beaubien, Brian P. Buttermann, Glenn R. Lew, William D. Wood, Kirkham B. TI In vitro comparison of bioresorbable and titanium anterior cervical plates in the immediate postoperative condition SO JOURNAL OF SPINAL DISORDERS & TECHNIQUES LA English DT Article DE bioresorbable; anterior cervical plate; ACDF; biomechanical ID GRAFT CONTAINMENT PLATE; BONE-MINERAL DENSITY; BIOMECHANICAL EVALUATION; INTERBODY FUSION; SPINE; FIXATION; SCREW; INSTRUMENTATION; CORPECTOMY; ARTIFACTS AB Bioresorbable plates have recently been used with anterior cervical discectomy and fusion (ACDF). Compared with metallic plates, bioresorbable plates provide segmental stabilization with minimal imaging artifact, eventual resorption, and increased load sharing. The objectives of the present study were to determine whether a bioresorbable plate can withstand simulated physiologic static and cyclic loading, to compare the reduction in flexibility provided by bioresorbable and titanium plates, and to quantify load sharing between the plate an spine with graft. Sixteen human cervical motion segments were tested to +/- 2.5 Nm in flexion-extension, lateral bending, a axial rotation. Range of motion (ROM) was measured (1) in the intact state, (2) with ACDF without plating, (3) after addition of either a bioresorbable or titanium plate, and (4) after 500 cycles of combined flexion-extension and axial torsion. Load sharing was evaluated by applying the same fixed rotation both without and with the plate, and was calculated as the moment resisted by the uninstrumented ACDF expressed as a percentage of the plated ACDF state. No plate failures or graft migration occurred during testing. Compared with the uninstrumented ACDF, bioresorbable plates reduced mean ROM by 49% in flexion-extension and 25% in lateral bending, with very little change in torsion. Titanium plates reduced uninstrumented ACDF ROM by 69% in flexion-extension, 45% in lateral bending, and 27% in torsion. Differences between bioresorbable and titanium plates were significant in flexion-extension and lateral bending. Cyclic loading did not significantly change ROM for either plate. More moment was shared in lateral bending by the spine/graft with bioresorbable plates (78%) compared with titanium plating (63%). Bioresorbable plates contained an intervertebral graft, provided some stabilization, remained intact throughout the simulated immediate postoperative loading, and shared more load with the graft and osteoligamentous spine than titanium plates. C1 Midwest Orthopaed Res Fdn, Orthopaed Biomech Lab, Minneapolis, MN 55415 USA. Midwest Spine Inst, Stillwater, MN USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Freeman, AL (reprint author), Midwest Orthopaed Res Fdn, Orthopaed Biomech Lab, 700 10th Ave S, Minneapolis, MN 55415 USA. EM afreeman@gustilocenter.com NR 31 TC 11 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1536-0652 J9 J SPINAL DISORD TECH JI J. Spinal Disord. Tech. PD DEC PY 2006 VL 19 IS 8 BP 577 EP 583 DI 10.1097/01.bsd.0000211228.81930.c9 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 115AZ UT WOS:000242708200007 PM 17146301 ER PT J AU Fotin, A Kirchhausen, T Grigorieff, N Harrison, SC Walz, T Cheng, YF AF Fotin, Alexander Kirchhausen, Tomas Grigorieff, Nikolaus Harrison, Stephen C. Walz, Thomas Cheng, Yifan TI Structure determination of clathrin coats to subnanometer resolution by single particle cryo-electron microscopy SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE clathrin coats; clathrin cages; cryo-clectron microscopy; single particle reconstruction; endocytosis ID ELECTRON CRYOMICROSCOPY; STABILIZATION; VISUALIZATION; ORGANIZATION; PROTEINS; VESICLES; COMPLEX; SYSTEM AB Clathrin triskelions can assemble into lattices of different shapes, sizes and symmetries. For many years, the structures of clathrin lattices have been studied by single particle cryo-electron microscopy, which probed the architecture of the D6 hexagonal barrel clathrin coat at the molecular level. By introducing additional image processing steps we have recently produced a density map for the D6 barrel clathrin coat at subnanometer resolution, enabling us to generate an atomic model for this lattice [Fotin, A., Cheng, Y., Sliz, P., Grigorieff, N., Harrison, S.C., Kirchhausen, T., Walz, T., 2004. Molecular model for a complete clathrin lattice from electron cryomicroscopy. Nature 432, 573-579]. We describe in detail here the image processing steps that we have added to produce a density map at this high resolution. These procedures should be generally applicable and may thus help determine the structures of other large protein assemblies to higher resolution by single particle cryo-electron microscopy. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Biophys Grad Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR, Biomed Res Inst, Boston, MA 02115 USA. Brandeis Univ, Howard Hughes Med Inst, Rosenstiel Basic Med Sci Res Ctr, Dept Biochem, Waltham, MA 02454 USA. Harvard Univ, Childrens Hosp, SchMed, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Cheng, YF (reprint author), Univ Calif San Francisco, Dept Biochem & Biophys, 600 16th St, San Francisco, CA 94143 USA. EM ycheng@biochem.ucsf.edu FU NIGMS NIH HHS [R01 GM036548, GM62580, R01 GM036548-25, GM36548, P01 GM062580, R01 GM075252] NR 31 TC 24 Z9 24 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD DEC PY 2006 VL 156 IS 3 BP 453 EP 460 DI 10.1016/j.jsb.2006.07.001 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 114EY UT WOS:000242650700007 PM 16908193 ER PT J AU Krupitsky, EM Zvartau, EE Masalov, DV Tsoy, MV Burakov, AM Egorova, VY Didenko, TY Romanova, TN Ivanova, EB Bespalov, AY Verbitskaya, EV Neznanov, NG Grinenko, AY O'Brien, CP Woody, GE AF Krupitsky, Evgeny M. Zvartau, Edwin E. Masalov, Dimitry V. Tsoy, Marina V. Burakov, Andrey M. Egorova, Valentina Y. Didenko, Tatyana Y. Romanova, Tatyana N. Ivanova, Eva B. Bespalov, Anton Y. Verbitskaya, Elena V. Neznanov, Nikolai G. Grinenko, Alexandr Y. O'Brien, Charles P. Woody, George E. TI Naltrexone with or without fluoxetine for preventing relapse to heroin addiction in St. Petersburg, Russia SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE naltrexone; heroin addiction; HIV ID CLINICAL-EXPERIENCE; ALCOHOL DEPENDENCE; LENINGRAD REGION; EFFICACY AB This randomized placebo-controlled trial tested the efficacy of oral naltrexone with or without fluoxetine for preventing relapse to heroin addiction and for reducing HIV risk, psychiatric symptoms, and outcome. All patients received drug counseling with parental or significant-other involvement to encourage adherence. Patients totaling 414 were approached, 343 gave informed consent, and 280 were randomized (mean age, 23.6 +/- 0.4 years). At 6 months, two to three times as many naltrexone patients as naltrexone placebo patients remained in treatment and had not relapsed, odds ratio (OR) = 3.5 (1.96-6.12), p < .0001. Overall, adding fluoxetine did not improve outcomes, OR = 1.35 (0.68-2.66), p = .49; however, women receiving naltrexone and fluoxetine showed a trend toward a statistically significant advantage when compared to women receiving naltrexone and fluoxetine placebo, OR = 2.4 (0.88-6.59), p = .08. HIV risk, psychiatric symptoms, and overall adjustment were markedly improved among all patients who remained on treatment and did not relapse, regardless of group assignment. More widespread use of naltrexone could be an important addition to addiction treatment and HIV prevention in Russia. (c) 2006 Elsevier Inc. All rights reserved. C1 St Petersburg State Pavlov Med Univ, St Petersburg Sci Res Ctr Addict & Psychopharmaco, St Petersburg, Russia. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Woody, GE (reprint author), Treatment Res Inst, 600 Publ Ledger Bldg,150 S Independence Mall, Philadelphia, PA 19106 USA. EM woody@tresearch.org RI Verbitskaya, Elena/N-3867-2015; Bespalov, Anton/R-6506-2016 OI Verbitskaya, Elena/0000-0003-3770-993X; FU NIDA NIH HHS [P60-DA051861, K05-DA17009, U10-DA13043] NR 24 TC 50 Z9 51 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD DEC PY 2006 VL 31 IS 4 BP 319 EP 328 DI 10.1016/j.jsat.2006.05.005 PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 105TU UT WOS:000242056000001 PM 17084785 ER PT J AU Jaklitsch, MT Herndon, JE Decamp, MM Richards, WG Kumar, P Krasna, MJ Green, MR Sugarbaker, DJ AF Jaklitsch, Michael T. Herndon, James E., II Decamp, Malcolm M., Jr. Richards, William G. Kumar, Parvesh Krasna, Mark J. Green, Mark R. Sugarbaker, David J. TI Nodal downstaging predicts survival following induction chemotherapy for stage IIIA (N2) non-small cell lung cancer in CALGB protocol #8935 SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE stage IIIA NSCLC; mediastinoscopy; N2 disease; neoadjuvant chemotherapy; adjuvant chemoradiotherapy; downstage; survival ID PREOPERATIVE CHEMOTHERAPY; PHASE-II; NEOADJUVANT CHEMOTHERAPY; SURGERY; TRIAL; CARCINOMA; THERAPY; CISPLATIN; SYSTEM; MEDIASTINOSCOPY AB Background and Objectives: CALGB 8935 was a phase II protocol for mediastinoscopically staged IIIA (N2) non-small cell lung cancer. Induction cisplatin/vinblastine chemotherapy was followed by surgical resection, adjuvant cisplatin/vinblastine, and radiotherapy. We now evaluate the prognosis of pathologic nodes. Methods: Failure-free survival was calculated from a landmark 3 months after resection to account for heterogeneity in adjuvant therapy. Results: Nine of 42 (21%) resected patients had no residual N2 disease. This subset of 9 had a median failure-free interval of 47.8 months from landmark, whereas the 33 patients (79%) with persistent N2 disease had a median failure-free survival of 8.2 months from landmark (P=0.01). Although 21/42 (50%) had an incomplete resection (positive highest resected node and/or margin), completeness of resection did not influence failure-free survival. There were 3 distant and no local recurrences among the N2 negative group, and 12 local recurrences among patients with residual N2 disease (P=0.041). Conclusions: These data suggest: (1) persistent N2 disease following induction chemotherapy is unfavorable; (2) patients downstaged to N2 negative may benefit from surgical resection; however, (3) 33% of N2 negative patients suffered disease relapse. C1 Brigham & Womens Hosp, Div Thorac Surg, Dana Farber Canc Inst, Boston, MA 02115 USA. CALGB Stat Ctr, Durham, NC USA. Beth Israel Deaconess Med Ctr, Thorac Surg Sect, Boston, MA 02215 USA. Univ So Calif, Dept Radiat Oncol, Los Angeles, CA USA. Univ Maryland, Sch Med, Div Thorac Surg, Baltimore, MD 21201 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Jaklitsch, MT (reprint author), Brigham & Womens Hosp, Div Thorac Surg, Dana Farber Canc Inst, 15 Francis St, Boston, MA 02115 USA. EM mjaklitsch@partners.org NR 29 TC 25 Z9 27 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD DEC 1 PY 2006 VL 94 IS 7 BP 599 EP 606 DI 10.1002/jso.20644 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 108ES UT WOS:000242223700010 PM 17039491 ER PT J AU Mukamal, KJ Alert, M Maclure, M Muller, JE Mittleman, MA AF Mukamal, Kenneth J. Alert, Marissa Maclure, Malcolm Muller, James E. Mittleman, Murray A. TI Tea consumption and infarct-related ventricular arrhythmias: The determinants of myocardial infarction onset study SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article ID CORONARY-HEART-DISEASE; ISCHEMIA-REPERFUSION INJURY; COFFEE CONSUMPTION; WAVE REFLECTIONS; CAFFEINE; RISK; FLAVONOIDS; INGESTION; MORTALITY; STIFFNESS AB Background: Tea consumption is associated with lower post-infarct mortality among patients with acute myocardial infarction. We previously found preliminary evidence that tea consumption may also be associated with lower risk of infarct-related ventricular arrhythmias. Methods: Between 1989 and 1996, 3882 subjects with AMI were enrolled in the two phases of the Determinants of Myocardial Infarction Onset Study a median of four days after admission. Trained interviewers assessed self-reported usual tea and coffee consumption during the year prior to infarction with a standardized questionnaire. We examined the prevalence of ventricular arrhythmias in the two phases of the study separately and together. Results: Among the 1912 patients with complete information in the first phase, the prevalence of ventricular arrhythmias was 16% among abstainers from tea, 11% among moderate tea drinkers (< 14 cups per week), and 14% among heavier tea drinkers (>= 14 cups per week) (p homogeneity = 0.03). Among the 1791 patients with comparable information in the second phase, the corresponding prevalence rates were 11%, 8%, and 8%, respectively (p = 0.06). When the phases were combined, the adjusted odds ratios for VA were 0.7 (95% confidence interval, 0.6-0.9) among moderate tea drinkers and 0.9 (95% confidence interval, 0.7-1.2) among heavier tea drinkers. The findings were of similar direction for both ventricular tachycardia and fibrillation. In contrast, there was higher risk of VA with increasing coffee intake (odds ratio for > 14 cups per week 1.3; 95% confidence interval, 1.0-1.7; p trend 0.02). Conclusions: Moderate tea intake is associated with a lower prevalence, and higher coffee intake with a slightly higher prevalence, of ventricular arrhythmias among patients hospitalized with acute myocardial infarction. If the association with tea intake is confirmed, it may suggest new approaches to prevention of ischemia-related arrhythmias. C1 Harvard Univ, Div Gen Med & Primary Care, Sch Publ Hlth, Beth Israel Deaconess Med Ctr,Massachusetts Gen, Brookline, MA 02446 USA. Harvard Univ, Div Cardiol, Sch Publ Hlth, Beth Israel Deaconess Med Ctr,Massachusetts Gen, Brookline, MA 02446 USA. Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Div Cardiol,Massachusetts Gen Hosp, Brookline, MA 02446 USA. RP Mukamal, KJ (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med, 1309 Beacon St,2nd Floor, Brookline, MA 02446 USA. EM kmukamal@bidmc.harvard.edu FU NCCIH NIH HHS [AT001899]; NHLBI NIH HHS [HL41016] NR 34 TC 6 Z9 6 U1 0 U2 1 PU AMER COLLEGE NUTRITION PI CLEARWATER PA 300 SOUTH DUNCAN AVENUE, STE 225, CLEARWATER, FL 33755 USA SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD DEC PY 2006 VL 25 IS 6 BP 472 EP 479 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 129PE UT WOS:000243740600002 PM 17229893 ER PT J AU Rumawas, ME McKeown, NM Rogers, G Meigs, JB Wilson, PWF Jacques, PF AF Rumawas, Marcella E. McKeown, Nicola M. Rogers, Gail Meigs, James B. Wilson, Peter W. F. Jacques, Paul F. TI Magnesium intake is related to improved insulin homeostasis in the framingham offspring cohort SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE observational; diet; magnesium; insulin; glucose; diabetes ID WHOLE-GRAIN INTAKE; FOOD FREQUENCY QUESTIONNAIRE; DEPENDENT DIABETES-MELLITUS; DIETARY MAGNESIUM; GLUCOSE-TOLERANCE; CARDIOVASCULAR-DISEASE; RESISTANCE ATHEROSCLEROSIS; METABOLIC SYNDROME; MODEL ASSESSMENT; US ADULTS AB Objective: Higher dietary intake of magnesium may protect against development of type 2 diabetes. The aim of this study was to examine the association between dietary magnesium intake and metabolic risk factors for diabetes. Methods: We examined cross-sectional associations between magnesium intake and fasting glucose and insulin, 2-hour post-challenge plasma glucose and, insulin, and insulin resistance assessed by the homeostasis model (HOMA-IR) in 1223 men and 1485 women without diabetes from the Framingham Offspring cohort. Magnesium intake was assessed by a food frequency questionnaire and magnesium intake was categorized into quintile categories. Geometric mean insulin, glucose, 2-hour post challenge plasma glucose and insulin concentrations and HOMA-IR were estimated across quintile categories of magnesium intake using Generalized Linear Models. Results: After adjustment for potential confounding factors, magnesium intake was inversely associated with fasting insulin (mean: 29.9 vs 26.7 mu U/mL in the lowest vs highest quintiles of magnesium intake; P trend < 0.001), post-glucose challenge plasma insulin (86.4 vs 72 mu U/mL; P trend < 0.001), and HOMA-IR (7.0 vs 6.2; P trend < 0.001). No significant association was found between magnesium intake and fasting glucose or 2-hour post challenge glucose. Conclusions: Improved insulin sensitivity may be one mechanism by which higher dietary magnesium intake may reduce the risk of developing type 2 DM. C1 Tufts Univ, Nutr Epidemiol Program, JM USDA, HNRC, Boston, MA 02111 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Med Univ S Carolina, Gen Clin Res Ctr, Charleston, SC 29425 USA. RP McKeown, NM (reprint author), Tufts Univ, Nutr Epidemiol Program, JM USDA, HNRC, 711 Washington St, Boston, MA 02111 USA. EM nicola.mckeown@tufts.edu FU NHLBI NIH HHS [N01-HC-25195] NR 54 TC 31 Z9 31 U1 1 U2 4 PU AMER COLLEGE NUTRITION PI CLEARWATER PA 300 SOUTH DUNCAN AVENUE, STE 225, CLEARWATER, FL 33755 USA SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD DEC PY 2006 VL 25 IS 6 BP 486 EP 492 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 129PE UT WOS:000243740600004 PM 17229895 ER PT J AU Hawn, MT Gray, SH Vick, CC Itani, KM Bishop, MJ Ordin, DL Houston, TK AF Hawn, Mary T. Gray, Stephen H. Vick, Catherine C. Itani, Kamal M. Bishop, Michael J. Ordin, Diana L. Houston, Thomas K. TI Timely administration of prophylactic antibiotics for major surgical procedures SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID OF-VETERANS-AFFAIRS; ANTIMICROBIAL PROPHYLAXIS; NOSOCOMIAL INFECTIONS; SITE INFECTIONS; WOUND INFECTION; PREVENTION; SURGERY; QUALITY; RISK; CARE AB BACKGROUND: Prophylactic antibiotics (PA) given within 60 minutes before surgical incision decrease risk of subsequent surgical site infection. Nationwide quality improvement initiatives have focused on improving the proportion of patients who receive timely prophylactic antibiotics. STUDY DESIGN: This is a cohort study of major surgical procedures performed in 108 Veterans Affairs hospitals between January and December 2005. Using data from the External Peer Review Program and the National Surgical Quality Improvement Program, we examined factors associated with timely PA administration. Univariate and multivariable analyses were performed. RESULTS: There were 8,137 major surgical procedures: cardiac (2,664), hip and knee arthroplasty (3,603), colon (1, 142), arterial vascular (606), and hysterectomy (122). Timely PA occurred in 76.2% of patients, 18.2% received them too early, and 5.4% received them too late. Early administration accounted for 79% of untimely PA. Differences in timeliness were seen by procedure type (68% to 87%; p < 0.0001), admission status (67% to 80%; p < 0.0001), and antibiotic class (65% to 89%; p < 0.0001). PA administration occurred in the operating room for 63.5% of patients. When PA administration occurred in the operating room, they were timely in 89% of patients, compared with 54% of patients where administration was outside the operating room (odds ratio, 7.74; 95% CI = 6.49 to 9.22). CONCLUSIONS: Early PA administration accounted for the majority of inappropriately timed PA. Efforts to improve performance on this measure should focus on administering antibiotics in the operating room. C1 Birmingham Vet Affairs Med Ctr, Deep S Ctr Effectiveness Res, Birmingham, AL 35294 USA. Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Hlth Serv & Outcomes Res Training Program, Birmingham, AL 35294 USA. VA Boston Hlth Care Syst, Dept Surg, W Roxbury, MA USA. Boston Univ, Dept Surg, Boston, MA 02215 USA. Univ Washington, Dept Vet Affairs, Off Patient Care Serv, Seattle, WA 98195 USA. Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. Dept Vet Affairs, Off Qual & Performance, Washington, DC USA. RP Hawn, MT (reprint author), Birmingham Vet Affairs Med Ctr, Deep S Ctr Effectiveness Res, KB 429,1530 3rd Ave S, Birmingham, AL 35294 USA. EM mhawn@uab.edu RI Houston, Thomas/F-2469-2013; OI Gray, Stephen/0000-0002-5702-7226 FU AHRQ HHS [5 T32 HS013852]; None [HS013852] NR 27 TC 19 Z9 19 U1 0 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 DEC PY 2006 VL 203 IS 6 BP 803 EP 811 DI 10.1016/j.jamcollsurg.2006.08.010 PG 9 WC Surgery SC Surgery GA 112ZQ UT WOS:000242567300003 PM 17116547 ER PT J AU Li, ZP Seeram, NP Carpenter, CL Thames, G Minutti, C Bowerman, S AF Li, Zhaoping Seeram, Navindra P. Carpenter, Catherine L. Thames, Gail Minutti, Chayo Bowerman, Susan TI Cranberry does not affect prothrombin time in male subjects on warfarin SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID JUICE; UROPATHOGENS; CAPACITY AB There have been case reports suggesting that cranberry beverages may interact with warfarin. To date, no research study has been conducted to examine the potential interaction of cranberry and warfarin. The current study is a randomized, placebo-controlled, double-blind, crossover study to investigate the effect of cranberry juice on prothrombin time as assessed by the international normalized ratio (INR). Seven subjects with atrial fibrillation on a stable dose of warfarin for 3 months were randomized to consume 250 mL of cranberry juice for 7 days, then placebo for 7 days, or vice versa. The washout period was 7 days. The prothrombin time/INR was measured at baseline, and on days 2, 4, 7, 10, 14, 16, 18, 21, and 24. Data were analyzed by the Student t test for paired values. The baseline INR was 2.28 +/- 0.54 for the cranberry group and 2.13 +/- 0.50 for the placebo group. For all test points, the INR did not change significantly from baseline. At day 7 on cranberry juice, the INR was 2.23 +/- 0.53 for cranberry first group and 2.16 +/- 0.40 for placebo first group. The mean differences between the cranberry and placebo groups were not statistically significant. Our results suggest no significant interaction between the daily consumption of 250 mL cranberry juice and warfarin. When counseling patients on dietary changes necessary during warfarin treatment, it does not seem necessary to eliminate daily cranberry juice consumption at amounts of 250 mL, but the INR should be followed up closely. C1 Univ Calif Los Angeles, Ctr Human Nutr, Geffen Sch Med, Div Clin Nutr, Los Angeles, CA 90095 USA. VA Great Los Angeles Hlth Care Syst, Div Hospitalist, Los Angeles, CA USA. Univ Calif Los Angeles, Ctr Human Nutr, Geffen Sch Med, Analyt Phytochem Lab, Los Angeles, CA USA. RP Li, ZP (reprint author), Univ Calif Los Angeles, Ctr Human Nutr, Geffen Sch Med, Div Clin Nutr, 900 Vet Ave,Room 12-217, Los Angeles, CA 90095 USA. EM zli@mednet.ucla.edu NR 13 TC 27 Z9 28 U1 0 U2 2 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD DEC PY 2006 VL 106 IS 12 BP 2057 EP 2061 DI 10.1016/j.jada.2006.09.012 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 112YH UT WOS:000242563600024 PM 17126638 ER PT J AU Kasinath, BS Mariappan, MM Sataranatarajan, K Lee, MJ Feliers, D AF Kasinath, Balakuntalam S. Mariappan, Meenalakshmi M. Sataranatarajan, Kavithalakshmi Lee, Myung Ja Feliers, Denis TI mRNA translation: Unexplored territory in renal science SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID ACTIVATED PROTEIN-KINASE; TUBULAR EPITHELIAL-CELLS; INITIATION-FACTOR EIF-4E; TUMOR-SUPPRESSOR GENE; RIBOSOME ENTRY SITES; ELONGATION FACTOR-II; P70 S6 KINASE; DIABETIC-NEPHROPATHY; MAMMALIAN TARGET; ENDOPLASMIC-RETICULUM AB Ambient protein levels are under coordinated control of transcription, mRNA translation, and degradation. Whereas transcription and degradation mechanisms have been studied in depth in renal science, the role of mRNA translation, the process by which peptide synthesis occurs according to the genetic code that is present in the mRNA, has not received much attention. mRNA translation occurs in three phases: Initiation, elongation, and termination. Each phase is controlled by unique eukaryotic factors. In the initiation phase, mRNA and ribosomal subunits are brought together. During the elongation phase, amino acids are added to the nascent peptide chain in accordance with codon sequences in the mRNA. During the termination phase, the fully synthesized peptide is released from the ribosome for posttranslational processing. Signaling pathways figure prominently in regulation of mRNA translation, particularly the phosphatidylinositol 3 kinase-Akt-mammalian target of rapamycin pathway, the AMP-activated protein kinase-tuberous sclerosis complex protein 1/tuberous sclerosis complex protein 2-Rheb pathway, and the extracellular signal-regulated kinase 1/2 type mitogen-activated protein kinase signaling pathway; there is significant cross-talk among these pathways. Regulation by mRNA translation is suggested when changes in mRNA and protein levels do not correlate and in the setting of rapid protein synthesis. Ongoing work suggests an important role for mRNA translation in compensatory renal growth, hypertrophy and extracellular matrix synthesis in diabetic nephropathy, growth factor synthesis by kidney cells, and glomerulonephritis. Considering that mRNA translation plays an important role in cell growth, development, malignancy, apoptosis, and response to stress, its study should provide novel insights in renal physiology and pathology. C1 Univ Texas, Hlth Sci Ctr, Dept Med,S Texas Vet Healthcare Syst, OBrien Kidney Res Ctr,Div Nephrol, San Antonio, TX 78229 USA. RP Kasinath, BS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med,S Texas Vet Healthcare Syst, OBrien Kidney Res Ctr,Div Nephrol, 7703 Floyd Curl Dr,MC7882, San Antonio, TX 78229 USA. EM Kasinath@uthscsa.edu NR 117 TC 43 Z9 46 U1 2 U2 4 PU AMERICAN SOCIETY 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 DEC PY 2006 VL 17 IS 12 BP 3281 EP 3292 DI 10.1681/ASN.2006050488 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 111WD UT WOS:000242485400006 PM 16959824 ER PT J AU Peralta, CA Ziv, E Katz, R Reiner, A Burchard, EG Fried, L Kwok, PY Psaty, B Shlipak, M AF Peralta, Carmen A. Ziv, Elad Katz, Ronit Reiner, Alex Burchard, Esteban Gonzalez Fried, Linda Kwok, Pui-Yan Psaty, Bruce Shlipak, Michael TI African ancestry, socioeconomic status, and kidney function in elderly African Americans: A genetic admixture analysis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; ADMIXED POPULATIONS; RACIAL-DIFFERENCES; MEXICAN-AMERICANS; PREVALENCE; HEALTH; MARKERS; RISK; ASSOCIATION; DIFFERENCE AB Kidney disease is a major public health problem in the United States that affects African Americans disproportionately. The relative contribution of environmental and genetic factors to the increased burden of kidney disease among African Americans is unknown. The associations of genetic African ancestry and socioeconomic status with kidney function were studied cross-sectionally and longitudinally among 736 community-dwelling African Americans who were aged > 65 yr and participating in the Cardiovascular Health Study. Genetic African ancestry was determined by genotyping 24 biallelic ancestry-informative markers and combining this information statistically to generate an estimate of ancestry for each individual. Kidney function was evaluated by cystatin C and estimated GFR (eGFR) using the Modification of Diet in Renal Disease equation. Longitudinal changes in serum creatinine and eGFR were estimated using baseline and follow-up values. In cross-sectional analyses, there was no association between genetic African ancestry and either measure of kidney function (P = 0.36 for cystatin C and 0.68 for eGFR). African ancestry was not associated with change in serum creatinine >= 0.05 mg/dl per yr (odds ratio [OR] 0.94; 95% confidence interval [CI] 0.83 to 1.06) or with change in eGFR >= 3 ml/min per 1.73 m(2) per yr (OR 1.02; 95% CI 0.92 to 1.13). In contrast, self reported African-American race was strongly associated with increased risk for kidney disease progression compared with white individuals for change in creatinine (OR 1.77; 95% CI 1.33 to 2.36) and for change in eGFR (OR 3.21; 95% CI 2.54 to 4.06). Among self-identified African Americans, low income (<$8000/yr) was strongly associated with prevalent kidney dysfunction by cystatin C > 1.29 g/dl (adjusted OR 2.7; 95% CI 1.0 to 7.5) or by eGFR < 60 ml/min per 1.73 m(2) (adjusted OR 3.2; 95% CI 1.1 to 9.4) compared with those with incomes >$35,000/yr. Alleles that are known to be present more frequently in the African ancestral group were not associated with kidney dysfunction or kidney disease progression. Rather, kidney dysfunction in elderly African Americans seems more attributable to differences in environmental and social factors. C1 Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Div Nephrol, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Human Genet, Dept Dermatol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA. San Francisco Gen Hosp, Lung Biol Ctr, San Francisco, CA 94110 USA. Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Cardivasc Hlth Res Unit, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. Univ Pittsburgh, Sch Med, Renal Sect, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. RP Shlipak, M (reprint author), VA Med Ctr, Gen Intern Med Sect 111A1, Dept Med, 4150 Clement St, San Francisco, CA 94124 USA. EM shlip@itsa.ucsf.edu RI Kwok, Pui-Yan/F-7725-2014 OI Kwok, Pui-Yan/0000-0002-5087-3059 FU NHLBI NIH HHS [N01-HC-85086, N01 HC-15103, N01-HC-35129, N01-HC-85079, R01-HL-073208-01] NR 28 TC 24 Z9 26 U1 0 U2 4 PU AMERICAN SOCIETY 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 DEC PY 2006 VL 17 IS 12 BP 3491 EP 3496 DI 10.1681/ASN.2006050493 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 111WD UT WOS:000242485400026 PM 17082243 ER PT J AU Jayadev, S Michelson, S Lipe, H Bird, T AF Jayadev, Suman Michelson, Sara Lipe, Hillary Bird, Thomas TI Cambodian founder effect for spinocerebellar ataxia type 3 (Machado-Joseph disease) SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE ataxia; spinocerebellar ataxia; Machado-Joseph disease; neurogenetics; Cambodia; trinucleotide repeats ID DOMINANT CEREBELLAR ATAXIAS; FREQUENCY-ANALYSIS; MOLECULAR CHARACTERIZATION; TRINUCLEOTIDE REPEATS; INDIAN POPULATION; FAMILIES; EXPANSION; FEATURES; PREVALENCE; HAPLOTYPE AB Four families from the same region of Cambodia immigrated to the Pacific Northwest of the United States. All four families have been discovered to have spinocerebellar ataxia type 3 (SCA 3; Machado-Joseph disease) with a similar clinical phenotype. CAG repeat expansions in the ATAN3 gene range from 72 to 77. Mean age of onset has varied from 19 to 44 years and mean age at death of 4 individuals has been 60 years. The prevalence of the various subtypes of SCA varies worldwide from country to country. Neurologists should be alert to the possibility of SCA 3 in Cambodian patients with unexplained cerebellar ataxia. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. RP Bird, T (reprint author), VA Med Ctr, S-182-GRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM tomnroz@u.washington.edu FU NIA NIH HHS [5T32AG000258-08] NR 24 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD DEC 1 PY 2006 VL 250 IS 1-2 BP 110 EP 113 DI 10.1016/j.jns.2006.08.006 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 111RI UT WOS:000242471500018 PM 17027034 ER PT J AU Cooper, GS Parks, CG Schur, PS Fraser, PA AF Cooper, Glinda S. Parks, Christine G. Schur, Peter S. Fraser, Patricia A. TI Occupational and environmental associations with antinuclear antibodies in a general population sample SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; AUTOANTIBODIES; RISK; CONCORDANCE; PREVALENCE; EXPOSURE; DISEASE; SILICA; TWINS AB Antinuclear antibodies are a hallmark feature of the autoimmune disease systemic lupus erythematosus, and can occur many years before onset of symptoms. The objective of this study was to examine the association between exposures and high-titer antinuclear antibodies in the general population (i.e., people who do not have lupus or other systemic autoimmune diseases). Serum was collected from 266 population-based controls who had been frequency-matched to the age and gender distribution of lupus cases in a 60-county study area in the southeastern United States. A detailed occupational history was collected using a structured interview; information was also collected on hair dye use. Antinuclear antibodies were assayed using HEp-2 cells as substrate. Logistic regression was used to estimate the odds ratio (OR) as a measure of association between exposures and high-titer antinuclear antibody levels, adjusting for age, gender, and race. High-titer antinuclear antibodies (>= 1:160) were observed in 21 subjects (8%). A twofold increased prevalence of high-titer antinuclear antibodies was seen with some occupational exposures (silica dust, pesticides, and sunlight), although none of these individual estimates were statistically significant. The association seen with use of hair dyes was weaker (OR 1.4). There was a suggestion of a dose response with a combined measure based on the summation of exposures (ORs of 1.7, 2.1, and 5.9 for 1, 2, and >= d 3 exposures). These data suggest that occupational exposures may influence the expression of antinuclear antibodies. Larger studies addressing these exposures may provide insights into the mechanisms by which various environmental factors affect the development of autoantibodies and the progression to clinical disease. C1 Natl Inst Environm Hlth Sci, Dept Hlth & Human Serv, NIH, Durham, NC USA. NIOSH, Morgantown, WV USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM gscooper1@gmail.com OI Parks, Christine/0000-0002-5734-3456 FU Intramural NIH HHS; NIEHS NIH HHS [ES10295, ES10457] NR 17 TC 15 Z9 17 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD DEC 1 PY 2006 VL 69 IS 23 BP 2063 EP 2069 DI 10.1080/15287390600746165 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 097HV UT WOS:000241438900001 PM 17060093 ER PT J AU Ahuja, N Ostomel, TA Rhee, P Stucky, GD Conran, R Chen, Z Al-Mubarak, GA Velmahos, G deMoya, M Alam, HB AF Ahuja, Naresh Ostomel, Todd A. Rhee, Peter Stucky, Galen D. Conran, Richard Chen, Zheng Al-Mubarak, Ghada A. Velmahos, George deMoya, Marc Alam, Hasan B. TI Testing of modified zeolite hemostatic dressings in a large animal model of lethal groin injury SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Western-Trauma-Association CY FEB 26-MAR 03, 2006 CL Big Sky, MT SP Western Trauma Assoc DE hemostatic dressing; battlefield injury; uncontrolled hemorrhage; chitosan; zeolite; swine; femoral vessels; groin; extremity; bandages ID OPERATION-IRAQI-FREEDOM; BLOOD-LOSS; HEMORRHAGE CONTROL; VENOUS HEMORRHAGE; HEPATIC-INJURY; LIVER-INJURY; SWINE; AGENTS; BATTLEFIELD; EXPERIENCE AB Background: We have previously identified a granular zeolite hemostat (ZH) as an effective agent for control of severe bleeding, and it is currently being used by the US troops in the battlefield. ZH causes an exothermic reaction on application, which theoretically can be decreased by altering its chemical composition or changing its physical properties. However, the effect of these alterations on the hemostatic efficacy is unknown. We tested modified zeolites and a chitosan based dressing against controls in a swine model of battlefield injury. Methods: A complex groin injury was created in 60 swine (40-55 kg). This included semi-transection of the proximal thigh (level of inguinal ligament), and complete division of the femoral artery and vein. After 3 minutes, the animals were assigned to (1) no dressing (ND), (2) standard dressing (SD), (3-5) SD + chemically modified ZHs, where calcium was substituted with sodium (Na), barium (Ba), or silver (Ag), respectively, (6) SD + physically modified ZH, where "beads" were packaged in a fabric bag, (7) SD + chitosan based dressing (CD). Resuscitation was started 15 minutes after application of dressing (500 mL of 6% hetastarch over 30 minutes). Survival for 180 minutes was the primary endpoint for this study. In addition, blood loss, wound temperatures, and histologic tissue damage were recorded. Results: Mortality in the group that was treated with the application of bagged ZH was 10% versus 100 % in the no dressing group and 50% in the SD group (p < 0.05 vs. ND and SD groups). The Na ZH group had a mortality rate of 43 %, whereas application of Ba and Ag substituted zeolites, and CD were associated with a mortality rate of 25%. Ionic substitution of zeolite decreased the in vivo temperature peak by 5 to 10 degrees C. No histologic evidence of tissue necrosis was noted in this experiment. Conclusions: The use of zeolite hemostat can control hemorrhage and dramatically reduce mortality from a lethal groin wound. Modifications of zeolite hemostat can decrease the exothermic reaction and attenuate tissue damage. C1 Harvard Univ, Div Trauma Emergency Surg & Surg Crit Care, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD USA. Washington Hosp Ctr, Washington, DC 20010 USA. Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA. Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. RP Alam, HB (reprint author), Harvard Univ, Div Trauma Emergency Surg & Surg Crit Care, Sch Med, Massachusetts Gen Hosp, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org NR 28 TC 55 Z9 55 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD DEC PY 2006 VL 61 IS 6 BP 1312 EP 1320 DI 10.1097/01.ta.0000240597.42420.8f PG 9 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 119CI UT WOS:000242989400004 PM 17159671 ER PT J AU Alam, HB Casas, F Chen, Z Smith, WA Reeves, A Velmahos, G de Moya, M Rhee, P AF Alam, Hasan B. Casas, Fernando Chen, Zhang Smith, William A. Reeves, Andrew Velmahos, George de Moya, Marc Rhee, Peter TI Development and testing of portable pump for the induction of profound hypothermia in a swine model of lethal vascular injuries SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Western-Trauma-Association CY FEB 26-MAR 03, 2006 CL Big Sky, MT SP Western Trauma Assoc DE bypass; lethal hemorrhage; portable; pump; hypothermia; shock; vascular injuries; survival ID OPERATION-IRAQI-FREEDOM; TRAUMA DEATHS; ARREST; SYSTEM; EPIDEMIOLOGY; EXPERIENCE; HEMORRHAGE; IMPACT; CARE AB Rapid induction of a profound hypothermic state (suspended animation) can maintain viability of key organs during repair of lethal injuries. Conventional cardiopulmonary bypass equipment (roller pump) used to induce and reverse hypothermia is expensive, bulky, requires standard electricity, and is not transportable. Development of a small, portable, battery operated, disposable, pump can logistically facilitate induction and maintenance of hypothermia. In this experiment, a portable prototype pump was tested and its performance was compared with the regular roller pump in a swine model of lethal vascular injuries. Methods. Uncontrolled hemorrhage was induced in 16 swine (80-120 lbs) by creating an iliac artery and vein injury (nonlethal). After 30 minutes of pulseless shock, the descending thoracic aorta was lacerated (lethal injury). Through a left thoracotomy approach, a catheter was placed in the aorta and cold organ preservation solution was infused to rapidly (2 degrees C/min) induce hypothermia (10 degrees C) for 60 minutes. The performance of the prototype pump was initially tested in a nonsurvival experiment (four animals). Then, 12 animals were cooled either with (n = 6/group) (1) conventional roller pump or (2) small prototype pump. The injuries were repaired during hypothermic arrest and the animals were re-warmed (0.5 degrees C/min). Whole blood was infused during resuscitation on cardiopulmonary bypass. Surviving animals were closely monitored for 3 weeks for postoperative complications, neurologic deficits, and organ dysfunction. Results. The flow rates and the time needed to induce and reverse profound hypothermia were no different between the prototype and the conventional roller pumps. Three-week survival rates were 83% in both groups. Only a transient increase in liver enzymes, and markers of cellular injury (creatine kinase, lactate dehydrogenase) was noted (no meaningful difference between groups), with no long-term organ dysfunction. Conclusions. In this large animal model of lethal vascular injuries, a portable, battery operated, disposable, rotary pump performed as well as the conventional roller pump. The logistical advantages of this system make it an attractive choice for inducing hypothermia in emergency departments and austere settings, and for maintaining hypothermia during transport. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. Cleveland Clin Fdn, Lerner Res Inst, Dept Biomed Engn, Cleveland, OH 44195 USA. RP Alam, HB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org FU NHLBI NIH HHS [R01 HL71698, K01 HL 073076] NR 22 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD DEC PY 2006 VL 61 IS 6 BP 1321 EP 1329 DI 10.1097/01.ta.0000244414.76523.d8 PG 9 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 119CI UT WOS:000242989400005 PM 17159672 ER PT J AU Sonis, J Triffleman, E King, DW King, LA AF Sonis, Jeffrey Triffleman, Ellsa King, Daniel W. King, Lynda A. TI Special section: Innovations in trauma research methods, 2005 SO JOURNAL OF TRAUMATIC STRESS LA English DT Editorial Material C1 Univ N Carolina, Sch Med, Dept Social Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Family Med, Chapel Hill, NC 27599 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Boston Univ, Dept Psychiat, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Sonis, J (reprint author), Univ N Carolina, Sch Med, Dept Social Med, CB 7240,Wing D, Chapel Hill, NC 27599 USA. EM jsonis@med.unc.edu FU NIMH NIH HHS [5 R13 MH068798-04] NR 1 TC 1 Z9 1 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2006 VL 19 IS 6 BP 755 EP 756 DI 10.1002/jts.20189 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 121VD UT WOS:000243184200001 PM 17195974 ER PT J AU King, LA King, DW McArdle, JJ Saxe, GN Doron-LaMarca, S Orazem, RI AF King, Lynda A. King, Daniel W. McArdle, John J. Saxe, Glenn N. Doron-LaMarca, Susan Orazem, Robert I. TI Latent difference score approach to longitudinal trauma research SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT 2nd Annual Conference on Innavations in Trauma Research Methods CY NOV 16-17, 2005 CL Toronto, CANADA ID POSTTRAUMATIC-STRESS-DISORDER; GAIN SCORES; VIETNAM VETERANS; RISK-FACTORS; SYMPTOMS; CHILDREN; BURNS; PTSD; RELIABILITY; RECOVERY AB In this article, the authors introduce a latent difference score (LDS) approach to analyzing longitudinal data in trauma research. The LDS approach accounts for internal sources of change in an outcome variable, including the inflence of prior status on subsequent levels of that variable and the tendency for individuals to experience natural change (e.g., a natural decrease in posttraumatic stress disorder [PTSD] symptoms over time). Under traditional model assumptions, the LDSs are maximally reliable and therefore less likely to introduce biases into model testing. The authors illustrate the method using a sample of children who experienced significant burns or other injuries to examine potential influences (i.e., age of child-adolescent at time of trauma and ongoing family strains) on PTSD symptom severity over time. C1 Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA USA. Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. RP King, LA (reprint author), Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA. EM lking@bu.edu OI Saxe, Glenn/0000-0002-4756-1169 FU NIMH NIH HHS [R01MH68626, R01MH57370] NR 49 TC 28 Z9 28 U1 2 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2006 VL 19 IS 6 BP 771 EP 785 DI 10.1002/jts.20188 PG 15 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 121VD UT WOS:000243184200003 PM 17195976 ER PT J AU Hoch, JS Smith, MW AF Hoch, Jeffrey S. Smith, Mark W. TI A guide to economic evaluation: Methods for cost-effectiveness analysis of person-level data SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT 2nd Annual Conference on Innavations in Trauma Research Methods CY NOV 16-17, 2005 CL Toronto, CANADA ID EFFECTIVENESS ACCEPTABILITY CURVES; POSTTRAUMATIC-STRESS-DISORDER; ADMINISTERED PTSD SCALE; MEDICAL LITERATURE; CLINICAL-PRACTICE; USERS GUIDES; HEALTH-CARE; TRIAL; AUSTRALIA; FRAMEWORK AB The authors introduce economic evaluation with particular attention to cost-effectiveness analysis. They begin by establishing why health care decisions should be guided by economics. They then explore different types of economic evaluations. To illustrate how to conduct and evaluate a cost-effectiveness analysis, a hypothetical study about the treatment of posttraumatic stress disorder with psychotherapy versus pharmacotherapy is considered. The authors conclude with recommendations for increasing the strength and relevance of economic evaluations. C1 Ctr Res Inner City Hlth, Toronto, ON M5B 1W8, Canada. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Univ Toronto, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada. US Dept Vet Affairs, Hlth Econ Resource Ctr, Menlo Pk, CA USA. Stanford Univ, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. RP Hoch, JS (reprint author), Ctr Res Inner City Hlth, 30 Bond St, Toronto, ON M5B 1W8, Canada. EM jeffrey.hoch@utoronto.ca RI Smith, Mark/G-1522-2012; OI Smith, Mark/0000-0002-4582-9088; Hoch, Jeffrey/0000-0002-4880-4281 NR 42 TC 16 Z9 18 U1 4 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2006 VL 19 IS 6 BP 787 EP 797 DI 10.1002/jts.20190 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 121VD UT WOS:000243184200004 PM 17195977 ER PT J AU Gutner, CA Rizvi, SL Monson, CM Resick, PA AF Gutner, Cassidy A. Rizvi, Shireen L. Monson, Candice M. Resick, Patricia A. TI Changes in coping strategies, relationship to the perpetrator, and posttraumatic distress in female crime victims SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID ADMINISTERED PTSD SCALE; CHILDHOOD SEXUAL-ABUSE; STRESS-DISORDER; DOMESTIC VIOLENCE; NONSEXUAL ASSAULT; RAPE VICTIMS; SYMPTOMS; SURVIVORS; SYMPTOMATOLOGY; INFORMATION AB This study examined the relationship between changes in coping and posttraumatic stress disorder (PTSD) symptomatology among recent female rape and physical assault victims as a function of assault Ope and perpetrator status. Participants were assessed within I month after trauma and again at 3 months after trauma. Results indicate that changes in coping strategies over time are associated with the severity of the PTSD symptoms. Assault type was not a significant factor in the association between changes in coping and PTSD, but perpetrator status was. Victims with known perpetrators, who coped more by social withdrawal, bad more severe PTSD symptoms over time. The importance of examining the dynamic nature of coping in the development of PTSD is discussed. C1 VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Resick, PA (reprint author), VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, 150 S Huntington Ave 116B, Boston, MA 02130 USA. EM Patricia.Resick@med.va.gov FU NIMH NIH HHS [R01 MH046992, R01 MH046992-05, R01-MH6992] NR 36 TC 35 Z9 35 U1 3 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2006 VL 19 IS 6 BP 813 EP 823 DI 10.1002/jts.20158 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 121VD UT WOS:000243184200006 PM 17195978 ER PT J AU Schumm, JA Briggs-Phillips, M Hobfoll, SE AF Schumm, Jeremiah A. Briggs-Phillips, Melissa Hobfoll, Stevan E. TI Cumulative interpersonal traumas and social support as risk and resiliency factors in predicting PTSD and depression among inner-city women SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; NATIONAL SAMPLE; ASSAULT; REVICTIMIZATION; IMPACT; RELIABILITY; DYSFUNCTION; PREVALENCE; VARIABLES AB This study represents one of the largest examinations of how child abuse, adult rape, and social support impact inner-city women (N = 777). Using retrospective self-report, the effects of interpersonal trauma were shown to be cumulative such that women who experienced either child abuse or adult rape were 6 times more likely to have probable postraumatic Stress disorder (PTSD), whereas women who experienced both child abuse and rape were 17 times more likely to have probable PTSD. High social support predicted lower PTSD severity for women who experienced both child abuse and adult rape, but not for women who reported one or none of these traumas. Results suggest that social support, when left intact, might buffer the cumulative impact of child and adult interpersonal traumas. C1 Harvard Univ, Sch Med, Brockton, MA 02301 USA. VA Boston Healthcare Syst, Brockton, MA 02301 USA. Ohio State Univ, Coll Med & Publ Hlth, Columbus, OH 43210 USA. Kent State Univ, Ctr Treatment & Study Traumat Stress, Kent, OH 44242 USA. Summa Hlth Syst, Kent, OH USA. RP Schumm, JA (reprint author), Harvard Univ, Sch Med, VAMC 116B-1,940 Belmont St, Brockton, MA 02301 USA. EM jeremiah_schumm@hms.harvard.edu FU NIMH NIH HHS [2 R01 MH45669-09A2] NR 46 TC 96 Z9 96 U1 4 U2 27 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2006 VL 19 IS 6 BP 825 EP 836 DI 10.1002/jts.20159 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 121VD UT WOS:000243184200007 PM 17195981 ER PT J AU Fitzsimons, NJ Presti, JC Kane, CJ Terris, MK Aronson, WJ Amling, CL Freedland, SJ AF Fitzsimons, Nicholas J. Presti, Joseph C., Jr. Kane, Christopher J. Terris, Martha K. Aronson, William J. Amling, Christopher L. Freedland, Stephen J. CA Shared Equal Access Regional Canc TI Is biopsy Gleason score independently associated with biochemical progression following radical prostatectomy after adjusting for pathological Gleason score? SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; prostatectomy; biopsy; disease progression ID CANCER-SPECIFIC MORTALITY; DISEASE RECURRENCE; RADIATION-THERAPY; RISK; SPECIMENS; GRADE; NOMOGRAMS AB Purpose: Biopsy Gleason score is known to be associated with prostate specific antigen failure following radical prostatectomy. However, it is unclear whether it remains associated with outcome after surgery when the pathological Gleason score is known. Materials and Methods: We determined the association between biopsy Gleason score and biochemical progression after correcting for preoperative and postoperative characteristics, including pathological Gleason score, in 1,931 men treated with radical prostatectomy between 1988 and 2005 in the Shared Equal Access Regional Cancer Hospital Database Study Group database. Gleason score was examined as a categorical variable of 2 to 6, 3 + 4 and 4 + 3 or greater. Results: Higher biopsy Gleason scores were positively associated with extracapsular extension (p < 0.001), positive surgical margins (p < 0.001), seminal vesicle invasion (p < 0.001), positive lymph nodes (p < 0.001) and biochemical progression (log rank p < 0.001). After adjusting for only preoperative characteristics biopsy Gleason 3 + 4 and 4 + 3 or greater were associated with increased risk of biochemical progression compared to biopsy Gleason 6 or less (p = 0.001 and. < 0.001, respectively). After further adjusting for multiple pathological characteristics, including pathological Gleason score, the association between higher biopsy Gleason score and progression was little changed, in that men with biopsy Gleason 3 + 4 and 4 + 3 or greater were significantly more likely to experience progression (p = 0.001 and < 0.001, respectively). Furthermore, when stratified by pathological Gleason score, higher biopsy Gleason scores were associated with an increased risk of biochemical progression in each pathological Gleason score category (log rank p <= 0.007). Conclusions: Biopsy Gleason score remained strongly associated with progression even when the pathological Gleason score was known and controlled for. If confirmed at other centers, incorporation of biopsy Gleason score into postoperative C1 Duke Univ, Sch Med, Med Ctr, Div Urol Surg,Dept Surg, Durham, NC 27710 USA. Duke Univ, Sch Med, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Sch Med, Duke Prostate Ctr, Durham, NC 27710 USA. Vet Adm Med Ctr, Dept Surg, Durham, NC USA. Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. Vet Adm Med Ctr, Dept Surg, Urol Sect, Palo Alto, CA 94304 USA. Vet Adm Med Ctr San Francisco, Dept Surg, Urol Sect, San Francisco, CA USA. Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90024 USA. Vet Adm Greater Los Angeles Healthcare Syst, Dept Surg, Urol Sect, Los Angeles, CA USA. USN, Med Ctr, Dept Urol, San Diego, CA 92152 USA. Med Coll Georgia, Vet Adm Med Ctr Augusta, Dept Surg, Augusta, GA 30912 USA. Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. Univ Alabama, Dept Urol, Birmingham, AL 35233 USA. RP Fitzsimons, NJ (reprint author), Duke Univ, Sch Med, Med Ctr, Div Urol Surg,Dept Surg, Box 3707, Durham, NC 27710 USA. EM nicholas.fitzsimons@duke.edu OI Terris, Martha/0000-0002-3843-7270 FU NCI NIH HHS [P50 CA 92131-01A1, R01 CA 100938] NR 20 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 DEC PY 2006 VL 176 IS 6 BP 2453 EP 2458 DI 10.1016/j.juro.2006.08.014 PN 1 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 105KM UT WOS:000242028800031 PM 17085127 ER PT J AU D'Amico, AV Hui-Chen, M Renshaw, AA Sussman, B Roehl, KA Catalona, WJ AF D'Amico, Anthony V. Hui-Chen, Ming Renshaw, Andrew A. Sussman, Brenda Roehl, Kimberly A. Catalona, William J. TI Identifying men diagnosed with clinically localized prostate cancer who are at high risk for death from prostate cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; risk; mortality; prostate-specific antigen ID RADICAL PROSTATECTOMY; RADIATION-THERAPY; ANDROGEN SUPPRESSION; ANTIGEN LEVELS; SURVIVAL; ERA; MITOXANTRONE; RADIOTHERAPY; PREDNISONE; DOCETAXEL AB Purpose: We identified factors at diagnosis that are significantly associated with time to prostate cancer specific mortality following radical prostatectomy or external beam radiation therapy. Materials and Methods: The study cohort included 1,453 men treated with radical prostatectomy (1,095) or external beam radiation therapy (358) for localized prostate cancer between 1989 and 2002. Cox regression multivariate analysis was used to evaluate whether prostate specific antigen, prostate specific antigen velocity, biopsy Gleason score and clinical tumor category at diagnosis were significantly associated with time to prostate cancer specific mortality following radical prostatectomy or external beam radiation therapy. Results: In addition to increasing prostate specific antigen (p <= 0.04) and biopsy Gleason score 8 to 10 disease (p <= 0.02), prostate specific antigen velocity more than 2 ng/ml yearly was significantly associated with shorter time to prostate cancer specific mortality in patients treated with radical prostatectomy (adjusted HR 12, 95% CI 3 to 54) and external beam radiation therapy (adjusted HR 12, 95% CI 3 to 54) compared with that in men with prostate specific antigen velocity 2 ng/ml yearly or less (p <= 0.001). Despite low risk disease 7-year estimates of prostate cancer specific mortality were 5% to 19% in patients in whom prostate specific antigen increased by more than 2 ng/ml during the year before diagnosis compared with less than 1% in those with a prostate specific antigen increase of 2 ng/ml or less. Conclusions: Despite prostate specific antigen level less than 10 ng/ml and Gleason score 6 cancer a prostate specific antigen increase of more than 2 ng/ml during the year before diagnosis places a man at high risk for prostate cancer death following radical prostatectomy or external beam radiation therapy. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. NW Feinberg Sch Med, Dept Urol, Chicago, IL USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. EM adamico@lroc.harvard.edu NR 20 TC 32 Z9 33 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 DEC PY 2006 VL 176 IS 6 BP S11 EP S15 DI 10.1016/j.juro.2006.06.075 PN 2 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 105KQ UT WOS:000242029200002 PM 17084157 ER PT J AU Visser, JJ Bosch, JL Hunink, MGM van Dijk, LC Hendriks, JM Poldermans, D van Sambeek, MRHM AF Visser, Jacob J. Bosch, Johanna L. Hunink, M. G. Myriam van Dijk, Lukas C. Hendriks, Johanna M. Poldermans, Don van Sambeek, Marc R. H. M. TI Endovascular repair versus open surgery in patients with ruptured abdominal aortic aneurysms: Clinical outcomes with 1-year follow-up SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the Society-for-Vascular-Surgery CY JUN 03, 2006 CL Philadelphia, PA SP Soc Vasc Surg ID PERIOPERATIVE MORTALITY; PREDICTION; FEASIBILITY; ENDOLEAKS; EUROSTAR; IMPACT AB Objective: To compare the clinical outcomes of treatment after endovascular repair and open surgery in patients with ruptured infrarenal abdominal aortic aneurysms (AAAs), including 1-year follow-up. Methods: All consecutive conscious patients with ruptured infrarenal AAAs who presented to our tertiary care teaching hospital between January 1, 2001, and December 31, 2005, were included in this study (n = 55). Twenty-six patients underwent endovascular repair, and 29 patients underwent open surgery. Patients who were hemodynamically too unstable to undergo a computed tomography angiography scan were excluded. Outcomes evaluated were intraoperative mortality, 30-day mortality, systemic complications, complications necessitating surgical intervention, and mortality and complications during 1-year follow-up. The statistical tests we used were the Student t test, chi(2) test, Fisher exact test, and Mann-Whitney U test (two sided; alpha = .05). Results. Thirty-day mortality was 8 (31%) of 26 patients who underwent endovascular repair and 9 (31%) of 29 patients who underwent open surgery (P =.98). Systemic complications and complications necessitating surgical intervention during the initial hospital stay were similar in both treatment groups (8/26 [31%] and 5/26 [19%] for endovascular repair, respectively, and 9/29 [31%] and 8/29 [28%] for open surgery, respectively; P > .40). During 1-year follow-up, two patients initially treated with enclovascular repair died as a result of non-aneurysm-related causes; no death occurred in the open surgery group. Complications during 1-year follow-up were 1 (5%) of 20 for endovascular repair and 4 (16%) of 25 for open surgery (P = .36). Conclusions. On the basis of our study with a highly selected population, the mortality and complication rates after endovascular repair may be similar compared with those after open surgery in patients treated for ruptured infrarenal AAAs. C1 Erasmus MC, Dept Surg, NL-3015 GD Rotterdam, Netherlands. Erasmus MC, Dept Epidemiol & Biostat, NL-3015 GD Rotterdam, Netherlands. Erasmus MC, Dept Radiol, NL-3015 GD Rotterdam, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP van Sambeek, MRHM (reprint author), Erasmus MC, Dept Surg, Room Hs-302,Dr Molewaterpl 40, NL-3015 GD Rotterdam, Netherlands. EM m.r.h.m.vansambeek@erasmusmc.nl NR 31 TC 48 Z9 50 U1 2 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD DEC PY 2006 VL 44 IS 6 BP 1148 EP 1155 DI 10.1016/j.jvs.2006.08.018 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 112YP UT WOS:000242564400002 PM 17145414 ER PT J AU Stone, DH Brewster, DC Kwolek, CJ LaMuraglia, GM Conrad, MF Chung, TK Cambria, RP AF Stone, David H. Brewster, David C. Kwolek, Christopher J. LaMuraglia, Glenn M. Conrad, Mark F. Chung, Thomas K. Cambria, Richard P. TI Stent-graft versus open-surgical repair of the thoracic aorta: Mid-term results SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 17, 2005 CL Stowe, VT SP New Enland Soc Vasc Surg ID THORACOABDOMINAL ANEURYSM REPAIR; ENDOVASCULAR TREATMENT; SINGLE-CENTER; EXPERIENCE; ENDOPROSTHESIS; DISSECTIONS; EXCLUSION; DISEASES; RISK AB Objective: Pivotal and comparative trial data are emerging for stent graft (SG) vs open repair of the thoracic aorta. We reviewed procedure-related perioperative morbidity, mortality, and mid-term outcomes in a contemporary series of patients treated with SG of the thoracic aorta. The data were compared with those of a patient cohort concurrently treated with open surgical repair confined to the descending aorta. Methods. A review of patients undergoing SG procedures and open surgery of the thoracic aorta from January 1, 1996, to November 30, 2005, was performed from a prospectively compiled database. Study end points included perioperative complications, late survival, freedom from reinterventions, and graft-related complications. Multivariate methods were used to assess variables potentially associated with study end points; late outcomes were compared with actuarial methods. Results. In 105 patients (mean age, 70 years; 66 male [62.9%]) SG repairs were done for 68 degenerative aneurysms (64.7%), 12 penetrating ulcers (11.4%), 15 pseudoaneurysms (14.3%), 9 traumatic tears (8.6%), and 1 acute dissection (0.9%). Mean follow-up was 22 months (range, 0 to 101 months). Eighty-nine (84.8%) SG patients were asymptomatic at presentation and underwent elective repair, whereas 16 (15.2%) presented with acute conditions and underwent urgent repair. Perioperative mortality was 7.6% (8/105), and actuarial survival at 48 months was 54% +/- 7%. The perioperative mortality rate among SG patients treated for degenerative pathology was 10.4% (8/77). Seven (6.7%) of 105 patients experienced spinal cord ischemic complications, including 2 patients with transient paraparesis that resolved by the time of discharge. Reinterventions were performed in 10.5% of patients (11/105), with freedom from reintervention approaching 81% by 48 months. Over the same interval, 93 patients were treated with open-surgical repair for descending thoracic aneurysm (anastomosis cephalad to the celiac axis). Perioperative mortality in the open cohort was 15.1% (14/93; P = .09 vs SG repair), and the 48-month actuarial survival was 64% +/- 6%. The incidence of spinal cord ischemic complications was 8.6% (8/93), including 4 patients with transient paraparesis (P = .44 vs SG repair). Nine patients (9.7%) required surgical reintervention during the follow-up period, with 48-month freedom from reintervention approaching 79% (P = .73 vs SG repair). Conclusions. Operative mortality was halved with SG, with similar late survival for both cohorts. Reinterventions were required at a nearly identical rate for open repair and SG, and both groups experienced similar rates of spinal cord ischemic complications. C1 Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Cambria, RP (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, 15 Parkman St,WAC 458, Boston, MA 02114 USA. EM rcambria@partners.org OI Chung, Thomas/0000-0001-6148-1184 NR 36 TC 152 Z9 164 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD DEC PY 2006 VL 44 IS 6 BP 1188 EP 1197 DI 10.1016/j.jvs.2006.08.005 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 112YP UT WOS:000242564400009 PM 17145420 ER PT J AU Gold, R Michael, YL Whitlock, EP Hubbell, FA Mason, ED Rodriguez, BL Safford, MM Sarto, GE AF Gold, Rachel Michael, Yvonne L. Whitlock, Evelyn P. Hubbell, F. Allan Mason, Ellen D. Rodriguez, Beatriz L. Safford, Monika M. Sarto, Gloria E. TI Race/ethnicity, socioeconomic status, and lifetime morbidity burden in the Women's Health Initiative: A cross-sectional analysis SO JOURNAL OF WOMENS HEALTH LA English DT Article ID CAUSE-SPECIFIC MORTALITY; AFRICAN-AMERICAN WOMEN; UNITED-STATES; RACIAL-DISCRIMINATION; BLOOD-PRESSURE; BREAST-CANCER; OLDER ADULTS; RISK-FACTORS; SOCIAL-CLASS; DISPARITIES AB Objectives: We sought to assess the extent to which race/ethnicity and socioeconomic status (SES) are independently and jointly related to lifetime morbidity burden by comparing the impact of SES on lifetime morbidity among women of different racial/ethnic groups: white, black, Hispanic, American Indian/Alaska Native (AIAN), and Asian/Pacific Islander (API). Methods: Using baseline data from the Women's Health Initiative (WHI), a national study of 162,000 postmenopausal women, we measured lifetime morbidity burden using a modified version of the Charlson Index, and measured SES with educational attainment and household income. In multivariable simple polytomous logistic regression models, we first assessed the effect of SES on lifetime morbidity burden among women of each racial/ethnic group, then assessed the combined effect of race/ethnicity and SES. Results: Five percent of all women in the study population had high lifetime morbidity burden. Women with high lifetime morbidity were more likely to be AIAN or black; poor; less educated; divorced, separated, or widowed; past or current smokers; obese; uninsured or publicly insured. Lower SES was associated with higher morbidity among most women. The extent to which morbidity was higher among lower SES compared to higher SES women was about the same among Hispanic women and white women, but was substantially greater among black and AIAN women compared with white women. Conclusions: This study demonstrates the importance of considering race/ethnicity and class together in relation to health outcomes. C1 Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR USA. Univ Calif Irvine, Irvine, CA USA. Rush Univ, Chicago, IL 60612 USA. Univ Hawaii, Honolulu, HI 96822 USA. Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. Univ Wisconsin, Madison, WI USA. RP Gold, R (reprint author), Kaiser Permanente Ctr Hlth Res, 3800 N Interstate Ave, Portland, OR 97227 USA. EM rachel.gold@kpchr.org NR 54 TC 24 Z9 24 U1 2 U2 8 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 DEC PY 2006 VL 15 IS 10 BP 1161 EP 1173 DI 10.1089/jwh.2006.15.1161 PG 13 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 126GB UT WOS:000243499500008 PM 17199457 ER PT J AU Alsop, DC Fearing, MA Johnson, K Sperling, R Fong, TG Inouye, SK AF Alsop, David C. Fearing, Michael A. Johnson, Keith Sperling, Reisa Fong, Tamara G. Inouye, Sharon K. TI The role of neuroimaging in elucidating delirium pathophysiology SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Review ID CEREBRAL-BLOOD-FLOW; SUBCLINICAL HEPATIC-ENCEPHALOPATHY; POSITRON-EMISSION-TOMOGRAPHY; REVERSIBLE SPLENIAL LESION; BRAIN-BARRIER PERMEABILITY; MATTER TRACT INTEGRITY; CHRONIC LIVER-DISEASE; ALZHEIMERS-DISEASE; BASAL GANGLIA; SPECT AB Understanding of delirium pathogenesis remains limited despite improved diagnosis, and elucidation of risk factors and prognosis. Major advances in neuroimaging offer the possibility of probing the mechanisms and networks involved in delirium and hence improving understanding of this often devastating syndrome. This review describes the current literature of imaging studies in delirium and related conditions, introduces some of the newer capabilities of neuroimaging with magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography, and discusses how these techniques may be applied to the study of delirium. Despite considerable challenges in patient recruitment, study design, intersubject variability, and scanner and contrast agent availability, imaging offers great potential for the identification and clarification of pathogenic mechanisms of delirium and its long-term sequelae. C1 Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. VA Boston Healthcare Syst, GRECC, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Div Gerontol, Sch Med, Boston, MA 02115 USA. Hebrew SeniorLife, Aging Brain Ctr, Boston, MA USA. RP Alsop, DC (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, Ansin 226,330 Brookine Ave, Boston, MA 02215 USA. RI Alsop, David/J-5764-2013 OI Alsop, David/0000-0002-8206-1995 FU NIA NIH HHS [P50AG005134, K24AG00949, R21AG025193]; NINDS NIH HHS [5F32NS047431] NR 62 TC 31 Z9 33 U1 3 U2 8 PU GERONTOLOGICAL SOCIETY 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 DEC PY 2006 VL 61 IS 12 BP 1287 EP 1293 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 129AR UT WOS:000243701300010 PM 17234822 ER PT J AU Xie, ZC Dong, YL Maeda, U Moir, R Inouye, SK Culley, DJ Crosby, G Tanzi, RE AF Xie, Zhongcong Dong, Yuanlin Maeda, Uta Moir, Robert Inouye, Sharon K. Culley, Deborah J. Crosby, Gregory Tanzi, Rudolph E. TI Isoflurane-induced apoptosis: A potential pathogenic link between delirium and dementia SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; AMYLOID-BETA; VOLATILE ANESTHETICS; NEURONAL APOPTOSIS; IN-VITRO; OLIGOMERS; SEVOFLURANE; HALOTHANE; INCREASES AB Background. Dementia and delirium have been postulated to share common pathophysiologic mechanisms; however, identification of these unifying mechanisms has remained elusive. The inhalation anesthetic isoflurane has been shown to enhance P-amyloid protein (A beta) oligomerization and generation, to potentiate the cytotoxicity of A beta, and to induce apoptosis. To address the molecular mechanisms of dementia and delirium associated with anesthesia and surgery, we assessed whether the A fibrillar aggregation inhibitor Congo red can attenuate isoflurane-induced caspase-3 activation in H4 human neuroglioma cells overexpressing human beta-amyloid precursor protein (APP). Methods. H4 human neuroglioma cells stably transfected to express human full-length wild-type APP were exposed to 2% isoflurane for 6 hours. The cells were harvested at the end of the treatment. Caspase-3 activation was measured with quantitative Western blotting. Results. We found that isoflurane induces cellular apoptosis in a dose-dependent manner, and that Congo red inhibits isoflurane-induced apoptosis in H4 human neuroglioma cells overexpressing APP. Interestingly, Congo red also inhibits staurosporine-induced apoptosis. Conclusion. The demonstration that isoflurane contributes to well-described mechanisms of Alzheimer's neuropathogenesis provides a plausible link between the acute effects of anesthesia, a well-described risk factor for delirium, and the more long-term sequelae of dementia. These findings suggest that isoflurane-induced A beta oligomerization and apoptosis may contribute to the risk of postoperative cognitive dysfunction and provide a potential pathogenic link between delirium and dementia. C1 Harvard Univ, Sch Med,MassGen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Genet & Aging Res Unit,Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02115 USA. Hebrew SeniorLife, Inst Aging Res, Aging Brain Ctr, Boston, MA USA. Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Tanzi, RE (reprint author), Harvard Univ, Sch Med,MassGen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Genet & Aging Res Unit,Dept Neurol, 114 16th St,C3009, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu FU NIA NIH HHS [P60 AG008812-15, R01AG 014713-07, K12AG 000294-17, R01 AG20253, P50AG005134, K24AG00949, R21AG025193]; NIMH NIH HHS [R01MH 60009-03]; NINDS NIH HHS [K08 NS048140-01] NR 38 TC 73 Z9 78 U1 2 U2 6 PU GERONTOLOGICAL SOCIETY 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 DEC PY 2006 VL 61 IS 12 BP 1300 EP 1306 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 129AR UT WOS:000243701300012 PM 17234824 ER PT J AU Miller, FG Joffe, S AF Miller, Franklin G. Joffe, Steven TI Evaluating the therapeutic misconception SO KENNEDY INSTITUTE OF ETHICS JOURNAL LA English DT Article ID PLACEBO-CONTROLLED TRIALS; INFORMED-CONSENT; RESEARCH PARTICIPANTS; CLINICAL-TRIALS AB The "therapeutic misconception," described by Paul Appelbaum and colleagues more than 20 years ago, refers to the tendency of participants in clinical trials to confuse the design and conduct of research with personalized medical care. Although the "therapeutic misconception" has become a term of art in research ethics, little systematic attention has been devoted to the ethical significance of this phenomenon. This article examines critically the way in which Appelbaum and colleagues formulate what is at stake in the therapeutic misconception, paying particular attention to assumptions and implications that clinical trial participation disadvantages research participants as compared with receiving standard medical care. After clarifying the ethical significance of the therapeutic misconception with respect to the decision making of patients, we offer policy recommendations for obtaining informed consent to participation in clinical trials. C1 NIH, Unit Clin Res, Dept Clin Bioeth, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Miller, FG (reprint author), NIH, Unit Clin Res, Dept Clin Bioeth, Bldg 10, Bethesda, MD 20892 USA. OI Joffe, Steven/0000-0002-0667-7384 NR 20 TC 30 Z9 30 U1 1 U2 1 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1054-6863 J9 KENNEDY INST ETHIC J JI Kennedy Inst. Ethics J. PD DEC PY 2006 VL 16 IS 4 BP 353 EP 366 DI 10.1353/ken.2006.0025 PG 14 WC Ethics; Philosophy; Social Issues SC Social Sciences - Other Topics; Philosophy; Social Issues GA 119TU UT WOS:000243037300003 PM 17847601 ER PT J AU Anderson, RR Farinelli, W Laubach, H Manstein, D Yaroslavsky, AN Gubeli, J Jordan, K Neil, GR Shinn, M Chandler, W Williams, GP Benson, SV Douglas, DR Dylla, HF AF Anderson, R. Rox Farinelli, William Laubach, Hans Manstein, Dieter Yaroslavsky, Anna N. Gubeli, Joseph, III Jordan, Kevin Neil, George R. Shinn, Michelle Chandler, Walter Williams, Gwyn P. Benson, Steven V. Douglas, David R. Dylla, H. F. TI Selective photothermolysis of lipid-rich tissues: A free electron laser study SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE dermis; fat; tissue optics ID RADIATION; SKIN AB Background and Objectives: In theory, infrared vibrational bands could be used for selective photothermolysis of lipid-rich tissues such as fat, sebaceous glands, or atherosclerotic plaques. Study Design/Materials and Methods: Absorption spectra of human fat were measured, identifying promising bands near 1,210 and 1,720 nm. Photothermal excitation of porcine fat and dermis were measured with a 3.5-5 mu m thermal camera during exposure to the free electron laser (FEL) at Jefferson National Laboratory. Thermal damage to full-thickness samples exposed at similar to 1,210 nm through a cold contact window, was assessed by nitrobluetetrazolium chloride staining in situ and by light microscopy. Results: Photothermal excitation of fat was twice that of dermis, at lipid absorption bands (1,210, 1,720 nm). At 1,210 nm, a subcutaneous fat layer several mm thick was damaged by FEL exposure, without apparent injury to overlying skin. Conclusion: Selective photothermal targeting of fatty tissues is feasible using infrared lipid absorption bands. Potential clinical applications are suggested by this FEL study. C1 Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. Thomas Jefferson Natl Accelerator Facil, Newport News, VA USA. RP Anderson, RR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BHX 630, Boston, MA 02114 USA. EM RRAnderson@partners.org NR 20 TC 114 Z9 118 U1 1 U2 9 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 DEC PY 2006 VL 38 IS 10 BP 913 EP 919 DI 10.1002/lsm.20393 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 122VC UT WOS:000243254200005 PM 17163478 ER PT J AU Yasui, H Hideshima, T Anderson, KC AF Yasui, Hiroshi Hideshima, Teru Anderson, Kenneth C. TI Non-steroidal anti-inflammatory drug therapy for chronic lymphocytic leukemia SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material ID ACTIVATION; ETODOLAC; SDX-101 C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu NR 8 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD DEC PY 2006 VL 47 IS 12 BP 2445 EP 2446 DI 10.1080/10428190601059779 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 117IN UT WOS:000242866700007 PM 17169789 ER PT J AU Grimm, DR Schilero, GJ Spungen, AM Bauman, WA Lesser, M AF Grimm, David R. Schilero, Gregory J. Spungen, Ann M. Bauman, William A. Lesser, Marvin TI Salmeterol improves pulmonary function in persons with tetraplegia SO LUNG LA English DT Article DE spinal cord injury; spirometry bronchodilator; respiratory muscle strength; salmeterol; tetraplegia ID SPINAL-CORD-INJURY; HEALTHY NONSMOKING ADULTS; AIRWAY HYPERRESPONSIVENESS; MUSCLE STRENGTH; COMPLICATIONS; INDIVIDUALS; SALBUTAMOL; ALBUTEROL; AGONIST; COPD AB beta(2)-Adrenergic agonists are known to improve muscle strength because of anabolic properties. The purpose of this study was to determine if long-term administration of a long-acting beta(2)-adrenergic agonist to subjects with tetraplegia is associated with improvement in pulmonary function parameters and maximal static inspiratory and expiratory mouth pressures (MIP and MEP, respectively), measures of respiratory muscle strength. The study was a randomized, prospective, double-blind, placebo-controlled, crossover trial and conducted at the James J. Peters Veterans Affairs Medical Center. Thirteen subjects who had complete or incomplete tetraplegia for more than one year participated in the study. Eleven subjects completed the study. All were clinically stable outpatients without any history of asthma or use of inhaled bronchodilators. Following baseline measurements, patients were randomized to receive salmeterol or placebo from identically marked Diskus containers for 4 weeks. Following a 4-week washout period, the subjects were randomized to receive the alternate preparation for 4 weeks. Pulmonary function parameters and static mouth pressure were measured during baseline and during the fourth week of the two study periods. During the 4-week period of salmeterol administration, forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow, MIP, and MEP improved significantly compared with placebo and baseline. Expiratory reserve volume increased significantly compared to baseline. Increases in MIP and MEP during salmeterol administration suggest improvement in respiratory muscle strength. However, this cannot be stated with certainty because MIP and MEP are dependent on volume parameters at which they are measured. Regardless of the mechanism, improvement in static mouth pressures indicates that salmeterol should benefit these individuals by improving cough effectiveness. C1 James J Peters Vet Affairs Med Ctr, Ctr Med Consequences Spinal Cord Injury, Bronx, NY 10468 USA. New York Chiropract Coll, Dept Basic Sci, Seneca Falls, NY 13148 USA. CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Rehabil Med, New York, NY 10029 USA. James J Peters Vet Affairs Med Ctr, Med Serv, Bronx, NY 10468 USA. James J Peters Vet Affairs Med Ctr, Spinal Cord Injury Serv, Bronx, NY 10468 USA. RP Schilero, GJ (reprint author), James J Peters Vet Affairs Med Ctr, Ctr Med Consequences Spinal Cord Injury, Room 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Greg.schilero@med.va.gov NR 28 TC 7 Z9 8 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0341-2040 J9 LUNG JI Lung PD DEC PY 2006 VL 184 IS 6 BP 335 EP 339 DI 10.1007/s00408-006-0011-6 PG 5 WC Respiratory System SC Respiratory System GA 111OU UT WOS:000242463600006 PM 17096182 ER PT J AU Chuang, TC Huang, TY Lin, FH Wang, FN Juan, CJ Chung, HW Chen, CY Kwong, KK AF Chuang, Tzu-Chao Huang, Teng-Yi Lin, Fa-Hsuan Wang, Fu-Nien Juan, Chun-Jung Chung, Hsiao-Wen Chen, Cheng-Yu Kwong, Kenneth K. TI PROPELLER-EPI with parallel imaging using a circularly symmetric phased-array RF coil at 3.0 T: Application to high-resolution diffusion tensor imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article; Proceedings Paper CT 12th Annual Meeting of the International-Society-for-Magnetic-Resonance-in-Medicine CY MAY 15-21, 2004 CL Kyoto, JAPAN SP Int Soc Magnet Resonance Med DE PROPELLER imaging; parallel imaging; high-resolution diffusion image; PROPELLER-EPI; geometric distortions ID MRI; SENSE; ECHO; HEAD AB A technique integrating multishot periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) and parallel imaging is presented for diffusion echo-planar imaging (EPI) at high spatial resolution. The method combines the advantages of parallel imaging to achieve accelerated sampling along the phase-encoding direction, and PROPELLER acquisition to further decrease the echo train length (ETL) in EPI. With an eight-element circularly symmetric RF coil, a parallel acceleration factor of 4 was applied such that, when combined with PROPELLER acquisition, a reduction of geometric distortions by a factor substantially greater than 4 was achieved. The resulting phantom and human brain images acquired with a 256 x 256 matrix and an ETL of only 16 were visually identical in shape to those acquired using the fast spin-echo (FSE) technique, even without field-map corrections. It is concluded that parallel PROPELLER-EPI is an effective technique that can substantially reduce susceptibility-induced geometric distortions at high field strength. C1 Natl Taiwan Univ, Dept Elect Engn, Taipei 10764, Taiwan. Natl Taiwan Univ Sci & Technol, Dept Elect Engn, Taipei, Taiwan. MIT, Massachusetts Gen Hosp, HMS A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Tri Serv Gen Hosp, Dept Radiol, Taipei, Taiwan. Natl Defense Med Ctr, Taipei, Taiwan. RP Chung, HW (reprint author), Natl Taiwan Univ, Dept Elect Engn, Taipei 10764, Taiwan. EM chung@cc.ee.ntu.edu.tw RI Teng-Yi, Huang/C-7433-2011; Lin, Fa-Hsuan/G-6988-2012; OI Lin, Fa-Hsuan/0000-0002-9539-1731; Juan, Chun Jung/0000-0001-5219-0406; Chung, Hsiao-Wen/0000-0001-7127-1244 NR 24 TC 26 Z9 26 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD DEC PY 2006 VL 56 IS 6 BP 1352 EP 1358 DI 10.1002/mrm.21064 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 110OO UT WOS:000242388400021 PM 17051531 ER PT J AU Duru, OK Mangione, CM Steers, NW Herman, WH Karter, AJ Kountz, D Marrero, DG Safford, MM Waitzfelder, B Gerzoff, RB Huh, S Brown, AF AF Duru, O. Kenrik Mangione, Carol M. Steers, Neil W. Herman, William H. Karter, Andrew J. Kountz, David Marrero, David G. Safford, Monika M. Waitzfelder, Beth Gerzoff, Robert B. Huh, Soonim Brown, Arleen F. CA TRIAD Study Grp TI The association between clinical care strategies and the attenuation of racial/ethnic disparities in diabetes care - The translating research into action for diabetes (TRIAD) study SO MEDICAL CARE LA English DT Article DE diabetes; quality of care; quality improvement; race and ethnicity; chronic disease ID QUALITY-OF-CARE; INFLUENZA VACCINATION RATES; MEDICARE MANAGED CARE; RACIAL DISPARITIES; UNITED-STATES; HEALTH-CARE; REDUCING DISPARITIES; ETHNIC DISPARITIES; AFRICAN-AMERICANS; DISEASE AB Objective: We sought to determine whether greater implementation of clinical care strategies in managed care is associated with attenuation of known racial/ethnic disparities in diabetes care. Research Design and Methods: Using cross-sectional data, we examined the quality of diabetes care as measured by frequencies of process delivery as well as medication management of intermediate outcomes, for 7426 black, Latinos, Asian/Pacific Islanders, and white participants enrolled in 10 managed care plans wit in provider groups. We stratified models by intensity of 3 clinical care strategies at the provider group level: physician reminders, physician feedback, or use of a diabetes registry. Results: Exposure to clinical care strategy implementation at the provider group level varied by race and ethnicity, with < 10% of black participants enrolled in provider groups in the highest-intensity quintile for physician feedback and < 10% of both black and Asian/Pacific Islander participants enrolled in groups in the highest-intensity quintile for diabetes registry use. Although disparities in care were confirmed, particularly for black relative to white subjects, we did not find a consistent pattern of disparity attenuation with increasing implementation intensity for either processes of care or medication management of intermediate outcomes. Conclusions: For the most part, high-intensity implementation of a diabetes registry, physician feedback, or physician reminders, 3 clinical care strategies similar to those used in many health care settings, are not associated with attenuation of known disparities of diabetes care in managed care. C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Michigan, Dept Internal Med, Div Endocrinol & Metab, Ann Arbor, MI 48109 USA. Kaiser Permanente, Div Res, Oakland, CA USA. UMDNJ Robert Wood Johnson Med Sch, Div Primary Care, New Brunswick, NJ USA. Indiana Univ, Dept Med, Sch Med, Indianapolis, IN USA. Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. Pacific Hlth Res Inst, Honolulu, HI USA. CDC, Ctr Dis Control & Prevent, Atlanta, GA USA. RP Duru, OK (reprint author), Univ Calif Los Angeles, Div Gen Internal Med, 911 Broxton Plaza, Los Angeles, CA 90024 USA. EM kduru@mednet.ucla.edu FU NIA NIH HHS [AG-02-004]; NIMHD NIH HHS [P20MD000148, P20 MD000148, P20MD000182]; PHS HHS [U58/CCU923530] NR 45 TC 20 Z9 20 U1 2 U2 2 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 DEC PY 2006 VL 44 IS 12 BP 1121 EP 1128 DI 10.1097/01.mlr.0000237423.05294.c0 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 111TI UT WOS:000242477200010 PM 17122717 ER PT J AU Huebert, DJ Kamal, M O'Donovan, A Bernstein, BE AF Huebert, Dana J. Kamal, Michael O'Donovan, Aisling Bernstein, Bradley E. TI Genome-wide analysis of histone modifications byChIP-on-chip SO METHODS LA English DT Article DE chromatin; histone modification; ChIP-on chip; microarray; mammalian; cell culture ID EMBRYONIC STEM-CELLS; DEVELOPMENTAL REGULATORS; TILING-ARRAYS; CHROMATIN; DNA; NORMALIZATION; MICROARRAYS; EXPRESSION; POLYCOMB; MODEL AB Post-translational modifications to histone proteins regulate the packaging of genomic DNA into chromatin, gene activity and other functions of the genome. They are understood to play key roles in embryonic development and disease pathogenesis. Recent advances in technology have made it possible to analyze chromatin structure genome-wide in mammalian cells. Global patterns of histone modifications can be observed using a technique called ChIP-on-chip, which combines the specificity of chromatin immunoprecipitation with the unbiased, high-throughput capabilities of microarrays. The resulting maps provide insight into the functions of, and relationships between, different modifications. Here, we provide validated ChIP-on-chip methods for analyzing histone modification patterns at genome-scale in mammalian cells. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. MIT, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Bernstein, BE (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. EM bbernstein@partners.org NR 22 TC 39 Z9 49 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 1046-2023 J9 METHODS JI Methods PD DEC PY 2006 VL 40 IS 4 BP 365 EP 369 DI 10.1016/j.ymeth.2006.07.032 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117VY UT WOS:000242902600012 PM 17101450 ER PT J AU Matsunaga, J Werneid, K Zuerner, RL Frank, A Haake, DA AF Matsunaga, James Werneid, Kristian Zuerner, Richard L. Frank, Ami Haake, David A. TI LipL46 is a novel surface-exposed lipoprotein expressed during leptospiral dissemination in the mammalian host SO MICROBIOLOGY-SGM LA English DT Article ID OUTER-MEMBRANE PROTEIN; PATHOGENIC LEPTOSPIRA; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; INTERROGANS; INFECTION; PREDICTION; BACTERIA; GROWTH; OMPL1 AB Leptospirosis is a widespread zoonosis caused by invasive spirochaetes belonging to the genus Leptospira. Pathogenic leptospires disseminate via the bloodstream to colonize the renal tubules of reservoir hosts. Little is known about leptospiral outer-membrane proteins expressed during the dissemination stage of infection. In this study, a novel surface-exposed lipoprotein is described; it has been designated LipL46 to distinguish it from a previously described 31 kDa peripheral membrane protein, P31 (LipL45), which is exported as a 45 kDa probable lipoprotein. The lipL46 gene encodes a 412 aa polypeptide with a 21 aa signal peptide. Lipid modification of cysteine at the lipoprotein signal peptidase cleavage site FSISC is supported by the finding that Leptospira interrogans intrinsically labels LipL46 during incubation in medium containing [C-14]palmitate. LipL46 appears to be exported to the leptospiral outer membrane as a 46 kDa lipoprotein, based on Triton X-114 solubilization and phase partitioning studies, which included the outer and inner membrane controls LipL32 and LipL31, respectively. Surface immunoprecipitation and whole-cell ELISA experiments indicate that LipL46 is exposed on the leptospiral surface. Immunohistochemistry studies demonstrated expression of LipL46 by leptospires found in the bloodstream of acutely infected hamsters. Leptospires expressing LipL46 were also found in the intercellular spaces of the liver, within splenic phagocytes, and invading the glomerular hilum of the kidney. Infection-associated expression is supported by the finding that LipL46 is a major antigen recognized by sera from infected hamsters. These findings indicate that LipL46 may be important in leptospiral dissemination, and that it may serve as a useful serodiagnostic antigen. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA USA. USDA ARS, Natl Anim Dis Ctr, Ames, IA 50010 USA. RP Haake, DA (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, 111F, Los Angeles, CA 90073 USA. EM dhaake@ucla.edu FU NIAID NIH HHS [R21 AI034431, R01 AI034431-09, R29 AI034431, AI-34431, R01 AI034431] NR 38 TC 33 Z9 33 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD DEC PY 2006 VL 152 BP 3777 EP 3786 DI 10.1099/mic.0.29163-0 PN 12 PG 10 WC Microbiology SC Microbiology GA 122DL UT WOS:000243205800031 PM 17159228 ER PT J AU Zhao, R Domann, FE Zhong, WX AF Zhao, Rui Domann, Frederick E. Zhong, Weixiong TI Apoptosis induced by selenomethionine and methioninase is superoxide mediated and p53 dependent in human prostate cancer cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID GENE-THERAPY; SE-METHYLSELENOCYSTEINE; METHYLSELENINIC ACID; IN-VITRO; SELENIUM SUPPLEMENTATION; CARCINOSTATIC ACTIVITY; OXIDATIVE STRESS; PREVENTION; METABOLITE; EXPRESSION AB Selenomethionine (SeMet) is the chemical form or major component of selenium used for cancer chemoprevention in several clinical trials. However, evidence from experimental studies indicates that SeMet has weaker anticancer effects than most other forms of selenium. Recent studies showed that the anticancer activity of SeMet can be enhanced by methioninase (METase), indicating that SeMet metabolites are responsible for its anticancer activity. In the present study, we showed that wild-type p53-expressing LNCaP human prostate cancer cells were more sensitive to cotreatment with SeMet and METase than p53-null PC3 human prostate cancer cells. SeMet and METase cotreatment significantly increased levels of superoxide and apoptosis in LNCaP cells. Cotreatment with SeMet and METase resulted in increased levels of phosphorylated p53 (Ser15), total p53, Bax, and p21(Waf1) proteins. LNCaP cells treated with SeMet and METase also showed p53 translocation to mitochondria, decreased mitochondrial membrane potential, cytochrome c release into the cytosol, and activation of caspase-9. The effects of SeMet and METase Were suppressed by pretreatment with a synthetic superoxide dismutase mimic or by knockdown of p53 via RNA interference. Reexpression of wild-type p53 in PC3 cells resulted in increases in superoxide production, apoptosis, and caspase-9 activity and a decrease in mitochondrial membrane potential following cotreatment with SeMet and METase. Our study shows that apoptosis induced by SeMet plus METase is superoxide mediated and p53 dependent via mitochondrial pathway(s). These results suggest that superoxide and p53 may play a role in cancer chemoprevention by selenium. C1 Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Ctr Clin Sci, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Madison, WI 53705 USA. Univ Iowa, Free Rad & Radiat Biol Program, Iowa City, IA USA. RP Zhong, WX (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Ctr Clin Sci, K4-868,Box 8550,600 Highland Ave, Madison, WI 53792 USA. EM wzhong3@wisc.edu OI Domann, Frederick/0000-0002-0489-2179 FU NCI NIH HHS [CA114281, CA73612, R01 CA073612, R01 CA114281, R29 CA073612, R56 CA073612] NR 51 TC 59 Z9 63 U1 0 U2 6 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 DEC PY 2006 VL 5 IS 12 BP 3275 EP 3284 DI 10.1158/1535-7163.MCT-06-0400 PG 10 WC Oncology SC Oncology GA 122UO UT WOS:000243252800036 PM 17172431 ER PT J AU LaPlante, JM Sun, M Falardeau, J Dai, D Brown, EM Slaugenhaupt, SA Vassilev, PM AF LaPlante, Janice M. Sun, Mei Falardeau, John Dai, sy Dai Brown, Edward M. Slaugenhaupt, Susan A. Vassilev, Peter M. TI Lysosomal exocytosis is impaired in mucolipidosis type IV SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE mucolipin; mucolipidosis; MLIV; lysosome; exocytosis; channel; late endosome; trafficking ID POLYCYSTIC KIDNEY-DISEASE; CATION CHANNEL; SYNAPTOTAGMIN-VII; CA2+-DEPENDENT EXOCYTOSIS; ABNORMAL TRANSPORT; STORAGE DISEASE; MEMBRANE REPAIR; GENE-THERAPY; IN-UTERO; CELLS AB Mucolipidosis type IV (MLIV) is an autosomal recessive disease characterized by severe neurological impairment, oplithalmologic defects, and gastric dysfunction. MLIV cells have a deficiency in the late endosomal/lysosomal (LEL) pathway that results in the buildup of lysosomal inclusions. Using a Xenopus oocyte expression system, we previously showed that mucolipin-1 (MLN1), the protein encoded by the MCOLN1 gene is a Ca2+-permeable non-selective cation channel that is transiently modulated by elevations in intracellular Ca2+. We further showed that MLN1 is translocated to the plasma membrane during lysosomal exocytosis. In this study we show that lysosomal exocytosis is impaired in fibroblasts from MLIV patients, indicating that MLN1 plays an active role in this process. Further, we show that transfection with wild type MLN1 cDNA rescues exocytosis, suggesting the possibility of treatments based on the restoration of this crucial cellular function. (c) 2006 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Dept Med, Div Endocrinol, Diabet & Hypertens & Membrane Biol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Vassilev, PM (reprint author), Brigham & Womens Hosp, Dept Med, Div Endocrinol, Diabet & Hypertens & Membrane Biol Program, 221 Longwood Ave, Boston, MA 02115 USA. EM pvassilev@rics.bwh.harvard.edu FU NINDS NIH HHS [NS39995] NR 49 TC 65 Z9 66 U1 0 U2 1 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 DEC PY 2006 VL 89 IS 4 BP 339 EP 348 DI 10.1016/j.ymgme.2006.05.016 PG 10 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 114MN UT WOS:000242670400007 PM 16914343 ER PT J AU Xiao, GP Deziel, E He, JX Lepine, F Lesic, B Castonguay, MH Milot, S Tampakaki, AP Stachel, SE Rahme, LG AF Xiao, Gaoping Deziel, Eric He, Jianxin Lepine, Francois Lesic, Biliana Castonguay, Marie-Helene Milot, Sylvain Tampakaki, Anastasia P. Stachel, Scott E. Rahme, Laurence G. TI MvfR, a key Pseudomonas aeruginosa pathogenicity LTTR-class regulatory protein, has dual ligands SO MOLECULAR MICROBIOLOGY LA English DT Article ID QUORUM-SENSING CIRCUITRY; TO-CELL COMMUNICATION; CAENORHABDITIS-ELEGANS; VIRULENCE FACTORS; QUINOLONE SIGNAL; LYSR FAMILY; GENES; PATHOGENESIS; INFECTION; FRAGMENT AB MvfR (PqsR), a Pseudomonas aeruginosa LysR-type transcriptional regulator, plays a critical role in the virulence of this pathogen. MvfR modulates the expression of multiple quorum sensing (QS)-regulated virulence factors; and the expression of the phnAB and pqsA-E genes that encode functions mediating 4-hydroxy-2-alkylquinolines (HAQs) signalling compounds biosynthesis, including 3,4-dihydroxy-2-heptylquinoline (PQS) and its precursor 4-hydroxy-2-heptylquinoline (HHQ). PQS enhances the in vitro DNA-binding affinity of MvfR to the pqsA-E promoter, to suggest it might function as the in vivo MvfR ligand. Here we identify a novel MvfR ligand, as we show that HHQ binds to the MvfR ligand-binding-domain and potentiates MvfR binding to the pqsA-E promoter leading to transcriptional activation of pqsA-E genes. We show that HHQ is highly produced in vivo, where it is not fully converted into PQS, and demonstrate that it is required for MvfR-dependent gene expression and pathogenicity; PQS is fully dispensable, as pqsH(-) mutant cells, which produce HHQ but completely lack PQS, display normal MvfR-dependent gene expression and virulence. Conversely, PQS is required for full production of pyocyanin. These results uncover a novel biological role for HHQ; and provide novel insights on MvfR activation that may aid in the development of therapies that prevent or treat P. aeruginosa infections in humans. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Shriners Burn Inst, Boston, MA 02114 USA. Inst Armand Frappier, INRS, Laval, PQ H7V 1B7, Canada. RP Rahme, LG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM rahme@amber.mgh.harvard.edu RI Deziel, Eric/A-7678-2008 OI Deziel, Eric/0000-0002-4609-0115 FU NIAID NIH HHS [1 R01 AI063433-01A2] NR 36 TC 131 Z9 135 U1 1 U2 19 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD DEC PY 2006 VL 62 IS 6 BP 1689 EP 1699 DI 10.1111/j.1365-2958.2006.05462.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 108JU UT WOS:000242236900016 PM 17083468 ER PT J AU Lamfers, MLM Fulci, G Gianni, D Tang, Y Kurozumi, K Kaur, B Moeniralm, S Saeki, Y Carette, JE Weissleder, R Vandertop, WP van Beusechem, VW Dirven, CMF Chiocca, EA AF Lamfers, Martine L. M. Fulci, Giulia Gianni, Davide Tang, Yi Kurozumi, Kazuhiko Kaur, Balveen Moeniralm, Sharif Saeki, Yoshinaga Carette, Jan E. Weissleder, Ralph Vandertop, W. Peter van Beusechem, Victor W. Dirven, Clemens M. F. Chiocca, E. Antonio TI Cyclophosphamide increases transgene expression mediated by an oncolytic adenovirus in glioma-bearing mice monitored by bioluminescence imaging SO MOLECULAR THERAPY LA English DT Article DE glioma; oncolytic adenovirus; transgene expression; bioluminescence imaging; immune suppression ID CONDITIONALLY REPLICATING ADENOVIRUS; CENTRAL-NERVOUS-SYSTEM; IN-VIVO; MALIGNANT GLIOMAS; THYMIDINE-KINASE; PRODRUG THERAPY; LIVE ANIMALS; VECTOR; BRAIN; GENE AB Approaches to improve the oncolytic potency of replication-competent adenoviruses include the insertion of therapeutic transgenes into the viral genome. Little is known about the levels and duration of in vivo transgene expression by cells infected with such "armed" viruses. Using a tumor-selective adenovirus encoding firefly luciferase (AdA24CMV-Luc) we investigated these questions in an intracranial mouse model for malignant glioma. Luciferase expression was detected by bioluminescence imaging, and the effect of the immunosuppressive agent cyclophosphamide (CPA) on transgene expression was assessed. Intratumoral AdA24CMV-Luc injection led to a localized dose-dependent expression of luciferase. Surprisingly, this expression decreased rapidly during the course of 14 days. In contrast, mice injected with nonreplicating Ad.CMV-Luc demonstrated stable transgene expression. Treatment of mice with CPA in combination with AdA24CMV-Luc retarded the loss of transgene expression. Staining of mouse brains for inflammatory cells demonstrated decreased tumor infiltration by immune cells in CPA-treated mice. Moreover, in immunodeficient NOD/SCID mice loss of transgene expression was less rapid and not prevented by CPA treatment. Together, our data demonstrate that transgene expression and viral replication decrease rapidly after intratumoral injection of oncolytic adenovirus in mouse brains and that treatment with the immunomodulator CPA prolongs viral-mediated gene expression. C1 VU Univ Med Ctr, Dept Neurosurg, NL-1007 MB Amsterdam, Netherlands. VU Univ Med Ctr, Dept Med Oncol, NL-1007 MB Amsterdam, Netherlands. VU Univ Med Ctr, Neurosurg Ctr Amsterdam, NL-1007 MB Amsterdam, Netherlands. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Mol Neurooncol Labs, Charlestown, MA 02129 USA. Ohio State Univ, Ctr Comprehens Canc, Dept Neurol Surg, Dardinger Ctr Neurooncol, Columbus, OH 43210 USA. RP Lamfers, MLM (reprint author), VU Univ Med Ctr, Dept Neurosurg, NL-1007 MB Amsterdam, Netherlands. EM M.Lamfers@vumc.nl RI kaur, Balveen/E-3355-2011; Lamfers, Martine/C-6246-2016; OI Lamfers, Martine/0000-0001-7745-9029 FU NCI NIH HHS [P01 CA069246, P01 CA069246-04, P01 CA69246, P50 CA086355, P50 CA86355, R01 CA085139, R01 CA85139, R24 CA092782, R24 CA92782]; NINDS NIH HHS [NS41571, R01 NS041571] NR 50 TC 66 Z9 68 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD DEC PY 2006 VL 14 IS 6 BP 779 EP 788 DI 10.1016/j.ymthe.2006.08.008 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 115GR UT WOS:000242723300004 PM 16996314 ER PT J AU Liu, TC Zhang, TG Fukuhara, H Kuroda, T Todo, T Martuza, RL Rabkin, SD Kurtz, A AF Liu, Ta-Chiang Zhang, Tingguo Fukuhara, Hiroshi Kuroda, Toshihiko Todo, Tomoki Martuza, Robert L. Rabkin, Samuel D. Kurtz, Andreas TI Oncolytic HSV armed with platelet factor 4, an antiangiogenic agent, shows enhanced efficacy SO MOLECULAR THERAPY LA English DT Article DE oncolytic virus; herpes simplex virus; platelet factor 4; cancer gene therapy; antiangiogenesis ID HERPES-SIMPLEX-VIRUS; RECOMBINANT PLATELET FACTOR-4; MESSENGER RIBONUCLEIC-ACID; TUMOR-GROWTH; ENDOGENOUS INHIBITORS; MALIGNANT GLIOMA; VIRAL REPLICATION; CXC-CHEMOKINE; GENE-TRANSFER; CELL-LINE AB Oncolytic herpes simplex viruses (HSV) have emerged as a promising platform for cancer therapy. However, efficacy as single agents has thus far been unsatisfactory. Tumor vasculature is critical in supporting tumor growth, but successful antiangiogenic approaches often require maintaining constant levels of antiangiogenic products. We hypothesized that oncolytic HSV has the potential to destroy tumor vasculature and that this effect can be enhanced by combination with antiangiogenic gene transfer. We examined the strategy of arming oncolytic HSV with an antiangiogenic transgene, platelet factor 4 (PF4). The PF4 transgene was inserted into oncolytic HSV G47 Delta utilizing a bacterial artificial chromosome construction system. Whereas bG47 Delta-empty showed robust cell killing and migration inhibition of proliferating endothelial cells (HUVEC and Py-4-1), the effect was further enhanced by PF4 expression. Importantly, enhanced potency did not impede viral replication. In vivo, bG47 Delta-PF4 was more efficacious than its nonexpressing parent bG47 Delta-empty at inhibiting tumor growth and angiogenesis in both human U87 glioma and mouse 37-3-18-4 malignant peripheral nerve sheath tumor models. Enhancing the antiangiogenic properties of oncolytic HSV through the expression of antiangiogenic factors such as PF4 is a powerful new strategy that targets both the tumor cells and tumor vasculature. C1 Massachusetts Gen Hosp, Mol Neurosurg Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kurtz, A (reprint author), Massachusetts Gen Hosp, Mol Neurosurg Lab, CPZN-3800 Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM rabkin@helix.mgh.harvard.edu; kurtz@rki.de RI rabkin, samuel/C-2443-2012; OI rabkin, samuel/0000-0003-2344-2795; Kuroda, Toshihiko/0000-0001-6660-8930 FU NINDS NIH HHS [R01 NS 32677] NR 50 TC 46 Z9 48 U1 2 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD DEC PY 2006 VL 14 IS 6 BP 789 EP 797 DI 10.1016/j.ymthe.2006.07.011 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 115GR UT WOS:000242723300005 PM 17045531 ER PT J AU Saeed, AI Schwartz, AP Limsukon, A AF Saeed, Ali Imran Schwartz, Andrew P. Limsukon, Atikun TI Superior vena cava syndrome (SVC syndrome): A rare cause of conjunctival suffusion SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article DE conjunctival suffusion; SVC syndrome; suffusion; SVC obstruction; lung cancer ID PRESENTING SIGN; EYELID EDEMA AB Obstruction of blood flow in the superior vena cava results in the signs and symptoms of superior vena cava (SVC) syndrome. Venous collaterals form, to establish alternative pathways for return of venous blood to the right atrium. The rapidity of onset of symptoms and signs from SVC obstruction is directly related to the rate at which obstruction occurs and how effective the formed collaterals are. Lung cancer and lymphoma account for more than 90% of cases of SVC syndrome. Recognition of signs and symptoms allows us to make an early diagnosis. Facial swelling, distended veins over the neck, upper extremity swelling, and dyspnea are common findings. Proptosis, periorbital swelling (including eyelid), conjunctival suffusion and elevated intraocular pressure are documented ophthalmic findings in SVC syndrome. We present a rare case of conjunctival suffusion in a 72-year-old male diagnosed with superior vena cava syndrome secondary to lung cancer. C1 James J Peters VA Med Ctr, Mt Sinai Sch Med Program, Bronx, NY USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. RP Saeed, AI (reprint author), James J Peters VA Med Ctr, Program Med, Room 7A11,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM docali@hotmail.com NR 11 TC 3 Z9 5 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD DEC PY 2006 VL 73 IS 8 BP 1082 EP 1085 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 128XF UT WOS:000243692300005 PM 17285199 ER PT J AU Shahzad, G Korsten, MA Blatt, C Motwani, P AF Shahzad, Ghulamullah Korsten, Mark A. Blatt, Charles Motwani, Pooja TI Angiotensin-converting enzyme (ACE) inhibitor-associated angioedema of the stomach and small intestine: A case report SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article DE angioedema; angiotensin-converting enzyme inhibitors; CT scan ID VISCERAL ANGIOEDEMA; MANAGEMENT AB This is a case report on a 45-year old African-American female with newly diagnosed hypertension, who was started on a combination pill of amlodipine/benazapril 10/5 mg. The very next day, she presented at the emergency room (ER) with abdominal pain, nausea and vomiting. Physical exam, complete metabolic panel, and hemogram were in the normal range. She was discharged from the ER after a few hours of treatment with fluid and analgesics. However, she returned to the ER the next day with the same complaints. This time the physical exam was significant for a distended abdomen with dullness to percussion. CT scan of the abdomen revealed markedly thickened antrum of the stomach, duodenum and jejunum, along with fluid in the abdominal and pelvic cavity. Angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema was suspected, and anti-hypertensive medications were discontinued. Her symptoms improved within the next 24 hours, and repeat CT after 72 hours revealed marked improvement in stomach and small bowel thickening and resolution of ascites. The recognition of angiotensin-converting enzyme (ACE) and angiotensin receptor blocker (ARB) intestinal angioedema constitutes a challenge to primary care physicians, internists, emergency room personal and surgeons. C1 James J Peters VA Med Ctr, Bronx, NY USA. N Cent Bronx Hosp, Jocobi Med Ctr, Bronx, NY USA. RP Shahzad, G (reprint author), 1003 Father Capdanno Blvd, Staten Isl, NY 10603 USA. EM shahzag@gmail.com NR 12 TC 13 Z9 14 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD DEC PY 2006 VL 73 IS 8 BP 1123 EP 1125 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 128XF UT WOS:000243692300015 PM 17285209 ER PT J AU Padera, RF Tse, JY Bellas, E Kohane, DS AF Padera, Robert F. Tse, Julie Y. Bellas, Evangelia Kohane, Daniel S. TI Tetrodotoxin for prolonged local anesthesia with minimal myotoxicity SO MUSCLE & NERVE LA English DT Article DE inflamation; local anesthetics; muscle injury; nerve blockade; tetrodotoxin ID SCIATIC-NERVE BLOCKADE; ADULT RATS; IN-VIVO; BUPIVACAINE; TOXICITY; AGONISTS; INJURY; INFANT AB Conventional local anesthetics such as bupivacaine cause considerable myotoxicity and neurotoxicity, whereas tetrodotoxin (TTX) does not. Tetrodotoxin combined with bupivacaine or vasoconstrictors produces long-duration nerve blockade. To assess whether these prolonged blocks can be produced without increased myotoxicity, Sprague-Dawley rats were injected with bupivacaine, TTX, and both, or TTX plus epinephrine. Median durations of thermal nociceptive blockade were, respectively, 188, 401, 882, and 972 min. On dissection 4 days later, all tissues appeared macroscopically pristine. Muscle injury was at most mild to moderate in all animals, and the muscle injury scores for the combination formulations were not higher than for bupivacaine alone. Similarly, in differentiated cells from a myoblast cell line (C2C12), TTX caused either no or minimal worsening of cell viability from bupivacaine at 2 or 7 days. Epinephrine did not worsen TTX's relatively minimal cytotoxicity. Tetrodotoxin may thus be useful in producing prolonged nerve block with minimal myotoxicity and perhaps neurotoxicity. C1 Massachusetts Gen Hosp, Pediat Intens Care Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Kohane, DS (reprint author), Massachusetts Gen Hosp, Pediat Intens Care Unit, Ellison 317,55 Fruit St, Boston, MA 02114 USA. EM dkohane@partners.org FU NIGMS NIH HHS [GM073626] NR 21 TC 27 Z9 27 U1 1 U2 3 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 DEC PY 2006 VL 34 IS 6 BP 747 EP 753 DI 10.1002/mus.20618 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 111SZ UT WOS:000242476300008 PM 16897761 ER PT J AU Snyder, JS Hannon, EE Large, EW Christiansen, MH AF Snyder, Joel S. Hannon, Erin E. Large, Edward W. Christiansen, Morten H. TI Synchronization and continuation tapping to complex meters SO MUSIC PERCEPTION LA English DT Article; Proceedings Paper CT 10th International Workshop on Rhythm Perception and Production CY JUL 02-06, 2005 CL Bilzen, BELGIUM DE complex meter; musical cues to meter; Balkan music; culture-specific knowledge; sensory-motor synchronization ID TEMPORAL PATTERNS; AUDITORY SEQUENCES; MUSICAL RHYTHMS; MELODIC ACCENT; PERCEPTION; TIME; PULSE; MODEL; CUES; RESONANCE AB THE GOAL OF THIS STUDY was to assess the ability of North American adults to synchronize and continue their tapping to complex meter patterns in the presence and absence of musical cues to meter. We asked participants to tap to drum patterns structured according to two different 7/8 meters common in Balkan music. Each meter contained three nonisochronous drumbeats per measure, forming intervals in a short-short-long (SSL) or a long-short-short (LSS) pattern. In the synchronization phase of each trial, participants were asked to tap in synchrony with a drum pattern that was accompanied by either a matching or a mismatching Balkan folk melody. In the continuation phase of the trial, the drum pattern was turned off and participants continued tapping the drum pattern accompanied by the same melody or by silence. Participants produced ratios of long to short inter-tap intervals during synchronization that were between the target ratio of 3:2 and a simple-meter ratio of 2:1. During continuation, participants maintained a similar ratio as long as the melody was present but when the melody was absent the ratios were stretched even more toward 2: 1. Tapping variability and tapping position relative to the target locations during synchronization and ratio production during both synchronization and continuation showed that the temporal grouping of tones in the drum pattern was more influential on tapping performance than the particular meter (i.e., SSL vs. LSS). These findings demonstrate that people raised in North America find it difficult to produce complex metrical patterns, especially in the absence of exogenous cues and even when provided with musical stimuli to aid them in tapping accurately. C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA 02301 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Florida Atlantic Univ, Ctr Complex Syst & Brain Sci, Boca Raton, FL 33431 USA. Cornell Univ, Dept Psychol, Ithaca, NY 14853 USA. RP Snyder, JS (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, 116A,940 Belmont St, Brockton, MA 02301 USA. EM joel_snyder@hms.harvard.edu RI Snyder, Joel/B-4675-2008 OI Snyder, Joel/0000-0002-5565-3063 NR 49 TC 28 Z9 28 U1 1 U2 8 PU UNIV CALIFORNIA PRESS PI BERKELEY PA C/O JOURNALS DIVISION, 2000 CENTER ST, STE 303, BERKELEY, CA 94704-1223 USA SN 0730-7829 J9 MUSIC PERCEPT JI Music Percept. PD DEC PY 2006 VL 24 IS 2 BP 135 EP 145 DI 10.1525/mp.2006.24.2.135 PG 11 WC Music; Psychology, Experimental SC Music; Psychology GA 126WB UT WOS:000243545100003 ER PT J AU Lewis, K Ausubel, FM AF Lewis, Kim Ausubel, Frederick M. TI Prospects for plant-derived antibacterials SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID MULTIDRUG-RESISTANCE; STAPHYLOCOCCUS-AUREUS; ANTIBIOTIC-ACTIVITY; NATURAL-PRODUCTS; PUMP INHIBITORS; BERBERINE; IDENTIFICATION; BACTERIA; ANTIMICROBIALS; TIGECYCLINE C1 Northeastern Univ, Antimicrobial Discovery Ctr, Boston, MA 02115 USA. Northeastern Univ, Dept Biol, Boston, MA 02115 USA. Harvard Univ, Dept Genet, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Lewis, K (reprint author), Northeastern Univ, Antimicrobial Discovery Ctr, Boston, MA 02115 USA. EM k.lewis@neu.edu; ausubel@molbio.mgh.harvard.edu FU NIAID NIH HHS [AI059483, AI064332] NR 28 TC 137 Z9 147 U1 2 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD DEC PY 2006 VL 24 IS 12 BP 1504 EP 1507 DI 10.1038/nbt1206-1504 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 116IL UT WOS:000242795800024 PM 17160050 ER PT J AU Gray, NS AF Gray, Nathanael S. TI Drug discovery through industry-academic partnerships SO NATURE CHEMICAL BIOLOGY LA English DT Editorial Material ID HIV-1 PROTEASE; INHIBITORS; INNOVATION; SCREEN; MOUSE AB Translational research in academia is extending beyond the traditional involvement in clinical trials to the early phases of the drug discovery process. Examples of successful academic-industrial partnerships illustrate the ways in which they can enable the discovery of new medicines. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Gray, NS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave, Boston, MA 02115 USA. EM nathanael_gray@DFCI.harvard.edu NR 19 TC 18 Z9 18 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD DEC PY 2006 VL 2 IS 12 BP 649 EP 653 DI 10.1038/nchembio1206-649 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 107KC UT WOS:000242168800003 PM 17108976 ER PT J AU Levitsky, LL AF Levitsky, Lynne L. TI Cognitive dysfunction following treatment of Cushing's syndrome SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material DE cognition; Cushing's syndrome; quality of life; remission ID QUALITY-OF-LIFE C1 Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Levitsky, LL (reprint author), Massachusetts Gen Hosp, Pediat Endocrine Unit, Bartlett 410 X,55 Fruit St, Boston, MA 02114 USA. EM llevitsky@partners.org NR 6 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD DEC PY 2006 VL 2 IS 12 BP 666 EP 667 DI 10.1038/ncpendmet0344 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 111HS UT WOS:000242442600007 PM 17143312 ER PT J AU Cole, AJ AF Cole, Andrew J. TI New screening tool for identifying major depression in patients with epilepsy SO NATURE CLINICAL PRACTICE NEUROLOGY LA English DT Editorial Material DE antiepileptic drugs; epilepsy; major depression C1 Massachusetts Gen Hosp, MGH Epilepsy Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Epilepsy Res Lab, Boston, MA 02114 USA. RP Cole, AJ (reprint author), Massachusetts Gen Hosp, MGH Epilepsy Serv, Fruit St, Boston, MA 02114 USA. EM cole.andrew@mgh.harvard.edu NR 4 TC 4 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-834X J9 NAT CLIN PRACT NEURO JI Nat. Clin. Pract. Neurol. PD DEC PY 2006 VL 2 IS 12 BP 656 EP 657 DI 10.1038/ncpneuro0346 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 107KF UT WOS:000242169100008 PM 17117168 ER PT J AU Hagendoorn, J Padera, TP Yock, TI Nielsen, GP di Tomaso, E Duda, DG Delaney, TF Gaissert, HA Pearce, J Rosenberg, AE Jain, RK Ebb, DH AF Hagendoorn, Jeroen Padera, Timothy P. Yock, Torunn I. Nielsen, G. Petur di Tomaso, Emmanuelle Duda, Dan G. Delaney, Thomas F. Gaissert, Henning A. Pearce, Jennifer Rosenberg, Andrew E. Jain, Rakesh K. Ebb, David H. TI Platelet-derived growth factor receptor-beta in Gorham's disease SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Article DE Gorham's disease; imatinib mesylate; lymphangiomatosis; pediatric; platelet-derived growth factor (PDGF) ID MASSIVE OSTEOLYSIS; MOLECULAR REGULATION; CANCER-PATIENTS; THERAPY; LYMPHANGIOGENESIS; RADIATION AB Background A 17-year-old male presented with pain in his lower-left chest. He had no significant medical history and was previously in good health. He had a fractured ninth left anterior rib and the tenth, eleventh and twelfth ribs were absent, which was thought to be a congenital anomaly. Several months later, he presented again with back pain, an enlarging mass in the lower- left chest wall, erosion of the lateral pedicles of the lower thoracic vertebrae and pleural effusion. Investigations Physical examination, chest X-ray, MRI of the spine, incisional biopsy, serial CT imaging of the hemithorax, immunohistochemistry, flow cytometry, and enzyme-linked immunosorbent assays. Diagnosis Gorham's lymphangiomatosis with expression of platelet-derived growth factor receptor-beta and elevated circulating platelet-derived growth factor-BB. Management Spine stabilization, thalidomide, celecoxib, interferon-alpha 2b, pamidronate, zoledronate, thoracotomy, pleurectomy, talc pleurodesis, and imatinib mesylate. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol,Dept Radiat Oncol, Boston, MA 02114 USA. Univ Med Ctr Utrecht, Utrecht, Netherlands. RP Jain, RK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol,Dept Radiat Oncol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu OI Padera, Timothy/0000-0002-3453-9384 FU NCI NIH HHS [R01 CA085140, R01 CA085140-09, R01-CA85140] NR 18 TC 38 Z9 41 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD DEC PY 2006 VL 3 IS 12 BP 693 EP 697 DI 10.1038/ncponc0660 PG 5 WC Oncology SC Oncology GA 115BR UT WOS:000242710100010 PM 17139320 ER PT J AU Hinkes, B Wiggins, RC Gbadegesin, R Vlangos, CN Seelow, D Nurnberg, G Garg, P Verma, R Chaib, H Hoskins, BE Ashraf, S Becker, C Hennies, HC Goyal, M Wharram, BL Schachter, AD Mudumana, S Drummond, I Kerjaschki, D Waldherr, R Dietrich, A Ozaltin, F Bakkaloglu, A Cleper, R Basel-Vanagaite, L Pohl, M Griebel, M Tsygin, AN Soylu, A Muller, D Sorli, CS Bunney, TD Katan, M Liu, JH Attanasio, M O'Toole, JF Hasselbacher, K Mucha, B Otto, EA Airik, R Kispert, A Kelley, GG Smrcka, AV Gudermann, T Holzman, LB Nurnberg, P Hildebrandt, F AF Hinkes, Bernward Wiggins, Roger C. Gbadegesin, Rasheed Vlangos, Christopher N. Seelow, Dominik Nuernberg, Gudrun Garg, Puneet Verma, Rakesh Chaib, Hassan Hoskins, Bethan E. Ashraf, Shazia Becker, Christian Hennies, Hans Christian Goyal, Meera Wharram, Bryan L. Schachter, Asher D. Mudumana, Sudha Drummond, Iain Kerjaschki, Dontscho Waldherr, Ruediger Dietrich, Alexander Ozaltin, Fatih Bakkaloglu, Aysin Cleper, Roxana Basel-Vanagaite, Lina Pohl, Martin Griebel, Martin Tsygin, Alexey N. Soylu, Alper Mueller, Dominik Sorli, Caroline S. Bunney, Tom D. Katan, Matilda Liu, Jinhong Attanasio, Massimo O'Toole, John F. Hasselbacher, Katrin Mucha, Bettina Otto, Edgar A. Airik, Rannar Kispert, Andreas Kelley, Grant G. Smrcka, Alan V. Gudermann, Thomas Holzman, Lawrence B. Nuernberg, Peter Hildebrandt, Friedhelm TI Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible SO NATURE GENETICS LA English DT Article ID PHOSPHOLIPASE-C-EPSILON; FOCAL SEGMENTAL GLOMERULOSCLEROSIS; MESANGIAL SCLEROSIS; PODOCYTE DEPLETION; GLOMERULAR PROTEIN; DRASH-SYNDROME; NEPHRIN; PODOCALYXIN; EXPRESSION; IQGAP1 AB Nephrotic syndrome, a malfunction of the kidney glomerular filter, leads to proteinuria, edema and, in steroid-resistant nephrotic syndrome, end-stage kidney disease. Using positional cloning, we identified mutations in the phospholipase C epsilon gene (PLCE1) as causing early-onset nephrotic syndrome with end-stage kidney disease. Kidney histology of affected individuals showed diffuse mesangial sclerosis (DMS). Using immunofluorescence, we found PLC epsilon 1 expression in developing and mature glomerular podocytes and showed that DMS represents an arrest of normal glomerular development. We identified IQ motif-containing GTPase-activating protein 1 as a new interaction partner of PLC epsilon 1. Two siblings with a missense mutation in an exon encoding the PLCe1 catalytic domain showed histology characteristic of focal segmental glomerulosclerosis. Notably, two other affected individuals responded to therapy, making this the first report of a molecular cause of nephrotic syndrome that may resolve after therapy. These findings, together with the zebrafish model of human nephrotic syndrome generated by plce1 knockdown, open new inroads into pathophysiology and treatment mechanisms of nephrotic syndrome. C1 Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Cologne, Cologne Ctr Genom, Cologne, Germany. RZPD Deutsches Ressourcenzentrum Genomforsch GmbH, Berlin, Germany. Univ Cologne, Inst Genet, Cologne, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Childrens Hosp, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02129 USA. Univ Vienna, Clin Inst Pathol, A-1090 Vienna, Austria. Gerneinschaftspraxis Pathol, D-69115 Heidelberg, Germany. Univ Marburg, Dept Pharmacol & Toxicol, Marburg, Germany. Univ Hacettepe, Fac Med, Dept Pediat Nephrol, TR-06100 Ankara, Turkey. Schneider Childrens Med Ctr, Dept Med Genet, Petah Tiqwa, Israel. Rabin Med Ctr, Petah Tiqwa, Israel. Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. Univ Freiburg, Dept Pediat, D-79106 Freiburg, Germany. Tech Univ Munich, Childrens Hosp, Schwabing, Germany. Sci Ctr Childrens Hlth, Moscow, Russia. Dokuz Eylul Univ, Dept Pediat, Izmir, Turkey. Charite Childrens Hosp, Dept Pediat Nephrol, Berlin, Germany. Inst Canc Res, Chester Beatty Labs, Ctr Cell & Mol Biol, Canc Res UK, London SW3 6JB, England. Hannover Med Sch, Inst Mol Biol, D-30625 Hannover, Germany. SUNY Upstate Med Univ, Dept Med, Syracuse, NY 13210 USA. Univ Rochester, Sch Med, Dept Pharmacol & Physiol, Rochester, NY 14642 USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RP Hildebrandt, F (reprint author), Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. EM fhilde@umich.edu RI Dietrich, Alexander/G-8619-2013; OI Otto, Edgar/0000-0002-2387-9973; Mucha, Bettina/0000-0002-6410-7320; Dietrich, Alexander/0000-0002-1168-8707 FU NIDDK NIH HHS [DK46073, P50-DK039255, R01-DK53093, R01-DK56294]; NIGMS NIH HHS [R01-GM053536] NR 41 TC 276 Z9 306 U1 1 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2006 VL 38 IS 12 BP 1397 EP 1405 DI 10.1038/ng1918 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 110TR UT WOS:000242404200016 PM 17086182 ER PT J AU Bromley, SK Luster, AD AF Bromley, Shannon K. Luster, Andrew D. TI Turning up the heat on HEVs SO NATURE IMMUNOLOGY LA English DT Editorial Material ID RECEPTOR; FEVER; TEMPERATURE; CYTOKINE; GP130; IL-6 AB Fever is a beneficial systemic response to infection. Such a thermal increase triggers enhanced lymph node recruitment of lymphocytes by augmenting high endothelial venule expression of the homing molecules ICAM-1 and CCL21. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Charlestown, MA 02129 USA. RP Bromley, SK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Charlestown, MA 02129 USA. EM luster.andrew@mgh.harvard.edu NR 12 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2006 VL 7 IS 12 BP 1288 EP 1290 DI 10.1038/ni1206-1288 PG 3 WC Immunology SC Immunology GA 106TU UT WOS:000242125200010 PM 17110949 ER PT J AU Chen, Q Fisher, DT Clancy, KA Gauguet, JMM Wang, WC Unger, E Rose-John, S von Andrian, UH Baumann, H Evans, SS AF Chen, Qing Fisher, Daniel T. Clancy, Kristen A. Gauguet, Jean-Marc M. Wang, Wan-Chao Unger, Emily Rose-John, Stefan von Andrian, Ulrich H. Baumann, Heinz Evans, Sharon S. TI Fever-range thermal stress promotes lymphocyte trafficking across high endothelial venules via an interieukin 6 trans-signaling mechanism SO NATURE IMMUNOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; L-SELECTIN; IMMUNE-RESPONSE; CELLS; HYPERTHERMIA; NODES; CHEMOKINES; MIGRATION; RECEPTOR; INFLAMMATION AB Fever is an evolutionarily conserved response during acute inflammation, although its physiological benefit is poorly understood. Here we show thermal stress in the range of fever temperatures increased the intravascular display of two 'gatekeeper' homing molecules, intercellular adhesion molecule 1 (ICAM-1) and CCL21 chemokine, exclusively in high endothelial venules (HEVs) that are chief portals for the entry of blood-borne lymphocytes into lymphoid organs. Enhanced endothelial expression of ICAM-1 and CCL21 was linked to increased lymphocyte trafficking across HEVs. A bifurcation in the mechanisms controlling HEV adhesion was demonstrated by evidence that the thermal induction of ICAM-1 but not of CCL21 involved an interleukin 6 trans. signaling pathway. Our findings identify the 'HEV axis' as a thermally sensitive alert system that heightens immune surveillance during inflammation by amplifying lymphocyte trafficking to lymphoid organs. C1 Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Kiel, Dept Biochem, D-24098 Kiel, Germany. Roswell Pk Canc Inst, Rochester, NY 14623 USA. RP Evans, SS (reprint author), Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. EM sharon.evans@roswellpark.org RI Rose-John, Stefan/A-7998-2010; von Andrian, Ulrich/A-5775-2008 OI Rose-John, Stefan/0000-0002-7519-3279; FU NCI NIH HHS [CA79765, CA094045, CA16056, CA85580]; NIAID NIH HHS [AI061663, AI069259]; NIAMS NIH HHS [P30 AR 42689]; NIDDK NIH HHS [DK33886] NR 51 TC 107 Z9 114 U1 0 U2 5 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 DEC PY 2006 VL 7 IS 12 BP 1299 EP 1308 DI 10.1038/ni1406 PG 10 WC Immunology SC Immunology GA 106TU UT WOS:000242125200012 PM 17086187 ER PT J AU Yun, SH Tearney, GJ Vakoc, BJ Shishkov, M Oh, WY Desjardins, AE Suter, MJ Chan, RC Evans, JA Jang, IK Nishioka, NS de Boer, JF Bouma, BE AF Yun, Seok H. Tearney, Guillermo J. Vakoc, Benjamin J. Shishkov, Milen Oh, Wang Y. Desjardins, Adrien E. Suter, Melissa J. Chan, Raymond C. Evans, John A. Jang, Ik-Kyung Nishioka, Norman S. de Boer, Johannes F. Bouma, Brett E. TI Comprehensive volumetric optical microscopy in vivo SO NATURE MEDICINE LA English DT Article ID COHERENCE TOMOGRAPHY; ATHEROSCLEROTIC PLAQUES; LASER; ESOPHAGUS; DYSPLASIA; DIAGNOSIS AB Comprehensive volumetric microscopy of epithelial, mucosal and endothelial tissues in living human patients would have a profound impact in medicine by enabling diagnostic imaging at the cellular level over large surface areas. Considering the vast area of these tissues with respect to the desired sampling interval, achieving this goal requires rapid sampling. Although noninvasive diagnostic technologies are preferred, many applications could be served by minimally invasive instruments capable of accessing remote locations within the body. We have developed a fiber-optic imaging technique termed optical frequency-domain imaging (OFDI) that satisfies these requirements by rapidly acquiring high-resolution, cross-sectional images through flexible, narrow-diameter catheters. Using a prototype system, we show comprehensive microscopy of esophageal mucosa and of coronary arteries in vivo. Our pilot study results suggest that this technology may be a useful clinical tool for comprehensive diagnostic imaging for epithelial disease and for evaluating coronary pathology and iatrogenic effects. C1 Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, Biophys Program, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Gastroenterol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Cardiol, Boston, MA 02114 USA. RP Bouma, BE (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, 55 Fruit St, Boston, MA 02114 USA. EM bouma@helix.mgh.harvard.edu RI Oh, Wang-Yuhl/C-2055-2011; de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NCI NIH HHS [R01 CA103769, R33 CA110130, R01 CA103769-03, R33 CA110130-02]; NCRR NIH HHS [R01 RR0119768, R01 RR019768-02]; NHLBI NIH HHS [R01 HL070039, R01 HL070039-03, R01 HL076398, R01 HL076398-03] NR 29 TC 226 Z9 227 U1 1 U2 33 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2006 VL 12 IS 12 BP 1429 EP 1433 DI 10.1038/nm1450 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 113SS UT WOS:000242618200025 PM 17115049 ER PT J AU Braun, P Cusick, ME Vidal, M AF Braun, Pascal Cusick, Michael E. Vidal, Marc TI QUICKstep and GS-TAP: new moves for protein-interaction analysis SO NATURE METHODS LA English DT Editorial Material ID SACCHAROMYCES-CEREVISIAE; MASS-SPECTROMETRY; PROTEOMICS; COMPLEXES C1 Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Braun, P (reprint author), Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA. EM pascal_braun@dfci.harvard.edu OI Falter-Braun, Pascal/0000-0003-2012-6746 NR 12 TC 2 Z9 2 U1 0 U2 3 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 DEC PY 2006 VL 3 IS 12 BP 975 EP 976 DI 10.1038/nmeth1206-975 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 108BC UT WOS:000242213900014 PM 17117154 ER PT J AU Soltesz, I Staley, K AF Soltesz, Ivan Staley, Kevin TI High times for memory: cannabis disrupts temporal coordination among hippocampal neurons SO NATURE NEUROSCIENCE LA English DT Editorial Material ID OSCILLATIONS; INHIBITION; REVEAL C1 Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92697 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Soltesz, I (reprint author), Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92697 USA. EM kstaley@partners.org NR 12 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 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 2006 VL 9 IS 12 BP 1461 EP 1463 DI 10.1038/nn1206-1461 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 110TP UT WOS:000242404000002 PM 17128279 ER PT J AU Darrow, KN Maison, SF Liberman, MC AF Darrow, Keith N. Maison, Stephane F. Liberman, M. Charles TI Cochlear efferent feedback balances interaural sensitivity SO NATURE NEUROSCIENCE LA English DT Article ID BRAIN-STEM; RESPONSES; PATHWAYS; SYSTEM; MOUSE; NOISE; CAT AB Neurons in the lateral superior olive (LSO) compute sound location based on differences in interaural intensity, coded in ascending signals from the two cochleas. Unilateral destruction of the neuronal feedback from the LSO to the cochlea, the lateral olivocochlear efferents, disrupted the normal interaural correlation in response amplitudes to sounds of equal intensity. Thus, lateral olivocochlear feedback maintains the binaural balance in neural excitability required for accurate localization of sounds in space. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard & MIT, Program Speech & Hearing Biosci & Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM Charles_Liberman@meei.harvard.edu FU NIDCD NIH HHS [R01 DC000188, P30 DC005209, P30 DC5209, R01 DC0188, T32 DC000038, T32 DC0038] NR 14 TC 65 Z9 65 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 2006 VL 9 IS 12 BP 1474 EP 1476 DI 10.1038/mn1807 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 110TP UT WOS:000242404000009 PM 17115038 ER PT J AU Kelly, KA Waterman, P Weissleder, R AF Kelly, Kimberly A. Waterman, Peter Weissleder, Ralph TI In vivo imaging of molecularly targeted phage SO NEOPLASIA LA English DT Article DE phage display; screening; drug discovery; molecular imaging; systems biology ID DISPLAY LIBRARIES; DRUG DISCOVERY; MOUSE MODEL; PEPTIDES; EXPRESSION; CANCER; VASCULATURE; PROSTATE; BINDING; TUMORS AB Rapid identification of in vivo affinity ligands would have far-reaching applications for imaging specific molecular targets, in vivo systems imaging, and medical use. We have developed a high-throughput method for identifying and optimizing ligands to map and image biologic targets of interest in vivo. We directly labeled viable phage clones with far-red fluorochromes and comparatively imaged them in vivo by multichannel fluorescence ratio imaging. Using Secreted Protein Acidic and Rich in Cysteine (osteonectin) and vascular cell adhesion molecule-1 as model targets, we show that: 1) fluorescently labeled phage retains target specificity on labeling; 2) in vivo distribution can be quantitated (detection thresholds of similar to 300 phage/mm(3) tissue) throughout the entire depth of the tumor using fluorescent tomographic imaging; and 3) fluorescently labeled phage itself can serve as a replenishable molecular imaging agent. The described method should find widespread application in the rapid in vivo discovery and validation of affinity ligands and, importantly, in the use of fluorochrome-labeled phage clones as in vivo imaging agents. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Room 5403,Bldg 149,13th St, Charlestown, MA 02129 USA. EM weissleder@helix.mgh.harvard.edu NR 43 TC 57 Z9 59 U1 2 U2 9 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD DEC PY 2006 VL 8 IS 12 BP 1011 EP 1018 DI 10.1593/neo.06610 PG 8 WC Oncology SC Oncology GA 124VL UT WOS:000243398100005 PM 17217618 ER PT J AU Garcia-Alloza, M Robbins, EM Zhang-Nunes, SX Purcell, SM Betensky, RA Raju, S Prada, C Greenberg, SM Bacskai, BJ Frosch, MP AF Garcia-Alloza, Monica Robbins, Elissa M. Zhang-Nunes, Sandy X. Purcell, Susan M. Betensky, Rebecca A. Raju, Susan Prada, Claudia Greenberg, Steven M. Bacskai, Brian J. Frosch, Matthew P. TI Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease SO NEUROBIOLOGY OF DISEASE LA English DT Article DE APPswe/PS1dE9; transgenic mouse; Alzheimer disease; cerebral amyloid angiopathy; amyloid-beta ID TRANSGENIC MICE; A-BETA; PRECURSOR-PROTEIN; SENILE PLAQUES; IN-VIVO; MULTIPHOTON MICROSCOPY; MUTANT PRESENILIN-1; APOLIPOPROTEIN-E; MEMORY DEFICITS; ANGIOPATHY AB Transgenic mice carrying disease-linked forms of genes associated with Alzheimer disease often demonstrate deposition of the beta-amyloid as senile plaques and cerebral amyloid angiopathy. We have characterized the natural history of beta-amyloid deposition in APPswe/PS1dE9 mice, a particularly aggressive transgenic mouse model generated with mutant transgenes for APP (APPswe: KM594/5NL) and PS1 (dE9: deletion of exon 9). Ex vivo histochemistry showed A beta deposition by 4 months with a progressive increase in plaque number up to 12 months and a similar increase of A beta levels. In vivo multiphoton microscopy at weekly intervals showed increasing beta-amyloid deposition as CAA and plaques. Although first appearing at an early age, CAA progressed at a significantly slower rate than in the Tg2576 mice. The consistent and early onset of beta-amyloid accumulation in the APPswe/PS1dE9 model confirms its utility for studies of biochemical and pathological mechanisms underlying P-amyloid deposition, as well as exploring new therapeutic treatments. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Alzheimers Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Frosch, MP (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimers Res Unit, B1114-2700,114 16th St, Charlestown, MA 02129 USA. EM mfrosch@partners.org OI Garcia-Alloza, Monica/0000-0003-1610-4114 FU NIA NIH HHS [AG020570, AG021084]; NIBIB NIH HHS [EB000768] NR 45 TC 290 Z9 294 U1 1 U2 23 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 DEC PY 2006 VL 24 IS 3 BP 516 EP 524 DI 10.1016/j.nbd.2006.08.017 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 109HN UT WOS:000242298900009 PM 17029828 ER PT J AU Vasios, CE Angelone, LM Purdon, PL Ahveninen, J Belliveau, JW Bonmassar, G AF Vasios, Christos E. Angelone, Leonardo M. Purdon, Patrick L. Ahveninen, Jyrki Belliveau, John W. Bonmassar, Giorgio TI EEG/(f)MRI measurements at 7 Tesla using a new EEG cap ("InkCap") SO NEUROIMAGE LA English DT Article DE EEG; MRI; conductive ink; Eddy currents; SAR; motion sensors ID FUNCTIONAL MRI; EVOKED POTENTIALS; CORTICAL ACTIVITY; AUDITORY-CORTEX; FMRI; ELECTRODES; ARTIFACT; ELECTROENCEPHALOGRAM; TEMPERATURE; RESPONSES AB We aimed at improving the signal-to-noise ratio (SNR) of electroencephalography (EEG) during magnetic resonance imaging (MRI) by introducing a new EEG cap ("InkCap") based on conductive ink technology. The InkCap was tested with temperature measurements on an electrically conductive phantom head and during structural and functional MRI (fMRI) recordings in 11 healthy human volunteers at 7 T. Combined EEG/fMRI measurements were conducted to study the interaction between the two modalities. The EEG recordings with the InkCap demonstrated up to a five-fold average decrease in signal variance during echo-planar imaging, with respect to a cap made of standard carbon fiber leads. During concurrent EEG/fMRI measurements in human volunteers, alpha oscillations were clearly detected at 7 T. Minimal artifacts were present in the T2* and high-resolution structural MR images of the brain parenchyma. Our results show that the InkCap technology considerably improves the quality of both EEG and (f)MRI during concurrent measurements even at 7 T. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA. RP Vasios, CE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St, Charlestown, MA 02129 USA. EM cvasios@nmr.mgh.harvard.edu OI Angelone, Leonardo/0000-0002-1105-021X FU NCRR NIH HHS [P41 RR14075]; NIBIB NIH HHS [R01 EB002459]; NICHD NIH HHS [HD 040712]; NINDS NIH HHS [R01 NS037462] NR 43 TC 32 Z9 33 U1 2 U2 5 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 DEC PY 2006 VL 33 IS 4 BP 1082 EP 1092 DI 10.1016/j.neuroimage.2006.07.038 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 108TU UT WOS:000242262900007 PM 17035045 ER PT J AU Hanemann, CO Bartelt-Kirbach, B Diebold, R Kampchen, K Langmesser, S Utermark, T AF Hanemann, C. O. Bartelt-Kirbach, B. Diebold, R. Kaempchen, K. Langmesser, S. Utermark, T. TI Differential gene expression between human schwannoma and control Schwann cells SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Article DE cells cultured; gene expression; human; neurofibromatosis; Schwann cells; schwannoma ID NF2 TUMOR-SUPPRESSOR; GROWTH-FACTOR-I; PERIPHERAL NERVOUS-SYSTEM; NEUROFIBROMATOSIS TYPE-2; PHOSPHATIDYLINOSITOL 3-KINASE; VESTIBULAR SCHWANNOMAS; PRION PROTEIN; CANCER-RISK; MERLIN; BINDING AB The NF2 gene encodes the tumour suppressor protein merlin. The mutation of a single allele of this gene causes the autosomal dominantly inherited disease neurofibromatosis type 2 (NF2), which is characterized mainly by vestibular schwannoma carrying a second hit mutation. Complete lack of merlin is also found in spontaneous schwannomas and meningiomas. As the events leading to schwannoma development are largely unknown we investigated the differences in gene expression between schwannoma cells from NF2 patients and normal human primary Schwann cells by cDNA array analysis. We identified 41 genes whose expression levels differed by more than factor 2. Most of these clones were corroborated by real-time reverse transcription polymerase chain reaction analysis. By this method a total of seven genes with increased and seven genes with decreased mRNA levels in schwannoma compared with normal Schwann cells could be identified. Regulated clones, some of which not been described in Schwann cells earlier, included matrix metalloproteinase's, growth factors, growth factor receptors and tyrosine kinases. C1 Peninsula Med Sch, Inst Biomed & Clin Sci, Plymouth PL6 8BU, Devon, England. Univ Ulm, Dept Heurol, Clin Res Ctr, Ulm, Germany. Univ Fribourg, Inst Biochim, CH-1700 Fribourg, Switzerland. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Hanemann, CO (reprint author), Peninsula Med Sch, Inst Biomed & Clin Sci, Tamar Sci Pk,Res Way, Plymouth PL6 8BU, Devon, England. EM oliver.hanemann@pms.ac.uk OI Hanemann, Clemens Oliver/0000-0002-1951-1025 NR 62 TC 28 Z9 29 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD DEC PY 2006 VL 32 IS 6 BP 605 EP 614 DI 10.1111/j.1365-2990.2006.00769.x PG 10 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 101XM UT WOS:000241774600005 PM 17083475 ER PT J AU Britton, J Williams, D Gold, AL Feczko, EJ Rauch, SL Wright, CI AF Britton, Jennifer Williams, Danielle Gold, Andrea L. Feczko, Eric J. Rauch, Scott L. Wright, Christopher I. TI Acute high dose D-cycloserine blunts early amygdala response to facial expressions SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S149 EP S150 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900405 ER PT J AU Childress, A Ehrman, R Wang, Z Li, Y Goldman, M Kampman, K Hakun, J Bernstiel, R Detre, J O'Brien, CP AF Childress, Anna Ehrman, Ronald Wang, Ze Li, Yin Goldman, Marina Kampman, Kyle Hakun, Jonathan Bernstiel, Ron Detre, John O'Brien, Charles P. TI Can the Gaba B agonist baclofen prevent limbic activation by both "seen" and "unseen" cocaine cues? SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Philadelphia VA Med Ctr, VA VISN 4 MIRECC, Philadelphia, PA USA. RI Wang, Ze/A-1043-2007 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S73 EP S73 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900216 ER PT J AU Dougherty, DD Bulhmann, U Rebecca, L Rauch, SL Deckersbach, T AF Dougherty, Darin D. Bulhmann, Ulrike Rebecca, Loh Rauch, Scott L. Deckersbach, Thilo TI The influence of negative affect on working memory in bipolar-I disorder patients and healthy volunteers: An fMRI investigation SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S105 EP S105 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900294 ER PT J AU Evans, KC Simon, NM Dougherty, DD Hoge, EA Worthington, JJ Chow, C Gold, A Fischman, AJ Pollack, MH Rauch, SL AF Evans, Karleyton C. Simon, Naomi M. Dougherty, Darin D. Hoge, Elizabeth A. Worthington, John J. Chow, Candice Gold, Andrea Fischman, Alan J. Pollack, Mark H. Rauch, Sott L. TI A PET study of tiagabine treatment implicates ventral medial prefrontal cortex in generalized social anxiety disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S151 EP S151 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900409 ER PT J AU Fava, M AF Fava, Maurizio TI Moderators of response to next-step strategies in resistant depression SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S38 EP S38 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900114 ER PT J AU Gold, AL Shin, LM Orr, SP Rauch, SL Pitman, RK AF Gold, Andrea L. Shin, Lisa M. Orr, Scott P. Rauch, Scott L. Pitman, Roger K. TI Decreased regional cerebral blood flow in the medial prefrontal cortex during non-traumatic stressful imagery in Vietnam veterans with PTSD SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S215 EP S216 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900571 ER PT J AU Haroutunian, V Gibson, G Pasinetti, GM AF Haroutunian, Vahram Gibson, Gary Pasinetti, Giulio M. TI Insulin receptor deficits in schizophrenia and in cellular and animal models of insulin receptor dysfunction SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Bronx Vet Affairs Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S17 EP S17 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900054 ER PT J AU Khachaturian, AS Zandi, PP Lyketsos, CG Hayden, KM Skoog, I Norton, MC Tschanz, JT Mayer, L Welsh-Bohmer, KA Breitner, JC AF Khachaturian, Ara S. Zandi, Peter P. Lyketsos, Constantine G. Hayden, Kathleen M. Skoog, Ingmar Norton, Maria C. Tschanz, JoAnn T. Mayer, Lawrence Welsh-Bohmer, Kathleen A. Breitner, John C. TI Antihypertensive medication use and incident Alzheimer disease: The cache county study SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Univ Washington, Sch Med, Div Geriatr Psychiat, VA Puget Sound Hlth Care Syst, Seattle, WA USA. RI Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013; Hayden, Kathleen/B-6442-2012 OI Hayden, Kathleen/0000-0002-7745-3513 NR 0 TC 2 Z9 2 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S39 EP S39 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900116 ER PT J AU Manoach, DS Polli, FE Thakkar, KN Ketwaroo, GA Goff, DC Tuch, DS Barton, JJ AF Manoach, Dara S. Polli, Frida E. Thakkar, Katharine N. Ketwaroo, G. A. Goff, Donald C. Tuch, David S. Barton, Jason J. TI Structural and functional abnormalities of the anterior cingulate cortex contribute to executive dysfunction in schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Charlestown, MA USA. RI Barton, Jason/A-6362-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S120 EP S120 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900331 ER PT J AU Milad, MR Orr, SP Pitman, RK Fischl, B Quirk, GJ Rauch, SL AF Milad, Mohammed R. Orr, Scott P. Pitman, Roger K. Fischl, Bruce Quirk, Gregory J. Rauch, Scott L. TI Functional and structural correlates of conditioned fear in human dorsal anterior cingulate cortex SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Harvard Med Sch, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S224 EP S225 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900592 ER PT J AU Papakostas, GI Fava, M AF Papakostas, George I. Fava, Maurizio TI Does the probability of receiving placebo influence the likelihood of responding to placebo or clinical trial outcome? A meta-regression of double-blind, randomized clinical trials in MDD SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA. RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 NR 0 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S158 EP S158 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900426 ER PT J AU Perlis, RH Houston, JP Sutton, VK Adams, DH Farmen, M Breier, A AF Perlis, Roy H. Houston, John P. Sutton, Virginia K. Adams, David H. Farmen, Mark Breier, Alan TI Genetic association study of treatment response with olanzapine/fluoxetine combination or lamotrigine in bipolar I depression SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S229 EP S229 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900605 ER PT J AU Pitman, RK Brunet, A Orr, SP Tremblay, J Nader, K AF Pitman, Roger K. Brunet, Alain Orr, Scott P. Tremblay, Jacques Nader, Karim TI A novel treatment for post-traumatic stress disorder by reconsolidation blockade with propranolol SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Harvard Med Sch, Charlestown, MA USA. NR 0 TC 3 Z9 3 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S8 EP S9 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900026 ER PT J AU Pollack, M Kinrys, G Krystal, A McCall, WV Roth, T Schaefer, K Rubens, R Roach, J Huang, H Krishnan, R AF Pollack, Mark Kinrys, Gustavo Krystal, Andrew McCall, W. Vaughn Roth, Thomas Schaefer, Kendyl Rubens, Robert Roach, Jim Huang, Holly Krishnan, Ranga TI Evaluation of eszopiclone and escitalopram oxalate co-therapy in patients with generalized anxiety disorder and insomnia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Krystal, Andrew/J-7109-2013 OI Krystal, Andrew/0000-0002-6702-781X NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S173 EP S173 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900465 ER PT J AU Raskind, MA Taylor, F Peskind, ER AF Raskind, Murray A. Taylor, Fletcher Peskind, Elaine R. TI The alpha-1 adrenoreceptor antagonist prazosin improves combat veteran and civilian posttraumatic stress disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 VA Puget Sound HCS, Mental Hlth Serv, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S54 EP S54 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900162 ER PT J AU Rauch, SL Dougherty, DD Eskandar, E Fischman, AJ Jameson, M Cosgrove, GR AF Rauch, Scott L. Dougherty, Darin D. Eskandar, Emad Fischman, Alan J. Jameson, Mariko Cosgrove, G. R. TI PET predictor of OCD response to anterior cingulotomy: Replication of findings suggests potential clinical utility SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Harvard Med Sch, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S217 EP S217 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900575 ER PT J AU Tsokas, P Ma, T Blitzer, RD Landau, EM AF Tsokas, Panayiotis Ma, Tao Blitzer, Robert D. Landau, Emmanuel M. TI Tagging and capture in synaptic plasticity SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 James J VAMC, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S188 EP S189 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900504 ER PT J AU Weiss, AP Jubelt, LE Barr, RS Goff, DC Rigotti, NA Evins, AE AF Weiss, Anthony P. Jubelt, Lindsay E. Barr, Ruth S. Goff, Donald C. Rigotti, Nancy A. Evins, A. E. TI The effect of transdermal nicotine on episodic memory performance in non-smoking patients with schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the American-College-of-Neuropsychopharmacolgy CY DEC 03-07, 2006 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2006 VL 31 SU 1 BP S112 EP S113 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 108BS UT WOS:000242215900313 ER PT J AU Proctor, SP Heaton, KJ Heeren, T White, RF AF Proctor, Susan P. Heaton, Kristin J. Heeren, Tim White, Roberta F. TI Effects of sarin and cyclosarin exposure during the 1991 Gulf War on neurobehavioral functioning in US army veterans SO NEUROTOXICOLOGY LA English DT Article DE sarin; neurobehavioral functioning; central nervous system effects; exposure assessment; Gulf War veterans ID LOW-LEVEL EXPOSURE; CHEMICAL MUNITIONS DESTRUCTION; POSTTRAUMATIC-STRESS-DISORDER; TOKYO SUBWAY; NERVOUS-SYSTEM; GUINEA-PIGS; LONG-TERM; HEALTH; KHAMISIYAH; AGENTS AB Background: During the Gulf War (GW), in early March 1991, a munitions dump at Khamisiyah, Iraq, was destroyed. Later, in 1996, the dump was found to have contained the organophosphate chemical warfare agents, sarin and cyclosarin. Methods: Data collected in a study conducted between 1994 and 1996, before the Khamisiyah incident was publicly disclosed, were used to examine neurobehavioral task performances of GW veterans (n = 140) categorized as having received high, moderate, or low-to-no exposure dose levels to sarin and cyclosarin at Khamisiyah, Iraq. Exposure levels were based on modeled estimates of the exposure plume and on troop location information at the time of the Khamisiyah event. Based on recent findings observed in follow-up studies of persons exposed to sarin during the 1995 terrorist attacks in Japan, we hypothesized that exposure to sarin and cyclosarin would be associated with poorer performances on objective neurobehavioral tasks in specific functional domains (particularly in visuospatial abilities and psychomotor functioning) in a dose-dependent manner. Results: Sarin and cyclosarin exposure was significantly associated with less proficient neurobehavioral functioning on tasks involving fine psychomotor dexterity and visuospatial abilities 4-5 years after exposure. Conclusions: Findings suggest a dose-response association between low-level exposure to sarin and cyclosarin and specific functional central nervous system effects 4-5 years after exposure. (c) 2006 Elsevier Inc. All rights reserved. C1 VA Boston Healthcare Syst, Boston Environm Hazards Ctr, Boston, MA 02130 USA. Boston Univ, Sch Publ Hlth Environm Hlth, Boston, MA 02215 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. USA, Res Inst Environm Med, Mil Performance Div, Natick, MA USA. Boston Univ, Sch Publ Hlth Biostat, Boston, MA 02215 USA. Boston Univ, Sch Med Neurol, Boston, MA 02215 USA. RP Proctor, SP (reprint author), VA Boston Healthcare Syst, Boston Environm Hazards Ctr, 116B-4,150 S Huntington Ave, Boston, MA 02130 USA. EM sproctor@bu.edu RI Heaton, Kristin/E-3660-2013; OI Heeren, Timothy/0000-0001-5643-3559 NR 61 TC 46 Z9 47 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2006 VL 27 IS 6 BP 931 EP 939 DI 10.1016/j.neuro.2006.08.001 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 122FO UT WOS:000243211300001 PM 16982099 ER PT J AU Herbert, M AF Herbert, Martha TI Autism: A brain disorder or a disorder that affects the brain? SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 23rd International Neurotoxicology Conference CY SEP 17-21, 2006 CL Little Rock, AR DE autism; brain; complex systems; connectivity; gene-environment interaction C1 Harvard Univ, Massachusetts Gen Hosp, Harvard Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2006 VL 27 IS 6 BP 1151 EP 1152 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 122FO UT WOS:000243211300037 ER PT J AU Herbert, M Pessah, I AF Herbert, Martha Pessah, Isaac TI Advancing the science of autism spectrum disorders: Introduction and overview. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 23rd International Neurotoxicology Conference CY SEP 17-21, 2006 CL Little Rock, AR C1 Harvard Univ, Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA. Univ Calif Davis, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2006 VL 27 IS 6 BP 1154 EP 1154 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 122FO UT WOS:000243211300044 ER PT J AU Heaton, KJ Palumbo, CL Proctor, SP Killany, RJ Yurgelun-Todd, DA White, RF AF Heaton, K. J. Palumbo, C. L. Proctor, S. P. Killany, R. J. Yurgelun-Todd, D. A. White, R. F. TI Quantitative magnetic resonance brain imaging of us army veterans with presumptive exposures to sarin and cyclosarin during the 1991 Gulf War. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 23rd International Neurotoxicology Conference CY SEP 17-21, 2006 CL Little Rock, AR C1 USA, Environm Med Res Inst, Mil Performance Div, Natick, MA 01760 USA. Boston Environm Hazards Res Ctr, VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. Harvard Med Sch, Dept Psychiat, Boston, MA USA. McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. RI Heaton, Kristin/E-3660-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2006 VL 27 IS 6 BP 1177 EP 1177 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 122FO UT WOS:000243211300109 ER PT J AU Graham, AL Papandonatos, GD Bock, BC Cobb, NK Baskin-Sommers, A Niaura, R Abrams, DB AF Graham, Amanda L. Papandonatos, George D. Bock, Beth C. Cobb, Nathan K. Baskin-Sommers, Arielle Niaura, Raymond Abrams, David B. TI Internet- vs. telephone-administered questionnaires in a randomized trial of smoking cessation SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID NICOTINE DEPENDENCE; PARTNER SUPPORT; SOCIAL SUPPORT; WEIGHTED KAPPA; LIFE-SPAN; AGREEMENT; RELAPSE; WEB; INTERVENTION; ABSTINENCE AB The Internet offers a promising channel to conduct smoking cessation research. Among the advantages of Internet research are the ability to access large numbers of participants who might not otherwise participate in a cessation trial, and the ability to conduct research efficiently and cost-effectively. To leverage the opportunity of the Internet in clinical research, it is necessary to establish that measures of known validity used in research trials are reliable when administered via the Internet. To date, no published studies examine the psychometric properties of measures administered via the Internet to assess smoking variables and psychosocial constructs related to cessation (e.g., stress, social support, quit methods). The purpose of the present study was to examine the reliability of measures of previous quit methods, perceived stress, depression, social support for cessation, smoking temptations, alcohol use, perceived health status, and income when administered via the Internet. Participants in the present study were enrolled in a randomized controlled trial of the efficacy of Internet smoking cessation. Following baseline telephone assessment and randomization into the parent trial, participants were recruited to the reliability substudy. An e-mail was sent 2 days after the telephone assessment with a link to the Internet survey and instructions to complete the survey that day. Of the 297 individuals invited to participate, 213 completed the survey within I week. Results indicate that the internal consistency and test-retest reliability of the measures examined are comparable when self-administered via the Internet or when interviewer-administered via telephone. C1 Brown Univ, Sch Med, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. Brown Univ, Miriam Hosp, Sch Med, Ctr Behav Med, Providence, RI USA. Brown Univ, Miriam Hosp, Sch Med, Ctr Prevent Med, Providence, RI USA. Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Brown Univ, Sch Med, Butler Hosp, Providence, RI 02912 USA. NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. RP Graham, AL (reprint author), Georgetown Univ, Med Ctr, Dept Oncol, 3300 Whitehaven St,NW,Suite 4100, Washington, DC 20007 USA. EM Amanda_Graham@brown.edu RI Papandonatos, George/J-2328-2014; OI Papandonatos, George/0000-0001-6770-932X; Baskin-Sommers, Arielle/0000-0001-6773-0508; Cobb, Nathan/0000-0003-4210-226X; Graham, Amanda/0000-0003-3036-9653 FU NCI NIH HHS [R01 CA104836-04, 5R01CA104836-02, R01 CA104836] NR 40 TC 28 Z9 28 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD DEC PY 2006 VL 8 SU 1 BP S49 EP S57 DI 10.1080/14622200601045367 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 132ZJ UT WOS:000243981100008 PM 17491171 ER PT J AU Graham, AL Bock, BC Cobb, NK Niaura, R Abrams, DB AF Graham, Amanda L. Bock, Beth C. Cobb, Nathan K. Niaura, Raymond Abrams, David B. TI Characteristics of smokers reached and recruited to an Internet smoking cessation trial: A case of denominators SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID DEPENDENCE; PROGRAM AB The Internet can deliver smoking cessation interventions to large numbers of smokers. Little is known about the feasibility, reach, or efficacy of Internet cessation interventions. Virtually no data exist on who enrolls in cessation programs or on differences between those who complete enrollment and those who do not. This paper reports recruitment and enrollment findings for the first 764 participants in an ongoing randomized controlled trial that tested the efficacy of a widely disseminated Internet smoking cessation service (www.QuitNet.com) alone and in conjunction with telephone counseling. Study participants were recruited through Internet search engines using an active user sampling protocol. During the first 16 weeks of the study, 28,297 individuals were invited. Of those, 11,147 accepted the invitation, 5,557 screened eligible, 3,614 were recruited, 1,489 provided online informed consent, and 764 were confirmed eligible and enrolled. Of those who were at least curious about a cessation trial (n=11,147), 6.9% enrolled. Of those who were eligible and recruited (n=3,614), 21.1% enrolled. Depending on the denominator selected, results suggest that 7% to 21% of smokers interested in cessation will enroll into a research trial. Internet recruitment provides unique challenges and opportunities for managing sample recruitment, analyzing sulisamples to determine generalizability, and understanding the characteristics of individuals who participate in online research. C1 Brown Univ, Ctr Alcohol & Addict Studies, Sch Med, Providence, RI 02912 USA. Brown Univ, Ctr Behav & Prevent Med, Sch Med, Miriam Hosp, Providence, RI 02912 USA. Massachusetts Gen Hosp, Pulm & Crit Care Univ, Boston, MA 02114 USA. Butler Hosp, Brown Med Sch, Providence, RI 02906 USA. NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. RP Graham, AL (reprint author), Georgetown Univ, Med Ctr, Dept Oncol, 3300 Whitehaven St,NW,Suite 4100, Washington, DC 20007 USA. EM Amanda_Graham@brown.edu OI Cobb, Nathan/0000-0003-4210-226X; Graham, Amanda/0000-0003-3036-9653 FU NCI NIH HHS [R01 CA104836-04, R01 CA104836, 5R01CA104836-02] NR 18 TC 48 Z9 48 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD DEC PY 2006 VL 8 SU 1 BP S43 EP S48 DI 10.1080/14622200601042521 PG 6 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 132ZJ UT WOS:000243981100007 PM 17491170 ER PT J AU Weinger, K Lee, J AF Weinger, Katie Lee, Jarim TI Psychosocial and psychiatric challenges of diabetes mellitus SO NURSING CLINICS OF NORTH AMERICA LA English DT Article ID COGNITIVE-BEHAVIOR THERAPY; EUROPEAN-AMERICAN PATIENTS; POOR GLYCEMIC CONTROL; EATING-DISORDERS; DISEASE MANAGEMENT; INTELLECTUAL DEFICITS; COMORBID DEPRESSION; INTENSIVE TREATMENT; INSULIN OMISSION; PROBLEM AREAS AB Diabetes mellitus is a chronic endocrine disorder that places considerable psychologic stress on individuals and their families. This article discusses psychosocial issues associated with diabetes and its management, and common psychiatric disorders in diabetes population. Psychosocial challenges and psychiatric disorders in people with diabetes can hinder patients' successful diabetes self-management and well-being. An understanding of mental health issues in diabetes is critical for all health care professionals who provide treatment to people with diabetes. C1 Joslin Diabet Ctr, Sect Behav & Mental Hlth Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Weinger, K (reprint author), Joslin Diabet Ctr, Sect Behav & Mental Hlth Res, 1 Joslin Pl, Boston, MA 02115 USA. EM katie.weinger@joslin.harvard.edu FU NIDDK NIH HHS [P30 DK36836, R01 DK60115] NR 88 TC 9 Z9 17 U1 5 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD DEC PY 2006 VL 41 IS 4 BP 667 EP + DI 10.1016/j.cnur.2006.07.002 PG 15 WC Nursing SC Nursing GA 105HM UT WOS:000242021000013 PM 17059981 ER PT J AU Zhang, YY Gottardo, L Thompson, R Powers, C Nolan, D Duffy, J Marescotti, MC Avogaro, A Doria, A AF Zhang, Yuan-Yuan Gottardo, Lucia Thompson, Ryan Powers, Christine Nolan, David Duffy, Jill Marescotti, Maria Cristina Avogaro, Angelo Doria, Alessandro TI A visfatin promoter polymorphism is associated with low-grade inflammation and type 2 diabetes SO OBESITY LA English DT Article DE genetics; inflammation; type 2 diabetes; visfatin/pre-B; cell colony-enhancing factor ID COLONY-ENHANCING FACTOR; VISCERAL ADIPOSE-TISSUE; HUMAN FETAL MEMBRANES; EXPRESSION; GENE; INSULIN; FAT; MELLITUS; HUMANS; PHASE AB Visfatin (also known as pre-B cell colony-enhancing factor, or PBEF) is a pro-inflammator, adipokine expressed prey dominantly in visceral fat. We investigated whether polymorphisms at the visfatin/PBEF locus influence the risk of type 2 diabetes (T2D). Linkage disequilibrium analysis of 52 single nucleotide polymorphisms spanning the entire gene (34.7 kb) plus 20.5 kb of the upstream region and 25.5 kb of the downstream region revealed a single haplotype block that could be tagged by seven single nucleotide polymorphisms. These seven tags were typed in a group of T2D patients (n = 814) and a group of non-diabetic controls (n = 320) of white origin. A significant association was observed at -948C > A, with minor allele frequencies of 0.157 in T2D cases and 0.119 in non-diabetic controls (p = 0.021). In a non-diabetic population (n = 630), the same -948 allele that conferred increased risk of T2D was significantly associated with higher plasma levels of fibrinogen and C-reactive protein (p = 0.0022 and 0.0038, respectively). However, no significant associations were observed with BMI, waist circumference, serum glucose levels, or fasting insulin levels. Our findings suggest that the visfatin/PBEF gene may play a role in determining T2D susceptibility, possibly by modulating chronic, low-grade inflammatory responses. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Padua, Dept Clin & Expt Med, Padua, Italy. RP Doria, A (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM alessandro.doria@joslin.harvard.edu FU NHLBI NIH HHS [HL71981, HL73168]; NIDDK NIH HHS [DK36836, DK60837] NR 25 TC 57 Z9 75 U1 0 U2 2 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1930-7381 J9 OBESITY JI Obesity PD DEC PY 2006 VL 14 IS 12 BP 2119 EP 2126 DI 10.1038/oby.2006.247 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 212OH UT WOS:000249606200001 PM 17189536 ER PT J AU Soares, CN Joffe, H Rubens, R Caron, J Roth, T Cohen, L AF Soares, Claudio N. Joffe, Hadine Rubens, Robert Caron, Judy Roth, Thomas Cohen, Lee TI Eszopiclone in patients with insomnia during perimenopause and early postmenopause - A randomized controlled trial SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID ESTROGEN PLUS PROGESTIN; QUALITY-OF-LIFE; MENOPAUSAL SYMPTOMS; DOUBLE-BLIND; SLEEP; WOMEN; POPULATION; EFFICACY AB Objective: To evaluate eszopiclone 3 mg for treatment of insomnia in perimenopausal and early postmenopausal women, as well as the impact of insomnia treatment on mood, menopause-related symptoms, and quality of life. Methods: This was a double-blind, placebo-controlled study with 410 women (aged 40-60; perimenopausal or early postmenopausal) who reported insomnia defined as sleep latency of at least 45 minutes and total sleep time less than or equal to 6 hours per night for at least 3 nights per week over the previous month. Patients were randomly assigned to eszopiclone 3 mg or placebo nightly for 4 weeks. Sleep data were collected once a day. Physician global assessments of menopause, menopause-specific questionnaire, Greene Climacteric Scale, the Montgomery Asberg Depression Rating Scale, and the Sheehan Disability Scale were collected at baseline and end of treatment. Results: Patients receiving eszopiclone reported improvements in sleep induction, sleep maintenance, sleep duration, sleep quality, and next-day functioning relative to placebo (P<.05). Patients receiving eszopiclone reported fewer total awakenings and awakenings due to hot flushes (P<.05). Eszopiclone use led to greater improvement in Montgomery Asberg Depression Rating Scale scores (P<.05) and physician global assessments of menopause scores (P<.001); total Greene Climacteric Scale score and the vasomotor and psychological subscores (P<.05); vasomotor and physical domains of the menopause- specific questionnaire (P<.05); and family life/home domain of the Sheehan Disability Scale (P<.05). Conclusion: In this study, eszopiclone provided significant improvements in sleep and positively impacted mood, quality of life, and menopause-related symptoms in perimenopausal and early postmenopausal women with insomnia. C1 McMaster Univ, Womens Hlth Concerns Clin, Dept Psychiat & Behav Neurosci, Hamilton, ON L8P 3B6, Canada. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Sepracor Inc, Marlborough, MA USA. Henry Ford Hosp, Sleep Ctr, Dept Psychiat & Behav Neurosci, Detroit, MI USA. RP Soares, CN (reprint author), McMaster Univ, Womens Hlth Concerns Clin, Dept Psychiat & Behav Neurosci, 301 James St S,FB 638, Hamilton, ON L8P 3B6, Canada. EM csoares@mcmaster.ca NR 26 TC 58 Z9 59 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 DEC PY 2006 VL 108 IS 6 BP 1402 EP 1410 DI 10.1097/01.AOG.0000245449.97365.97 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171XX UT WOS:000246769800010 PM 17138773 ER PT J AU Gordon, LK Goldhardt, R Holland, GN Yu, F Levinson, RD AF Gordon, Lynn K. Goldhardt, Raquel Holland, Gary N. Yu, Fei Levinson, Ralph D. TI Standardized visual field assessment for patients with birdshot chorioretinopathy SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE birdshot chorioretinopathy; retinochoroidopathy; HLA-A29; optic disc edema; visual field; choroidal lesions ID NEURITIS TREATMENT TRIAL; OPTIC NEURITIS; FOLLOW-UP; THRESHOLD ALGORITHMS; FULL THRESHOLD; RETINOCHOROIDOPATHY; CYCLOSPORINE; THERAPY; PROFILE AB Purpose: To adapt a standardized technique for assessment of visual fields to the study of patients with birdshot chorioretinopathy and to describe visual field patterns and changes over time for affected individuals. Methods: A retrospective chart review was performed of patients with a diagnosis of birdshot chorioretinopathy who had undergone at least two automated visual field studies. A masked evaluation of each visual field was performed using standardized criteria. Subjective symptoms and visual acuity measurements were compared to visual field data from the same examination dates. Serial visual field studies were evaluated for changes in the findings over time. Results: Six patients met inclusion criteria. A total of 104 visual field studies ( ranging from 2 - 19 studies per eye) were evaluated. Visual field abnormalities occurred in all tested eyes and were observed even in eyes with a Snellen visual acuity of 20/15. Discordant patterns were observed in the two eyes of some individual patients. On serial testing, multiple patterns of visual field abnormality were observed in the same eye over time. Conclusions: A standardized protocol for systematic evaluation of visual field measurements can be used to characterize disturbances of vision in patients with birdshot chorioretinopathy. Abnormalities of visual fields may occur even when central visual acuity is preserved. C1 Univ Calif Los Angeles, Jules Stein Eye Inst, Ocular Inflammatory Dis Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Ophthalmol Sect, Los Angeles, CA USA. RP Gordon, LK (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, Ocular Inflammatory Dis Ctr, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM lgordon@ucla.edu NR 23 TC 13 Z9 14 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD DEC PY 2006 VL 14 IS 6 BP 325 EP 332 DI 10.1080/09273940600966400 PG 8 WC Ophthalmology SC Ophthalmology GA 115CI UT WOS:000242712000001 PM 17162602 ER PT J AU Jurkunas, U Azar, DT AF Jurkunas, Ula Azar, Dimitri T. TI Potential complications of ocular surgery in patients with coexistent keratoconus and Fuchs' endothelial dystrophy SO OPHTHALMOLOGY LA English DT Article ID CORNEAL THICKNESS; CATARACT-SURGERY; CELL DENSITY; KERATOPLASTY; PACHYMETRY; MUTATION; DEEP; EYES AB Purpose: To describe the potential complications of cataract and refractive surgery in patients with Fuchs' endothelial dystrophy (FED) and keratoconus. Design: Retrospective case series. Participants: Eight patients with FED and keratoconus in a large university group practice. Methods: We reviewed the clinical and topographic findings of 8 patients (15 eyes) with FED and keratoconus. Clinical examination, corneal topography, specular microscopy were done, and sequential central corneal thickness (CCT) was obtained. Follow-up ranged from 1 month to 6 years. Main Outcome Measures: Findings of keratoconus and FED in preoperative evaluation. Results: Five patients had concomitant cataracts; 3 had refractive errors and sought surgical correction. Cataract surgery was performed on 3 of 5 patients (5 eyes). LASIK was performed on one eye of 3 patients. Of 5 eyes that underwent cataract extraction, 4 had blurry vision after surgery. The interval between the surgical procedure and onset of symptoms ranged from 1 month to 4 years. The causes of decreased vision after cataract surgery were corneal edema and/or corneal ectasia. The CCT readings ranged from 426 to 824 mu m. One of 4 symptomatic eyes underwent penetrating keratoplasty. The CCTs of 3 patients (6 eyes) who presented with refractive error ranged from 507 to 565 mu m. One eye had undergone an attempted LASIK procedure resulting in a lost cap. Corneal topography and specular microscopy showed the coexistence of keratoconus and FED, and the patients were advised against having LASIK surgery. Conclusions: Corneal thinning caused by keratoconus and concurrent increase in corneal thickness caused by FED may combine to normalize the corneal pachymetry readings; disease severity may be underestimated, which may lead to unexpected postoperative visual outcomes. Routine use of preoperative topography and specular microscopy may help to avert potential surgical complications. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea & Refract Surg Serv, Boston, MA USA. RP Azar, DT (reprint author), Univ Illinois, Dept Ophthalmol, 1855 W Taylor St,Room 250, Chicago, IL 60612 USA. EM dazar@uic.edu NR 34 TC 7 Z9 7 U1 0 U2 0 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 DEC PY 2006 VL 113 IS 12 BP 2187 EP 2197 DI 10.1016/j.ophtha.2006.06.036 PG 11 WC Ophthalmology SC Ophthalmology GA 114KH UT WOS:000242664600010 PM 16996603 ER PT J AU Abraham, P Adelman, RA Alfaro, DV Anand, R Antoszyk, A Bergsma, D Hartnett, ME Brucker, AJ Carr, T Casey, RC Rubino, J Chandler, TW Charles, S Chaudhry, N Combs, J Doft, B Young, LHY Drouilhet, JH Dugel, PU Feman, SS Finkelstein, D Foster, RE Petersen, MR Fox, G Garretson, B Gieser, JP Gentile, RC Giovinazzo, V Glazer, L Goodart, RA Gottlieb, J Greven, C Grizzard, WS Hainsworth, DP Halperin, L Heier, JS Jackson, W Kubacki, JJ Kanter, ED Keyser, B Kingsley, R Ko, P Kokame, GT Kuppermann, B Lambert, HM Lewis, H Lewis, RA Marcus, D Nussbaum, J Maturi, RK Mines, J Morse, LS Kingsley, R Olson, J Pakalnis, A Park, DW Paschal, J Pavan, PR Peyman, GA Pfister, R Puglisi, J Quillen, DA Reichel, E Sall, K Sebag, J Schwartz, SD Sharuk, G Shugarman, R Singerman, LJ Stoller, G Teske, MP Thompson, JT Tornambe, PE Tweeten, J Wong, K Aiello, LP Davis, MD Girach, A Kles, KA Milton, RC Sheetz, MJ Vignati, L Zhi, X AF Abraham, Prema Adelman, Ron A. Alfaro, Daniel Virgil, III Anand, Rajiv Antoszyk, Andrew Bergsma, Donald Hartnett, Mary Elizabeth Brucker, Alexander J. Carr, Tyree Casey, Raynor C. Rubino, John Chandler, Thomas W. Charles, Steven Chaudhry, Nauman Combs, James Doft, Bernard Young, Lucy H. Y. Drouilhet, John H. Dugel, Pravin U. Feman, Stephen S. Finkelstein, Daniel Foster, Robert E. Petersen, Michael R. Fox, Gregory Garretson, Bruce Gieser, Jon P. Gentile, Ronald C. Giovinazzo, Vincent Glazer, Louis Goodart, Roy A. Gottlieb, Justin Greven, Craig Grizzard, William S. Hainsworth, Dean P. Halperin, Lawrence Heier, Jeffrey S. Jackson, William Kubacki, Joseph J. Kanter, Eric D. Keyser, Bruce Kingsley, Ronald Ko, Paula Kokame, Gregg T. Kuppermann, Baruch Lambert, H. Michael Lewis, Hilel Lewis, Richard Alan Marcus, Dennis Nussbaum, Julian Maturi, Raj K. Mines, Jonathan Morse, Lawrence S. Kingsley, Ronald Olson, John Pakalnis, Al Park, Donald W. Paschal, John Pavan, Peter Reed Peyman, Gholam A. Pfister, Roswell Puglisi, John Quillen, David A. Reichel, Elias Sall, Kenneth Sebag, J. Schwartz, Steven D. Sharuk, George Shugarman, Richard Singerman, Lawrence J. Stoller, Glenn Teske, Michael P. Thompson, John T. Tornambe, Paul E. Tweeten, James Wong, Keye Aiello, Lloyd Paul Davis, Matthew D. Girach, Aniz Kles, Keri A. Milton, Roy C. Sheetz, Matthew J. Vignati, Louis Zhi, Xin (Eric) CA PKC-DRS2 Grp TI Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 109th Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 15-18, 2005 CL Chicago, IL SP Amer Acad Ophthalmol ID PROTEIN-KINASE-C; ENDOTHELIAL GROWTH-FACTOR; BLOOD-RETINAL BARRIER; PKC BETA INHIBITOR; MACULAR EDEMA; SELECTIVE INHIBITOR; VISION LOSS; RATS; PROGRESSION; COMPLICATIONS AB Objective: To evaluate the effect of ruboxistaurin, an orally administered protein kinase C beta (PKC beta) isozyme-selective inhibitor, on vision loss in patients with diabetes. Design: Thirty-six-month, randomized, double-masked, placebo-controlled, parallel, multicenter trial. Participants: Six hundred eighty-five patients randomized at 70 clinical sites. Methods: Ophthalmologic examination was performed at screening and at each 3-month visit. Retinopathy status was assessed every 6 months with Early Treatment Diabetic Retinopathy Study (ETDRS) standard 7-field 30 color stereoscopic fundus photography. Levels of diabetic retinopathy and diabetic macular edema were determined by 2 independent graders masked to site and treatment assignment, with additional independent adjudication as required. Eligible patients had a best-corrected visual acuity (VA) score of >= 45 letters, retinopathy level >= 47A and <= 53E, and no prior panretinal photocoagulation in at least one eye. Main Outcome Measure: Effect of oral ruboxistaurin (32 mg/day) on reduction of sustained moderate visual loss (>= 15-letter decrease in ETDRS VA score maintained >= 6 months) in patients with moderately severe to very severe nonproliferative diabetic retinopathy. Results: Sustained moderate visual loss occurred in 9.1% of placebo-treated patients versus 5.5% of ruboxistaurin-treated patients (40% risk reduction, P = 0.034). Mean VA was better in the ruboxistaurin-treated patients after 12 months. Baseline-to-end point visual improvement of >= 15 letters was more frequent (4.9% vs. 2.4%) and >= 15-letter worsening was less frequent (6.7% vs. 9.9%) in ruboxistaurin-treated patients relative to placebo (P = 0.005). When clinically significant macular edema was > 100 p,m from the center of the macula at baseline, ruboxistaurin treatment was associated with less frequent progression of edema to within 100 mu m (68% vs. 50%, P = 0.003). Initial laser treatment for macular edema was 26% less frequent in eyes of ruboxistaurin-treated patients (P = 0.008). Conclusion: Oral ruboxistaurin treatment reduced vision loss, need for laser treatment, and macular edema progression, while increasing occurrence of visual improvement in patients with non proliferative retinopathy. C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Aiello, LP (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM LPAiello@Joslin.Harvard.edu RI Pavan, Peter/B-6473-2013 NR 43 TC 134 Z9 142 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 2006 VL 113 IS 12 BP 2221 EP 2230 DI 10.1016/j.ophtha.2006.07.032 PG 10 WC Ophthalmology SC Ophthalmology GA 114KH UT WOS:000242664600015 ER PT J AU Aguirre, AD Chen, Y Fujimoto, JG Ruvinskaya, L Devor, A Boas, DA AF Aguirre, A. D. Chen, Y. Fujimoto, J. G. Ruvinskaya, L. Devor, A. Boas, D. A. TI Depth-resolved imaging of functional activation in the rat cerebral cortex using optical coherence tomography SO OPTICS LETTERS LA English DT Article ID NEURAL ACTIVITY; HEMOGLOBIN CONCENTRATION; SCATTERING CHANGES; BLOOD-FLOW; OXYGENATION AB Co-registered optical coherence tomography (OCT) and video microscopy of the rat somatosensory cortex were acquired simultaneously through a thinned skull during forepaw electrical stimulation. Fractional signal change measured by OCT revealed a functional signal time course corresponding to the hemodynamic signal measurement made with video microscopy. OCT can provide high-resolution, cross-sectional images of functional neurovascular activation and may offer a new tool for basic neuroscience research in the important rat cerebral cortex model. (c) 2006 Optical Society of America. C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. RP Aguirre, AD (reprint author), MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. FU NCI NIH HHS [R01 CA075289-09, R01 CA075289, R01-CA75289-09]; NEI NIH HHS [R01 EY011289, R01 EY011289-20, R01-EY011289-20]; NIBIB NIH HHS [F31 EB005978, R01 EB000790-05, R01 EB000790, R01-EB00790, F31 EB005978-01] NR 15 TC 31 Z9 32 U1 0 U2 6 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 DEC 1 PY 2006 VL 31 IS 23 BP 3459 EP 3461 DI 10.1364/OL.31.003459 PG 3 WC Optics SC Optics GA 106LR UT WOS:000242102500019 PM 17099749 ER PT J AU Capito, RM Spector, M AF Capito, R. M. Spector, M. TI Effect of expansion medium on ex vivo gene transfer and chondrogenesis in type II collagen-glycosaminoglycan scaffolds in vitro SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE cartilage; tissue engineering; gene transfer; growth factors ID HUMAN ARTICULAR CHONDROCYTES; GROWTH-FACTOR-I; CARTILAGE REPAIR; MATRIX; TISSUE; EXPRESSION; DEFECTS; MODEL; PHENOTYPE; STIFFNESS AB Objective: Growth factors can profoundly affect the behaviour of chondrocytes during expansion and subsequent growth in three-dimensional (3-D) scaffolds. Prolonging such effects has stimulated investigation of the transfer of growth factor genes to chondrocytes. This study evaluated the effects of the monolayer expansion medium on the proliferation and cartilage matrix molecule synthesis of chondrocytes in 3-D pellet culture and in type II collagen-glycosaminoglycan (CG) scaffolds, and on ex vivo insulin-like growth factor-1 (IGF-1) gene transfer to articular chondrocytes in monolayer. The possibility of transfecting cells in 3-D culture using CG scaffolds was also investigated and the resulting effect of IGF-1 overexpression on glycosaminoglycan (GAG) biosynthesis in 3-D culture was assessed. Methods: Two expansion media were compared-one that has been widely used for growing chondrocytes (Medium 1) and one that has been found to increase chondrocyte proliferation rates and preserve the redifferentiation potential of monolayer-expanded chondrocytes when subsequently placed in pellet cultures (Medium 2). Chondrocytes were expanded in monolayer culture and then 1) redifferentiated in 3-D culture, or 2) infected with the IGF-1 gene in monolayer or in type II CG scaffolds. Results: The cell count for first passage chondrocytes was more than 3-fold higher when using Medium 2. In 3-D culture, cells expanded with Medium 2 and seeded in CG scaffolds produced more total GAG/DNA and displayed more intense immunohistochemical staining for collagen type II. Gene transfer and IGF-1 release kinetics from infected cells in monolayer were significantly affected by the composition of the expansion medium, the gene transfer method and time. IGF-1 gene transfer in CG scaffolds resulted in a 35-fold elevation in accumulated IGF-1 released from transfected Medium 2-expanded chondrocytes over controls, and resulted in a 40% increase in accumulated GAG/DNA. Conclusion: The composition of the expansion medium significantly affects monolayer proliferation of adult canine chondrocytes, GAG synthesis when the cells are subsequently grown in CG scaffolds, and ex vivo IGF-1 gene transfer. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Boston Campus,Room D1-152,Mail Stop 151 Res,150 S, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu RI Shah, Ramille/E-3737-2010 NR 27 TC 11 Z9 11 U1 1 U2 4 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD DEC PY 2006 VL 14 IS 12 BP 1203 EP 1213 DI 10.1016/j.joca.2006.06.001 PG 11 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 116LV UT WOS:000242805300001 PM 16875848 ER PT J AU Wan, L de Asla, RJ Rubash, HE Li, G AF Wan, L. de Asla, R. J. Rubash, H. E. Li, G. TI Determination of in-vivo articular cartilage contact areas of human talocrural joint under weightbearing conditions SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE cartilage; cartilage contact; in-vivo biomechanics; ankle joint; talocrural joint ID HUMAN ANKLE JOINT; PRESSURE DISTRIBUTION; TIBIOTALAR JOINT; ANGULAR DEFORMITIES; STANCE PHASE; KINEMATICS; KNEE; BIOMECHANICS; VARIABILITY; FLEXION AB Objective: The knowledge of in-vivo cartilage contact biomechanics is important to the understanding of the pathogenesis of joint diseases such as osteoarthritis. This study investigated the in-vivo contact areas of human talocrural joint under weightbearing conditions that simulated the stance phase of walking using a combined magnetic resonance (MR) and dual-orthogonal fluoroscopic imaging technique. Design: Nine healthy ankles of living subjects were recruited for this study. The in-vivo talocrural joint positions were recorded using the dual-orthogonal fluoroscopic images at three ankle positions that simulated those occurring during the stance phase of walking: heel strike, mid-stance, and toe off. Three-dimensional (3D) models of the talocrural joints were created from MR images and used to reproduce the in-vivo ankle positions recorded on the fluoroscopic images. The talocrural cartilage contact area was defined as the overlap area of the distal tibial and the proximal talar cartilage surfaces. The method was validated using an in-vitro experimental setup to evaluate its accuracy in determination of cartilage contact area. Results: The validation study demonstrated that the articular cartilage contact area of the talocrural joint determined using the imaging technique was approximately 4% lower than that of the experimental measurement. In the nine living ankles, the average cartilage coverage area was 964.9 +/- 156.1 mm(2) on the distal tibia and 1304.8 +/- 208.4 mm(2) on the proximal talus. The average talocrural cartilage contact areas were 272.7 +/- 61.1 mm(2) at heel strike, 416.8 +/- 51.7 mm(2) at mid-stance, and 335.7 +/- 64.5 mm(2) at toe off. The contact area at mid-stance was significantly larger than those at heel strike and toe off, while the contact area at toe off was significantly larger than that at heel strike. Conclusion: The combined dual fluoroscopic and MR imaging technique was shown to be capable of determining in-vivo talo crural cartilage contact areas. During the simulated stance phase of walking, the contact areas were less than 44% and 31% of the cartilage coverage areas of the distal tibia and the proximal talus, respectively. These data may be useful for understanding in-vivo biomechanical function of the cartilage as well as the etiology of osteoarthritis. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. MIT, Dept Phys, Cambridge, MA 02139 USA. RP Li, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU NIAMS NIH HHS [AR052408] NR 31 TC 34 Z9 34 U1 0 U2 7 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD DEC PY 2006 VL 14 IS 12 BP 1294 EP 1301 DI 10.1016/j.joca.2006.05.012 PG 8 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 116LV UT WOS:000242805300011 PM 16787752 ER PT J AU Mehta, RP Harris, JP AF Mehta, Ritvik P. Harris, Jeffrey P. TI Mastoid obliteration SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID CHRONIC OTITIS-MEDIA; CANAL WALL; RECONSTRUCTION; HYDROXYAPATITE; FLAP; TYMPANOMASTOIDECTOMY; SURGERY; CAVITY AB Mastoid obliteration is most commonly performed to reduce the size of the mastoidectomy cavity following canal wall-down tympanomastoidectomy for chronic otitis media. The indications and techniques for mastoid obliteration as well as total tympanomastoid obliteration will be reviewed. The vast majority of obliteration techniques consist of either local flaps or free grafts (bone, cartilage, fat, hydroxyapatite). The radiographic and histopathologic features of mastoid obliteration will also be reviewed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Univ Calif San Diego, Sch Med, Dept Surg, Div Otolaryngol Head & Neck Surg, San Diego, CA 92103 USA. RP Mehta, RP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. EM jpharris@ucsd.edu NR 31 TC 20 Z9 26 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 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD DEC PY 2006 VL 39 IS 6 BP 1129 EP + DI 10.1016/j.otc.2006.08.007 PG 15 WC Otorhinolaryngology SC Otorhinolaryngology GA 115LB UT WOS:000242734700005 PM 17097437 ER PT J AU White, WM McKenna, MJ Deschler, DG AF White, W. Matthew McKenna, Michael J. Deschler, Daniel G. TI Use of the thoracodorsal nerve for facial nerve grafting in the setting of pedicled latissimus dorsi reconstruction SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 107th Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery-Foundation CY SEP 21-24, 2003 CL ORLANDO, FL SP Amer Acad Otolaryngol Head & Neck Surg Fdn ID REANIMATION; MUSCLE; FLAP C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Deschler, DG (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Daniel_Deschler@meei.harvard.edu NR 7 TC 5 Z9 5 U1 0 U2 1 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 DEC PY 2006 VL 135 IS 6 BP 962 EP 964 DI 10.1016/j.otohns.2005.09.017 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 114MP UT WOS:000242670600029 PM 17141095 ER PT J AU Pelletier, AJ Mansbach, JM Camargo, CA AF Pelletier, Andrea J. Mansbach, Jonathan M. Camargo, Carlos A., Jr. TI Direct medical costs of bronchiolitis hospitalizations in the United States SO PEDIATRICS LA English DT Article DE bronchiolitis; cost; HCUP ID RESPIRATORY SYNCYTIAL VIRUS; YOUNG-CHILDREN; ECONOMIC-EVALUATION; TRACT DISEASE; US CHILDREN; INFECTION; INFLUENZA; INFANTS; CORONAVIRUS; BURDEN AB OBJECTIVES. Although bronchiolitis is the leading cause of hospitalization for infants, there are limited data describing the epidemiology of bronchiolitis hospitalizations, and the associated cost is unknown. Our objective was to determine nationally representative estimates of the frequency of bronchiolitis hospitalizations and its associated costs. PATIENTS AND METHODS. We analyzed the 2002 Health Care Utilization Project-National Inpatient Sample, a federal, stratified random survey of hospital discharges. For admissions age < 2 years with a discharge diagnosis of bronchiolitis (International Classification of Diseases, Ninth Revision, Clinical Modification, code 466.1), we used nationally representative weighted estimates to determine frequency and total hospital charges. Costs were estimated from reported charges by applying hospital-specific cost/charge ratios based on all-payer inpatient cost. RESULTS. In 2002, an estimated 149 000 patients were hospitalized with bronchiolitis. Frequency of hospitalizations was higher among children age < 1 year of age, male gender, and nonwhite race. Mean length of stay was 3.3 days. Total annual costs for bronchiolitis-related hospitalizations were $543 million, with a mean cost of $3799 per hospitalization. Mean cost of bronchiolitis with a codiagnosis of pneumonia was $6191. In a multivariate analysis controlling for 3 confounding factors (including length of stay), cost per hospitalization was higher for children < 1 year and lower for those in the South versus Northeast. CONCLUSIONS. Bronchiolitis admissions cost more than $500 million annually. A codiagnosis of bronchiolitis and pneumonia almost doubles the cost of the hospitalization. Inpatient health care costs of bronchiolitis are higher than estimated previously and highlight the need for initiatives to safely reduce bronchiolitis hospitalizations and thereby decrease health care costs. C1 Massachusetts Gen Hosp, EMNet Coordinating Ctr, Dept Emergency Med, Boston, MA 02114 USA. Boston Childrens Hosp, Dept Med, Boston, MA USA. RP Pelletier, AJ (reprint author), Massachusetts Gen Hosp, EMNet Coordinating Ctr, Dept Emergency Med, 216 Cambridge St,4th Floor, Boston, MA 02114 USA. EM apelletier1@partners.org NR 37 TC 108 Z9 113 U1 1 U2 3 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 DEC PY 2006 VL 118 IS 6 BP 2418 EP 2423 DI 10.1542/peds.2006-1193 PG 6 WC Pediatrics SC Pediatrics GA 111TX UT WOS:000242478900019 PM 17142527 ER PT J AU Banerjee, S Selim, H Suliman, G Geller, AI Juppner, H Bringhurst, FR Divieti, P AF Banerjee, Santanu Selim, Hafez Suliman, Gihan Geller, Andrew I. Juppner, Harald Bringhurst, F. Richard Divieti, Paola TI Synthesis and characterization of novel biotinylated carboxyl-terminal parathyroid hormone peptides that specifically crosslink to the CPTH-receptor SO PEPTIDES LA English DT Article DE parathyroid hormone; carboxy-terminal parathyroid; hormone; parathyroid hormone receptor type-1; benzoylphenylalanine ID PROTEIN-RECEPTOR; PTH/PTHRP RECEPTOR; BINDING DOMAIN; PTH RECEPTOR; REGION; CELLS; IDENTIFICATION; CONTACT; DETERMINANTS; AGONIST AB Parathyroid hormone (PTH) regulates calcium, phosphorous and skeletal homeostasis via interaction with the G protein-coupled PTH/PTHrP receptor, which is fully activated by the amino-terminal 34 amino-acid portion of the hormone. Recent evidence points to the existence of another class of receptors for PTH that recognize the carboxyl (C)-terminal region of intact PTH (1-84) (CPTHRs) and are highly expressed by osteocytes. Here we report the synthesis and characterization of two novel bifunctional CPTH ligands that include benzoylphenylalanine (Bpa) substitutions near their amino-termini and carboxyl-terminal biotin moieties, as well as a tyrosine" substitution to enable radioiodination. These peptides are shown to bind to CPTHRs with affinity similar to that of PTH (1-84) and to be specifically and covalently crosslinked to CPTHRs upon exposure to ultraviolet light. Crosslinking to osteocytes or osteoblastic cells generates complexes of 80 and 220 kDa, of which the larger form represents an aggregate that can be resolved into the 80 kDa. The crosslinked products can be further purified using immunoaffinity and avidin-based affinity procedures. While the molecular structure of the CPTHR(s) remains undefined, these bifunctional ligands represent powerful new tools for use in isolating and characterizing CPTHR protein(s). (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Divieti, P (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA. EM divieti@helix.mgh.harvard.edu FU NIAMS NIH HHS [AR 47062, R01 AR047062]; NIDDK NIH HHS [DK-65032, P30 DK040561-11, R03 DK065032, K08 DK002889, P30 DK040561, DK-02889] NR 24 TC 3 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 0196-9781 J9 PEPTIDES JI Peptides PD DEC PY 2006 VL 27 IS 12 BP 3352 EP 3362 DI 10.1016/j.peptides.2006.08.022 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 116RZ UT WOS:000242821300041 PM 17028061 ER PT J AU Michalik, L Auwerx, J Berger, JP Chatterjee, VK Glass, CK Gonzalez, FJ Grimaldi, PA Kadowaki, T Lazar, MA O'Rahilly, S Palmer, CNA Plutzky, J Reddy, JK Spiegelman, BM Staels, B Wahli, W AF Michalik, Liliane Auwerx, Johan Berger, Joel P. Chatterjee, V. Krishna Glass, Christopher K. Gonzalez, Frank J. Grimaldi, Paul A. Kadowaki, Takashi Lazar, Mitchell A. O'Rahilly, Stephen Palmer, Colin N. A. Plutzky, Jorge Reddy, Janardan K. Spiegelman, Bruce M. Staels, Bart Wahli, Walter TI International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors SO PHARMACOLOGICAL REVIEWS LA English DT Review ID RETINOID-X-RECEPTOR; NUCLEAR HORMONE-RECEPTORS; LOW-DENSITY-LIPOPROTEIN; PPAR-ALPHA AGONIST; CAUSES INSULIN-RESISTANCE; POTENT ANTIDIABETIC THIAZOLIDINEDIONE; INHIBITS ADIPOCYTE DIFFERENTIATION; FOLLICULAR THYROID CARCINOMAS; PALMITOYLTRANSFERASE I GENE; DOMINANT-NEGATIVE MUTATIONS AB The three peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of the nuclear hormone receptor superfamily. They share a high degree of structural homology with all members of the superfamily, particularly in the DNA-binding domain and ligand- and cofactor-binding domain. Many cellular and systemic roles have been attributed to these receptors, reaching far beyond the stimulation of peroxisome proliferation in rodents after which they were initially named. PPARs exhibit broad, isotype-specific tissue expression patterns. PPAR alpha is expressed at high levels in organs with significant catabolism of fatty acids. PPAR beta/delta has the broadest expression pattern, and the levels of expression in certain tissues depend on the extent of cell proliferation and differentiation. PPAR alpha is expressed as two isoforms, of which PPAR gamma 2 is found at high levels in the adipose tissues, whereas PPAR gamma 1 has a broader expression pattern. Transcriptional regulation by PPARs requires heterodimerization with the retinoid X receptor (RXR). When activated by a ligand, the dimer modulates transcription via binding to a specific DNA sequence element called a peroxisome proliferator response element (PPRE) in the promoter region of target genes. A wide variety of natural or synthetic compounds was identified as PPAR ligands. Among the synthetic ligands, the lipid-lowering drugs, fibrates, and the insulin sensitizers, thiazolidinediones, are PPAR alpha and PPAR gamma agonists, respectively, which underscores the important role of PPARs as therapeutic targets. Transcriptional control by PPAR/RXR heterodimers also requires interaction with coregulator complexes. Thus, selective action of PPARs in vivo results from the interplay at a given time point between expression levels of each of the three PPAR and RXR isotypes, affinity for a specific promoter PPRE, and ligand and cofactor availabilities. C1 Univ Lausanne, Ctr Integrat Genom, Natl Res Ctr Frontiers Genet, CH-1015 Lausanne, Switzerland. Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France. Merck Res Labs, Rahway, NJ USA. Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 2QQ, England. Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol Diabet & Hypertens, Los Angeles, CA USA. NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Nice Sophia Antipolis, INSERM, U636, Ctr Biochim,Unite Format & Rech Sci, Nice, France. Univ Tokyo, Grad Sch Med, Tokyo, Japan. Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Ctr, Dundee DD1 9SY, Scotland. Harvard Univ, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Inst Pasteur, INSERM, Unite Rech 545, F-59019 Lille, France. RP Wahli, W (reprint author), Univ Lausanne, Ctr Integrat Genom, Natl Res Ctr Frontiers Genet, CH-1015 Lausanne, Switzerland. EM walter.wahli@unil.ch RI Palmer, Colin/C-7053-2008; Reddy, Jay/K-7200-2014; Wahli, Walter/B-1398-2009; OI Palmer, Colin/0000-0002-6415-6560; Reddy, Jay/0000-0003-4082-9254; Wahli, Walter/0000-0002-5966-9089; Staels, Bart/0000-0002-3784-1503 NR 294 TC 468 Z9 483 U1 5 U2 41 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD DEC PY 2006 VL 58 IS 4 BP 726 EP 741 DI 10.1124/pr.58.4.5 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110JP UT WOS:000242374900005 PM 17132851 ER PT J AU Patharkar, OR Cushman, JC AF Patharkar, O. Rahul Cushman, John C. TI A novel coiled-coil protein co-localizes and interacts with a calcium-dependent protein kinase in the common ice plant during low-humidity stress SO PLANTA LA English DT Article DE calcium-dependent protein kinase; yeast two-hybrid; coiled-coil protein; low-humidity stress; cytoskeletal trafficking ID CALMODULIN-LIKE DOMAIN; SUBCELLULAR-LOCALIZATION; ENDOPLASMIC-RETICULUM; GENE FAMILY; RICE PLANTS; PSI-BLAST; ARABIDOPSIS; CELLS; CDPK; CYTOSKELETON AB McCPK1 (Mesembryanthemurn crystallinum calcium-dependent protein kinase 1) mRNA expression is induced transiently by salinity and water deficit stress and also McCPKI undergoes dynamic subcellular localization changes in response to these same stresses. Here we have confirmed that low humidity is capable of causing a drastic change in McCPK1's subcellular localization. We attempted to elucidate this phenomenon by isolating components likely to be involved in this process. McCAP1 (M. crystallinum CDPK adapter protein 1) was cloned in a yeast two-hybrid screen with a constitutively active McCPK1 as bait. We show that McCPK1 and McCAP1 can interact in the yeast two-hybrid system, in vitro, and in vivo as demonstrated by coinimunoprecipitation experiments from plant extracts. However, McCAP1 does not appear to be a substrate for McCPK1. DsRed-McCAP1 and EGFP-McCPK1 fusions colocalize in epidermal cells of ice plants exposed to low humidity. McCAP1 is homologous to a family of proteins in Arabidopsis with no known function. Computational threading analysis suggests that McCAP1 is likely to be an intermediate filament protein of the cytoskeleton. C1 Univ Nevada, Dept Biochem MS200, Reno, NV 89557 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Patharkar, OR (reprint author), Univ Nevada, Dept Biochem MS200, 311 Fleischmann Agr, Reno, NV 89557 USA. EM jcushman@unr.edu NR 65 TC 10 Z9 10 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0032-0935 J9 PLANTA JI Planta PD DEC PY 2006 VL 225 IS 1 BP 57 EP 73 DI 10.1007/s00425-006-0330-0 PG 17 WC Plant Sciences SC Plant Sciences GA 119LH UT WOS:000243013300005 PM 16773372 ER PT J AU Lin, Y Ulanov, AV Lozovaya, V Widholm, J Zhang, GR Guo, JH Goodman, HM AF Lin, Yun Ulanov, Alexander V. Lozovaya, Vera Widholm, Jack Zhang, Guirong Guo, Jinhua Goodman, Howard M. TI Genetic and transgenic perturbations of carbon reserve production in Arabidopsis seeds reveal metabolic interactions of biochemical pathways SO PLANTA LA English DT Article DE seeds; storage; metabolite profiling; carbon metabolism; oil; starch; Arabidopsis thaliana ID ADP-GLUCOSE PYROPHOSPHORYLASE; ESCHERICHIA-COLI-B; STARCH SYNTHESIS; GAS-CHROMATOGRAPHY; BACTERIAL GLYCOGEN; REGULATORY ENZYME; MASS-SPECTROMETRY; ALLOSTERIC MUTANT; BRASSICA-NAPUS; ENDOSPERM AB The biosynthesis of seed oil and starch both depend on the supply of carbon from the maternal plant. The biochemical interactions between these two pathways are not fully understood. In the Arabidopsis mutant shrunken seed 1 (sse1)/pex16, a reduced rate of fatty acid synthesis leads to starch accumulation. To further understand the metabolic impact of the decrease in oil synthesis, we compared soluble metabolites in sse1 and wild type (WT) seeds. Sugars, sugar phosphates, alcohols, pyruvate, and many other organic acids accumulated in sse1 seeds as a likely consequence of the reduced carbon demand for lipid synthesis. The enlarged pool size of hexose-P, the metabolites at the crossroad of sugar metabolism, glycolysis, and starch synthesis, was likely a direct cause of the increased flow into starch. Downstream of glycolysis, more carbon entered the TCA cycle as an alternative to the fatty acid pathway, causing the total amount of TCA cycle intermediates to rise while moving the steady state of the cycle away from fumarate. To convert the excess carbon metabolites into starch, we introduced the Escherichia coli starch synthetic enzyme ADP-glucose pyrophosphorylase (AGPase) into sse1 seeds. Expression of AGPase enhanced net starch biosynthesis in the mutant, resulting in starch levels that reached 37% of seed weight. However, further increases above this level were not achieved and most of the carbon intermediates remained high in comparison with the WT, indicating that additional mechanisms limit starch deposition in A rabidopsis seeds. C1 Univ Illinois, Dept Crop Sci, Urbana, IL 61801 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA. RP Lin, Y (reprint author), Univ Illinois, Dept Crop Sci, Urbana, IL 61801 USA. EM yunlin@uiuc.edu NR 39 TC 11 Z9 13 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0032-0935 J9 PLANTA JI Planta PD DEC PY 2006 VL 225 IS 1 BP 153 EP 164 DI 10.1007/s00425-006-0337-6 PG 12 WC Plant Sciences SC Plant Sciences GA 119LH UT WOS:000243013300012 PM 16896794 ER PT J AU May, JW AF May, James W., Jr. TI Bradford Cannon, MD, 1907 to 2005 - Obituary SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP May, JW (reprint author), Massachusetts Gen Hosp, WACC 453,15 Parkman St, Boston, MA 02114 USA. EM jwmay@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 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD DEC PY 2006 VL 118 IS 7 BP 1670 EP 1671 DI 10.1097/01.prs.0000244009.38941.1f PG 2 WC Surgery SC Surgery GA 107QT UT WOS:000242186800039 ER PT J AU Lee, JC Vivanco, I Beroukhim, R Huang, JHY Feng, WL DeBiasi, RM Yoshimoto, K King, JC Nghiemphu, P Yuza, Y Xu, Q Greulich, H Thomas, RK Paez, JG Peck, TC Linhart, DJ Glatt, KA Getz, G Onofrio, R Ziaugra, L Levine, RL Gabriel, S Kawaguchi, T O'Neill, K Khan, H Liau, LM Nelson, SF Rao, PN Mischel, P Pieper, RO Cloughesy, T Leahy, DJ Sellers, WR Sawyers, CL Meyerson, M Mellinghoff, IK AF Lee, Jeffrey C. Vivanco, Igor Beroukhim, Rameen Huang, Julie H. Y. Feng, Whei L. DeBiasi, Ralph M. Yoshimoto, Koji King, Jennifer C. Nghiemphu, Phioanh Yuza, Yuki Xu, Qing Greulich, Heidi Thomas, Roman K. Paez, J. Guillermo Peck, Timothy C. Linhart, David J. Glatt, Karen A. Getz, Gad Onofrio, Robert Ziaugra, Liuda Levine, Ross L. Gabriel, Stacey Kawaguchi, Tomohiro O'Neill, Keith Khan, Haumith Liau, Linda M. Nelson, Stanley F. Rao, P. Nagesh Mischel, Paul Pieper, Russell O. Cloughesy, Tim Leahy, Daniel J. Sellers, William R. Sawyers, Charles L. Meyerson, Matthew Mellinghoff, Ingo K. TI Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain SO PLOS MEDICINE LA English DT Article ID HEMATOPOIETIC-CELL LINE; HUMAN-BRAIN TUMORS; OVERCOMES RESISTANCE; COLORECTAL CANCERS; KINASE INHIBITOR; ERBB RECEPTORS; EGF RECEPTORS; HUMAN GLIOMAS; LUNG-CANCER; GENE AB Background Protein tyrosine kinases are important regulators of cellular homeostasis with tightly controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory constraints on kinase activity, can promote malignant transformation, and appear to be a major determinant of response to kinase inhibitor therapy. Missense mutations in the EGFR kinase domain, for example, have recently been identified in patients who showed clinical responses to EGFR kinase inhibitor therapy. Methods and Findings Encouraged by the promising clinical activity of epidermal growth factor receptor (EGFR) kinase inhibitors in treating glioblastoma in humans, we have sequenced the complete EGFR coding sequence in glioma tumor samples and cell lines. We identified novel missense mutations in the extracellular domain of EGFR in 13.6% (18/132) of glioblastomas and 12.5% (1/8) of glioblastoma cell lines. These EGFR mutations were associated with increased EGFR gene dosage and conferred anchorage-independent growth and tumorigenicity to NIH-3T3 cells. Cells transformed by expression of these EGFR mutants were sensitive to small-molecule EGFR kinase inhibitors. Conclusions Our results suggest extracellular missense mutations as a novel mechanism for oncogenic EGFR activation and may help identify patients who can benefit from EGFR kinase inhibitors for treatment of glioblastoma. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurosurg, Los Angeles, CA 90024 USA. Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90024 USA. RP Meyerson, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu; imellinghoff@mednet.ucla.edu RI King, Jennifer/F-8318-2010; Nelson, Stanley/D-4771-2009; Meyerson, Matthew/E-7123-2012; Sawyers, Charles/G-5327-2016; OI Vivanco, Igor/0000-0001-6347-9416 FU NCI NIH HHS [T32 CA009172, R01 CA116020] NR 46 TC 141 Z9 145 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD DEC PY 2006 VL 3 IS 12 BP 2264 EP 2273 AR e485 DI 10.1371/journal.pmed.0030485 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 125ZR UT WOS:000243482500019 PM 17177598 ER PT J AU Kim, AY Wiesch, JSZ Kuntzen, T Timm, J Kaufmann, DE Duncan, JE Jones, AM Wurcel, AG Davis, BT Gandhi, RT Robbins, GK Allen, TM Chung, RT Lauer, GM Walker, BD AF Kim, Arthur Y. Wiesch, Julian Schulze zur Kuntzen, Thomas Timm, Joerg Kaufmann, Daniel E. Duncan, Jared E. Jones, Andrea M. Wurcel, Alysse G. Davis, Benjamin T. Gandhi, Rajesh T. Robbins, Gregory K. Allen, Todd M. Chung, Raymond T. Lauer, Georg M. Walker, Bruce D. TI Impaired hepatitis C virus-specific T cell responses and recurrent hepatitis C virus in HIV coinfection SO PLOS MEDICINE LA English DT Article ID IMMUNE-RESPONSES; VIRAL CLEARANCE; INFECTION; CD4(+); PERSISTENCE; HCV; PROLIFERATION; DETERMINANTS; RESTORATION; HIV/HCV AB Background Hepatitis C virus (HCV)-specific T cell responses are critical for spontaneous resolution of HCV viremia. Here we examined the effect of a lymphotropic virus, HIV-1, on the ability of coinfected patients to maintain spontaneous control of HCV infection. Methods and Findings We measured T cell responsiveness by lymphoproliferation and interferon-gamma ELISPOT in a large cohort of HCV-infected individuals with and without HIV infection. Among 47 HCV/ HIV-1-coinfected individuals, spontaneous control of HCV was associated with more frequent HCV-specific lymphoproliferative (LP) responses (35%) compared to coinfected persons who exhibited chronic HCV viremia (7%, p = 0.016), but less frequent compared to HCV controllers who were not HIV infected (86%, p = 0.003). Preservation of HCV-specific LP responses in coinfected individuals was associated with a higher nadir CD4 count (r(2) = 0.45, p < 0.001) and the presence and magnitude of the HCV-specific CD8(+) T cell interferon-c response (p = 0.0014). During long-term follow-up, recurrence of HCV viremia occurred in six of 25 coinfected individuals with prior control of HCV, but in 0 of 16 HIV-1-negative HCV controllers (p = 0.03, log rank test). In these six individuals with recurrent HCV viremia, the magnitude of HCV viremia following recurrence inversely correlated with the CD4 count at time of breakthrough (r = -0.94, p = 0.017). Conclusions These results indicate that HIV infection impairs the immune response to HCV-including in persons who have cleared HCV infection-and that HIV-1-infected individuals with spontaneous control of HCV remain at significant risk for a second episode of HCV viremia. These findings highlight the need for repeat viral RNA testing of apparent controllers of HCV infection in the setting of HIV-1 coinfection and provide a possible explanation for the higher rate of HCV persistence observed in this population. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Div, Boston, MA 02115 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. Lemuel Shattuck Hosp, Jamaica Plain, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. RP Kim, AY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. EM akim1@partners.org RI Robbins, Gregory/F-7988-2011; Allen, Todd/F-5473-2011 FU NIAID NIH HHS [T32 AI007433, AI 031563, AI 042851, AI 054379, AI07433, K23 AI054379, P30 AI042851, R01 AI031563] NR 37 TC 63 Z9 65 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD DEC PY 2006 VL 3 IS 12 BP 2324 EP 2334 AR e492 DI 10.1371/journal.pmed.0030492 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 125ZR UT WOS:000243482500025 PM 17194190 ER PT J AU Ranjbar, S Tsytsykova, AV Lee, SK Rajsbaum, R Falvo, JV Lieberman, J Shankar, P Goldfeld, AE AF Ranjbar, Shahin Tsytsykova, Alla V. Lee, Sang-Kyung Rajsbaum, Ricardo Falvo, James V. Lieberman, Judy Shankar, Premlata Goldfeld, Anne E. TI NFAT5 regulates HIV-1 in primary monocytes via a highly conserved long terminal repeat site SO PLOS PATHOGENS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NF-KAPPA-B; ACTIVATED T-CELLS; TRANSCRIPTION FACTOR NFATP; GENE-EXPRESSION; NUCLEAR-FACTOR; TYPE-1 SUBTYPES; STIMULATES TRANSCRIPTION; BINDING-PROTEIN; MACROPHAGES AB To replicate, HIV-1 capitalizes on endogenous cellular activation pathways resulting in recruitment of key host transcription factors to its viral enhancer. RNA interference has been a powerful tool for blocking key checkpoints in HIV-1 entry into cells. Here we apply RNA interference to HIV-1 transcription in primary macrophages, a major reservoir of the virus, and specifically target the transcription factor NFAT5 (nuclear factor of activated T cells 5), which is the most evolutionarily divergent NFAT protein. By molecularly cloning and sequencing isolates from multiple viral subtypes, and performing DNase I footprinting, electrophoretic mobility shift, and promoter mutagenesis transfection assays, we demonstrate that NFAT5 functionally interacts with a specific enhancer binding site conserved in HIV-1, HIV-2, and multiple simian immunodeficiency viruses. Using small interfering RNA to ablate expression of endogenous NFAT5 protein, we show that the replication of three major HIV-1 viral subtypes (B, C, and E) is dependent upon NFAT5 in human primary differentiated macrophages. Our results define a novel host factor-viral enhancer interaction that reveals a new regulatory role for NFAT5 and defines a functional DNA motif conserved across HIV-1 subtypes and representative simian immunodeficiency viruses. Inhibition of the NFAT5-LTR interaction may thus present a novel therapeutic target to suppress HIV-1 replication and progression of AIDS. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Hanyang Univ, Dept Bioengn, Seoul 133791, South Korea. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Goldfeld, AE (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM goldfeld@cbrinstitute.org RI Rajsbaum, Ricardo/F-2046-2014; Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [R21 AI060433, AI065285-01A1, AI065342, R01 AI065285, R21 AI065342, R21AI060433-01, R56 AI065285]; PHS HHS [P30 A060354] NR 60 TC 26 Z9 27 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD DEC PY 2006 VL 2 IS 12 BP 1176 EP 1186 AR e130 DI 10.1371/journal.ppat.0020130 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 122EY UT WOS:000243209700008 PM 17173480 ER PT J AU Nicholas, PK Smith, MF AF Nicholas, Patrice K. Smith, Mary F. TI Demographic challenges and health in Germany SO POPULATION RESEARCH AND POLICY REVIEW LA English DT Article DE demographic challenges; aging; low birth rates; quality of life; Germany; health professions ID CARE AB Demographic challenges are affecting the health care system in Germany and globally: a growing aging population; low birth rates; sociopolitical, women's health, and health care economic issues; and immigration. During a recent Fulbright Scholar program, scholars from several disciplines including demography, sociology, medicine, and nursing examined these demographic challenges facing Germany and other industrialized countries. Enormous challenges exist for industrialized and developing countries related to these demographic changes, the complexity of health care economics, and population issues. In Germany, the shifting population demographics are affecting health care, financing of the German health care system, and the growth of immigrant populations. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02129 USA. Brigham & Womens Hosp, Ctr Nursing Excellence, Boston, MA 02120 USA. Brigham & Womens Hosp, Div Social Med & Hlth Inequalities, Boston, MA 02120 USA. Albany Med Coll, Dept Family & Community Med, Albany, NY 12208 USA. RP Nicholas, PK (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, 36 1st Ave, Boston, MA 02129 USA. EM pnicholas@mghihp.edu; smithmf@mail.amc.edu NR 14 TC 1 Z9 1 U1 1 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-5923 J9 POPUL RES POLICY REV JI Popul. Res. Policy Rev. PD DEC PY 2006 VL 25 IS 5-6 BP 479 EP 487 DI 10.1007/s11113-006-9009-2 PG 9 WC Demography SC Demography GA 146SE UT WOS:000244954200006 ER PT J AU Cody, V Pace, J Chisum, K Rosowsky, A AF Cody, Vivian Pace, Jim Chisum, Kim Rosowsky, Andre TI New insights into DHFR interactions: Analysis of Pneumocystis carinii and mouse DHFR complexes with NADPH and two highly potent 5-(omega-carboxy(alkyloxy) trimethoprim derivatives reveals conformational correlations with activity and novel parallel ring stacking interactions SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE dihydrofolate reductase; Pneumocystis carinii; mouse; AIDS; antifolates; conformational analysis; parallel ring stacking ID CASEI DIHYDROFOLATE-REDUCTASE; CRYSTAL-STRUCTURE; MYCOBACTERIUM-AVIUM; SPECIES SELECTIVITY; BOUND TRIMETHOPRIM; WILD-TYPE; RESISTANCE; ENZYME; ANALOGS; BINDING AB Structural data are reported for two highly potent antifolates, 2,4-diamino-5[3',4'-dimethoxy-5'-(5-carboxy-1-pentynyl)]benzylpyrimidine (PY1011), with 5000-fold selectivity for Pneumocystis carinii dihydrofolate reductase (pcDHFR), relative to rat liver DHFR, and 2,4-diamino-5-[2methoxy-5-(4-carboxybutyloxy)benzyl]pyrimidine (PY957), that has 80-fold selectivity for pcDHFR. Crystal structures are reported for NADPH ternary complexes with PY957 and pcDHFR, refined. p to 2.2 A resolution; with PY1011 and pcDHFR, refined to 2.0 angstrom resolution; and with PY1011 and mouse DHFR (mDHFR), refined to 2.2 angstrom resolution. These results reveal that the carboxylate of the omega-carboxyalkyloxy side chain of these inhibitors form ionic interactions with the conserved Arg in the substrate binding pocket of DHFR. These data suggest that the enhanced inhibitory activity of PY1011 compared with PY957 is, in part, due to the favorable contacts with Phe69 of pcDHFR by the methylene carbons of the inhibitor side chain that are oriented by the triple bond of the I-pentynyl side chain. These contacts are not present in the PY957 pcDHFR complex, or in the PY1011 mDHFR complex. In the structure of mDHFR the site of Phe69 in pcDHFR is occupied by Asn64. These data also revealed a preference for an unusual parallel ring stacking interaction between Tyr35 of the active site helix and Phe199 of the C-terminal beta sheet in pcDHFR and by Tyr33 and Phel.79 in mDHFR that is independent of bound ligand. A unique His174-His187 parallel ring stacking interaction was also observed only in the structure of pcDHFR. These ring stacking interactions are rarely found in any other protein families and may serve to enhance protein stability. C1 Hauptman Woodward Med Res Inst, Dept Biol Struct, Buffalo, NY 14203 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cody, V (reprint author), Hauptman Woodward Med Res Inst, Dept Biol Struct, 700 Ellicott St, Buffalo, NY 14203 USA. EM cody@hwi.buffalo.edu FU NIAID NIH HHS [AI29904]; NIGMS NIH HHS [GM51670] NR 44 TC 23 Z9 25 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD DEC 1 PY 2006 VL 65 IS 4 BP 959 EP 969 DI 10.1002/prot.21131 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 105TZ UT WOS:000242056500017 PM 17019704 ER PT J AU Plante, DT Winkelman, JW AF Plante, David T. Winkelman, John W. TI Parasomnias SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID SLEEP BEHAVIOR DISORDER; NIGHT-EATING SYNDROME; POSTTRAUMATIC-STRESS-DISORDER; SLOW-WAVE ACTIVITY; REM-SLEEP; GENERAL-POPULATION; CONTROLLED TRIAL; ADULT PATIENTS; SLEEPWALKING; TERRORS AB Parasomnias are undesirable behaviors that arise from sleep but arc not fully under voluntary control. Parasormu'as are grouped broadly according to whether they arise from non-rapid eye movement (NRE M) or rapid eye movement (NREM) sleep. NREM parasomnias arc disordeys of arousal that occur along a continuum of behavioral, affective, and autonomic activation. REM-related parasomnias include REM sleep behavior disorder, sleep paralysis, and nightmare disorder. Parasommas can often be managed successfully using behavioral and pharmacologic therapies. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Sleep Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Psychiat, Boston, MA 02115 USA. Brigham & Womens Hosp, Sleep Hlth Ctr, Brighton, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, McLean Hosp, Sch Med, Boston, MA 02115 USA. RP Winkelman, JW (reprint author), Sleep Hlth Ctr, 1505 Comonwealth Ave, Brighton, MA 02135 USA. EM jwwinkelman@partners.org NR 90 TC 4 Z9 5 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 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 2006 VL 29 IS 4 BP 969 EP + DI 10.1016/j.psc.2006.08.006 PG 20 WC Psychiatry SC Psychiatry GA 118ZT UT WOS:000242982700008 PM 17118277 ER PT J AU Levitt, JJ Chen, QCC May, FS Gilbertson, MW Shenton, ME Pitman, RK AF Levitt, James J. Chen, Q. Cece May, Flavia S. Gilbertson, Mark W. Shenton, Martha E. Pitman, Roger K. TI Volume of cerebellar vermis in monozygotic twins discordant for combat exposure: Lack of relationship to post-traumatic stress disorder SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE cerebellum; vermis; stress disorders, post-traumatic; magnetic resonance imaging; twins; monozygotic ID ANATOMIC-MR CORRELATION; SAGITTAL PLANE; SCHIZOPHRENIA; CHILDHOOD AB Several functional neuroimaging studies have implicated the cerebellar vermis in post-traumatic stress disorder (PTSD), but there have been no structural neuroimaging studies of this brain structure in PTSD. We utilized magnetic resonance imaging (MRI) with manual tracing to quantify the volumes of three divisions of the mid-sagittal vermis, and their total, within an identical, cotwin control design that employed Vietnam veterans discordant for combat exposure in Vietnam. Each structure's volume was significantly correlated between twins, indicating a partial familial determination: for anterior superior vermis, r=0.731 for posterior superior vermis, r=0.47; for inferior posterior vermis, r=0.51; and for total vermis, r=0.57. There were no significant differences between the PTSD and non-PTSD veterans for any vermis volume, and no significant main effects or interactions when their non-combat-exposed co-twins were added to the analyses. Thus, the results do not support the structural abnormality of cerebellar vermis in combat-related PTSD. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 VA Boston Healthcare Syst, Clin Neurosci Div, Neurosci Lab, Brockton, MA 02301 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, MRI Div,Surg Planning Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. MIT, Boston, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. VA Med Ctr, Res Serv, Manchester, NH USA. RP Pitman, RK (reprint author), MGH East,Room 2616,Bldg 149,13th St, Charlestown, MA 02129 USA. EM roger_pitman@hms.harvard.edu FU NIMH NIH HHS [K02 MH001110, K02 MH001110-10, K02-MH01110, R01 MH054636, R01-MH54636] NR 18 TC 10 Z9 13 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD DEC 1 PY 2006 VL 148 IS 2-3 BP 143 EP 149 DI 10.1016/j.pscychresns.2006.01.013 PG 7 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 117PR UT WOS:000242885800007 PM 17097862 ER PT J AU Cavanagh, SR Shin, LM Karamouz, N Rauch, SL AF Cavanagh, Sarah R. Shin, Lisa M. Karamouz, Nasser Rauch, Scott L. TI Psychiatric and emotional sequelae of surgical amputation SO PSYCHOSOMATICS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; LOWER-LIMB AMPUTATIONS; TRAUMA EXPOSURE; RISK-FACTORS; ADJUSTMENT; PREDICTORS; INJURY; PTSD; PAIN; METAANALYSIS AB The prevalence of posttraumatic stress symptoms after the experience of amputation is not well established. The current study gathered data on the prevalence of posttraumatic stress disorder ( PTSD) and other psychiatric disorders after amputation. Participants were recruited from a large Northeastern rehabilitation hospital and were assessed with structured clinical interviews. The data suggest that planned surgical amputations resulting from chronic illness do not frequently lead to PTSD symptoms. In contrast, data suggest that amputation resulting from accidental injury may lead to a higher prevalence of PTSD, in part because of the emotional stress surrounding the accident. C1 Tufts Univ, Dept Psychol, Medford, MA 02155 USA. RP Rauch, SL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,13th St,Room 2618, Charlestown, MA 02129 USA. EM rauch@psych.mgh.harvard.edu NR 28 TC 8 Z9 9 U1 3 U2 8 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 DEC PY 2006 VL 47 IS 6 BP 459 EP 464 DI 10.1176/appi.psy.47.6.459 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 107NE UT WOS:000242177500001 PM 17116945 ER PT J AU Maytal, G Smith, FA Stern, TA AF Maytal, Guy Smith, Felicia A. Stern, Theodore A. TI Naked patients in the general hospital: Differential diagnosis and management strategies SO PSYCHOSOMATICS LA English DT Article ID CARE AB Physicians and patients are frequently concerned, and, at times, distressed, by nakedness during clinical encounters. When nakedness appears, clinicians should attempt to establish the reason for it and determine whether it is appropriate for the situation. Establishing the etiology of nudity can facilitate care by hospital staff and help to modulate their countertransference reactions and behavior. The authors present and discuss three cases involving nudity at times other than during the physical examination, within the context of differential diagnosis and treatment alternatives. C1 Massachusetts Gen Hosp, Psychiat Consultat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. McLean Hosp, Belmont, MA 02178 USA. RP Maytal, G (reprint author), Massachusetts Gen Hosp, Psychiat Consultat Serv, Fruit St,Warren Bldg,Rm 605, Boston, MA 02114 USA. EM GMaytal@Partners.org NR 10 TC 2 Z9 2 U1 1 U2 2 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 DEC PY 2006 VL 47 IS 6 BP 486 EP 490 DI 10.1176/appi.psy.47.6.486 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 107NE UT WOS:000242177500005 PM 17116949 ER PT J AU Hinton, DE Pich, V Chhean, D Safren, SA Pollack, MH AF Hinton, Devon E. Pich, Vuth Chhean, Dara Safren, Steven A. Pollack, Mark H. TI Somatic-focused therapy for traumatized refugees: Treating posttraumatic stress disorder and comorbid neck-focused panic attacks among Cambodian refugees SO PSYCHOTHERAPY LA English DT Article DE cognitive-behavioral therapy; muscle relaxation; Cambodian refugees; posttraumatic stress disorder; panic disorder ID GENERALIZED ANXIETY DISORDER; COGNITIVE-BEHAVIORAL TREATMENT; TREATMENT-RESISTANT PTSD; LOW-BACK-PAIN; MENTAL-HEALTH; BHUTANESE REFUGEES; APPLIED RELAXATION; EXPRESSED EMOTION; PREVALENCE; DEPRESSION AB The authors outline six steps to develop culturally sensitive treatment for traumatized refugees, which focus on somatic symptoms. Among Cambodian refugees with posttraumatic stress disorder, the authors describe a somatic presentation (viz., neck-focused panic attacks) that forms a key aspect of trauma-related disorder, how those panic attacks are generated, and a treatment that specifically targets those panic attacks. Evidence of treatment efficacy is provided through a multiple-baseline, across-subjects design (N = 3), and one treatment case is described to illustrate clinical presentation and treatment. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Hinton, DE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu NR 90 TC 9 Z9 9 U1 3 U2 7 PU AMER PSYCHOLOGICAL ASSOC, DIV PSYCHOTHERAPY PI CORAL GABLES PA 1390 SOUTH DIXIE HIGHWAY, STE 2222, CORAL GABLES, FL 33146-2946 USA SN 0033-3204 J9 PSYCHOTHERAPY JI Psychotherapy PD WIN PY 2006 VL 43 IS 4 BP 491 EP 505 DI 10.1037/0033-3204.43.4.491 PG 15 WC Psychology, Clinical SC Psychology GA 123GA UT WOS:000243283200011 PM 22122139 ER PT J AU Handler, SM Castle, NG Studenski, SA Perera, S Fridsma, DB Nace, DA T Hanlon, J AF Handler, S. M. Castle, N. G. Studenski, S. A. Perera, S. Fridsma, D. B. Nace, D. A. T Hanlon, J. TI Patient safety culture assessment in the nursing home SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID LONG-TERM-CARE; ORGANIZATIONAL CULTURE; OUTCOMES; QUALITY; CLIMATE AB Objective: To assess patient safety culture (PSC) in the nursing home setting, to determine whether nursing home professionals differ in their PSC ratings, and to compare PSC scores of nursing homes with those of hospitals. Methods: The Hospital Survey on Patient Safety Culture was modified for use in nursing homes (PSC-NH) and distributed to 151 professionals in four non-profit nursing homes. Mean scores on each PSC-NH dimension were compared across professions (doctors, pharmacists, advanced practitioners and nurses) and with published benchmark scores from 21 hospitals. Results: Response rates were 68.9% overall and 52-100% for different professions. Most respondents (76%) were women and had worked in nursing homes for an average of 9.8 years, and at their current facility for 5.4 years. Professions agreed on 11 of 12 dimensions of the survey and differed significantly (p < 0.05) only in ratings for one PSC dimension (attitudes about staffing issues), where nurses and pharmacists believed that they had enough employees to handle the workload. Nursing homes scored significantly lower (ie, worse) than hospitals (p < 0.05) in five PSC dimensions (non-punitive response to error, teamwork within units, communication openness, feedback and communication about error, and organisational learning). Conclusions: Professionals in nursing homes generally agree about safety characteristics of their facilities, and the PSC in nursing homes is significantly lower than that in hospitals. PSC assessment may be helpful in fostering comparisons across nursing home settings and professions, and identifying targets for interventions to improve patient safety. C1 Univ Pittsburgh, Div Geriatr Med, Dept Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15260 USA. VA Pittsburgh, GRECC, Pittsburgh, PA USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res, Pittsburgh, PA USA. RP Handler, SM (reprint author), Univ Pittsburgh, Div Geriatr Med, Dept Med, 3471 5th Ave,Suite 500, Pittsburgh, PA 15213 USA. EM handlersm@upmc.edu RI Perera, Subashan/D-7603-2014; OI Handler, Steven/0000-0002-3940-3224 FU NCRR NIH HHS [8K12 RR 023267, K12 RR023267]; NIA NIH HHS [T32 AG021885, 5T32AG021885, P30 AG024827, P30-AG024827] NR 41 TC 29 Z9 31 U1 3 U2 11 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD DEC PY 2006 VL 15 IS 6 BP 400 EP 404 DI 10.1136/qshc.2006.018408 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 111UY UT WOS:000242481800006 PM 17142586 ER PT J AU Carroll, JS Rudolph, JW AF Carroll, J. S. Rudolph, J. W. TI Design of high reliability organizations in health care SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID IMPROVEMENT; HOSPITALS; KNOWLEDGE; NETWORKS; MEDICINE; BARRIERS; ERROR AB To improve safety performance, many healthcare organizations have sought to emulate high reliability organizations from industries such as nuclear power, chemical processing, and military operations. We outline high reliability design principles for healthcare organizations including both the formal structures and the informal practices that complement those structures. A stage model of organizational structures and practices, moving from local autonomy to formal controls to open inquiry to deep self-understanding, is used to illustrate typical challenges and design possibilities at each stage. We suggest how organizations can use the concepts and examples presented to increase their capacity to self-design for safety and reliability. C1 MIT, Alfred P Sloan Sch Management, Cambridge, MA 02142 USA. VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Carroll, JS (reprint author), MIT, Alfred P Sloan Sch Management, 50 Mem Dr, Cambridge, MA 02142 USA. EM jcarroll@mit.edu NR 54 TC 18 Z9 18 U1 2 U2 14 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD DEC PY 2006 VL 15 SU 1 BP I4 EP I9 DI 10.1136/qshc.2005.015867 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 112GO UT WOS:000242514000002 PM 17142607 ER PT J AU Thrall, JH AF Thrall, James H. TI Building research programs in diagnostic radiology - Part 1. Framing the issues SO RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, MZ-FND 216,Box 9657,14 Fruit St, Boston, MA 02114 USA. EM thrall.james@mgh.harvard.edu NR 7 TC 8 Z9 8 U1 0 U2 0 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 DEC PY 2006 VL 241 IS 3 BP 646 EP 650 DI 10.1148/radiol.2413061449 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 109BM UT WOS:000242282900002 PM 17114614 ER PT J AU Kim, DE Tsuji, K Kim, YR Mueller, FJ Eom, HS Snyder, EY Lo, EH Weissleder, R Schellingerhout, D AF Kim, Dong-Eog Tsuji, Kiyoshi Kim, Young Ro Mueller, Franz-Josef Eom, Hyeon-Seok Snyder, Evan Y. Lo, Eng H. Weissleder, Ralph Schellingerhout, Dawid TI Neural stem cell transplant survival in brains of mice: Assessing the effect of immunity and ischemia by using real-time bioluminescent imaging SO RADIOLOGY LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; PROGENITOR CELLS; INTERFERON-GAMMA; MHC EXPRESSION; FLOW-CYTOMETRY; ADULT BRAIN; IFN-GAMMA; IN-VIVO; MIGRATION; PROLIFERATION AB Purpose: tu use bioluminiscent imaging in a murine transplant model to monitor the in vivo responses of transplanted luciferase-gene-positive neural progenitor cells (NPCs) to host immunity and ischemia. Materials and Methods: All animal studies were conducted according to institutional guidelines, with approval of the Subcommittee on Research Animal Care. Cranial windows were created in all animals, and all animals underwent NPC (C17.2 Luc-GFP gal) transplantation into the right basal ganglia. An observational study was performed on C57 BL/6 (n = 5). nude (n = 4) mice, with bioluminescent imaging performed at days 7, 11, and 14 after transplantation. A study on the effects of ischemia was performed in a similar manner, but with the following differences: On day 9 after transplantation, the C57 BL/6 mice underwent 18 minutes of transient forebrain ischemia by means of temporary bilateral carotid occlusions (n = 6). A control group of C57 BL/6 mice underwent sham surgery (n =6). Bioluminescent imaging was performed on the ischemic animals and control animals at days 7, 9, 11, and 14. Repeated-measures analysis of variance or Student t test was used,to compare the means of the luciferase activities. Results: In vivo cell tracking demonstrated that (a) C 17.2-Luc-GFPgal NPCs survived and proliferated better in the T-cell deficient nude mice than in the immunocompetent C57 BL/6 or CDA mice, in which progressive immune mediated cell loss was shown, and (b) transient forebrain ischemia appeared unexpectedly, to act as a short-term stimulus to transplanted NPC growth and survival in immunocompetent mice. Conclusion: Immune status and host immunity can have an influence on NPC graft survival, and these changes can be noninvasively assessed with bioluminescent imaging in this experimental model. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr,Dept Radiol, Charlestown, MA USA. Burnham Inst, Program Dev & Regenerat Cell Biol, La Jolla, CA 92037 USA. Catholic Univ Korea, Catholic Hematopoiet Stem Cell Transplantat Ctr, Seoul, South Korea. RP Schellingerhout, D (reprint author), Univ Texas, MD Anderson Canc Ctr, Neuroradiol Sect, Dept Radiol, Box 57,1515 Holcombe Blvd, Houston, TX 77030 USA. EM dawid.schellingerhout@di.mdacc.ut.edu RI MAller, Franz-Josef/E-3336-2010 NR 46 TC 35 Z9 37 U1 0 U2 7 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 DEC PY 2006 VL 241 IS 3 BP 822 EP 830 DI 10.1148/radiol.2413050466 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 109BM UT WOS:000242282900024 PM 17114629 ER PT J AU Weber, DC Chan, AW Lessell, S McIntyre, JF Goldberg, SI Bussiere, MR Fitzek, MM Thornton, AF DeLaney, TF AF Weber, Damien C. Chan, Annie W. Lessell, Simmons McIntyre, James F. Goldberg, Saveli I. Bussiere, Marc R. Fitzek, Markus M. Thornton, Altan F. DeLaney, Thomas F. TI Visual outcome of accelerated fractionated radiation for advanced sinonasal malignancies employing photons/protons SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE paranasal sinus cancer; proton beam radiation therapy; accelerated fractionated radiation; late visual complications ID EXTERNAL-BEAM IRRADIATION; PARANASAL SINUS CARCINOMA; SQUAMOUS-CELL CARCINOMAS; TIME-DOSE FACTORS; OPTIC NEUROPATHY; MAXILLARY SINUS; NASAL CAVITY; THERAPY; RADIOTHERAPY; EYE AB Purpose: To investigate the visual outcomes of patients with advanced sinonasal malignancies treated with proton/ photon accelerated fractionated radiation (AFR). Patients and methods: Between 1991 and 2001, AFR was used to treat 36 patients with advanced stage primary (n = 33) or recurrent (n = 3) nasal or paranasal malignant tumors. Full ophthalmologic follow-up was documented. The median dose to the gross tumor volume (GTV) was 69.6 CGE (range 60.8-77). Visual complications were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) and the late effects of normal tissue (LENT) scoring systems. The median follow-up was 52.4 months (range 17-122.8). Results: Thirteen patients developed late visual/ocular toxicity. Cataracts were LENT grade 1 and 3 in 2 patients and 1 patient, respectively. One LENT grade 1 vascular retinopathy and I optic neuropathy were also observed. Three and five patients presented with nasolacrimal duct stenosis (CTC grade 2, 2 patients; CTC grade 3, 1 patient) and dry-eye syndrome (CTC grade 1, 1 patient; CTC grade 2, 4 patients), respectively. The 3- and 5-year probability of LENT/CTC grade >= 2 visual toxicity were 15.8 +/- 6.7% and 20.7 +/- 7.8%, respectively. Conclusions: AFR for locally advanced nasal cavity and paranasal sinus tumors enables delivery of 70 CGE to the tumor with acceptable ophthalmologic complications. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Ophthalmol, Boston, MA 02115 USA. PSI, Villigen, Switzerland. Tufts Univ New England Med Ctr, Boston, MA USA. RP Weber, DC (reprint author), Univ Hosp Geneva, Dept Radiat Oncol, 24 Rue Micheli Crest, CH-1211 Geneva 14, Switzerland. EM damien.weber@hcuge.ch NR 35 TC 31 Z9 34 U1 0 U2 2 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 DEC PY 2006 VL 81 IS 3 BP 243 EP 249 DI 10.1016/j.radonc.2006.09.009 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 122FI UT WOS:000243210700004 PM 17050017 ER PT J AU Stoller, JK Niewoehner, DE Fan, VS AF Stoller, James K. Niewoehner, Dennis E. Fan, Vincent S. TI Disease management as an evolving role for respiratory therapists SO RESPIRATORY CARE LA English DT Editorial Material ID CARE C1 Cleveland Clin Fdn, Dept Pulm Allergy & Crit Care Med, Sect Resp Therapy, Cleveland, OH 44195 USA. Univ Minnesota, Minneapolis Vet Affairs Med Ctr, Pulm Sect, Minneapolis, MN USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Stoller, JK (reprint author), Cleveland Clin Fdn, Dept Pulm & Crit Care Med, A90,9500 Euclid Ave, Cleveland, OH 44195 USA. EM stollej@ccf.org NR 13 TC 4 Z9 4 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESPIR CARE JI Respir. Care PD DEC PY 2006 VL 51 IS 12 BP 1400 EP 1402 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 119BF UT WOS:000242986500001 PM 17134519 ER PT J AU Tamada, RS Amaral, JA Issler, CK Nierenberg, AA Lafer, B AF Tamada, Renata Sayuri Amaral, Jose Antonio Issler, Cilly Kluger Nierenberg, Andrew Alan Lafer, Beny TI Antidepressant treatment-emergent affective switch in bipolar disorder: a prospective case-control study of outcome SO REVISTA BRASILEIRA DE PSIQUIATRIA LA English DT Article DE bipolar disorder; clinical protocol; antidepressive agents; treatment outcome; affective symptoms ID DOUBLE-BLIND; RATING-SCALE; FOLLOW-UP; DEPRESSION; MANIA; IMIPRAMINE; GUIDELINES; BUPROPION; ILLNESS AB Objective: Treatment-emergent affective switch has been associated to cycle acceleration and poorer outcome, but there are few studies addressing this issue. The aim of this study was to prospectively compare the outcome of patients presenting treatment-emergent affective switch with patients with spontaneous mania, regarding presence and polarity of a new episode and time to relapse. Method: Twenty-four patients with bipolar disorder according to the DSM-IV were followed for 12 months. Twelve patients had treatment-emergent affective switch and twelve had spontaneous mania. Patients were evaluated weekly with the Young Mania Rating Scale and the Hamilton Depression Scale until remission of the index episode, and monthly until completion of the 12-month follow-up. Results: Eleven patients with treatment-emergent affective switch had a recurrence on follow-up, all of them with major depressive episodes. In the group with spontaneous mania, six patients had a recurrence: two had a depressive episode, and four had a manic episode (p = 0.069 for new episode, p = 0.006 for polarity of the episode). Patients with treatment-emergent affective switch relapsed in a shorter period than patients with spontaneous mania (p = 0.016). Conclusions: In this first prospective study, treatment-emergent affective switch patients were at greater risk of relapses, especially depressive episodes, and presented a shorter duration of remission when compared with patients with spontaneous mania. C1 Univ Sao Paulo, Sch Med, Hosp Clin, Inst Psychiat,Bipolar Disorder Res Program, Sao Paulo, SP, Brazil. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin & Res Program, Boston, MA USA. RP Tamada, RS (reprint author), Av Padre Pereira Andrade,545,Apto 153F, BR-05469900 Sao Paulo, SP, Brazil. EM rstamada@uol.com.br RI Lafer, Beny/C-1055-2012; Lafer, Beny/F-9390-2015 OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999 NR 30 TC 3 Z9 3 U1 1 U2 2 PU ASSOCIACAO BRASILEIRA DE PSIQUIATRIA PI SAO PAULO PA SUBSCRIPTION DEPARTMENT, RUA PEDRO DE TOLEDO, 967 - CASA 01, SAO PAULO, SP, BRAZIL SN 1516-4446 J9 REV BRAS PSIQUIATR JI Rev. Bras. Psiquiatr. PD DEC PY 2006 VL 28 IS 4 BP 297 EP 300 DI 10.1590/S1516-44462006005000013 PG 4 WC Psychiatry SC Psychiatry GA 114XX UT WOS:000242700000009 PM 17242809 ER PT J AU Duerr, RH Taylor, KD Brant, SR Rioux, JD Silverberg, MS Daly, MJ Steinhart, AH Abraham, C Regueiro, M Griffiths, A Dassopoulos, T Bitton, A Yang, HY Targan, S Datta, LW Kistner, EO Schumm, LP Lee, AT Gregersen, PK Barmada, MM Rotter, JI Nicolae, DL Cho, JH AF Duerr, Richard H. Taylor, Kent D. Brant, Steven R. Rioux, John D. Silverberg, Mark S. Daly, Mark J. Steinhart, A. Hillary Abraham, Clara Regueiro, Miguel Griffiths, Anne Dassopoulos, Themistocles Bitton, Alain Yang, Huiying Targan, Stephan Datta, Lisa Wu Kistner, Emily O. Schumm, L. Philip Lee, Annette T. Gregersen, Peter K. Barmada, M. Michael Rotter, Jerome I. Nicolae, Dan L. Cho, Judy H. TI A genome-wide association study identifies IL23R as an inflammatory bowel disease gene SO SCIENCE LA English DT Article ID ACTIVE CROHNS-DISEASE; AUTOIMMUNE INFLAMMATION; T-CELLS; IL-23; CYTOKINE; IL-12; SUSCEPTIBILITY; EXPRESSION; SUBUNIT; INTERLEUKIN-17 AB The inflammatory bowel diseases Crohn's disease and ulcerative colitis are common, chronic disorders that cause abdominal pain, diarrhea, and gastrointestinal bleeding. To identify genetic factors that might contribute to these disorders, we performed a genome-wide association study. We found a highly significant association between Crohn's disease and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the proinflammatory cytokine interleukin-23. An uncommon coding variant (rs11209026, c. 1142G> A, p. Arg381Gln) confers strong protection against Crohn's disease, and additional noncoding IL23R variants are independently associated. Replication studies confirmed IL23R associations in independent cohorts of patients with Crohn's disease or ulcerative colitis. These results and previous studies on the proinflammatory role of IL-23 prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease. C1 Yale Univ, IBD Ctr, Sect Digest Dis, Dept Med, New Haven, CT 06519 USA. Univ Pittsburgh, Med Ctr, Sch Med,Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. Cedars Sinai Med Ctr, Div Gastroenterol, IBD Ctr, Los Angeles, CA 90048 USA. Johns Hopkins Univ, Sch Med, Dept Med, Harvey M & Lyn P Meyerhoff Inflammatory Bowel Dis, Baltimore, MD 21231 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Univ Montreal, Montreal, PQ H1T 1C8, Canada. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. MIT, Broad Inst, Med & Populat Genet Program, Cambridge, MA 02142 USA. Harvard Univ, Cambridge, MA 02142 USA. Univ Toronto, Mt Sinai Hosp, IBD Ctr, Toronto, ON M5G 1X5, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada. McGill Univ, Royal Victoria Hosp, Ctr Hlth, Montreal, PQ H3A 1A1, Canada. Cedars Sinai Med Ctr, Immunobiol Res Inst, Los Angeles, CA 90048 USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Feinstein Inst Med Res, Manhasset, NY 11030 USA. Univ Chicago, Dept Stat, Chicago, IL 60637 USA. Yale Univ, IBD Ctr, Sect Digest Dis, Dept Genet, New Haven, CT 06519 USA. RP Cho, JH (reprint author), Yale Univ, IBD Ctr, Sect Digest Dis, Dept Med, S155A,300 Cedar St, New Haven, CT 06519 USA. EM judy.cho@yale.edu RI Silverberg, Mark/B-4183-2008; Rioux, John/A-9599-2015; OI Rioux, John/0000-0001-7560-8326; Duerr, Richard/0000-0001-6586-3905; Barmada, M Michael/0000-0002-3604-6460 FU NIDDK NIH HHS [DK62429, DK62413, DK62420, DK62422, DK62423, DK62431, DK62432, P30 DK063491, P30 DK063491-019004, P30 DK063491-029004, P30 DK063491-039004, P30 DK063491-049004, U01 DK062413, U01 DK062420, U01 DK062422, U01 DK062423, U01 DK062429, U01 DK062431, U01 DK062432] NR 28 TC 1721 Z9 1782 U1 17 U2 122 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 DEC 1 PY 2006 VL 314 IS 5804 BP 1461 EP 1463 DI 10.1126/science.1135245 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 110UF UT WOS:000242406100044 PM 17068223 ER PT J AU Cohen, DM AF Cohen, David M. TI Regulation of TRP channels by N-linked glycosylation SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE review; transient receptor potential; ion channel ID SHAKER POTASSIUM CHANNEL; CELL-SURFACE EXPRESSION; KLOTHO GENE; SODIUM-CHANNELS; POSTMENOPAUSAL WOMEN; VANILLOID RECEPTOR-1; FUNCTIONAL VARIANT; CA2+ CHANNEL; BONE-DENSITY; PORE REGION AB A subset of TRP channel proteins undergoes regulatory N-linked glycosylation. A glycosylation site in the first extracellular loop of TRPV5 is enzymatically cleaved by a secreted glucuronidase, indirectly regulating channel function. Members of the TRPC family share a similar site, although details about a regulatory role are lacking. A second conserved TRP channel glycosylation site is found immediately adjacent to the channel pore-forming loop; both TRPV1 and TRPV4 - and perhaps other TRPV family members - are influenced by glycosylation at this site. N-linked glycosylation, and the dynamic regulation of this process, substantially impacts function and targeting of TRP channels. (c) 2006 Elsevier Ltd. All rights reserved. C1 Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. RP Cohen, DM (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Mailcode PP262, Portland, OR 97239 USA. EM cohend@ohsu.edu NR 68 TC 30 Z9 30 U1 0 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD DEC PY 2006 VL 17 IS 6 BP 630 EP 637 DI 10.1016/j.semcdb.2006.11.007 PG 8 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 139HP UT WOS:000244423200004 PM 17215147 ER PT J AU Vazquez, J Kassarjian, A AF Vazquez, Josue Kassarjian, Ara TI MRI of shoulder trauma SO SEMINARS IN MUSCULOSKELETAL RADIOLOGY LA English DT Article DE MRI; shoulder; arthrography; MR arthrography; rotator cuff; labrum; cartilage; trauma ID ROTATOR CUFF TEARS; TENDON TEARS; ARTHROGRAPHY; IMPINGEMENT; MORPHOLOGY AB Magnetic resonance imaging (MRI) is an invaluable tool for evaluating traumatic injuries of the shoulder. This article discusses MRI of shoulder trauma based on mechanism of injury. Acute direct traumatic injuries, acute indirect traumatic injuries, and repetitive microtraumatic injuries (impingement/traction) are discussed. Finally, common pitfalls in shoulder imaging are addressed. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Boston, MA 02115 USA. RP Kassarjian, A (reprint author), Paseo Castellana 141,Edificio Cuzco 4,Planta 18,O, E-28046 Madrid, Spain. NR 19 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1089-7860 J9 SEMIN MUSCULOSKEL R JI Semin. Musculoskelet. Radiol. PD DEC PY 2006 VL 10 IS 4 BP 268 EP 283 DI 10.1055/s-2007-971998 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 177KI UT WOS:000247151600005 PM 17387641 ER PT J AU Tanabe, KK AF Tanabe, Kenneth K. TI New techniques of liver surgery SO SEMINARS IN ONCOLOGY LA English DT Article; Proceedings Paper CT 2nd Annual International-Society-of-Gastrointestinal-Oncology Conference CY JUL 14-16, 2005 CL Arlington, VA SP Int* Soc* Gasrointestinal Oncol ID COLORECTAL METASTASES; RESECTION; SURVIVAL; CANCER; CHEMOTHERAPY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Yawkey Bldg 7-924,55 Fruit St, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2006 VL 33 IS 6 SU 11 BP S39 EP S41 DI 10.1053/j.seminoncol.2006.10.010 PG 3 WC Oncology SC Oncology GA 125DD UT WOS:000243421000010 PM 17178285 ER PT J AU Bandipalliam, P AF Bandipalliam, Prathap TI MALT lymphomas - A closer look in the genornics era SO SOUTHERN MEDICAL JOURNAL LA English DT Editorial Material ID B-CELL LYMPHOMA; MARGINAL-ZONE LYMPHOMA; NON-HODGKINS-LYMPHOMA; TISSUE LYMPHOMA; HELICOBACTER-PYLORI; CLINICAL ACTIVITY; DNA MICROARRAYS; GENE; T(11/18)(Q21,Q21); CHEMOTHERAPY C1 Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. RP Bandipalliam, P (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Smith 205,44 Binney St, Boston, MA 02115 USA. EM prathap_bandipalliam@dfci.harvard.edu NR 40 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD DEC PY 2006 VL 99 IS 12 BP 1322 EP 1324 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 172AS UT WOS:000246777100002 PM 17233185 ER PT J AU Brugge, WR AF Brugge, William R. TI Advances in the endoscopic management of patients with pancreatic and biliary malignancies SO SOUTHERN MEDICAL JOURNAL LA English DT Review DE pancreatic cancer; cholangiocarcinoma; endoscopic retrograde cholangiopancreatography; endoscopic ultrasound; magnetic resonance cholangiopancreatography; transhepatic cholangiography ID RADIOLOGIC-PATHOLOGICAL CORRELATION; PAPILLARY MUCINOUS NEOPLASMS; FINE-NEEDLE-ASPIRATION; CYSTIC NEOPLASMS; INTRAEPITHELIAL NEOPLASIA; BRUSH CYTOLOGY; CHOLANGIOCARCINOMA; TUMORS; LESIONS; EUS AB Major advances in endoscopic techniques to diagnose and manage pancreatic biliary diseases have fundamentally changed the approach to these difficult clinical challenges. The diagnosis of benign and malignant pancreatic-biliary diseases is much more readily obtained through a combination of cross-sectional imaging and endoscopic procedures. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are the most important endoscopic tools for imaging and accessing the pancreatic biliary system. The review summarizes the major imaging methods for providing a diagnosis of bile duct malignancy, including ERCP, transhepatic cholangiography (THC), and magnetic resonance cholangiopancreatography (MRCP). High quality image examples of cholangiocarcinoma are provided. EUS has provided a new imaging modality for the detection of pancreatic and biliary malignancy. EUS is particularly sensitive for the detection of early pancreatic malignancy. Furthermore, EUS excels at the guidance of fine needle aspiration of pancreatic lesions. Diagnostic tissue acquisition for cholangiocarcinoma remains an important challenge. The endoscopic therapy for pancreatic-biliary malignancy involves the use of stenting which relieves the biliary obstruction commonly seen in these patients. C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Unit, Blake 452C, Boston, MA 02114 USA. EM WBrugge@partners.org NR 47 TC 11 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD DEC PY 2006 VL 99 IS 12 BP 1358 EP 1366 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 172AS UT WOS:000246777100011 PM 17233192 ER PT J AU Basile, JN Ventura, H AF Basile, Jan N. Ventura, Hector TI A historical look at hypertension: Celebrating 100 years with the Southern Medical Association SO SOUTHERN MEDICAL JOURNAL LA English DT Editorial Material ID UNITED-STATES C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Primary Care Serv Line, Charleston, SC 29401 USA. Med Univ S Carolina, Div Gen Internal Med Geriatr, Charleston, SC 29401 USA. Tulane Univ, Sch Med, Sect Cardiomyopathy & Heart Transplant Ctr, New Orleans, LA USA. RP Basile, JN (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Primary Care Serv Line, 109 Bee St, Charleston, SC 29401 USA. RI Ventura, Hector/A-7691-2011 NR 20 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD DEC PY 2006 VL 99 IS 12 BP 1412 EP 1413 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 172AS UT WOS:000246777100032 PM 17233212 ER PT J AU Vincent, R Treff, N Budde, M Kastenberg, Z Odorico, J AF Vincent, Robert Treff, Nathan Budde, Melisa Kastenberg, Zachary Odorico, Jon TI Generation and characterization of novel tetracycline-inducible pancreatic transcription factor-expressing murine embryonic stem cell lines SO STEM CELLS AND DEVELOPMENT LA English DT Article ID INSULIN-PRODUCING CELLS; BETA-CELLS; IN-VITRO; ISLET DIFFERENTIATION; GENE-EXPRESSION; ENDODERM; PROTEIN; PDX-1; MICE; NEUROGENIN-3 AB Pancreatic development in mammals is controlled in part by the expression and function of numerous genes encoding transcription factors. Yet, how these regulate each other and their target genes is incompletely understood. Embryonic stem (ES) cells have recently been shown to be capable of differentiating into pancreatic progenitor cells and insulin-producing cells, representing a useful in vitro model system for studying pancreatic and islet development. To generate tools to study the relationships of transcription factors in pancreatic development we have established seven unique mouse ES cell lines with tetracycline-inducible expression of either Hnf4 alpha, Hnf6, Nkx2.2, Nkx6.1, Pax4, Pdx1, and Ptf1a cDNAs. Each of the cell lines was characterized for induction of transgene expression after exposure to doxycycline (DOX) by quantitative real-time PCR and immunofluorescence microscopy. Transgene expression in the presence of DOX was at least 97-fold that seen in untreated cells. Immunofluorescent staining of DOX-treated cultures showed efficient (> 95% of cells) transgene protein expression while showing < 5% positive staining in uninduced cells. Each of the ES cell lines maintained their pluripotency as measured by teratoma formation. Furthermore, transgene expression can be efficiently achieved in vivo through DOX administration to mice. The establishment of ES cell lines with temporally controllable induction of critical pancreatic transcription factor genes provides a new set of tools that could be used to interrogate gene regulatory networks in pancreatic development and potentially generate greater numbers of ss cells from ES cells. C1 Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Madison, WI 53705 USA. Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI 53792 USA. WiCell Res Inst, Madison, WI 53707 USA. Reprod Med Associates New Jersey, Morristown, NJ 07960 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Vincent, R (reprint author), Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, 2500 Overlook Terrace, Madison, WI 53705 USA. EM rkvincent@wisc.edu NR 42 TC 10 Z9 10 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD DEC PY 2006 VL 15 IS 6 BP 953 EP 962 DI 10.1089/scd.2006.15.953 PG 10 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 129TL UT WOS:000243752900019 PM 17253956 ER PT J AU van Leyen, K Kim, HY Lee, SR Jin, G Arai, K Lo, EH AF van Leyen, Klaus Kim, Hahn Young Lee, Seong-Ryong Jin, Guang Arai, Ken Lo, Eng H. TI Baicalein and 12/15-lipoxygenase in the ischemic brain SO STROKE LA English DT Article DE antioxidant; baicalein; ischemia; lipoxygenase neuron ID GLUTATHIONE DEPLETION; CEREBRAL-ISCHEMIA; OXIDATIVE STRESS; CORTICAL-NEURONS; 12-LIPOXYGENASE; STROKE; INHIBITION; GENE; LIPOXYGENASE; DEATH AB Background and Purpose - The natural product baicalein is a specific inhibitor of 12/15-lipoxygenase, but it also has antioxidant properties. The current study was designed to test if the neuroprotective properties of baicalein are related to its lipoxygenase inhibition. Methods - The presence of 12/15-lipoxygenase in the ischemic mouse brain was demonstrated by immunohistochemistry. A mouse model of transient middle cerebral artery occlusion was used to study lipoxygenase-dependent protection of the ischemic brain by baicalein. Rat primary neurons were subjected to oxidative stress in the presence or absence of baicalein. Results - In a mouse model of transient middle cerebral artery occlusion, 12/15-lipoxygenase is increased in the peri-infarct area surrounding the primary infarction, predominantly in neurons. Oxidative toxicity in primary rat neurons is reduced by baicalein. C57B16J mice are protected against transient focal ischemia by intraperitoneal injection of baicalein, and a similar degree of protection is seen in 12/15-lipoxygenase knockout mice compared with wild-type mice. In contrast, the 12/15-LOX knockout mice are not further protected by baicalein. Conclusion - Baicalein protects against ischemia/reperfusion injury by inhibiting the 12/15-lipoxygenase pathway to neuronal cell death. C1 Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Stroke & Neurovasc Res Grp, Charlestown, MA 02129 USA. RP van Leyen, K (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Stroke & Neurovasc Res Grp, 149 13th St,R 2401, Charlestown, MA 02129 USA. EM klaus_vanleyen@hms.harvard.edu RI van Leyen, Klaus/C-9126-2013 FU NINDS NIH HHS [R01NS049430] NR 31 TC 102 Z9 105 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 2006 VL 37 IS 12 BP 3014 EP 3018 DI 10.1161/01.STR.0000249004.25444.a5 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 124ZO UT WOS:000243411500037 PM 17053180 ER PT J AU Murie, JA Sarr, MG Warshaw, AL AF Murie, J. A. Sarr, M. G. Warshaw, A. L. TI A tale of three papers SO SURGERY LA English DT Editorial Material ID BILE-DUCT; CHOLECYSTECTOMY; INJURIES C1 Royal Infirm, Dept Vasc Surg, Edinburgh, Midlothian, Scotland. Mayo Clin & Mayo Fdn, Div Gastroenterol & Gen Surg, Rochester, MN 55905 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Murie, JA (reprint author), Royal Infirm, Dept Vasc Surg, Edinburgh, Midlothian, Scotland. NR 6 TC 4 Z9 4 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 DEC PY 2006 VL 140 IS 6 BP 1063 EP 1064 DI 10.1016/j.surg.2006.11.001 PG 2 WC Surgery SC Surgery GA 123ZG UT WOS:000243335800054 PM 17188158 ER PT J AU Rattner, DW AF Rattner, David W. TI Innovation, disruption, and the perils of success - SAGES Presidential Address, 14 April 2005 SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD DEC PY 2006 VL 20 IS 12 BP 1802 EP 1808 DI 10.1007/s00464-005-0818-x PG 7 WC Surgery SC Surgery GA 118VS UT WOS:000242972200002 PM 17063291 ER PT J AU Seim, AR Andersen, B Berger, DL Sokal, SM Sandberg, WS AF Seim, Andreas R. Andersen, Bjorn Berger, David L. Sokal, Suzanne M. Sandberg, Warren S. TI The effect of direct-from-recovery room discharge of laparoscopic cholecystectomy patients on recovery room workload SO SURGICAL INNOVATION LA English DT Article DE ambulatory surgery; perioperative systems design; OR economics; laparoscopic cholecystectomy; PACU workload ID OPERATING-ROOM; COST-EFFECTIVENESS; SURGERY; IMPACT; PACU; CARE AB Ambulatory laparoscopic cholecystectomy pathways move patients through the hospital without encountering delays caused by congested inpatient bed units. However, redirecting patients to a direct discharge pathway might not be beneficial if recovery capacity is further taxed by additional workload. In this study, we attempt to assess the operational impact on recovery room workload of directly discharging laparoscopic cholecystectomy patients to home. We conducted a retrospective case-control review of recovery room flow sheets to determine recovery room time and effort required for laparoscopic cholecystectomy patients. The study was restricted to patients of a single surgeon to minimize confounds from surgical technique. Fifty-seven case patients (May 1, 2004, through November 30, 2004), all managed with intent to directly discharge from the recovery room, were compared with control patients (n = 81) from the corresponding 6 months in the year before the direct-discharge plan. The times (mean; 95% confidence interval) to meet objective criteria for adequate pain control (3.5 minutes [2.1 to 5.9] versus 4.0 minutes [2.6 to 6.1]) and readiness for discharge from phase 1 recovery (8.1 minutes [4.8 to 13.6] versus 6.1 minutes [4.0 to 9.5]) were not different between the groups. The number and distribution of interventions documented in the recovery process were not different between groups, nor was there a difference in recovery room length of stay (15 8 minutes [ 13 8 to 182] versus 149 minutes [ 132 to 167]). In our study, recovery room records reveal little if any increased workload associated with the direct-to-home discharge of laparoscopic cholecystectomy patients. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Norwegian Univ Sci & Technol, Dept Prod & Qual Engn, N-7034 Trondheim, Norway. RP Sandberg, WS (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Clin 3, Boston, MA 02114 USA. EM wsandberg@partners.org NR 14 TC 4 Z9 4 U1 0 U2 1 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1553-3506 J9 SURG INNOV JI Surg. Innov. PD DEC PY 2006 VL 13 IS 4 BP 257 EP 264 DI 10.1177/1553350606297053 PG 8 WC Surgery SC Surgery GA 150HB UT WOS:000245205200006 PM 17227924 ER PT J AU Qureshi, AA Brandling-Bennett, HA Wittenberg, E Chen, SC Sober, AJ Kvedar, JC AF Qureshi, Abrar A. Brandling-Bennett, Heather A. Wittenberg, Eve Chen, Suephy C. Sober, Arthur J. Kvedar, Joseph C. TI Willingness-to-pay stated preferences for telemedicine versus in-person visits in patients with a history of psoriasis or melanoma SO TELEMEDICINE JOURNAL AND E-HEALTH LA English DT Article ID QUALITY-OF-LIFE; SATISFACTION; TELEDERMATOLOGY; SERVICES AB The objective of this study was to evaluate willingness-to-pay stated preferences for telemedicine versus in-person clinic visits in patients with a history of psoriasis or melanoma. Face-to-face interviews were conducted with 92 (n = 92) adult participants with a history of psoriasis or melanoma recruited primarily from hospital-based dermatology practices. Data were collected on patient demographics and willingness-to-pay responses. In a combined analysis for patients with melanoma and psoriasis, 73% of participants preferred telemedicine over in-person visits if access to the physician was quicker. The majority of those choosing telemedicine (95%) were also willing to pay a median of $25 ($5 -$500) out-of-pocket. When time to see a physician was held constant for telemedicine and in-person visits, 19% of participants preferred telemedicine and about 58% of these participants were willing to pay a median of $25 ($10-$125) out-of-pocket. This preliminary work suggests that dermatology patients prefer telemedicine if this modality provides quicker access to their physician. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Emory Univ, Dept Dermatol, Atlanta, GA 30322 USA. Atlanta VA Med Ctr, Div Dermatol, Dept HSR&D, Atlanta, GA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. Partners Telemed, Boston, MA USA. RP Qureshi, AA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, 45 Francis St,221L, Boston, MA 02115 USA. EM aqureshi@partners.org FU NIAMS NIH HHS [K23AR02185.01A1] NR 12 TC 19 Z9 19 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED J E-HEALTH JI Telemed. J. e-Health PD DEC PY 2006 VL 12 IS 6 BP 639 EP 643 DI 10.1089/tmj.2006.12.639 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 129TJ UT WOS:000243752700020 PM 17250485 ER PT J AU Dobscha, SK Corson, K Pruitt, S Crutchfield, M Gerrity, MS AF Dobscha, Steven K. Corson, Kathryn Pruitt, Stephanie Crutchfield, Megan Gerrity, Martha S. TI Measuring depression and pain with home health monitors SO TELEMEDICINE JOURNAL AND E-HEALTH LA English DT Article ID SEVERITY; VETERANS; RECALL; PHQ-9 AB The objective of this pilot study was to test the feasibility of using home health monitors to administer standardized measures for depression and pain in a Veterans Affairs (VA) patient population. Five patients were recruited from a larger study of collaborative depression care, and were asked to use Viterion(TM) 100 Telehealth monitors to transmit depression (Patient Health Questionnaire-9) and pain severity (SF36-V bodily pain items) scores on a weekly basis for 24 weeks. Information was received and reviewed by a nurse care manager, who recommended treatment changes as appropriate. The care manager occasionally followed up reports of changes in symptom severity with phone calls; in one case, she called to inquire why a patient was not submitting data. Overall, four patients were able to use the monitors successfully and frequently. Patient satisfaction was high: 5 of 5 reported that they would use monitors again, and 3 of 5 preferred monitors to phone or mail for completing questionnaires. Patients expressed no concerns about privacy. The data allowed tracking of the longitudinal interrelationship between depression and pain severity. However, the monitors were limited in their ability to display questionnaire items, and the system could neither directly compute measure scores nor transfer data to patient medical records. These results suggest that with modifications, home health monitoring shows promise for monitoring symptom severity for a variety of medical and mental health conditions, for either clinical or research purposes. C1 Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97207 USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR USA. Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97207 USA. Portland VA Med Ctr, Div Hosp & Specialty Med, Portland, OR 97207 USA. Oregon Hlth & Sci Univ, Dept Med, Portland, OR USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, POB 1034 P3MHDC, Portland, OR 97207 USA. EM steven.dobscha@med.va.gov NR 14 TC 8 Z9 8 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED J E-HEALTH JI Telemed. J. e-Health PD DEC PY 2006 VL 12 IS 6 BP 702 EP 706 DI 10.1089/tmj.2006.12.702 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 129TJ UT WOS:000243752700028 PM 17250493 ER PT J AU O'Barr, SA Oh, JS Ma, C Brent, GA Schultz, JJ AF O'Barr, Stephen A. Oh, Jin S. Ma, Chan Brent, Gregory A. Schultz, James J. TI Thyroid hormone regulates endogenous amyloid-beta precursor protein gene expression and processing in both in vitro and in vivo models SO THYROID LA English DT Article ID ALZHEIMERS-DISEASE; MESSENGER-RNA; NEUROBLASTOMA-CELLS; REGIONAL EXPRESSION; NEGATIVE REGULATION; RESPONSE ELEMENTS; RAT-BRAIN; RECEPTOR; TRIIODOTHYRONINE; DIFFERENTIATION AB Thyroid hormone negatively regulates the amyloid-beta precursor protein (APP) gene in thyroid hormone receptor (TR)-transfected neuroblastoma cells. A negative thyroid hormone response element (nTRE) that mediates this regulation has been identified in the first exon of the APP gene. We demonstrate in an in vivo system that expression of APP mRNA, APP protein, and APP secretase cleavage products in mouse brain is influenced by thyroid status. Adult female mice were made hyperthyroid or hypothyroid for 3weeks and compared to euthyroid mice. APP gene product expression was increased in hypothyroid mouse brain and reduced in hyperthyroid mouse brain, when compared to euthyroid controls. We observed similar effects of thyroid hormone on endogenous APP gene expression in human neuroblastoma cells. The incidence of hypothyroidism increases with age, and localized hypothyroidism of central nervous system has been reported in some patients with Alzheimer's disease (AD). Reduced action of thyroid hormone on the APP gene may contribute to AD pathology by increasing APP expression and the levels of processed APP products. These findings may be an underlying mechanism contributing to the association of hypothyroidism with AD in the elderly, as well as identifying a potential therapeutic target. Pharmacologic supplementation of thyroid hormone, or its analogs, may reduce APP gene expression and beta amyloid peptide accumulation. C1 Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab,Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab,Dept Physiol, Los Angeles, CA 90073 USA. Western Univ Hlth Sci, Coll Pharm, Dept Pharmaceut Sci, Pomona, CA USA. RP Brent, GA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab,Dept Med, Bldg 114,Rm 230,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gbrent@ucla.edu FU NIDDK NIH HHS [R01 DK67233] NR 35 TC 21 Z9 21 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD DEC PY 2006 VL 16 IS 12 BP 1207 EP 1213 DI 10.1089/thy.2006.16.1207 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 123RD UT WOS:000243312200003 PM 17199430 ER PT J AU Jonklaas, J Sarlis, NJ Litofsky, D Ain, KB Bigos, ST Brierley, JD Cooper, DS Haugen, BR Ladenson, PW Magner, J Robbins, J Ross, DS Skarulis, M Maxon, HR Sherman, SI AF Jonklaas, Jacqueline Sarlis, Nicholas J. Litofsky, Danielle Ain, Kenneth B. Bigos, S. Thomas Brierley, James D. Cooper, David S. Haugen, Bryan R. Ladenson, Paul W. Magner, James Robbins, Jacob Ross, Douglas S. Skarulis, Monica Maxon, Harry R. Sherman, Steven I. TI Outcomes of patients with differentiated thyroid carcinoma following initial therapy SO THYROID LA English DT Article ID HIGH-RISK PAPILLARY; RADIOACTIVE IODINE; THYROTROPIN SUPPRESSION; DEATH CERTIFICATES; OBSERVER VARIATION; PROGNOSTIC FACTORS; I-131 THERAPY; CANCER; SURVIVAL; DISEASE AB This analysis was performed to determine the effect of initial therapy on the outcomes of thyroid cancer patients. The study setting was a prospectively followed multi-institutional registry. Patients were stratified as low risk (stages I and II) or high risk (stages III and IV). Treatments employed included near-total thyroidectomy, administration of radioactive iodine, and thyroid hormone suppression therapy. Outcome measures were overall survival, disease-specific survival, and disease-free survival. Near-total thyroidectomy, radioactive iodine, and aggressive thyroid hormone suppression therapy were each independently associated with longer overall survival in high-risk patients. Near-total thyroidectomy followed by radioactive iodine therapy, and moderate thyroid hormone suppression therapy, both predicted improved overall survival in stage II patients. No treatment modality, including lack of radioactive iodine, was associated with altered survival in stage I patients. Based on our overall survival data, we confirm that near-total thyroidectomy is indicated in high-risk patients. We also conclude that radioactive iodine therapy is beneficial for stage II, III, and IV patients. Importantly, we show for the first time that superior outcomes are associated with aggressive thyroid hormone suppression therapy in high-risk patients, but are achieved with modest suppression in stage II patients. We were unable to show any impact, positive or negative, of specific therapies in stage I patients. C1 Georgetown Univ, Ctr Med, Washington, DC 20007 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX USA. Univ Kentucky, Ctr Med, Lexington, KY USA. Maine Med Ctr, Portland, ME USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Sinai Hosp, Baltimore, MD 21215 USA. Univ Colorado, Denver, CO USA. Hlth Sci Ctr, Aurora, CO USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Genzyme Corp, Cambridge, MA USA. NIH, Bethesda, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Cincinnati, Ctr Med, Cincinnati, OH USA. RP Jonklaas, J (reprint author), Georgetown Univ, Ctr Med, 4000 Reservoir Rd,NW Bldg D,Ste 230, Washington, DC 20007 USA. EM jj@bc.georgetown.edu RI Jonklaas, Jacqueline/G-2807-2010; OI Jonklaas, Jacqueline/0000-0002-2238-2666; Ain, Kenneth/0000-0002-2668-934X; Sherman, Steven/0000-0002-3079-5153 FU NCRR NIH HHS [K23 RR16524] NR 61 TC 263 Z9 285 U1 1 U2 11 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 DEC PY 2006 VL 16 IS 12 BP 1229 EP 1242 DI 10.1089/thy.2006.16.1229 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 123RD UT WOS:000243312200006 PM 17199433 ER PT J AU Mikos, AG Herring, SW Ochareon, P Elisseeff, J Lu, HH Kandel, R Schoen, FJ Toner, M Mooney, D Atala, A Van Dyke, ME Kaplan, D Vunjak-Novakovic, G AF Mikos, Antonios G. Herring, Susan W. Ochareon, Pannee Elisseeff, Jennifer Lu, Helen H. Kandel, Rita Schoen, Frederick J. Toner, Mehmet Mooney, David Atala, Anthony Van Dyke, Mark E. Kaplan, David Vunjak-Novakovic, Gordana TI Engineering complex tissues SO TISSUE ENGINEERING LA English DT Article; Proceedings Paper CT Workshop on Tissue Engineering - The Next Generation CY MAY 02-04, 2005 CL Boston, MA ID MESENCHYMAL STEM-CELLS; ANTERIOR CRUCIATE LIGAMENT; ARTICULAR-CARTILAGE REPAIR; ENDOTHELIAL GROWTH-FACTOR; CALCIUM POLYPHOSPHATE SCAFFOLDS; BONE SUBSTITUTE APPLICATIONS; MEDIAL COLLATERAL LIGAMENT; BIOPROSTHETIC HEART-VALVE; TOTAL HIP-ARTHROPLASTY; FORMED IN-VITRO AB This article summarizes the views expressed at the third session of the workshop "Tissue Engineering - The Next Generation,'' which was devoted to the engineering of complex tissue structures. Antonios Mikos described the engineering of complex oral and craniofacial tissues as a "guided interplay'' between biomaterial scaffolds, growth factors, and local cell populations toward the restoration of the original architecture and function of complex tissues. Susan Herring, reviewing osteogenesis and vasculogenesis, explained that the vascular arrangement precedes and dictates the architecture of the new bone, and proposed that engineering of osseous tissues might benefit from preconstruction of an appropriate vasculature. Jennifer Elisseeff explored the formation of complex tissue structures based on the example of stratified cartilage engineered using stem cells and hydrogels. Helen Lu discussed engineering of tissue interfaces, a problem critical for biological fixation of tendons and ligaments, and the development of a new generation of fixation devices. Rita Kandel discussed the challenges related to the re-creation of the cartilage-bone interface, in the context of tissue engineered joint repair. Frederick Schoen emphasized, in the context of heart valve engineering, the need for including the requirements derived from "adult biology'' of tissue remodeling and establishing reliable early predictors of success or failure of tissue engineered implants. Mehmet Toner presented a review of biopreservation techniques and stressed that a new breakthrough in this field may be necessary to meet all the needs of tissue engineering. David Mooney described systems providing temporal and spatial regulation of growth factor availability, which may find utility in virtually all tissue engineering and regeneration applications, including directed in vitro and in vivo vascularization of tissues. Anthony Atala offered a clinician's perspective for functional tissue regeneration, and discussed new biomaterials that can be used to develop new regenerative technologies. C1 Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA. Columbia Univ, Coll Dent Med, New York, NY 10027 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. Univ Washington, Dept Orthodont, Seattle, WA 98195 USA. Rice Univ, Dept Bioengn, Houston, TX 77251 USA. Univ Toronto, Dept Pathol & Lab Med, Toronto, ON, Canada. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Shriners Hosp Children, Boston, MA USA. Harvard Univ, Div Engn & Appl Sci, Cambridge, MA 02138 USA. Wake Forest Univ, Sch Med, Wake Forest Inst Regenerat Med, Winston Salem, NC 27109 USA. Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA. RP Vunjak-Novakovic, G (reprint author), Columbia Univ, Dept Biomed Engn, 363G Engn Terrace,Mail Code 8904,1210 Amsterdam A, New York, NY 10027 USA. EM gv2131@columbia.edu RI Kandel, Rita/E-2149-2017; OI Kandel, Rita/0000-0003-4047-3913; Atala, Anthony/0000-0001-8186-2160; Vunjak-Novakovic, Gordana/0000-0002-9382-1574 FU NIAMS NIH HHS [AR052402, R21 AR052402]; NIBIB NIH HHS [P41 EB002520]; NIDCR NIH HHS [DE08513, R01 DE008513, R01 DE008513-18, R01 DE015164, R01 DE15164] NR 285 TC 301 Z9 318 U1 16 U2 136 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD DEC PY 2006 VL 12 IS 12 BP 3307 EP 3339 DI 10.1089/ten.2006.12.3307 PG 33 WC Cell & Tissue Engineering SC Cell Biology GA 122CB UT WOS:000243202200005 PM 17518671 ER PT J AU Luo, Y Kobler, JB Zeitels, SM Langer, R AF Luo, Ying Kobler, James B. Zeitels, Steven M. Langer, Robert TI Effects of growth factors on extracellular matrix production by vocal fold fibroblasts in 3-dimensional culture SO TISSUE ENGINEERING LA English DT Article; Proceedings Paper CT Workshop on Tissue Engineering - The Next Generation CY MAY 02-04, 2005 CL Boston, MA ID PEPTIDE SCAFFOLDS; HYALURONIC-ACID; LAMINA PROPRIA; PROTEOGLYCANS; BIOMECHANICS; COLLAGEN; DESIGN; MODEL AB Culturing cells in 3-dimensional (3D) systems is important in tissue engineering and in fundamental studies of cellular mechanisms that are sensitive or specific to the 3D environment. To guide the engineering of artificial vocal fold lamina propria tissue, we developed 3D cultures containing human vocal fold fibroblasts (hVFFs) dispersed in a synthetic peptide hydrogel matrix. Growth factors were added to the culture to examine their influence on extracellular matrix (ECM) synthesis, cell proliferation, and matrix contraction. The hVFF-hydrogel constructs were treated with transforming growth factor-beta 1 (TGF-beta 1), basic fibroblast growth factor (bFGF), or hepatocyte growth factor (HGF), and the culture was maintained for 21 days. TGF-beta 1 induced matrix contraction and enhanced collagen and sulfated glycosaminoglycan production, bFGF effectively increased cell proliferation, and HGF stimulated synthesis of hyaluronic acid and elastin with less collagen accumulation than other conditions. Of the growth factors tested, HGF appears to be most useful for stimulating essential tissue components for restoring vocal fold pliability. The results also suggest that multiple growth factors might be employed sequentially or in combination to program the makeup of cell-hydrogel constructs for vocal fold tissue repair. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. RP Langer, R (reprint author), MIT, Dept Chem Engn, 77 Massachusetts Ave,E25-342, Cambridge, MA 02139 USA. EM rlanger@mit.edu RI Luo, Ying/A-9920-2012 OI Luo, Ying/0000-0001-9834-9419 FU NIDCR NIH HHS [R01DE01302306] NR 27 TC 34 Z9 34 U1 0 U2 15 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD DEC PY 2006 VL 12 IS 12 BP 3365 EP 3374 DI 10.1089/ten.2006.12.3365 PG 10 WC Cell & Tissue Engineering SC Cell Biology GA 122CB UT WOS:000243202200007 PM 17518673 ER PT J AU Ballen, KK Haley, NR Kurtzberg, J Lane, TA Lindgren, BR Miller, JP Newman, B McCullough, J AF Ballen, Karen K. Haley, N. Rebecca Kurtzberg, Joanne Lane, Thomas A. Lindgren, Bruce R. Miller, John P. Newman, Bruce McCullough, Jeff TI Outcomes of 122 diverse adult and pediatric cord blood transplant recipients from a large cord blood bank SO TRANSFUSION LA English DT Article ID BONE-MARROW-TRANSPLANTATION; UNRELATED DONORS; ACUTE-LEUKEMIA; SURVIVAL; CELLS; ENGRAFTMENT; THALASSEMIA; DISEASES; UNITS AB BACKGROUND: Umbilical cord blood is a useful stem cell source for some patients. The American Red Cross Cord Blood Program was established as a national network of cord blood banks. Nine thousand cord blood units were cryopreserved for transplant use. STUDY DESIGN AND METHODS: This report summarizes the experience with the first 125 cord blood units that have been distributed for transplant for 122 patients at 36 different transplant centers worldwide. Patients were treated with a variety of conditioning regimens. RESULTS: Most patients had acute myelogeneous leukemia (21%), genetic disorders (22%), or acute lymphoblastic leukemia (18%). The median age of the patients was 11 years with a range of 2 months to 63 years. The patients ranged in size from 3 to 120 kg (median, 39 kg). The median number of days to neutrophil engraftment was 22, and the median number of days to platelet engraftment was 63. Thirty percent of patients experienced Grades III to IV acute graft-versus-host disease (GVHD). Survival at 1 year after transplant was 35 percent, with recurrent disease the major cause of death. In multivariate analysis, only age less than 18 years was a significant predictor for improved survival. Forty-two percent of patients were non-Caucasian. Engraftment, GVHD, survival, and disease-free survival were similar among Caucasian and non-Caucasian patients. CONCLUSION: Umbilical cord blood serves as a satisfactory stem cell source for a diverse group of pediatric and adult patients. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Amer Red Cross, Cord Blood Program, St Paul, MN USA. Aldagen Inc, Durham, NC USA. Duke Univ, Ctr Med, Durham, NC USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Amer Red Cross, Biomed Serv, Detroit, MI USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 100 Blossom St Cox 640, Boston, MA 02114 USA. EM kballen@partners.org NR 33 TC 14 Z9 16 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD DEC PY 2006 VL 46 IS 12 BP 2063 EP 2070 DI 10.1111/j.1537-2995.2006.01032.x PG 8 WC Hematology SC Hematology GA 108LT UT WOS:000242242000006 PM 17176317 ER PT J AU Uehara, S Chase, CM Colvin, RB Madsen, JC Russell, PS AF Uehara, S. Chase, C. M. Colvin, R. B. Madsen, J. C. Russell, P. S. TI T-Cell depletion eliminates the development of cardiac allograft vasculopathy in mice rendered tolerant by the induction of mixed chimerism SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 1st World Transplant Congress (WTC 2006) CY JUL 23-27, 2006 CL Boston, MA SP Transplantat Soc, Amer Soc Transplantat, Amer Soc Transplan Surg AB We previously demonstrated that cardiac allografts to fully tolerant chimeric mice developed cardiac allograft vasculopathy (CAV). Here we begin to examine which components of the immune system are responsible for the pathogenesis of CAV in such tolerant recipients. B10.A/136 mixed chimeric mice were created by receiving injections of bone marrow cells from B10.A (H-2(k)) mice given to C57BL/6 (136; H-2(b)) mice with some preparations. B10.A skin grafts were first placed onto B10.A/136 mixed chimeric recipients. When the donor strain skin grafts had survived perfectly for at least 56 days, B10.A hearts were transplanted heterotopically into B10.A/B6 mixed chimeric recipients. Hearts were examined for the presence of CAV 56 days later. To determine the effector cells that contribute to the development of CAV, they were treated weekly with a combination of anti-CD4/CD8 monoclonal antibodies (mAbs) or anti-NK1.1 mAb continuing until 56 days. 1.4 B10.A cardiac transplants of 18 otherwise untreated B10.A/136 chimeric recipients developed CAV; concurrent 136 isografts were unaffected (0/7). In chimeric recipients treated with anti-CD4/8 mAbs, the prevalence of CAV was greatly reduced (0/6, P < .01 compared to the untreated group). Anti-NK1.1 mAb was not effective in the prevention of CAV (4/5). These data suggest that T cells may contribute in some way to the development of CAV that occurs in those fully tolerant recipients. Host T cells that may still be responsive to non-major histocompatability complex antigens, including tissue-specific antigens presented not on skin but on heart, may also be responsible for the development of CAV in tolerant animals. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Russell, PS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, White 510,55 Fruit St, Boston, MA 02114 USA. EM psrussell@partners.org FU NHLBI NIH HHS [R01 HL071932] NR 10 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 2006 VL 38 IS 10 SI SI BP 3169 EP 3171 DI 10.1016/j.transproceed.2006.10.147 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 120PY UT WOS:000243098400002 PM 17175214 ER PT J AU Hoerbelt, R Benjamin, LC Shoji, T Johnston, DR Muniappan, A Guenther, DA Allan, JS Houser, SL Madsen, JC AF Hoerbelt, R. Benjamin, L. C. Shoji, T. Johnston, D. R. Muniappan, A. Guenther, D. A. Allan, J. S. Houser, S. L. Madsen, J. C. TI Effects of tolerance induction on the actions of interferon-gamma on porcine cardiac allografts SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 1st World Transplant Congress (WTC 2006) CY JUL 23-27, 2006 CL Boston, MA SP Transplantat Soc, Amer Soc Transplantat, Amer Soc Transplan Surg ID MINIATURE SWINE; INTERLEUKIN-10; EXPRESSION; CELLS; MODEL AB It is well known that interferon-gamma (IFN-gamma) not only plays a critical role in antigen-dependent but also in antigen-independent tissue injury; however, it is not clear how tolerance induction affects the actions of IFN-gamma in the transplant setting. To address this question, we compared the effects of IFN-gamma on porcine recipients of near-syngeneic, rejecting, and tolerant heart transplants. IFN-gamma was infused continuously into the left anterior descending artery of hearts transplanted into 3 groups of major histocompatibility complex (MHC) inbred miniature swine, each treated with a 12-day course of cyclosporine A (CyA). Group I recipients received a MHC class I disparate heart, group 2 recipients received a near-syngeneic heart, and group 3 recipients were cotransplanted with a MHC class I disparate heart and kidney, which uniformly induces tolerance to both grafts. An additional group of animals was not transplanted but received intracoronary IFN-gamma infusion into their native hearts. IFN-gamma perfusion not only accelerated the acute rejection of MHC class I disparate hearts (mean survival time = 19 +/- 7.21 vs 38 +/- 8.19 days, P = .025), but caused near-syngeneic heart transplants, which otherwise survive indefinitely, to reject within 35 days (n = 3). In contrast, IFN-gamma perfusion had no demonstrable effects on interstitial rejection, the development of vascular lesions, or graft survival in tolerant heart plus kidney allograft recipients (n = 4) or in autologous hearts (n = 2). These results suggest that tolerance induction mitigates the damaging effects of IFN-gamma itself and that the beneficial effects of tolerance induction on acute and chronic rejection may extend to antigen-independent factors like ischemia/reperfusion injury. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg Cardiac Transplantat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Surg, Boston, MA 02114 USA. EM madsen@helix.mgh.harvard.edu FU NHLBI NIH HHS [R01 HL54211, R01 HL054211]; NIAID NIH HHS [P01 AI050157]; PHS HHS [P01A150157] NR 10 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 2006 VL 38 IS 10 SI SI BP 3196 EP 3198 DI 10.1016/j.transproceed.2006.10.119 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 120PY UT WOS:000243098400008 PM 17175220 ER PT J AU Schnickel, GT Hsieh, GR Garcia, C Shefizadeh, A Fishbein, MC Ardehali, A AF Schnickel, G. T. Hsieh, G. R. Garcia, C. Shefizadeh, A. Fishbein, M. C. Ardehali, A. TI Role of CXCR3 and CCR5 in allograft rejection SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 1st World Transplant Congress (WTC 2006) CY JUL 23-27, 2006 CL Boston, MA SP Transplantat Soc, Amer Soc Transplantat, Amer Soc Transplan Surg ID CHEMOKINE RECEPTOR CXCR3; PROLIFERATION; RECRUITMENT; SURVIVAL; EFFECTOR AB Chemokines are known to participate in allograft rejection by mediating leukocyte trafficking. Despite redundancy in chemokine family, several chemokine-chemokine receptor interactions have proven critical in alloimmune responses. We sought to determine the effect of combined blockade of CXCR3 and CCR5, two critical chemokine receptors, in acute rejection. Methods: Heterotopic heart transplantation was performed using BALB/c to 136/129 mice deficient in CCR5. Following transplantation these mice were treated with goat anti-CXCR3 serum every other day. In the control group, BALB/c hearts were transplanted in wild type 136/129 recipients and treated with goat serum alone. No immunosuppression was given to either group. Recipient mice were then assessed daily for allograft function by abdominal palpation, and graft survival was confirmed by laparotomy. Methods: Heterotopic heart transplantation was performed using BALB/c to B6/129 mice deficient in CCR5. Following transplantation these mice were treated with goat anti-CXCR3 serum every other day. In the control group, BALB/c hearts were transplanted in wild type B6/129 recipients and treated with goat serum alone. No immunosuppression was given to either group. Recipient mice were then assessed daily for allograft function by abdominal palpation, and graft survival was confirmed by laparotomy. Results: The donor hearts in the control group were rejected at 6 +/- 1 days posttransplantation. Combined blockade of CXCR3 and CCR5 prolonged allograft survival versus control; all allografts survived to 24 days. In addition, there was a decrease in graft infiltrating CD4 and CD8 lymphocytes in the experimental group at 24 days. Conclusion: Combined CXCR3 and CCR5 blockade is effective in prolonging allograft survival in a fully MHC mismatched murine model. Combined chemokine blockade holds promise in control of acute rejection in organ transplantation. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Cardiac Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Schnickel, GT (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Cardiac Surg, 10833 LeConte Ave,62-186 CHS, Los Angeles, CA 90095 USA. OI Schnickel, Gabriel/0000-0003-4392-2200 NR 14 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 2006 VL 38 IS 10 SI SI BP 3221 EP 3224 DI 10.1016/j.transproceed.2006.10.164 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 120PY UT WOS:000243098400016 PM 17175228 ER PT J AU Sahara, H Weiss, MJ Ng, CY Houser, SL Pujara, AC Sayre, JK Wain, JC Sachs, DH Madsen, JC Allan, JS AF Sahara, H. Weiss, M. J. Ng, C. Y. Houser, S. L. Pujara, A. C. Sayre, J. K. Wain, J. C. Sachs, D. H. Madsen, J. C. Allan, J. S. TI Thymectomy does not abrogate long-term acceptance of MHC class I-disparate lung allografts in miniature swine SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 1st World Transplant Congress (WTC 2006) CY JUL 23-27, 2006 CL Boston, MA SP Transplantat Soc, Amer Soc Transplantat, Amer Soc Transplan Surg ID MISMATCHED RENAL-ALLOGRAFTS; TRANSPLANTATION TOLERANCE; INDUCTION; REJECTION; THYMUS AB We have previously reported that tolerance to class I disparate lung allografts in miniature swine could be induced using an intensive 12-day course of tacrolimus and that pretransplant sensitization with immunogenic MHC class I allopeptides failed to block the induction of tolerance. We also have previously reported the importance of the presence of the thymus in the induction of tolerance to isolated heart, kidney, and combined heart-kidney transplants. In this study, we examined the impact of thymectomy on tolerance induction in lung transplantation. Methods. Orthotopic left lung transplantation was performed using MHC class I-disparate donors. The recipients received a 12-day course of high-dose tacrolimus (n = 6). Total thymectomies were performed in three of the swine 21 days prior to transplantation. Lung grafts were monitored by chest radiography and serial open lung biopsy. Results. All euthymic recipients maintained their grafts for over 1 year. None of the thymectomized recipients has experienced graft loss in the 6 to 10 months following transplantation. Although isolated lesions of obliterative bronchiolitis were occasionally seen in one thymectomized animal on biopsy, donor-specific unresponsiveness has been observed on assays of cell-mediated lymphocytotoxicity in all recipients. Moreover, co-culture assays have shown that recipient lymphocytes can strongly inhibit the normally robust response of naive recipient-matched lymphocytes to donor antigen. This inhibition was not seen when using stimulators primed with third-party antigens against appropriate targets. Conclusions. These data suggest that thymus-independent peripheral regulatory mechanisms may be sufficient to induce and maintain long-term acceptance of the lung allografts. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Allan, JS (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM jallan@partners.org OI Pujara, Akshat/0000-0003-1342-8981 FU NHLBI NIH HHS [R01 HL067110, 1R01-HL67110-01-A1] NR 8 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 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 2006 VL 38 IS 10 SI SI BP 3253 EP 3255 DI 10.1016/j.transproceed.2006.10.064 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 120PY UT WOS:000243098400028 PM 17175240 ER PT J AU Sahara, H Shoji, T Ng, CY Weiss, MJ Muniappan, A Guenther, DA Houser, SL Pujara, AC Sayre, JK Wain, JC Sachs, DH Madsen, JC Allan, JS AF Sahara, H. Shoji, T. Ng, C. Y. Weiss, M. J. Muniappan, A. Guenther, D. A. Houser, S. L. Pujara, A. C. Sayre, J. K. Wain, J. C. Sachs, D. H. Madsen, J. C. Allan, J. S. TI The role of indirect recognition of MHC class I and II allopeptides in a fully mismatched miniature swine model of lung transplantation SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 1st World Transplant Congress (WTC 2006) CY JUL 23-27, 2006 CL Boston, MA SP Transplantat Soc, Amer Soc Transplantat, Amer Soc Transplan Surg ID ALLOGRAFT-REJECTION AB Considerable evidence suggests that indirect recognition of MHC allopeptides plays an important role in solid-organ rejection. Here, we examine whether immunization with class I or class 11 allopeptides accelerates rejection in a fully MHC-mismatched lung transplant model in miniature swine. Methods: Recipients were immunized with either donor-derived class I or class 11 peptides. Sensitization to the peptides was confirmed by DTH testing and in vitro proliferation assays. Nonimmunized control (n = 6), class I peptide-immunized (n = 3), and class 11 peptide-immunized (n = 3) swine were transplanted with fully mismatched lungs using only a 12-day course of tacrolimus. Results: One control animal rejected its graft on postoperative day 103, while the others maintained their grafts for over I year. In the class I peptide-immunized group, two recipients rejected their grafts (days 14 and 52). The third animal has not rejected the graft (day 120, experiment is ongoing). In contrast, in the class II-peptide immunized group, only one animal rejected its graft on day 52, while the others maintained their grafts over 1 year. Both anti-donor IgM and IgG antibodies were detectable in all acute rejectors, although no alloantibody was detectable in long-term acceptors. Regardless of the fate of the graft, all animals have maintained their proliferative responses to the peptides. However, only acceptors maintained donor-specific hyporesponsiveness in cell-mediated lymphocytotoxity and mixed lymphocyte reaction assays. Conclusions: Pretransplant sensitization of lung allograft recipients to donor allopeptides accelerates graft rejection. This appears particularly true for class I-derived allopeptides, suggesting that class 11 molecules may be less antigenic when presented indirectly. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Allan, JS (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM jallan@partners.org OI Pujara, Akshat/0000-0003-1342-8981 FU NHLBI NIH HHS [1 R01-HL67110-01-A1, R01 HL067110-01A1, R01 HL067110-03, R01 HL067110-04, R01 HL067110, R01 HL067110-02] NR 5 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 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 2006 VL 38 IS 10 SI SI BP 3256 EP 3258 DI 10.1016/j.transproceed.2006.10.059 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 120PY UT WOS:000243098400029 PM 17175241 ER PT J AU Shoji, T Sahara, H Muniappan, A Guenther, DA Houser, SL Pujara, AC Bravard, MA Wain, JC Sachs, DH Madsen, JC Allan, JS AF Shoji, T. Sahara, H. Muniappan, A. Guenther, D. A. Houser, S. L. Pujara, A. C. Bravard, M. A. Wain, J. C. Sachs, D. H. Madsen, J. C. Allan, J. S. TI An MHC class II disparity raises the threshold for tolerance induction in pulmonary allografts in miniature swine SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 1st World Transplant Congress (WTC 2006) CY JUL 23-27, 2006 CL Boston, MA SP Transplantat Soc, Amer Soc Transplantat, Amer Soc Transplan Surg ID MAJOR HISTOCOMPATIBILITY COMPLEX; TRANSPLANTATION; REJECTION; LUNG AB Objectives. The mechanisms and treatment of chronic rejection in pulmonary allotransplantation remain elusive. We have induced robust tolerance to class I-disparate lung allografts in miniature swine using an intensive 12-day course of tacrolimus. Here, we tested whether a tolerant state can be induced in swine receiving fully mismatched lung allografts. Methods. Orthotopic left lung allografts were performed using MHC class I-disparate (group 1: n = 3) or fully disparate (group 2: n = 6) donors. The recipients received a 12-day postoperative course of tacrolimus (continuous intravenous infusion; target level 35-50 ng/mL) as their only immunosuppression. Results. All swine in group 1 maintained their grafts long term without developing any lesions of chronic rejection (> 497, > 432, > 451 days). These recipients exhibited donor-specific hyporesponsiveness in cell-mediated lymphocytotoxity (CML) and mixed lymphocyte reaction (MLR) assays. In group 2, five of the six recipients maintained their grafts long term (sacrificed on postoperative days 515, 389, 429, 481, and 438 with viable grafts). Isolated lesions of obliterative bronchiolitis were occasionally seen on biopsy, and donor-specific hyporesponsiveness on assays was consistently observed. The remaining recipient rejected its graft on day 103 with histologic findings of obliterative bronchiolitis. Conclusions. We report long-term graft acceptance without chronic immunosuppression in five of six recipients across a full MHC disparity, albeit with some evidence of obliterative bronchiolitis. These data suggest that the class 11 disparity inherent in a fully mismatched transplant increases the requirement for tolerance induction. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Allan, JS (reprint author), 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM jallan@partners.org OI Pujara, Akshat/0000-0003-1342-8981 FU NHLBI NIH HHS [R01 HL067110-01A1, R01 HL067110-03, R01 HL067110-02, R01 HL067110-04, R01 HL067110] NR 6 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 2006 VL 38 IS 10 SI SI BP 3268 EP 3270 DI 10.1016/j.transproceed.2006.10.161 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 120PY UT WOS:000243098400033 PM 17175245 ER PT J AU Collins, AB Chicano, SL Cornell, LD Tolkoff-Rubin, N Goes, NB Saidman, SL Farrell, ML Cosimi, AB Colvin, RB AF Collins, A. B. Chicano, S. L. Cornell, L. D. Tolkoff-Rubin, N. Goes, N. B. Saidman, S. L. Farrell, M. L. Cosimi, A. B. Colvin, R. B. TI Putative antibody-mediated rejection with C4d deposition in HLA-identical, ABO-compatible renal allografts SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 1st World Transplant Congress (WTC 2006) CY JUL 23-27, 2006 CL Boston, MA SP Transplantat Soc, Amer Soc Transplantat, Amer Soc Transplan Surg ID CAPILLARIES AB We sought evidence for non-MHC antibody-mediated rejection in renal allografts by a systematic study of rejected HLA-identical sibling renal allografts. Among 162 recipients of HLA-identical, ABO-compatible sibling donor kidneys transplanted at the Massachusetts General Hospital from 1964 to 2005, we identified 15 grafts that were lost from rejection and two additional grafts with reversible acute rejection, which provided 30 samples for study. All samples were stained for C4d by immunofluorescence in frozen tissue (n = 7) or by immunohistochemistry in paraffin embedded tissues (n = 10). We found that two of 17 grafts had positive C4d staining of peritubular capillaries. Histology revealed acute antibody-mediated rejection in one and acute cellular rejection type I in the other. Both grafts were matched at HLA-A, B, and C loci and had a nonreactive mixed lymphocyte response. Genotyping and serological analysis were not available. Compared with a published series, C4d+ irreversible rejection was more common in HLA nonidentical than HLA-identical grafts (75% vs 6.7%, respectively, P < .002). We conclude that antibody-mediated rejection, presumably due to non-MHC antigens other than ABO-blood groups does occur, but infrequently. This may account for some of the HLA antibody negative cases that develop antibody-mediated rejection. C1 Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, Med & Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Collins, AB (reprint author), Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, Med & Surg Serv, Warren 5, Boston, MA 02114 USA. EM collins@helix.mgh.harvard.edu NR 4 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 2006 VL 38 IS 10 SI SI BP 3427 EP 3429 DI 10.1016/j.transproceed.2006.10.159 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 120PY UT WOS:000243098400081 PM 17175293 ER PT J AU Akoad, M Wagener, M Francis, F Ahmed, J Ulizio, D Cacciarelli, TV AF Akoad, M. Wagener, M. Francis, F. Ahmed, J. Ulizio, D. Cacciarelli, T. V. TI Outcome of imported liver allografts and impact on patient access to liver transplantation SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 1st World Transplant Congress (WTC 2006) CY JUL 23-27, 2006 CL Boston, MA SP Transplantat Soc, Amer Soc Transplantat, Amer Soc Transplan Surg ID POSITIVE GRAFTS; DONOR AGE; EXPERIENCE; RECIPIENTS; INFECTION AB Liver allografts declined by local transplant centers are then offered regionally or nationally as imported grafts. Most of these grafts are declined because of poor donor quality. We retrospectively reviewed the medical records of patients who underwent liver transplantation between January 2004 and December 2005. There were 102 liver transplants in 98 recipients. They were divided into two groups: imported graft recipients (n = 37) and locally procured grafts recipients (n = 61). Eighty-six percent (32 of 37) of imported grafts were obtained from extended criteria donors defined as subjects treated with high doses of ionotropes with elevated liver enzymes, donor age over 70 years, macrosteatosis above 25%, positive hepatitis C or hepatitis B core antibody serology, systemic disease, history of cancer, hypernatremia, or with infection. The remaining grafts were declined due to unavailability of suitable recipients or social history. Recipient age and etiology of liver disease were similar for both groups. The mean MELD score was 22.1 +/- .9 among the imported graft recipients and 26.1 +/- 1 for the locally procured graft recipients (P < .01). There was no difference in blood loss or postoperative complications. Postoperative mean peak total bilirubin was similar in both groups. However, imported graft recipients had significantly higher mean peak AST (2436 +/- 282 vs 1380 +/- 165 U/L, P < .001) and ALT (1098 +/- 114 vs 803 +/- 87 U/L, P < .05). Primary graft nonfunction as well as 30 day and 1-year patient and graft survivals were similar for both groups. In conclusion, imported grafts can be transplanted in selected patients with outcomes comparable to locally procured grafts. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15237 USA. RP Akoad, M (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr C,Suite 112F, Pittsburgh, PA 15237 USA. EM mohamed.akoad@med.va.gov NR 9 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 2006 VL 38 IS 10 SI SI BP 3564 EP 3566 DI 10.1016/j.transproceed.2006.10.037 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 120PY UT WOS:000243098400120 PM 17175332 ER PT J AU Nankoe, SR Sever, S AF Nankoe, Sharif R. Sever, Sanja TI Dynasore puts a new spin on dynamin: a surprising dual role during vesicle formation SO TRENDS IN CELL BIOLOGY LA English DT Article ID CLATHRIN-MEDIATED ENDOCYTOSIS; TEMPERATURE-SENSITIVE MUTANT; CELL; TUBULATION; DROSOPHILA; PROTEINS; BLOCKAGE; FISSION; AUXILIN AB During clathrin-mediated endocytosis, dynamin promotes the formation of clathrin-coated vesicles, but its mode of action is unresolved. In a recent study, Macia and colleagues made use of dynasore, a dynamin-specific inhibitor, to show that dynamin plays a dual role in endocytosis: they confirmed that dynamin is involved in detaching fully formed coated pits from the membrane, and also propose a new role for dynamin earlier in the process at the point of invagination. C1 Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Sever, S (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02129 USA. EM ssever@partners.org NR 22 TC 16 Z9 16 U1 0 U2 2 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 DEC PY 2006 VL 16 IS 12 BP 607 EP 609 DI 10.1016/j.tcb.2006.10.004 PG 3 WC Cell Biology SC Cell Biology GA 120PU UT WOS:000243098000001 PM 17064900 ER PT J AU Plassman, BL Steffens, DC Burke, JR Welsh-Bohmer, KA Newman, TN Drosdick, D Helms, MJ Potter, GG Breitner, JCS AF Plassman, Brenda L. Steffens, David C. Burke, James R. Welsh-Bohmer, Kathleen A. Newman, Tiffany N. Drosdick, Deborah Helms, Michael J. Potter, Guy G. Breitner, John C. S. TI Duke Twins Study of Memory in Aging in the NAS-NRC Twin Registry SO TWIN RESEARCH AND HUMAN GENETICS LA English DT Article ID ELDERLY MALE TWINS; ALZHEIMERS-DISEASE; INTERNATIONAL WORKSHOP; COGNITIVE STATUS; DEMENTIA QUESTIONNAIRE; DIAGNOSIS; VETERANS; RELIABILITY; VALIDITY; CRITERIA AB The Duke Twins Study of Memory in Aging is an ongoing, longitudinal study of cognitive change and dementia in the population-based National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry of World War II Male Veterans. The primary goal of this study has been to estimate the overall genetic and environmental contributions to dementia with a specific focus on Alzheimer's disease. An additional goal has been to examine specific genetic and environmental antecedents of cognitive decline and dementia. Since 1989, we have completed 4 waves of data collection. Each wave included a 2-phase telephone cognitive screening protocol, followed by an in-home standardized clinical assessment for those with suspected dementia. For many participants, we have obtained postmortem neuropathological confirmation of the diagnosis of dementia. In addition to data on cognition, we have also collected information on occupational history, medical history, medications and other lifetime experiences that may influence cognitive function in late life. We provide an overview of the study's methodology and describe the focus of recent research. C1 Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27701 USA. Duke Univ, Med Ctr, Dept Neurol, Durham, NC USA. Duke Univ, Med Ctr, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Durham, NC USA. Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Plassman, BL (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, 905 W Main St,Box 41,Suite 25-D, Durham, NC 27701 USA. EM brenda.plassman@duke.edu RI Burke, James/E-4245-2016 OI Burke, James/0000-0002-3408-7787 FU NIA NIH HHS [R03 AG 22683-01, AG 08549] NR 37 TC 18 Z9 18 U1 2 U2 5 PU AUSTRALIAN ACAD PRESS PI BOWEN HILLS PA 32 JEAYS ST, BOWEN HILLS, QLD 4006, AUSTRALIA SN 1832-4274 J9 TWIN RES HUM GENET JI Twin Res. Hum. Genet. PD DEC PY 2006 VL 9 IS 6 BP 950 EP 957 DI 10.1375/183242706779462381 PG 8 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 122HO UT WOS:000243216600042 PM 17254435 ER PT J AU Tsai, HK Katz, MS Coen, JJ Zietman, AL Kaufman, DS Shipley, WU AF Tsai, Henry K. Katz, Matthew S. Coen, John J. Zietman, Anthony L. Kaufman, Donald S. Shipley, William U. TI Association of statin use with improved local control in patients treated with selective bladder preservation for muscle-invasive bladder cancer SO UROLOGY LA English DT Article ID RAS ONCOGENES; PHASE-II; N-RAS; RADIATION; LOVASTATIN; THERAPY; CELLS; ATORVASTATIN; PROGRESSION; RESISTANCE AB Objectives. To assess whether statin use improves local control (LC) in patients undergoing organ-preserving trimodality therapy for muscle-invasive bladder cancer. Methods. We retrospectively analyzed the data from 286 patients with muscle-invasive, transitional cell carcinoma of the bladder treated with maximal transurethral resection of the bladder tumor followed by chemoradiotherapy from 1986 to 2003 at the Massachusetts General Hospital. Patients with a complete response after induction chemoradiotherapy received consolidation chemoradiotherapy and those with an incomplete response underwent cystectomy. Of the 286 patients, 35 (12%) were known to be taking a statin during chemoradiotherapy. LC was defined as freedom from the development of muscle-invasive bladder cancer or superficial bladder cancer necessitating cystectomy. Results. The median follow-up time was 2.7 years for all patients and 3.1 years for survivors. The overall 5-year LC rate was 55%. On univariate analysis, tumor stage, completeness of transurethral resection of the bladder tumor, hydronephrosis, chemotherapy type, treatment era, and statin use were significantly associated with LC. The 5-year LC rate for patients taking a statin was 73% versus 52% for patients not taking a statin (P = 0.04). On multivariate analysis incorporating covariates that were statistically significant (P < 0.05) on univariate analysis, only chemotherapy with cisplatin (P = 0.02) and the absence of hydronephrosis (P = 0.01) remained significantly associated with LC. Conclusions. Statin use was associated with an improvement in LC on univariate analysis but was not found to be independently associated with LC after controlling for known prognostic factors. The potential beneficial interaction between statin use and chemoradiotherapy in bladder cancer warrants further investigation in a prospective study. C1 Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Dept Med Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Tsai, HK (reprint author), Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, 100 Blossom St,Cox LL, Boston, MA 02114 USA. EM htsai@partners.org NR 25 TC 14 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 0090-4295 J9 UROLOGY JI Urology PD DEC PY 2006 VL 68 IS 6 BP 1188 EP 1192 DI 10.1016/j.urology.2006.08.1078 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 117JR UT WOS:000242869900011 PM 17141846 ER PT J AU Latini, DM Chan, JM Cowan, JE Arredondo, SA Kane, CJ Penson, DF DuChane, J Carroll, PR AF Latini, David M. Chan, June M. Cowan, Janet E. Arredondo, Shelley A. Kane, Christopher J. Penson, David F. DuChane, Janeen Carroll, Peter R. CA CaPSURE Investigators TI Health-related quality of life for men with prostate cancer and diabetes: A longitudinal analysis from CaPSURE SO UROLOGY LA English DT Article ID RADICAL PROSTATECTOMY; ERECTILE DYSFUNCTION; OBESITY; DISEASE; RISK; MANAGEMENT; RECURRENCE; PREDICTOR; DATABASE; EXCEED AB Objectives. To compare diabetic versus nondiabetic men with prostate cancer to understand whether diabetes mellitus (DM) imposes an additional burden on health-related quality of life (HRQOL) before and after radical prostatectomy, adjusting for obesity. Methods. Data were abstracted from Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a disease registry of 12,005 men with localized prostate cancer. Men were included who had undergone surgical treatment from 1989 to 2003, had body mass index (BMI) information available, and had completed both a pretreatment and at least one posttreatment HRQOL questionnaire within 24 months. A repeated-measures model adjusted for baseline clinical and demographic variables was used to evaluate group differences. Results. The 1248 men were divided into two groups (117 with DM and 1131 without DM) on the basis of a history of DM or the reporting of diabetes medication use. The diabetic men were significantly more likely to be older and nonwhite, have lower education and income, and be less likely to have private insurance. They also had significantly more comorbid conditions (other than DM) and a greater BM I at baseline. Urinary function differed by diabetes status, BMI, and the DM x BMI interaction, with diabetic men who had a greater BMI reporting greater declines in urinary function over time. No other statistically significant differences in HRQOL were observed, although trends by BMI were noted in sexual function and bowel bother. Conclusions. Although previous studies of men with prostate cancer have found differences in HRQOL by obesity level, our results have indicated that the presence or absence of DM and a high BMI may have a greater impact on HRQOL than obesity alone. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Dept Urol, Houston, TX 77030 USA. Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. Univ Calif San Francisco, Dept Urol, Program Urol Oncol, Genitourinary Canc Epidemiol & Populat Sci Progra, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Comprehens Canc, Sch Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Sch Med, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Univ So Calif, Dept Urol & Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. RP Latini, DM (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM latini@bcm.tmc.edu OI Latini, David/0000-0002-6161-4861 FU PHS HHS [P50 C89520] NR 22 TC 13 Z9 13 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 DEC PY 2006 VL 68 IS 6 BP 1242 EP 1247 DI 10.1016/j.urology.2006.08.1096 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 117JR UT WOS:000242869900021 PM 17141841 ER PT J AU Dahl, DM He, WL Lazarus, R McDougal, WS Wu, CL AF Dahl, Douglas M. He, Wenlei Lazarus, Ross McDougal, W. Scott Wu, Chin-Lee TI Pathologic outcome of laparoscopic and open radical prostatectomy SO UROLOGY LA English DT Article ID POSITIVE SURGICAL MARGINS; RETROPUBIC PROSTATECTOMY; SPECIMENS; PERINEAL; CANCER; PROGRESSION; EXPERIENCE AB Objectives. To compare the clinicopathologic data of 286 laparoscopic radical prostatectomies (LRPs) and 714 open radical prostatectomies (RRPs) performed at the Massachusetts General Hospital from 2001 to 2005. Methods. A total of 1000 radical prostatectomy procedures were analyzed for prostate weight, pathologic stage, Gleason score, surgical margin status, and positive margin location. Results. The mean patient age was 58.6 and 59.1 years for the LRP and RRP groups, respectively. The mean preoperative prostate-specific antigen level was 5.96 and 6.00 ng/mL, respectively. Clinical Stage T1 c cancer was seen in 86.4% of the LRP and 90.5% of the RRP patients. Gleason score 7 or less disease was seen on biopsy in 97.5% of the LRP and 96.9% of the RRP patients. The average prostate weight was 46.8 g for LRP and 46.0 g for RRP. In the radical prostatectomy specimens, 94.4% of LRP and 93.3% of RRP patients had Gleason score 7 or less disease and 86.0% of LRP and 81.7% of RRP patients had pathologic Stage pT2 cancer. The rate of positive surgical margins was 15.0% and 17.4% for the LRP and RRP groups, respectively. The positive margins occurred mainly at the peripheral and apical regions in both groups. No significant difference was found in the preoperative variables or final pathologic findings between the two surgical groups. Conclusions. With similar case selection, LRP and RRP achieve similar pathologic outcomes. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Channing Labs, Boston, MA USA. RP Wu, CL (reprint author), Massachusetts Gen Hosp, Dept Urol, Warren 235,55 Fruit St, Boston, MA 02114 USA. EM cwu2@partners.org OI lazarus, ross/0000-0003-3939-1961 NR 23 TC 22 Z9 24 U1 0 U2 0 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 DEC PY 2006 VL 68 IS 6 BP 1253 EP 1256 DI 10.1016/j.urology.2006.08.1054 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 117JR UT WOS:000242869900023 PM 17141845 ER PT J AU Ray, ME Levy, LB Horwitz, EM Kupelian, PA Martinez, AA Michalski, JM Pisansky, TM Zelefsky, MJ Zietman, AL Kuban, DA AF Ray, Michael E. Levy, Larry B. Horwitz, Eric M. Kupelian, Patrick A. Martinez, Alvaro A. Michalski, Jeff M. Pisansky, Thomas M. Zelefsky, Michael J. Zietman, Anthony L. Kuban, Deborah A. TI Nadir prostate-specific antigen within 12 months after radiotherapy predicts biochemical and distant failure SO UROLOGY LA English DT Article ID BEAM RADIATION-THERAPY; DISEASE-FREE SURVIVAL; PSA NADIR; MULTIINSTITUTIONAL ANALYSIS; CANCER; CARCINOMA; LEVEL; CURE; IRRADIATION; DEFINITION AB Objectives. To determine whether nadir prostate-specific antigen (PSA) levels within 12 months (nadir PSA12) after completion of radiotherapy (RT) can be used as an early marker of recurrence risk. Methods. A total of 4839 patients were treated with RT and without hormonal therapy from 1986 to 1995 for Stage T1-T2 prostate cancer at nine institutions. Of these 4839 patients, 4833, with a median follow-up of 6.3 years, met the criteria for analysis. The study endpoints included freedom from PSA failure, initiation of androgen deprivation, or documented local or distant failure (PSA-DFS); freedom from clinically apparent distant metastasis (DMFS); and overall survival (OS). Results. Patients with a nadir PSA12 of 2.0 ng/mL or less had an 8-year PSA-DFS, DMFS, and OS rate of 55%, 95%, and 73%, respectively, compared with 40%, 88%, and 69%, respectively, for patients with a nadir PSA12 of more than 2.0 ng/mL. Multivariate analysis confirmed that a nadir PSA12 of greater than 2 ng/mL was an independent predictor of PSA-DFS, DMFS, and OS. Classification and regression tree analysis identified the nadir PSA12 levels after RT associated with PSA-DFS, DMFS, and OS. Nadir PSA12, combined with the pretreatment PSA level, identified patients at particularly high risk of distant metastasis. Conclusions. The results of this large, multi-institutional study have demonstrated that nadir PSA12 is predictive of clinical outcomes for patients with localized prostate cancer after RT. A high pretreatment PSA level and high nadir PSA12 will identify patients at particularly high risk who might benefit from early adjuvant therapy. C1 Univ Michigan, Med Ctr, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biomath, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Div Radiat Oncol, Houston, TX 77030 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Cleveland Clin Fdn, Dept Radiat Oncol, Cleveland, OH 44195 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Washington Univ, Mallinckrodt Inst Radiol, Dept Radiat Oncol, St Louis, MO 63130 USA. Mayo Clin, Dept Radiat Oncol, Rochester, MN USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Ray, ME (reprint author), Univ Michigan, Med Ctr, Dept Radiat Oncol, UH-B2C490,Box 0010,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM mray@umich.edu NR 24 TC 16 Z9 18 U1 0 U2 1 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 DEC PY 2006 VL 68 IS 6 BP 1257 EP 1262 DI 10.1016/j.urology.2006.08.1056 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 117JR UT WOS:000242869900024 PM 17141830 ER PT J AU Sim, HG Kliot, M Lange, PH Ellis, WJ Takayama, TK Yang, CC AF Sim, Hong Gee Kliot, Michel Lange, Paul H. Ellis, William J. Takayama, Thomas K. Yang, Claire C. TI Two-year outcome of unilateral sural nerve interposition graft after radical prostatectomy SO UROLOGY LA English DT Article ID RESTORE ERECTILE FUNCTION; RETROPUBIC PROSTATECTOMY; EXTRACAPSULAR EXTENSION; INTERNATIONAL INDEX; CAVERNOUS NERVES; SEXUAL FUNCTION; CANCER; DYSFUNCTION; RATS AB Objectives. To study 41 men treated for prostate cancer with unilateral nerve-sparing radical prostatectomy and contralateral sural nerve grafting from January 2000 to September 2003. Methods. Patients were considered for sural nerve grafting if they were considered at high risk of extracapsular extension before or during surgery, were younger than 70 years of age with good preoperative erectile function, were sexually active, and had no significant risk factors for erectile dysfunction. Potency was assessed by patient-reported questionnaires, including the International Index of Erectile Function erectile domain and Rigiscan testing. Results. The mean follow-up was 27.4 +/- 14.5 months. At 24 months, 24 (63.2%) of 38 men had erections sufficient for intercourse, with or without phosphodiesterase type 5 inhibitor use. Four men had partial erections that were occasionally satisfactory (10.5%), and 10 men reported no sexual activity, no spontaneous erections, or partial erections unsatisfactory for intercourse (26.3%). In contrast, in a group of 49 men who underwent unilateral nerve-sparing prostatectomy without nerve grafting during the same period at our institution, 13 (26.5%) had rigid erections adequate for intercourse with or without phosphodiesterase type 5 inhibitor use at 24 months of follow-up. Conclusions. At 24 months of follow-up, men who had undergone unilateral nerve-sparing prostatectomy with contralateral sural nerve interposition graft repair of a cut cavernosal nerve had a greater rate of return of erectile function than men undergoing unilateral nerve-sparing prostatectomy alone. C1 Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Neurosurg, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Yang, CC (reprint author), Univ Washington, Sch Med, Dept Urol, Box 356510, Seattle, WA 98195 USA. EM cyang@u.washington.edu NR 21 TC 16 Z9 18 U1 0 U2 0 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 DEC PY 2006 VL 68 IS 6 BP 1290 EP 1294 DI 10.1016/j.urology.2006.08.1064 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 117JR UT WOS:000242869900030 PM 17141842 ER PT J AU Eisner, BH McAleer, SJ Gargollo, PC Perez-Atayde, A Diamond, DA Elder, JS AF Eisner, Brian H. McAleer, Sarah J. Gargollo, Patricio C. Perez-Atayde, Antonio Diamond, David A. Elder, Jack S. TI Pediatric penile tumors of mesenchymal origin SO UROLOGY LA English DT Article ID GIANT-CELL FIBROBLASTOMA; DERMATOFIBROSARCOMA PROTUBERANS; SPECTRUM; CHILDREN AB Objectives. To describe 2 cases of mesenchymal pediatric penile tumors in a 13-year-old boy and an 11-month-old infant. Mesenchymal tumors are rare in the male external genitalia. Methods. Two patients, one aged 13 years and one 11 months, presented with painless penile masses at the penoscrotal junction. The evaluation included serial clinical examinations and ultrasonography. Both lesions were surgically excised after increasing in size. Because of malignancy, the first patient underwent wide reexcision of the tumor site. Results. The pathologic findings of the first case were combined dermatofibrosarcoma protuberans, giant cell fibroblastoma, and fibrosarcoma, a malignant tumor. Immunohistochemical staining showed strong and diffuse CD34 cytoplasmic positivity in the giant cell fibroblastoma and dermatofibrosarcoma protuberans components; the dedifferentiated fibrosarcoma tumor cells were negative for this antibody. The second case was myofibroma, a benign fibroblastic tumor with a prominent myofibroblastic component that is congenital and tends to occur within the first few months after birth. Neither patient had recurrence at 16 months and 3 years of follow-up. To our knowledge, this is the first reported case of combined dermatofibrosarcoma protuberans, giant cell fibroblastoma, and fibrosarcoma of the penis and the second reported case of isolated penile myofibroma. Conclusions. Penile tumors should be included in the differential diagnosis of pediatric penile masses. Surgical resection is often curative, but patients with malignant tumors should receive careful follow-up to monitor for recurrence. C1 Childrens Hosp, Dept Urol, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Sch Med, Dept Urol,Div Pediat Urol, Cleveland, OH 44106 USA. RP Eisner, BH (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 14 TC 2 Z9 3 U1 0 U2 0 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 DEC PY 2006 VL 68 IS 6 BP 1327 EP 1330 DI 10.1016/j.urology.2006.08.1103 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 117JR UT WOS:000242869900038 PM 17169655 ER PT J AU Shiotani, A Haruma, K Uedo, N Iishi, H Ishihara, R Tatsuta, M Kumamoto, M Nakae, Y Ishiguro, S Graham, DY AF Shiotani, Akiko Haruma, Ken Uedo, Noriya Iishi, Hiroyasu Ishihara, Ryu Tatsuta, Masaharu Kumamoto, Mitutaka Nakae, Yukinori Ishiguro, Shingo Graham, David Y. TI Histological risk markers for non-cardia early gastric cancer - Pattern of mucin expression and gastric cancer SO VIRCHOWS ARCHIV LA English DT Article DE early gastric cancer; type III intestinal metaplasia; MUC2; MUC5AC; MUC6 ID INTESTINAL METAPLASIA; HUMAN STOMACH; CHROMOSOMAL LOCALIZATION; PHENOTYPIC-EXPRESSION; CARCINOMA; ADENOCARCINOMAS; CARCINOGENESIS; ATROPHY; GENES; CLASSIFICATION AB There are limited data regarding the prognostic value of the pattern of mucin expression in IM. To examine the role of the type of IM and pattern of mucin expression in IM as histological risk markers of gastric cancer, 80 patients with a history of endoscopic mucosal resection (EMR) for early gastric cancer and 80 sex and age-matched controls were studied. Serum levels of pepsinogen (PG) were measured by RIA, and MUC2, MUC5AC and MUC6 were evaluated immunohistochemically. There is a significant association between types of IM and atrophic scores or PG levels. The most incomplete IM (type II and III) preserving gastric mucin is the gastric and intestinal mixed (GI) type, whereas the complete type is the intestinal (I) type especially in the corpus lesser curve. Gastric cancer was most significantly associated with incomplete IM in the corpus lesser curve (OR=6.4; 95% CI, 2.0-21, p=0.002). Asynchronous multiple lesions were associated with incomplete IM in the corpus greater curve (OR=4.8; 95% CI, 1.4-16, p=0.01). Classification of IM obtained using fixed-point biopsy samples may enhance the ability of surveillance programs to detect patients at increased risk of gastric cancer. C1 Kawasaki Med Univ, Dept Internal Med, Okayama, Japan. Osaka Med Ctr Canc & Cardiovasc Dis, Dept Gastrointestinal Oncol, Osaka, Japan. Aishinkai Nakae Hosp, Dept Med, Wakayama, Japan. VA Med Ctr, Dept Med, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Shiotani, A (reprint author), 577 Matsushima, Kurashiki, Okayama 7010192, Japan. EM shiotani@med.kawasaki-m.ac.jp NR 40 TC 11 Z9 11 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD DEC PY 2006 VL 449 IS 6 BP 652 EP 659 DI 10.1007/s00428-006-0300-8 PG 8 WC Pathology SC Pathology GA 109ST UT WOS:000242329600007 PM 17058096 ER PT J AU Farris, AB Kradin, RL AF Farris, A. B., III Kradin, R. L. TI Follicular localization of dendritic cells in a xanthomatous inflammatory tumor of lung associated with human herpes virus-8 infection SO VIRCHOWS ARCHIV LA English DT Article DE lung; inflammatory myofibroblastic tumor; xanthoma; factor XIIIa; CD1a ID MYOFIBROBLASTIC TUMOR; PSEUDOTUMOR; AIDS AB A 17-year-old man was treated with chemotherapy and radiation for nodular sclerosing Hodgkin lymphoma that presented as a left chest wall mass. Ten years later, a left upper lobe lung tumor was identified. The tumor resection demonstrated a 1.3-cm yellow lung nodule composed of epithelioid and spindled lipid-laden CD68+ and Factor XIIIa+ macrophages. Distinct follicular structures with dendritic cells positive for CD1a, fascin, and ALK-1 and largely devoid of intracytoplasmic lipid were a distinguishing feature of the lesion. Most of the xanthomatous macrophages expressed human herpes virus-8 antigen. The current World Health Organization classification of "inflammatory myofibroblastic tumors" is examined, and the association of a subset of "inflammatory pseudotumors" with immunodeficiency states and opportunistic infection is discussed. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM rkradin@partners.org NR 14 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD DEC PY 2006 VL 449 IS 6 BP 726 EP 729 DI 10.1007/s00428-006-0318-y PG 4 WC Pathology SC Pathology GA 109ST UT WOS:000242329600017 PM 17106709 ER PT J AU Belfort, R Harrison, SA Brown, K Darland, C Finch, J Hardies, J Balas, B Gastaldelli, A Tio, F Pulcini, J Berria, R Ma, JZ Dwivedi, S Havranek, R Fincke, C DeFronzo, R Bannayan, GA Schenker, S Cusi, K AF Belfort, Renata Harrison, Stephen A. Brown, Kenneth Darland, Celia Finch, Joan Hardies, Jean Balas, Bogdan Gastaldelli, Amalia Tio, Fermin Pulcini, Joseph Berria, Rachele Ma, Jennie Z. Dwivedi, Sunil Havranek, Russell Fincke, Chris DeFronzo, Ralph Bannayan, George A. Schenker, Steven Cusi, Kenneth TI A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID FATTY LIVER-DISEASE; HEPATIC INSULIN-RESISTANCE; ACTIVATED PROTEIN-KINASE; TYPE-2 DIABETIC-PATIENTS; WEIGHT-LOSS; PLASMA ADIPONECTIN; ADIPOSE-TISSUE; OBESE SUBJECTS; RAT-LIVER; VITAMIN-E AB BACKGROUND: No pharmacologic therapy has conclusively proved to be effective for the treatment of nonalcoholic steatohepatitis, which is characterized by insulin resistance, steatosis, and necroinflammation with or without centrilobular fibrosis. Pioglitazone is a thiazolidinedione that ameliorates insulin resistance and improves glucose and lipid metabolism in type 2 diabetes mellitus. METHODS: We randomly assigned 55 patients with impaired glucose tolerance or type 2 diabetes and liver biopsy-confirmed nonalcoholic steatohepatitis to 6 months of treatment with a hypocaloric diet (a reduction of 500 kcal per day in relation to the calculated daily intake required to maintain body weight) plus pioglitazone (45 mg daily) or a hypocaloric diet plus placebo. Before and after treatment, we assessed hepatic histologic features, hepatic fat content by means of magnetic resonance spectroscopy, and glucose turnover during an oral glucose tolerance test ([(C-14]glucose given with the oral glucose load and [H-3]glucose given by intravenous infusion). RESULTS: Diet plus pioglitazone, as compared with diet plus placebo, improved glycemic control and glucose tolerance (P<0.001), normalized liver aminotransferase levels as it decreased plasma aspartate aminotransferase levels (by 40% vs. 21%, P=0.04), decreased alanine aminotransferase levels (by 58% vs. 34%, P<0.001), decreased hepatic fat content (by 54% vs. 0%, P<0.001), and increased hepatic insulin sensitivity (by 48% vs. 14%, P=0.008). Administration of pioglitazone, as compared with placebo, was associated with improvement in histologic findings with regard to steatosis (P=0.003), ballooning necrosis (P=0.02), and inflammation (P=0.008). Subjects in the pioglitazone group had a greater reduction in necroinflammation (85% vs. 38%, P=0.001), but the reduction in fibrosis did not differ significantly from that in the placebo group (P=0.08). Fatigue and mild lower-extremity edema developed in one subject who received pioglitazone; no other adverse events were observed. CONCLUSIONS: In this proof-of-concept study, the administration of pioglitazone led to metabolic and histologic improvement in subjects with nonalcoholic steatohepatitis. Larger controlled trials of longer duration are warranted to assess the long-term clinical benefit of pioglitazone. C1 Univ Texas, Hlth Sci Ctr, Diabet Div, San Antonio, TX 78229 USA. Brooke Army Med Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. CNR, Inst Clin Physiol, Pisa, Italy. RP Cusi, K (reprint author), Univ Texas, Hlth Sci Ctr, Diabet Div, Rm 3-3805,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM cusi@uthscsa.edu RI Gastaldelli, Amalia/H-3319-2014 OI Gastaldelli, Amalia/0000-0003-2594-1651 FU NCRR NIH HHS [M01-RR-01346] NR 38 TC 794 Z9 818 U1 1 U2 21 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 NOV 30 PY 2006 VL 355 IS 22 BP 2297 EP 2307 DI 10.1056/NEJMoa060326 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 110CG UT WOS:000242355300005 PM 17135584 ER PT J AU Campbell, EG Weissman, JS Vogeli, C Clarridge, BR Abraham, M Marder, JE Koski, G AF Campbell, Eric G. Weissman, Joel S. Vogeli, Christine Clarridge, Brian R. Abraham, Melissa Marder, Jessica E. Koski, Greg TI Financial relationships between institutional review board members and industry SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CONFLICTS-OF-INTEREST; FACULTY; SALE AB BACKGROUND: Little is known about the nature, extent, and consequences of financial relationships between industry and institutional review board (IRB) members in academic institutions. We surveyed IRB members about such relationships. METHODS: We surveyed a random sample of 893 IRB members at 100 academic institutions (response rate, 67.2%). The questionnaire focused on the financial relationships that the members had with industry (e.g., employment, membership on boards, consulting, receipt of royalties, and paid speaking). RESULTS: We found that 36% of IRB members had had at least one relationship with industry in the past year. Of the respondents, 85.5% said they never thought that the relationships that another IRB member had with industry affected his or her IRB-related decisions in an inappropriate way, 11.9% said they thought this occurred rarely, 2.4% thought it occurred sometimes, and 0.2% thought it occurred often. Seventy-eight respondents (15.1%) reported that at least one protocol came before their IRB during the previous year that was sponsored either by a company with which they had a relationship or by a competitor of that company, both of which could be considered conflicts of interest. Of these 78 members (62 voting members and 16 nonvoting members), 57.7% reported that they always disclosed the relationship to an IRB official, 7.7% said they sometimes did, 11.5% said they rarely did, and 23.1% said they never did. Of the 62 voting members who reported conflicts, 64.5% reported that they never voted on the protocol, 4.8% said they rarely did, 11.3% said they sometimes did, and 19.4% said they always did. Most respondents reported that the views of IRB members who had experience working with industry were beneficial in reviewing industry-sponsored protocols. CONCLUSIONS: Relationships between IRB members and industry are common, and members sometimes participate in decisions about protocols sponsored by companies with which they have a financial relationship. Current regulations and policies should be examined to be sure that there is an appropriate way to handle conflicts of interest stemming from relationships with industry. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. RP Campbell, EG (reprint author), 50 Staniford St,9th Fl, Boston, MA 02114 USA. EM ecampbell@partners.org FU NCI NIH HHS [3R01CA095400-02-51] NR 16 TC 60 Z9 62 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 NOV 30 PY 2006 VL 355 IS 22 BP 2321 EP 2329 DI 10.1056/NEJMsa061457 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 110CG UT WOS:000242355300007 PM 17135585 ER PT J AU Hampson, LA Agrawal, M Joffe, S Gross, CP Verter, J Emanuel, EJ AF Hampson, Lindsay A. Agrawal, Manish Joffe, Steven Gross, Cary P. Verter, Joel Emanuel, Ezekiel J. TI Patients' views on financial conflicts of interest in cancer research trials SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID POTENTIAL RESEARCH PARTICIPANTS; ACADEMIC MEDICAL-CENTERS; INFORMED CONSENT; TRUST; PHYSICIANS; DISCLOSURE; PROFESSION AB BACKGROUND: Financial ties between researchers or medical centers and companies whose drugs are being tested have come under increasing scrutiny. METHODS: We conducted in-person interviews with 253 patients in cancer-research trials (a 93% response rate) at five U.S. medical centers to determine their attitudes regarding potential financial conflicts of interest among researchers and medical centers. RESULTS: More than 90% of patients expressed little or no worry about financial ties that researchers or institutions might have with drug companies. Most patients said they would have enrolled in the trial even if the drug company had paid the researcher for speaking (82% of those interviewed) or consulting (75%) or if the researcher had received royalty payments (70%) or owned stock in the company (76%). Similarly, most patients would have enrolled in the trial if their cancer center had owned stock in the drug company (77%) or received royalty payments from the company (79%). Most patients believed it was ethical for researchers to receive speaking fees (81%) or consulting fees (82%) from the company. However, a substantial minority of patients wanted disclosure of the oversight system for researchers (40%) and of researchers' financial interests (31%); 17% thought no disclosure to patients was necessary. CONCLUSIONS: Most patients in cancer-research trials were not worried about financial ties between researchers or medical centers and drug companies and would still have enrolled in the trial if they had known about such financial ties. A substantial minority wanted to be informed about the oversight system to protect against financial conflicts of interest and about researchers' financial interests. C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Ann Arbor, MI USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT USA. Yale Univ, Sch Med, Gen Internal Med Sect, New Haven, CT USA. Stat Collaborat, Washington, DC USA. RP Emanuel, EJ (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10,Rm 1C118, Bethesda, MD 20892 USA. EM eemanuel@nih.gov OI Joffe, Steven/0000-0002-0667-7384 NR 33 TC 70 Z9 71 U1 0 U2 7 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 NOV 30 PY 2006 VL 355 IS 22 BP 2330 EP 2337 DI 10.1056/NEJMsa064160 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 110CG UT WOS:000242355300008 PM 17135586 ER PT J AU Grady, D AF Grady, Deborah TI Management of menopausal symptoms SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HORMONE REPLACEMENT THERAPY; CONJUGATED EQUINE ESTROGENS; MILD COGNITIVE IMPAIRMENT; HEALTH INITIATIVE MEMORY; INDUCED HOT FLASHES; POSTMENOPAUSAL WOMEN; BREAST-CANCER; VASOMOTOR SYMPTOMS; DOUBLE-BLIND C1 Univ Calif San Francisco, Womens Hlth Clin Res Ctr, San Francisco, CA 94115 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Grady, D (reprint author), Univ Calif San Francisco, Womens Hlth Clin Res Ctr, 1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA. NR 61 TC 83 Z9 85 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 NOV 30 PY 2006 VL 355 IS 22 BP 2338 EP 2347 DI 10.1056/NEJMcp054015 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 110CG UT WOS:000242355300009 PM 17135587 ER PT J AU Chung, DC Faquin, WC Maher, MM Harris, NL AF Chung, Daniel C. Faquin, William C. Maher, Michael M. Harris, Nancy Lee TI Case 37-2006: A 19-year-old woman with thyroid cancer and lower gastrointestinal bleeding - Cribriform-morular variant of papillary thyroid carcinoma, with associated familial adenomatous polyposis caused by a new mutation arising in the APC gene SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID SULINDAC; COLI C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Chung, DC (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 22 TC 11 Z9 11 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 NOV 30 PY 2006 VL 355 IS 22 BP 2349 EP 2357 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 110CG UT WOS:000242355300012 PM 17135589 ER PT J AU Harel, O Zhou, XH AF Harel, Ofer Zhou, Xiao-Hua TI Multiple imputation for correcting verification bias SO STATISTICS IN MEDICINE LA English DT Article DE missing data; multiple imputations; software; Bayesian methods; verification bias ID INTERVAL ESTIMATION; DIAGNOSTIC-TESTS; DISTRIBUTIONS; SELECTION; SAMPLES AB In the case in which all subjects are screened using a common test and only a subset of these subjects are tested using a golden standard test, it is well documented that there is a risk for bias, called verification bias. When the test has only two levels (e.g. positive and negative) and we are trying to estimate the sensitivity and specificity of the test, we are actually constructing a confidence interval for a binomial proportion. Since it is well documented that this estimation is not trivial even with complete data, we adopt multiple imputation framework for verification bias problem. We propose several imputation procedures for this problem and compare different methods of estimation. We show that our imputation methods are better than the existing methods with regard to nominal coverage and confidence interval length. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98108 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. RP Zhou, XH (reprint author), VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, 1660 S Columbian Way,1-424, Seattle, WA 98108 USA. EM oharel@stat.uconn.edu; azhou@u.washington.edu FU NIMH NIH HHS [K01 MH087219] NR 24 TC 33 Z9 33 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 30 PY 2006 VL 25 IS 22 BP 3769 EP 3786 DI 10.1002/sim.2494 PG 18 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 111CT UT WOS:000242429400001 PM 16435337 ER PT J AU Jensen, RJ AF Jensen, Ralph J. TI Activation of group II metabotropic glutamate receptors reduces directional selectivity in retinal ganglion cells SO BRAIN RESEARCH LA English DT Article DE directional selectivity; retinal ganglion cell; group II metabotropic glutamate receptor; starburst amacrine cell ID CHOLINERGIC AMACRINE CELLS; RAT SPINAL-CORD; RABBIT RETINA; BIPOLAR CELLS; MAMMALIAN RETINA; TRANSMISSION; SYNAPSES; NEURONS; NUCLEUS; GABA AB In the mammalian retina, high levels of the group II metabotropic glutamate receptor (mGluR) subtype are expressed in starburst amacrine cells. A prominent role of starburst amacrine cells is the generation of directional selectivity in ON-OFF directionally selective retinal ganglion cells (DS RGCs). Extracellular microelectrodes were used to study the effects of activation of group II mGluRs on the responses of rabbit ON-OFF DS RGCs to a moving light stimulus. Directionally selective responses in these RGCs were substantially reduced by the selective group II mGluR agonist DCG-IV. DCG-IV brought out a response to movement in the null direction that was similar in magnitude and time course to the response to movement in the preferred direction. This effect of DCG-IV was reversed by the group II mGluR antagonist EGLU. Application of EGLU alone failed to alter directional selectivity in the RGCs but did reduce the response to movement in the preferred direction. To determine whether group II mGluRs modulate the release of the neurotransmitter acetylcholine from starburst amacrine cells, the effect of DCG-IV on ON-OFF DS RGCs was examined in the presence of ambenonium, an acetylcholinesterase inhibitor. When applied alone, ambenonium greatly prolonged the responses of ON-OFF DS RGCs to a light stimulus. This effect of ambenonium was completely abolished upon application of DCG-IV. Overall, the results suggest that postsynaptic group II mGluRs have the potential to influence directional selectivity in RGCs by inhibiting transmitter release from starburst amacrine cells. (c) 2006 Elsevier B.V. All rights reserved. C1 VA Boston Healthcare Syst, Ctr Innovat Visual Rehab, Boston, MA 02130 USA. RP Jensen, RJ (reprint author), VA Boston Healthcare Syst, Ctr Innovat Visual Rehab, 150 S Huntigton Ave,MS 151E, Boston, MA 02130 USA. EM Ralph.Jensen@med.va.gov NR 44 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 29 PY 2006 VL 1122 BP 86 EP 92 DI 10.1016/j.brainres.2006.08.119 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 114LU UT WOS:000242668500011 PM 17010323 ER PT J AU Mernitz, H Smith, DE Zhu, AX Wang, XD AF Mernitz, Heather Smith, Donald E. Zhu, Andrew X. Wang, Xiang-Dong TI 9-cis-Retinoic acid inhibition of lung carcinogenesis in the A/J mouse model is accompanied by increased expression of RAR-beta but no change in cyclooxygenase-2 SO CANCER LETTERS LA English DT Article DE lung cancer; 9-cis-retinoic acid; RAR-beta; cyclooxygenase-2 ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; 9-CIS RETINOIC ACID; CANCER CELL-LINES; RECEPTOR-SELECTIVE RETINOIDS; SQUAMOUS CARCINOMA-CELLS; EPITHELIAL-CELLS; GASTROINTESTINAL TOXICITY; RHEUMATOID-ARTHRITIS; BRONCHIAL EPITHELIUM; GROWTH-INHIBITION AB 9-cis-Retinoic acid (9cRA) binds both retinoic acid receptors (RARs) and retinoid X receptors (RXRs) and has been shown to be a potential chernopreventive agent both in lung cancer cell culture studies and in clinical trials studying former smokers. However, direct evidence of the efficacy of 9cRA against lung tumor development in vivo is lacking. In the present study, we determined whether treatment with 9cRA has the potential to inhibit lung carcinogenesis by upregulating RAR-beta and down-regulating COX-2 expression in the A/J mouse lung cancer model. A/J mice (n = 14-15/group) were treated as follows: (1) Control (Sham treated); (2) NNK (100 mg NNK/kg body weight); (3) NNK + 9cRA (15 mg/kg diet); and (4) NNK + celecoxib (a COX-2-specific inhibitor, 500 mg/kg diet). Tumor incidence, tumor multiplicity, RAR-beta mRNA, COX-2 mRNA, and COX-2 protein levels in lung samples of mice were determined 4 months after carcinogen injection. The results showed that mice receiving 9cRA supplementation had significantly lower tumor multiplicity (48% reduction, P < 0.05) and showed a trend toward lower tumor incidence (40% reduction, P=0.078), as compared with the mice given NNK alone. Although, celecoxib treatment resulted in greater declines in tumor incidence and tumor multiplicity (75 and 88%, respectively, P < 0.05), the chentoprotective effects of celecoxib were accompanied by increased mortality while 9cRA treatment resulted in no weight-loss associated toxicity or mortality. Supplementation with 9cRA was effective in increasing RAR-beta mRNA, but this increase was not accompanied by decreased levels of COX-2 mRNA or protein. These results suggest that 9cRA supplementation may provide protection against lung carcinogenesis and this effect may be mediated in part by 9cRA induction of RAR-beta, but not inhibition of COX-2 transcription. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Nutr & Canc Biol Lab, Boston, MA 02111 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Wang, XD (reprint author), Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Nutr & Canc Biol Lab, 711 Washington St, Boston, MA 02111 USA. EM xiang-dong.wang@tufts.edu FU NCI NIH HHS [R01CA104932] NR 69 TC 13 Z9 16 U1 0 U2 4 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 NOV 28 PY 2006 VL 244 IS 1 BP 101 EP 108 DI 10.1016/j.canlet.2005.12.001 PG 8 WC Oncology SC Oncology GA 118OR UT WOS:000242952100014 PM 16413115 ER PT J AU Neilan, TG Januzzi, JL Lee-Lewandrowski, E Ton-Nu, TT Yoerger, DM Jassal, DS Lewandrowski, KB Siegel, AJ Marshall, JE Douglas, PS Lawlor, D Picard, MH Wood, MJ AF Neilan, Tomas G. Januzzi, James L. Lee-Lewandrowski, Elizabeth Ton-Nu, Thanh-Thao Yoerger, Danita M. Jassal, Davinder S. Lewandrowski, Kent B. Siegel, Arthur J. Marshall, Jane E. Douglas, Pamela S. Lawlor, David Picard, Michael H. Wood, Malissa J. TI Myocardial injury and ventricular dysfunction related to training levels among nonelite participants in the Boston marathon SO CIRCULATION LA English DT Article DE echocardiography; exercise; natriuretic peptides ID CARDIAC TROPONIN-T; BRAIN NATRIURETIC PEPTIDE; CORONARY HEART-DISEASE; DOPPLER-ECHOCARDIOGRAPHY; PULMONARY-EMBOLISM; PROLONGED EXERCISE; STRENUOUS EXERCISE; RUNNERS; DEATH; RECOMMENDATIONS AB Background - Multiple studies have individually documented cardiac dysfunction and biochemical evidence of cardiac injury after endurance sports; however, convincing associations between the two are lacking. We aimed to determine the associations between the observed transient cardiac dysfunction and biochemical evidence of cardiac injury in amateur participants in endurance sports and to elicit the risk factors for the observed injury and dysfunction. Methods and Results - We screened 60 nonelite participants, before and after the 2004 and 2005 Boston Marathons, with echocardiography and serum biomarkers. Echocardiography included conventional measures as well as tissue Doppler-derived strain and strain rate imaging. Biomarkers included cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP). All subjects completed the race. Echocardiographic abnormalities after the race included altered diastolic filling, increased pulmonary pressures and right ventricular dimensions, and decreased right ventricular systolic function. At baseline, all had unmeasurable troponin. After the race, > 60% of participants had increased cTnT > 99th percentile of normal (> 0.01 ng/ mL), whereas 40% had a cTnT level at or above the decision limit for acute myocardial necrosis (>= 0.03 ng/mL). After the race, NT-proBNP concentrations increased from 63 (interquartile range [IQR] 21 to 81) pg/mL to 131 (IQR 82 to 193) pg/mL (P < 0.001). The increase in biomarkers correlated with post-race diastolic dysfunction, increased pulmonary pressures, and right ventricular dysfunction (right ventricular mid strain, r = -0.70, P < 0.001) and inversely with training mileage (r = -0.71, P < 0.001). Compared with athletes training > 45 miles/ wk, athletes who trained <= 35 miles/wk demonstrated increased pulmonary pressures, right ventricular dysfunction (mid strain 16 +/- 5% versus 25 +/- 4%, P < 0.001), myocyte injury (cTnT 0.09 versus > 0.01 ng/mL, P < 0.001), and stress (NT-proBNP 182 versus 106 pg/mL, P < 0.001). Conclusions - Completion of a marathon is associated with correlative biochemical and echocardiographic evidence of cardiac dysfunction and injury, and this risk is increased in those participants with less training. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, McLean Hosp, Dept Med, Boston, MA 02115 USA. Duke Univ, Med Ctr, Div Cardiovasc Med, Durham, NC USA. RP Wood, MJ (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, 55 Fruit St,VBK 508, Boston, MA 02115 USA. EM mjwood@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 34 TC 258 Z9 264 U1 2 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 28 PY 2006 VL 114 IS 22 BP 2325 EP 2333 DI 10.1161/CIRCULATIONAHA.106.647461 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 125XS UT WOS:000243477400008 PM 17101848 ER PT J AU Waxman, S Ishibashi, F Muller, JE AF Waxman, Sergio Ishibashi, Fumiyuki Muller, James E. TI Detection and treatment of vulnerable plaques and vulnerable patients - Novel approaches to prevention of coronary events SO CIRCULATION LA English DT Review ID ACUTE MYOCARDIAL-INFARCTION; OPTICAL COHERENCE TOMOGRAPHY; INTRAVASCULAR MAGNETIC-RESONANCE; C-REACTIVE-PROTEIN; ENDOTHELIAL SHEAR-STRESS; HUMAN ATHEROSCLEROTIC LESIONS; RADIOFREQUENCY DATA-ANALYSIS; ESTER TRANSFER PROTEIN; RANDOMIZED CONTROLLED-TRIAL; NEAR-INFRARED SPECTROSCOPY C1 Lahey Clin Fdn, Dept Cardiovasc Med, Burlington, MA 01805 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Massachusetts Gen Hosp, Div Cardiovasc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Waxman, S (reprint author), Lahey Clin Fdn, Dept Cardiovasc Med, 41 Mall Rd, Burlington, MA 01805 USA. EM Sergio.Waxman@lahey.org NR 226 TC 116 Z9 128 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 28 PY 2006 VL 114 IS 22 BP 2390 EP 2411 DI 10.1161/CIRCULATIONAHA.105.540013 PG 22 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 125XS UT WOS:000243477400015 PM 17130356 ER PT J AU Cannon, CP AF Cannon, Christopher P. CA TIMI Study Grp MEDAL Steering Comm TI Multinational etoricoxib and diclofenac arthritis long-term (MEDAL) study program: Cardiovascular outcomes following long-term treatment with etoricoxib versus diclofenac in patients with osteoarthritis and rheumatoid arthritis SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 28 PY 2006 VL 114 IS 22 BP 2424 EP 2424 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 125XS UT WOS:000243477400019 ER PT J AU O'Donoghue, M Wiviott, SD AF O'Donoghue, Michelle Wiviott, Stephen D. TI Clopidogrel response variability and future therapies - Clopidogrel: Does one size fit all? SO CIRCULATION LA English DT Editorial Material ID ST-SEGMENT ELEVATION; PERCUTANEOUS CORONARY INTERVENTION; ACUTE MYOCARDIAL-INFARCTION; PLATELET-AGGREGATION; STENT THROMBOSIS; ANTIPLATELET THERAPY; PRASUGREL CS-747; UNSTABLE ANGINA; ATHEROTHROMBOTIC EVENTS; P2Y(12) ANTAGONIST C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. RP Wiviott, SD (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. EM swiviott@partners.org NR 58 TC 75 Z9 76 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 28 PY 2006 VL 114 IS 22 BP E600 EP E606 DI 10.1161/CIRCULATIONAHA.106.643171 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 125XS UT WOS:000243477400035 PM 17130347 ER PT J AU Corboy, JR Gault, J Kleinschmidt-DeMasters, BK AF Corboy, John R. Gault, Judith Kleinschmidt-DeMasters, B. K. TI An adult case of leukoencephalopathy with intracranial calcifications and cysts SO NEUROLOGY LA English DT Article ID MUTATIONS AB Leukoencephalopathies are generally volume-losing processes, although several variants, such as Alexander disease and Canavan disease, may cause megalencephaly. Leukoencephalopathies that generate severe edema, are mass producing, and mimic neoplasms are rare. In 1996, a new cerebral disorder was described in three unrelated children who had onset in early infancy to adolescence of slowed cognitive performance, seizures, and extrapyramidal, cerebellar, and pyramidal signs.(1) Neuroimaging studies demonstrated a striking triad of findings: progressive calcifications in the basal ganglia, cerebellar nuclei, and deep white matter; diffuse abnormal signal on MRI in the white matter; and large, space-occupying parenchymal brain cysts generating mass effect. 1 Neuropathologic examination of surgically resected material from one patient revealed "angiomatous-like rearrangements of the microvessels..." that "suggest a constitutional, diffuse cerebral microangiopathy..."(1) Profuse numbers of Rosenthal fibers were identified around the "pseudoangiomatous" blood vessels. The disease did not fit descriptions for any previously known phakomatosis or dysgenetic syndrome. A descriptive name was given to this new syndrome, which was initially thought to be a leukodystrophy. Three more patients were subsequently reported, all of whom also had onset in childhood between the ages 9 and 14 years.(2) More extensive neuroimaging studies suggested that the white matter abnormalities were due to "increased water content rather than a demyelinating process," consistent with a leukoencephalopathy, rather than a leukodystrophy. We now present an adult patient with clinical and pathologic findings nearly identical to these six previously reported children. Because this disorder seemed somewhat similar to adult-onset Alexander disease and was associated with apparent microangiopathy, we also searched for polymorphisms in glial fibrillary acidic protein (GFAP) and cerebral cavernous malformation (CCM) genes. C1 Univ Colorado, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Dept Neurosurg, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Dept Neurol, Denver, CO USA. RP Corboy, JR (reprint author), Univ Colorado, Dept Neurol, Box B-183,4200 E 9th Ave, Denver, CO 80262 USA. EM john.corboy@uchsc.edu NR 5 TC 20 Z9 23 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 NOV 28 PY 2006 VL 67 IS 10 BP 1890 EP 1892 DI 10.1212/01.wnl.0000244470.06748.18 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 109WI UT WOS:000242339900039 PM 17130435 ER PT J AU Sharov, AA Sharova, TY Mardaryev, AN di Vignano, AT Atoyan, R Weiner, L Yang, S Brissette, JL Dotto, GP Botchkarev, VA AF Sharov, Andrey A. Sharova, Tatyana Y. Mardaryev, Andrei N. di Vignano, Alice Tommasi Atoyan, Ruzanna Weiner, Lorin Yang, Shi Brissette, Janice L. Dotto, G. Paolo Botchkarev, Vladimir A. TI Bone morphogenetic protein signaling regulates the size of hair follicles and modulates the expression of cell cycle-associated genes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Noggin; proliferation; skin ID STEM-CELLS; SHAFT DIFFERENTIATION; DERMAL PAPILLA; GROWTH CYCLE; CROSS-TALK; NUMBER; MATRIX; NOGGIN; MICE; SKIN AB Bone morphogenetic protein (BMP) signaling is involved in the regulation of a large variety of developmental programs, including those controlling organ sizes. Here, we show that transgenic (TG) mice overexpressing the BMP antagonist noggin (promoter, K5) are characterized by a marked increase in size of anagen hair follicles (HFs) and by the replacement of zig-zag and auchen hairs by awl-like hairs, compared with the age-matched WT controls. Markedly enlarged anagen HFs of TG mice show increased proliferation in the matrix and an increased number of hair cortex and medulla cells compared with WT HFs. Microarray and real-time PCR analyses of the laser-captured hair matrix cells show a strong decrease in expression of Cdk inhibitor p27(Kip1) and increased expression of selected cyclins in TG vs. WT mice. Similar to TG mice, p27(Kip1) knockout mice also show an increased size of anagen HFs associated with increased cell proliferation in the hair bulb. Primary epidermal keratinocytes (KC) from TG mice exhibit significantly increased proliferation and decreased p27(Kip1) expression, compared with WT KC. Alternatively, activation of BMP signaling in HaCaT KC induces growth arrest, stimulates p27(Kip1) expression, and positively regulates p27(Kip1) promoter activity, thus further supporting a role of p27(Kip1) in mediating the effects of BMP signaling on HF size. These data suggest that BMP signaling plays an important role in regulating cell proliferation and controls the size of anagen HI's by modulating the expression of cell-cycle-associated genes in hair matrix KC. C1 Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. Univ Bradford, Sch Life Sci, Bradford BD7 1DP, W Yorkshire, England. RP Botchkarev, VA (reprint author), Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. EM vladbotc@bu.edu FU NCI NIH HHS [R01 CA092090, CA092090]; NIAMS NIH HHS [AR48573, AR49778, K02 AR048573, R01 AR049778, R56 AR049778] NR 50 TC 51 Z9 52 U1 0 U2 6 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 NOV 28 PY 2006 VL 103 IS 48 BP 18166 EP 18171 DI 10.1073/pnas.0608899103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 111PJ UT WOS:000242465200026 PM 17114283 ER PT J AU Trivedi, V Zhang, SC Castoreno, AB Stockinger, W Shieh, EC Vyas, JM Frickel, EM Nohturfft, A AF Trivedi, Vishal Zhang, Shao C. Castoreno, Adam B. Stockinger, Walter Shieh, Eugenie C. Vyas, Jatin M. Frickel, Eva-Maria Nohturfft, Axel TI Immunoglobulin G signaling activates lysosome/phagosome docking SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE membrane fusion; protein kinase C; scintillation proximity assay; Fc receptor; macrophages ID RECEPTOR-MEDIATED PHAGOCYTOSIS; SCINTILLATION PROXIMITY ASSAY; FC-GAMMA RECEPTORS; CELL-LINE; CULTURED MACROPHAGES; PHAGOSOME MATURATION; TOXOPLASMA-GONDII; FUSION; KINASE; ACTIN AB An important role of IgG antibodies in the defense against microbial infections is to promote the ingestion and killing of microbes by phagocytes. Here, we developed in vivo and in vitro approaches to ask whether opsonization of particles with IgG enhances intracellular targeting of lysosomes to phagosomes. To eliminate the effect of IgG on the ingestion process, cells were exposed to latex beadsat 15-20 degrees C, which allows engulfment of both IgG-coated and uncoated beads but prevents the fusion of lysosomes with phagosomes. Upon shifting the temperature to 37 degrees C, phagosomes containing IgG beads matured significantly faster into phagolysosomes as judged by colocalization with lysosomal markers. The IgG effect was independent of other particle-associated antigens or serum factors. Lysosome/phagosome attachment was also quantified biochemically with a cytosol-dependent scintillation proximity assay. Interactions were enhanced significantly in reactions containing cytosol from mouse macrophages that had been exposed to IgG-coated beads, indicating that IgG signaling modulates the cytosolic-targeting machinery. Similar results were obtained with cytosol from primary human monocytes, human U-937 histiocytic lymphoma cells and from Chinese hamster ovary (CHO) cells transfected with a human IgG (Fc-y) receptor. IgG-induced activation is shown to affect the actin-dependent tethering/docking stage of the targeting process and to proceed through a pathway involving protein kinase C. These results provide a rare example of an extracellular signal controlling membrane targeting on the level of tethering and docking. We propose that this pathway contributes to the role of antibodies in the protection against microbial infections. C1 Harvard Univ, Biol Labs, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Nohturfft, A (reprint author), Harvard Univ, Biol Labs, Dept Mol & Cellular Biol, 16 Divin Ave, Cambridge, MA 02138 USA. EM axno@mcb.harvard.edu RI Vyas, Jatin/Q-1627-2016 OI Vyas, Jatin/0000-0002-9985-9565 FU NIAID NIH HHS [K08 AI057999]; NIDDK NIH HHS [R01 DK059934, R01 DK59934] NR 40 TC 17 Z9 17 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 NOV 28 PY 2006 VL 103 IS 48 BP 18226 EP 18231 DI 10.1073/pnas.0609182103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 111PJ UT WOS:000242465200036 PM 17110435 ER PT J AU Palomero, T Lim, WK Odom, DT Sulis, ML Real, PJ Margolin, A Barnes, KC O'Neil, J Neuberg, D Weng, AP Aster, JC Sigaux, F Soulier, J Look, AT Young, RA Califano, A Ferrando, AA AF Palomero, Teresa Lim, Wei Keat Odom, Duncan T. Sulis, Maria Luisa Real, Pedro J. Margolin, Adam Barnes, Kelly C. O'Neil, Jennifer Neuberg, Donna Weng, Andrew P. Aster, Jon C. Sigaux, Francois Soulier, Jean Look, A. Thomas Young, Richard A. Califano, Andrea Ferrando, Adolfo A. TI NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE T cell lymphoblastic leukemia ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GAMMA-SECRETASE INHIBITORS; TARGET; GENE; EXPRESSION; DROSOPHILA; MUTATIONS AB The NOTCH1 signaling pathway directly links extracellular signals with transcriptional responses in the cell nucleus and plays a critical role during T cell development and in the pathogenesis over 50% of human T cell lymphoblastic leukemia (T-ALL) cases. However, little is known about the transcriptional programs activated by NOTCH1. Using an integrative systems biology approach we show that NOTCH1 controls a feed-forward-loop transcriptional network that promotes cell growth. Inhibition of NOTCH1 signaling in TALL cells led to a reduction in cell size and elicited a gene expression signature dominated by down-regulated biosynthetic pathway genes. By integrating gene expression array and ChIP-on-chip data, we show that NOTCH1 directly activates multiple biosynthetic routes and induces c-MYC gene expression. Reverse engineering of regulatory networks from expression profiles showed that NOTCH1 and c-MYC govern two directly interconnected transcriptional programs containing common target genes that together regulate the growth of primary T-ALL cells. These results identify c-MYC as an essential mediator of NOTCH1 signaling and integrate NOTCH1 activation with oncogenic signaling pathways upstream of c-MYC. C1 Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. Columbia Univ, Joint Ctr Syst Biol, New York, NY 10032 USA. Whitehead Inst, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. British Columbia Canc Res Ctr, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Hop St Louis, U728, Inst Natl Sante & Rech Med, Genome Rearrangements & Canc Grp, F-75010 Paris, France. RP Ferrando, AA (reprint author), Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. EM af2196@columbia.edu RI Young, Richard/F-6495-2012; Califano, Andrea/F-7239-2012; Weng, Andrew/I-5015-2014; Real, Pedro/K-2994-2014; Ferrando, Adolfo /Q-7026-2016; OI Young, Richard/0000-0001-8855-8647; Real, Pedro/0000-0001-7968-5353; Odom, Duncan/0000-0001-6201-5599 FU NCI NIH HHS [1R01CA109755-01, R01 CA109755, 1U54CA121852-01A1, U54 CA121852]; NHGRI NIH HHS [R01 HG002668, R01 HG002668-03]; NIAID NIH HHS [R01 AI066116]; NLM NIH HHS [5 T15 LM007079-13, T15 LM007079] NR 24 TC 406 Z9 425 U1 4 U2 20 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 NOV 28 PY 2006 VL 103 IS 48 BP 18261 EP 18266 DI 10.1073/pnas.0606108103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 111PJ UT WOS:000242465200042 PM 17114293 ER PT J AU Dublin, S French, B Glazer, NL Wiggins, KL Lumley, T Psaty, BM Smith, NL Heckbert, SR AF Dublin, Sascha French, Benjamin Glazer, Nicole L. Wiggins, Kerri L. Lumley, Thomas Psaty, Bruce M. Smith, Nicholas L. Heckbert, Susan R. TI Risk of new-onset atrial fibrillation in relation to body mass index SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst ID C-REACTIVE PROTEIN; MYOCARDIAL-INFARCTION; POSTMENOPAUSAL WOMEN; INSULIN SENSITIVITY; OBESITY; ADIPONECTIN; POPULATION; ADULTS; INFLAMMATION; PREVALENCE AB Background: Obesity is associated with increased risk of atrial fibrillation (AF), but it is unknown whether the association differs by duration or persistence of AF. It is also unknown to what extent cardiovascular risk factors may mediate this association. Methods: This population-based case-control study included 425 subjects with new-onset AF and 707 controls. The AF cases were identified through International Classification of Diseases, Ninth Revision codes for inpatient and outpatient visits and verified by medical record review. Medical records provided data on height, weight, and cardiovascular risk factors. Results: On average, AF risk was 3% higher (95% confidence interval [CI], 1%-5%) per unit increment in body mass index (BMI) ( calculated as weight in kilograms divided by height in meters squared). For sustained AF ( duration >= 6 months), risk was higher by 7% (95% CI, 3%-11%) per unit BMI increment; for intermittent AF ( duration >= 8 days or recurrent), 4% ( 95% CI, 1%-6%); and for transitory AF ( duration < 8 days), 1% ( 95% CI, -1% to +4%). Compared with those with normal BMI, the odds ratios for overweight and obese subjects were as follows: overweight, 0.97 ( 95% CI, 0.68-1.38); obese class 1,1.18 ( 95% CI, 0.80-1.73); obese class 2, 1.34 ( 95% CI, 0.82-2.18); and obese class 3, 2.31 ( 95% CI, 1.36-3.91) (P = .002 for trend). When diabetes mellitus, a possible mediator, was added to the model, the odds ratio per unit increment of BMI decreased from 1.034 to 1.028. Adjustment for other cardiovascular risk factors including hyperlipidemia and blood pressure did not attenuate the BMI-AF association. Conclusions: The association with BMI was stronger for sustained AF than for transitory or intermittent AF. The obesity-AF association appears to be partially mediated by diabetes mellitus but minimally through other cardiovascular risk factors. C1 Univ Washington, Hlth Serv Res & Dev, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98101 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Dublin, S (reprint author), Univ Washington, Hlth Serv Res & Dev, Vet Affairs Puget Sound Hlth Care Syst, Metropolitan Pk W,1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM Sascha.Dublin@va.gov FU NHLBI NIH HHS [HL 043201, HL 068639, HL 068986, HL 073410] NR 27 TC 127 Z9 131 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 27 PY 2006 VL 166 IS 21 BP 2322 EP 2328 DI 10.1001/archinte.166.21.2322 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 109MQ UT WOS:000242312700004 PM 17130384 ER PT J AU Bogunovic, M Ginhoux, F Wagers, A Loubeau, M Isola, LM Lubrano, L Najfeld, V Phelps, RG Grosskreutz, C Scigliano, E Frenette, PS Merad, M AF Bogunovic, Milena Ginhoux, Florent Wagers, Amy Loubeau, Martine Isola, Luis M. Lubrano, Lauren Najfeld, Vesna Phelps, Robert G. Grosskreutz, Celia Scigliano, Eilleen Frenette, Paul S. Merad, Miriam TI Identification of a radio-resistant and cycling dermal dendritic cell population in mice and men SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID VERSUS-HOST-DISEASE; ANTIGEN-PRESENTING CELLS; DONOR LYMPHOCYTE INFUSIONS; MONOCLONAL-ANTIBODY KI-67; MEMORY T-CELLS; LANGERHANS CELLS; HEMATOPOIETIC STEM; IN-VIVO; BONE-MARROW; HUMAN SKIN AB In this study, we explored dermal dendritic cell (DC) homeostasis in mice and humans both in the steady state and after hematopoietic cell transplantation. We discovered that dermal DCs proliferate in situ in mice and human quiescent dermis. In parabiotic mice with separate organs but shared blood circulation, the majority of dermal DCs failed to be replaced by circulating precursors for > 6 mo. In lethally irradiated mice injected with donor congenic bone marrow (BM) cells, a subset of recipient DCs remained in the dermis and proliferated locally throughout life. Consistent with these findings, a large proportion of recipient dermal DCs remained in patients' skin after allogeneic hematopoietic cell transplantation, despite complete donor BM chimerism. Collectively, our results oppose the traditional view that DCs are nondividing terminally differentiated cells maintained by circulating precursors and support the new paradigm that tissue DCs have local proliferative properties that control their homeostasis in the steady state. Given the role of residual host tissue DCs in transplant immune reactions, these results suggest that dermal DC homeostasis may contribute to the development of cutaneous graft-versus-host disease in clinical transplantation. C1 CUNY Mt Sinai Sch Med, Dept Gene & Cell Med, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Dermatol, New York, NY 10029 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Merad, M (reprint author), CUNY Mt Sinai Sch Med, Dept Gene & Cell Med, New York, NY 10029 USA. EM Miriam.Merad@mssm.edu RI Frenette, Paul/J-8272-2012 FU NCI NIH HHS [R01-CA112100, R01 CA112100]; NHLBI NIH HHS [R01-HL069438, R01 HL069438] NR 68 TC 97 Z9 99 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 27 PY 2006 VL 203 IS 12 BP 2627 EP 2638 DI 10.1084/jem.20060667 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 109WG UT WOS:000242339700006 PM 17116734 ER PT J AU Gauduin, MC Yu, Y Barabasz, A Carville, A Piatak, M Lifson, JD Desrosiers, RC Johnson, RP AF Gauduin, Marie-Claire Yu, Yi Barabasz, Amy Carville, Angela Piatak, Mike Lifson, Jeffrey D. Desrosiers, Ronald C. Johnson, R. Paul TI Induction of a virus-specific effector-memory CD4(+) T cell response by attenuated SIV infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SIMIAN-IMMUNODEFICIENCY-VIRUS; PLASMA VIRAL LOAD; HIV-1 INFECTION; RHESUS-MACAQUES; INVERSE RELATIONSHIP; CD8(+) LYMPHOCYTES; HELPER RESPONSES; IN-VITRO; EX-VIVO; LIVE AB We investigated simian immunodeficiency virus (SIV)-specific CD4(+) T cell responses in rhesus macaques chronically infected with attenuated or pathogenic SIV strains. Analysis of SIV Delta nef-infected animals revealed a relatively high frequency of SIV-specific CD4+ T cells representing 4-10% of all CD4+ T lymphocytes directed against multiple SIV proteins. Gag-specific CD4+ T cells in wild-type SIV-infected animals were 5-10-fold lower in frequency and inversely correlated with the level of plasma viremia. SIV-specific CD4+ cells from SIV Delta nef animals were predominantly CD27(-)CD28(-)CD45RA(low)CCR7(-)CCR5(-), consistent with an effector-memory subset, and included a fully differentiated CD45RA(+)CCR7(-) subpopulation. In contrast, SIV-specific CD4(+) T cells from SIV-infected animals were mostly CD27(+)C D28(+)CD45RA(-)CCR7(+)CCR5(+), consistent with an early central memory phenotype. The CD45RA(+)CCR7(-)CD(4+) subset from SIV Delta nef animals was highly enriched for effector CD4(+) T cells, as indicated by the perforin expression and up- regulation of the lysosomal membrane protein CD107a after SIV Gag stimulation. SIV-specific CD4(+) T cells in attenuated SIV-infected animals were increased in frequency in bronchioalveolar lavage and decreased in lymph nodes, consistent with an effector-memory T cell population. The ability of SIV Delta nef to induce a high frequency virus-specific CD4(+)T cell response with direct effector function may play a key role in protective immunity produced by vaccination with attenuated SIV strains. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, Southborough, MA 01772 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Microbiol, Southborough, MA 01772 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Primate Med, Southborough, MA 01772 USA. Inst Appl Int Corp Frederick Inc, AIDS Vaccine Program, NCI, Frederick, MD 21702 USA. Massachusetts Gen Hosp, Infect Dis Unit, Partners AIDS Res Ctr, Boston, MA 02115 USA. RP Gauduin, MC (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, Southborough, MA 01772 USA. EM mcgauduin@sfbr.org FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NCRR NIH HHS [K26 RR000168, P51 RR000168, RR00168]; NIAID NIH HHS [AI45314, AI62412, R01 AI043890, R01 AI062412, AI43890] NR 47 TC 51 Z9 52 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 27 PY 2006 VL 203 IS 12 BP 2661 EP 2672 DI 10.1084/jem.20060134 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 109WG UT WOS:000242339700009 PM 17116733 ER PT J AU Mrass, P Takano, H Ng, LG Daxini, S Lasaro, MO Iparraguirre, A Cavanagh, LL von Andrian, UH Ertl, HCJ Haydon, PG Weninger, W AF Mrass, Paulus Takano, Hajime Ng, Lai Guan Daxini, Sachin Lasaro, Marcio O. Iparraguirre, Amaya Cavanagh, Lois L. von Andrian, Ulrich H. Ertl, Hildegund C. J. Haydon, Philip G. Weninger, Wolfgang TI Random migration precedes stable target cell interactions of tumor-infiltrating T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TIME-LAPSE MICROCINEMATOGRAPHY; DENDRITIC CELLS; IN-VIVO; IMMUNE-SYSTEM; LYMPH-NODES; EXTRACELLULAR-MATRIX; CANCER-IMMUNOTHERAPY; ANTIGEN PRESENTATION; 2-PHOTON MICROSCOPY; LYMPHOCYTES AB The tumor microenvironment is composed of an intricate mixture of tumor and host-derived cells that engage in a continuous interplay. T cells are particularly important in this context as they may recognize tumor-associated antigens and induce tumor regression. However, the precise identity of cells targeted by tumor-infiltrating T lymphocytes (TILs) as well as the kinetics and anatomy of TIL-target cell interactions within tumors are incompletely understood. Furthermore, the spatiotemporal conditions of TIL locomotion through the tumor stroma, as a prerequisite for establishing contact with target cells, have not been analyzed. These shortcomings limit the rational design of immunotherapeutic strategies that aim to overcome tumor- immune evasion. We have used two- photon microscopy to determine, in a dynamic manner, the requirements leading to tumor regression by TILs. Key observations were that TILs migrated randomly throughout the tumor microenvironment and that, in the absence of cognate antigen, they were incapable of sustaining active migration. Furthermore, TILs in regressing tumors formed long-lasting (= 30 min), cognate antigen-dependent contacts with tumor cells. Finally, TILs physically interacted with macrophages, suggesting tumor antigen cross-presentation by these cells. Our results demonstrate that recognition of cognate antigen within tumors is a critical determinant of optimal TIL migration and target cell interactions, and argue against TIL guidance by long-range chemokine gradients. C1 Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Neurosci, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Conte Ctr Integrat Tripartite Synapse, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Weninger, W (reprint author), Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA. EM weninger@wistar.org RI Ng, Lai Guan/E-5673-2011; von Andrian, Ulrich/A-5775-2008 OI Ng, Lai Guan/0000-0003-1905-3586; FU NCI NIH HHS [R21 CA114114]; NCRR NIH HHS [S10 RR021100]; NIAID NIH HHS [AI061663, R01 AI061663] NR 51 TC 133 Z9 135 U1 2 U2 15 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 27 PY 2006 VL 203 IS 12 BP 2749 EP 2761 DI 10.1084/jem.20060710 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 109WG UT WOS:000242339700017 PM 17116735 ER PT J AU Swers, JS Widom, A Phan, U Springer, TA Wittrup, KD AF Swers, Jeffrey S. Widom, Angela Phan, Uyen Springer, Timothy A. Wittrup, K. Dane TI A high affinity human antibody antagonist of P-selectin mediated rolling SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE antibody; P-selectin; leukocyte rolling ID GLYCOPROTEIN LIGAND-1; IN-VIVO; PSGL-1; BINDING; RECOGNITION; MODEL; FLOW AB We have characterized the IgG form of a previously isolated and engineered single-chain Fv (scFv), named RR2r3s4-1, that binds to human PSGL-1. This fully human IgG was determined to have a K-d of 1.8 +/- 0.7 nM by fluorescence quenching titration. It better inhibits P-selectin-PSGL-1 interactions than a commercially available murine monoclonal antibody KPL1 and better inhibits neutrophil rolling than KPL1. Thus, RR2r3s4-1 is the most effective antibody at inhibiting P-selectin-PSGL-1 interactions known. Specificity analysis reveals that RR2r3s4-1 does not cross react with murine PSGL-1 and thus requires more than tyrosine sulfate for binding to human PSGL-1. This evidence demonstrates the therapeutic potential of this antibody as a potent anti-inflammatory therapeutic. (c) 2006 Elsevier Inc. All rights reserved. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. MIT, Biol Engn Div, Cambridge, MA 02139 USA. Wyeth Res, Cambridge, MA 02140 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res Inc, Boston, MA 02115 USA. RP Wittrup, KD (reprint author), MIT, Dept Chem Engn, 66-552,25 Ames St, Cambridge, MA 02139 USA. EM wittrup@mit.edu FU NIGMS NIH HHS [GM08334] NR 19 TC 5 Z9 5 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 24 PY 2006 VL 350 IS 3 BP 508 EP 513 DI 10.1016/j.bbrc.2006.08.197 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 099HN UT WOS:000241584300002 PM 17027652 ER PT J AU Demichelis, F Magni, P Piergiorgi, P Rubin, MA Bellazzi, R AF Demichelis, Francesca Magni, Paolo Piergiorgi, Paolo Rubin, Mark A. Bellazzi, Riccardo TI A hierarchical Naive Bayes Model for handling sample heterogeneity in classification problems: an application to tissue microarrays SO BMC BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION DATA; PROSTATE-CANCER; SELECTION; SPECIMENS; RACEMASE; DESIGN AB Background: Uncertainty often affects molecular biology experiments and data for different reasons. Heterogeneity of gene or protein expression within the same tumor tissue is an example of biological uncertainty which should be taken into account when molecular markers are used in decision making. Tissue Microarray ( TMA) experiments allow for large scale profiling of tissue biopsies, investigating protein patterns characterizing specific disease states. TMA studies deal with multiple sampling of the same patient, and therefore with multiple measurements of same protein target, to account for possible biological heterogeneity. The aim of this paper is to provide and validate a classification model taking into consideration the uncertainty associated with measuring replicate samples. Results: We propose an extension of the well-known Naive Bayes classifier, which accounts for biological heterogeneity in a probabilistic framework, relying on Bayesian hierarchical models. The model, which can be efficiently learned from the training dataset, exploits a closed- form of classification equation, thus providing no additional computational cost with respect to the standard Naive Bayes classifier. We validated the approach on several simulated datasets comparing its performances with the Naive Bayes classifier. Moreover, we demonstrated that explicitly dealing with heterogeneity can improve classification accuracy on a TMA prostate cancer dataset. Conclusion: The proposed Hierarchical Na ve Bayes classifier can be conveniently applied in problems where within sample heterogeneity must be taken into account, such as TMA experiments and biological contexts where several measurements ( replicates) are available for the same biological sample. The performance of the new approach is better than the standard Naive Bayes model, in particular when the within sample heterogeneity is different in the different classes. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Trent, Dept Informat & Commun Technol, Trento, Italy. IRST, ITC, SRA, Trento, Italy. Harvard Univ, Sch Med, Boston, MA USA. Univ Pavia, Dipartimento Informat & Sistemist, I-27100 Pavia, Italy. Harvard Univ, Dana Farber Canc Ctr, Boston, MA 02115 USA. RP Rubin, MA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM fdemichelis@partners.org; paolo.magni@unipv.it; Ppiergiorgi@gmail.com; marubin@partners.org; riccardo.bellazzi@unipv.it OI Rubin, Mark/0000-0002-8321-9950; Magni, Paolo/0000-0002-8931-4676; Demichelis, Francesca/0000-0002-8266-8631 NR 39 TC 29 Z9 30 U1 0 U2 1 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 NOV 24 PY 2006 VL 7 AR 514 DI 10.1186/1471-2105-7-514 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 118OF UT WOS:000242950900001 PM 17125514 ER PT J AU Ahmad, R Raina, D Meyer, C Kharbanda, S Kufe, D AF Ahmad, Rehan Raina, Deepak Meyer, Colin Kharbanda, Surender Kufe, Donald TI Triterpenoid CDDO-Me blocks the NF-kappa B pathway by direct inhibition of IKK beta on Cys-179 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 2-CYANO-3,12-DIOXOOLEANA-1,9-DIEN-28-OIC ACID CDDO; ACUTE MYELOGENOUS LEUKEMIA; ACTIVATED RECEPTOR-GAMMA; TUMOR-NECROSIS-FACTOR; BREAST-CANCER CELLS; INDUCE APOPTOSIS; 2-CYANO-3,12-DIOXOOLEAN-1,9-DIEN-28-OIC ACID; KINASE; MECHANISM; DIFFERENTIATION AB The novel oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9,-dien-28-oic acid ( CDDO) and the C-28 methyl ester (CDDO-Me) induce apoptosis of human tumor cells by disruption of redox balance and are currently in clinical trials. The present studies show that CDDO and CDDO-Me block tumor necrosis factor alpha-induced targeting of NF-kappa B p65 to the nucleus. CDDO- Me also blocked tumor necrosis factor alpha-induced phosphorylation of I kappa B alpha. In concert with these results, we found that CDDO- Me inhibits I kappa B alpha kinase beta(IKK beta) activity in cells. In support of a direct mechanism, CDDO- Me inhibited recombinant IKK beta activity in vitro. The results also demonstrate that (i) CDDO and CDDO- Me form adducts with IKK beta, but not IKK beta with mutation of Cys-179 to Ala, and (ii)CDDO- Me inhibits IKK beta by a mechanism dependent on oxidation of Cys-179. These findings indicate that CDDO and CDDO-Me directly block IKK beta activity and thereby the NF-kappa B pathway by interacting with Cys-179 in the IKK beta activation loop. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Reata Pharmaceut Inc, Dallas, TX 75207 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA100707, CA42802, CA98628] NR 30 TC 138 Z9 139 U1 2 U2 6 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 NOV 24 PY 2006 VL 281 IS 47 BP 35764 EP 35769 DI 10.1074/jbc.M607160200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 106KX UT WOS:000242100500022 PM 16998237 ER PT J AU Yamamoto-Furusho, JK Barnich, N Xavier, R Hisamatsu, T Podolsky, DK AF Yamamoto-Furusho, Jesus K. Barnich, Nicolas Xavier, Ramnik Hisamatsu, Tadakazu Podolsky, Daniel K. TI Centaurin beta 1 down-regulates nucleotide-binding oligomerization domains 1- and 2-dependent NF-kappa B activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; ESCHERICHIA-COLI; NOD2; EXPRESSION; BACTERIAL; INNATE; SUSCEPTIBILITY; RECOGNITION AB Centaurin beta 1 (CENTB1), a GTPase-activating protein, is a member of the ADP-ribosylation factor family encoded by a gene located on the short arm of human chromosome 17. A yeast two-hybrid screen first suggested a direct interaction between CENTB1 and NOD2. Co-immunoprecipitation experiments confirmed direct interaction between CENTB1 and NOD2 and demonstrated similar interaction between CENTB1 and NOD1. We also demonstrate that endogenous CENTB1 interacts with endogenous NOD2 and NOD1 in SW480 and HT-29 intestinal epithelial cells. CENTB1 partially co-localized with NOD2 and NOD1 proteins in the cytoplasm of mammalian cells. CENTB1 expression in epithelial cells was highly induced by tumor necrosis factor alpha,interleukin 1 beta, and the NOD1 and NOD2 ligands (gamma-D-glutamyl-meso-diaminopimelic acid and muramyl dipeptide, respectively). In addition, CENTB1 mRNA level is increased in the inflamed mucosa of patients with inflammatory bowel disease. Functionally, CENTB1 overexpression inhibited NOD1- and NOD2-dependent activation of NF-kappa B, whereas small inhibitory RNA against CENTB1 increased NF-kappa B activation following NOD1- or NOD2-mediated recognition of the bacterial components gamma-D-glutamyl-meso-diaminopimelic acid and muramyl dipeptide, respectively. In contrast, CENTB1 had no effect on NF-kappa B activation induced by Toll-like receptors. In conclusion, CENTB1 selectively down-regulates NF-kappa B activation via NODs pathways, creating a "feedback" loop and suggesting a novel role of CENTB1 in innate immune responses to bacteria and inflammatory responses. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Ctr Study Inflammatory Bowel Dis, 55 Fruit St, Boston, MA 02114 USA. EM dpodolsky@partners.org FU NIDDK NIH HHS [DK069344, DK43351] NR 34 TC 44 Z9 48 U1 0 U2 1 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 NOV 24 PY 2006 VL 281 IS 47 BP 36060 EP 36070 DI 10.1074/jbc.M602383200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 106KX UT WOS:000242100500055 PM 17005562 ER PT J AU Popescu, G Ikeda, T Goda, K Best-Popescu, CA Laposata, M Manley, S Dasari, RR Badizadegan, K Feld, MS AF Popescu, Gabriel Ikeda, Takahiro Goda, Keisuke Best-Popescu, Catherine A. Laposata, Michael Manley, Suliana Dasari, Ramachandra R. Badizadegan, Kamran Feld, Michael S. TI Optical measurement of cell membrane tension SO PHYSICAL REVIEW LETTERS LA English DT Article ID RED-BLOOD-CELL; FREQUENCY ELECTRIC-FIELDS; ERYTHROCYTE-MEMBRANE; ELASTIC-MODULI; FLUCTUATIONS; DEFORMATION; SHAPE; CYTOSKELETON; MICROSCOPY; VISCOSITY AB Using a novel noncontact technique based on optical interferometry, we quantify the nanoscale thermal fluctuations of red blood cells (RBCs) and giant unilamellar vesicles (GUVs). The measurements reveal a nonvanishing tension coefficient for RBCs, which increases as cells transition from a discocytic shape to a spherical shape. The tension coefficient measured for GUVs is, however, a factor of 4-24 smaller. By contrast, the bending moduli for cells and vesicles have similar values. This is consistent with the cytoskeleton confinement model, in which the cytoskeleton inhibits membrane fluctuations. C1 MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. Hamamatsu Photon KK, Hamamatsu, Shizuoka 4348601, Japan. MIT, Dept Phys, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Popescu, G (reprint author), MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. RI Manley, Suliana/D-3818-2012 OI Manley, Suliana/0000-0002-4755-4778 NR 32 TC 112 Z9 114 U1 1 U2 20 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD NOV 24 PY 2006 VL 97 IS 21 AR 218101 DI 10.1103/PhysRevLett.97.218101 PG 4 WC Physics, Multidisciplinary SC Physics GA 108DG UT WOS:000242219900046 PM 17155774 ER PT J AU Faustman, DL Tran, SD Kodama, S Lodde, BM Szalayova, I Key, S Toth, ZE Mezey, E AF Faustman, Denise L. Tran, Simon D. Kodama, Shohta Lodde, Beatrijs M. Szalayova, Ildiko Key, Sharon Toth, Zsuzsanna E. Mezey, Eva TI Comment on papers by Chong et al., Nishio et al., and Suri et al. on diabetes reversal in NOD mice SO SCIENCE LA English DT Editorial Material ID REGENERATION; CELLS C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. McGill Univ, Montreal, PQ, Canada. Brigham & Womens Hosp, Boston, MA 02215 USA. NIH, Bethesda, MD 20892 USA. RP Faustman, DL (reprint author), Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM faustman@helix.mgh.harvard.edu; mezeye@mail.nih.gov NR 10 TC 0 Z9 0 U1 0 U2 1 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 NOV 24 PY 2006 VL 314 IS 5803 DI 10.1126/science.1129811 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 108BR UT WOS:000242215800019 ER PT J AU Nishio, J Gaglia, JL Turvey, SE Campbell, C Benoist, C Mathis, D AF Nishio, Junko Gaglia, Jason L. Turvey, Stuart E. Campbell, Christopher Benoist, Christophe Mathis, Diane TI Response to comment on Nishio et al. on diabetes reversal in NOD mice SO SCIENCE LA English DT Editorial Material ID REGENERATION C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Stem Cell Inst, Boston, MA 02215 USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Joslin Diabet Ctr,Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 0 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 NOV 24 PY 2006 VL 314 IS 5803 DI 10.1126/science.1129919 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 108BR UT WOS:000242215800021 ER PT J AU Klibanski, A Stephen, AE Greene, MF Blake, MA Wu, CL Utz, AL AF Klibanski, Anne Stephen, Antonia E. Greene, Michael F. Blake, Michael A. Wu, Chin-Lee Utz, Andrea L. TI A pregnant woman with new hypertension - Cushing's syndrome due to adrenal cortical carcinoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID LAPAROSCOPIC ADRENALECTOMY; ADRENOCORTICAL TUMORS; DEXAMETHASONE-SUPPRESSION; METYRAPONE; PHEOCHROMOCYTOMA; HYPERCORTISOLISM; DIFFERENTIATION; COMPLICATIONS; DIAGNOSIS; CORTISOL C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Obstet & Gynecol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. NR 34 TC 19 Z9 19 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 NOV 23 PY 2006 VL 355 IS 21 BP 2237 EP 2245 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 107KQ UT WOS:000242170900012 PM 17124022 ER PT J AU Greene, MF AF Greene, Michael F. TI Obstetricians still await a deus ex machina SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID FETAL PULSE OXIMETRY; CONTROLLED-TRIAL; CEREBRAL-PALSY; MULTICENTER C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Greene, MF (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 11 TC 13 Z9 13 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 NOV 23 PY 2006 VL 355 IS 21 BP 2247 EP 2248 DI 10.1056/NEJMe068176 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 107KQ UT WOS:000242170900013 PM 17124023 ER PT J AU Gruen, RL Campbell, EG Blumenthal, D AF Gruen, Russell L. Campbell, Eric G. Blumenthal, David TI Public roles of US physicians - Community participation, political involvement, and collective advocacy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MEDICAL PROFESSIONALISM; UNITED-STATES AB Context Whether physicians have a professional responsibility to address health-related issues beyond providing care to individual patients has been vigorously debated. Yet little is known about practicing physicians' attitudes about or the extent to which they participate in public roles, which we defined as community participation, political involvement, and collective advocacy. Objectives To determine the importance physicians assign to public roles, their participation in related activities, and sociodemographic and practice factors related to physicians' rated levels of importance and activity. Design, Setting, and Participants Mail survey conducted between November 2003 and June 2004 of 1662 US physicians engaged in direct patient care selected from primary care specialties (family practice, internal medicine, pediatrics) and 3 non primary care specialties (anesthesiology, general surgery, cardiology). Main Outcome Measures Rated importance of community participation, political involvement, collective advocacy, and relevant self-reported activities encompassing the previous 3 years; rated importance of physician action on different issues. Results Community participation, political involvement, and collective advocacy were rated as important by more than 90% of respondents, and a majority rated community participation and collective advocacy as very important. Nutrition, immunization, substance abuse, and road safety issues were rated as very important by more physicians than were access-to-care issues, unemployment, or illiteracy. Two thirds of respondents had participated in at least 1 of the 3 types of activities in the previous 3 years. Factors independently related to high overall rating of importance (civic-mindedness) included age, female sex, underrepresented race/ethnicity, and graduation from a non-US or non-Canadian medical school. Civic mindedness, medical specialty, practice type, underrepresented race/ethnicity, preceptors of physicians in training, rural practice, and graduation from a non-US or non-Canadian medical school were independently related to civic activity. Conclusions Public roles are definable entities that have widespread support among physicians. Civic-mindedness is associated primarily with sociodemographic factors, but civic action is associated with specialty and practice-based factors. C1 Univ Melbourne, Royal Melbourne Hosp, Dept Surg, Melbourne, Vic 3050, Australia. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gruen, RL (reprint author), Univ Melbourne, Royal Melbourne Hosp, Dept Surg, Parkville, Vic 3050, Australia. EM rgruen@unimelb.edu.au NR 18 TC 69 Z9 70 U1 0 U2 12 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 NOV 22 PY 2006 VL 296 IS 20 BP 2467 EP 2475 DI 10.1001/jama.296.20.2467 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 107KR UT WOS:000242171000028 PM 17119143 ER PT J AU Vickrey, BG Mittman, BS Connor, KI Pearson, ML Della Penna, RD Ganiats, TG DeMonte, RW Chodosh, J Cui, XP Vassar, S Duan, NH Lee, M AF Vickrey, Barbara G. Mittman, Brian S. Connor, Karen I. Pearson, Marjorie L. Della Penna, Richard D. Ganiats, Theodore G. DeMonte, Robert W., Jr. Chodosh, Joshua Cui, Xinping Vassar, Stefanie Duan, Naihua Lee, Martin TI The effect of a disease management intervention on quality and outcomes of dementia care - A randomized, controlled trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID MANAGING ALZHEIMERS-DISEASE; LONGITUDINAL DATA-ANALYSIS; CONTROLLED CLINICAL-TRIAL; IMPROVING PRIMARY-CARE; CHRONIC ILLNESS; HEART-FAILURE; OF-CARE; DEPRESSION; GUIDELINES; HEALTH AB Background: Adherence to dementia guidelines is poor despite evidence that some guideline recommendations can improve symptoms and delay institutionalization of patients. Objective: To test the effectiveness of a dementia guideline-based disease management program on quality of care and outcomes for patients with dementia. Design: Clinic-level, cluster randomized, controlled trial. Setting: 3 health care organizations collaborating with 3 community agencies in southern California. Participants: 18 primary care clinics and 408 patients with dementia age 65 years or older paired with 408 informal caregivers. Intervention: Disease management program led by care managers and provided to 238 patient-caregiver pairs at 9 intervention clinics for more than 12 months. Measurements: Adherence to 23 guideline recommendations (primary outcome) and receipt of community resources and patient and caregiver health and quality-of-care measures (secondary outcomes). Results: The mean percentage of per-patient guideline recommendations to which care was adherent was significantly higher in the intervention group than in the usual care group (63.9% vs. 32.9%, respectively; adjusted difference, 30.1% [95% Cl, 25.2% to 34.9%]; P < 0.001). Participants who received the intervention had higher care quality on 21 of 23 guidelines (P <= 0.013 for all), and higher proportions received community agency assistance (P <= 0.03) than those who received usual care. Patient health-related quality of life, overall quality of patient care, caregiving quality, social support, and level of unmet caregiving assistance needs were better for participants in the intervention group than for those in the usual care group (P < 0.05 for all). Caregiver health-related quality of life did not differ between the 2 groups. Limitations: Participants were well-educated, were predominantly white, had a usual source of care, and were not institutionalized. Generalizability to other patients and geographic regions is unknown. Also, costs of a care management program under fee-for-service reimbursement may impede adoption. Conclusions: A dementia guideline-based disease management program led to substantial improvements in quality of care for patients with dementia. C1 Univ Calif Los Angeles, Dept Neurol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. RAND Corp, Santa Monica, CA USA. Kaiser Permanente Federat, San Diego, CA USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Calif Riverside, Riverside, CA 92521 USA. Scripps Clin, La Jolla, CA USA. RP Vickrey, BG (reprint author), Univ Calif Los Angeles, Dept Neurol, VA Greater Los Angeles Healthcare Syst, C-109 RNRC,Box 951769, Los Angeles, CA 90095 USA. EM bvickrey@ucla.edu OI Penna, Maria Pietronilla/0000-0002-0982-3893 NR 63 TC 189 Z9 190 U1 2 U2 26 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 21 PY 2006 VL 145 IS 10 BP 713 EP 726 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 110OB UT WOS:000242387100001 PM 17116916 ER PT J AU Covinsky, KE Johnston, CB AF Covinsky, Kenneth E. Johnston, C. Bree TI Envisioning better approaches for dementia care SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID CAREGIVER CHARACTERISTICS; ALZHEIMERS-DISEASE; DEPRESSION; PATIENT; PROGRAM; TRIAL C1 Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Covinsky, KE (reprint author), Univ Calif San Francisco, Div Geriatr, 4150 Clement 181G, San Francisco, CA 94121 USA. EM ken.covinsky@ucsf.edu FU NIA NIH HHS [R0AG023626] NR 13 TC 16 Z9 16 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 21 PY 2006 VL 145 IS 10 BP 780 EP 781 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 110OB UT WOS:000242387100008 PM 17116923 ER PT J AU Tsai, TT Fattori, R Trimarchi, S Isselbacher, E Myrmel, T Evangelista, A Hutchison, S Sechtem, U Cooper, JV Smith, DE Pape, L Froehlich, J Raghupathy, A Januzzi, JL Eagle, KA Nienaber, CA AF Tsai, Thomas T. Fattori, Rossella Trimarchi, Santi Isselbacher, Eric Myrmel, Truls Evangelista, Arturo Hutchison, Stuart Sechtem, Udo Cooper, Jeanna V. Smith, Dean E. Pape, Linda Froehlich, James Raghupathy, Arun Januzzi, James L. Eagle, Kim A. Nienaber, Christoph A. CA IRAD Grp TI Long-term survival in patients presenting with type B acute aortic dissection - Insights from the International Registry of Acute Aortic Dissection SO CIRCULATION LA English DT Article; Proceedings Paper CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc DE aorta; risk factors; mortality; follow-up studies ID STENT-GRAFT PLACEMENT; CURRENT ERA; MANAGEMENT; OUTCOMES; THERAPY; IRAD AB Background-Follow-up survival studies in patients with acute type B aortic dissection have been restricted to a small number of patients in single centers. We used data from a contemporary registry of acute type B aortic dissection to better understand factors associated with adverse long-term survival. Methods and Results-We examined 242 consecutive patients discharged alive with acute type B aortic dissection enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2003. Kaplan-Meier survival curves were constructed, and Cox proportional hazards analysis was performed to identify independent predictors of follow-up mortality. Three-year survival for patients treated medically, surgically, or with endovascular therapy was 77.6 +/- 6.6%, 82.8 +/- 18.9%, and 76.2 +/- 25.2%, respectively (median follow-up 2.3 years, log-rank P=0.61). Independent predictors of follow-up mortality included female gender (hazard ratio [HR],1.99; 95% confidence interval [CI], 1.07 to 3.71; P=0.03), a history of prior aortic aneurysm (HR, 2.17; 95% CI, 1.03 to 4.59; P=0.04), a history of atherosclerosis (HR, 2.48; 95% CI, 1.32 to 4.66; P < 0.01), in-hospital renal failure (HR, 2.55; 95% CI, 1.15 to 5.63; P=0.02), pleural effusion on chest radiograph (HR, 2.56; 95% CI, 1.18 to 5.58; P=0.02), and in-hospital hypotension/shock (HR, 12.5; 95% CI, 3.24 to 48.21; P < 0.01). Conclusions-Contemporary follow-up mortality in patients who survive to hospital discharge with acute type B aortic dissection is high, approaching 1 in every 4 patients at 3 years. Current treatment and follow-up surveillance require further study to better understand and optimize care for patients with this complex disease. C1 Univ Michigan, Med Ctr, Dept Internal Med, Div Cardiol, Ann Arbor, MI 48106 USA. Univ Hosp S Orsola, Bologna, Italy. Ist Policlin San Donato, San Donato Milanese, Italy. Univ Rostock, D-2500 Rostock 1, Germany. Univ Tromso Hosp, N-9012 Tromso, Norway. Hos Gen Univ Vall Hebron, Barcelona, Spain. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Robert Bosch Krankenhaus, Stuttgart, Germany. Univ Massachusetts Hosp, Worcester, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tsai, TT (reprint author), Univ Michigan, Med Ctr, Dept Internal Med, Div Cardiol, 24 Frank Lloyd Weight Dr,Lobby A,Room 3201,POB 38, Ann Arbor, MI 48106 USA. EM hsianshi@umich.edu RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 FU NHLBI NIH HHS [5T32HL007853-08] NR 26 TC 210 Z9 224 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 21 PY 2006 VL 114 IS 21 BP 2226 EP 2231 DI 10.1161/CIRCULATIONAHA.106.622340 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 124XR UT WOS:000243406300008 PM 17101856 ER PT J AU Hoffmann, U Nagurney, JT Moselewski, F Pena, A Ferencik, M Chae, CU Cury, RC Butler, J Abbara, S Brown, DF Manini, A Nichols, JH Achenbach, S Brady, TJ AF Hoffmann, Udo Nagurney, John T. Moselewski, Fabian Pena, Antonio Ferencik, Maros Chae, Claudia U. Cury, Ricardo C. Butler, Javed Abbara, Suhny Brown, David F. Manini, Alex Nichols, John H. Achenbach, Stephan Brady, Thomas J. TI Coronary multidetector computed tomography in the assessment of patients with acute chest pain SO CIRCULATION LA English DT Article DE angina; atherosclerosis; imaging; prognosis; tomography ID ACUTE CARDIAC ISCHEMIA; ELEVATION MYOCARDIAL-INFARCTION; PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; EMERGENCY-DEPARTMENT; ARTERY-DISEASE; PRACTICAL IMPLEMENTATION; INTRAVASCULAR ULTRASOUND; AMERICAN-COLLEGE; CARE AB Background-Noninvasive assessment of coronary atherosclerotic plaque and significant stenosis by coronary multidetector computed tomography (MDCT) may improve early and accurate triage of patients presenting with acute chest pain to the emergency department. Methods and Results-We conducted a blinded, prospective study in patients presenting with acute chest pain to the emergency department between May and July 2005 who were admitted to the hospital to rule out acute coronary syndrome (ACS) with no ischemic ECG changes and negative initial biomarkers. Contrast-enhanced 64-slice MDCT coronary angiography was performed immediately before admission, and data sets were evaluated for the presence of coronary atherosclerotic plaque and significant coronary artery stenosis. All providers were blinded to MDCT results. An expert panel, blinded to the MDCT data, determined the presence or absence of ACS on the basis of all data accrued during the index hospitalization and 5-month follow-up. Among 103 consecutive patients (40% female; mean age, 54 +/- 12 years), 14 patients had ACS. Both the absence of significant coronary artery stenosis (73 of 103 patients) and nonsignificant coronary atherosclerotic plaque (41 of 103 patients) accurately predicted the absence of ACS (negative predictive values, 100%). Multivariate logistic regression analyses demonstrated that adding the extent of plaque significantly improved the initial models containing only traditional risk factors or clinical estimates of the probability of ACS (c statistic, 0.73 to 0.89 and 0.61 to 0.86, respectively). Conclusions-Noninvasive assessment of coronary artery disease by MDCT has good performance characteristics for ruling out ACS in subjects presenting with possible myocardial ischemia to the emergency department and may be useful for improving early triage. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Div Cardiol, Erlangen, Germany. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, 165 Charles River Plaza,Ste 400, Boston, MA 02114 USA. EM uhoffman@partners.org FU NHLBI NIH HHS [R01 HL080053] NR 33 TC 229 Z9 232 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 21 PY 2006 VL 114 IS 21 BP 2251 EP 2260 DI 10.1161/CIRCULATIONAHA.106.634808 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 124XR UT WOS:000243406300011 PM 17075011 ER PT J AU Skouri, HN Dec, GW Friedrich, MG Cooper, LT AF Skouri, Hadi N. Dec, G. William Friedrich, Matthias G. Cooper, Leslie T. TI Noninvasive imaging in myocarditis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CARDIOVASCULAR MAGNETIC-RESONANCE; CLINICALLY SUSPECTED MYOCARDITIS; CARDIAC ALLOGRAFT-REJECTION; INDIUM-111-MONOCLONAL ANTIMYOSIN ANTIBODY; ASYMMETRIC SEPTAL HYPERTROPHY; LEFT-VENTRICULAR DYSFUNCTION; TERM-FOLLOW-UP; DILATED CARDIOMYOPATHY; ENDOMYOCARDIAL BIOPSY; IN-VIVO AB lncreased recognition of the role of inflammation in acute and chronic dilated cardiomyopathy has revived an interest in noninvasive imaging for detection of myocarditis. Diagnostic strategies that are based on molecular imaging promise to further advance our understanding and improve diagnostic precision. This article reviews the strengths and limitations of common clinical tests used for the diagnosis of myocarditis, with a focus on the emerging role of cardiovascular magnetic resonance imaging. Novel imaging modalities that are currently in preclinical development are discussed with recommendations for future clinical research. C1 Mayo Clin, Cardiovasc Dept, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Univ Calgary, Stephenson CMR Ctr, Calgary, AB T2N 1N4, Canada. RP Cooper, LT (reprint author), Mayo Clin, Cardiovasc Dept, 5 Gonda,200 1st St SW, Rochester, MN 55905 USA. EM Cooper.leslie@mayo.edu NR 77 TC 94 Z9 106 U1 1 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 NOV 21 PY 2006 VL 48 IS 10 BP 2085 EP 2093 DI 10.1016/j.jacc.2006.08.017 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 108NX UT WOS:000242247600021 PM 17112998 ER PT J AU Newton, AJ Kirchhausen, T Murthy, VN AF Newton, A. Jamila Kirchhausen, Tom Murthy, Venkatesh N. TI Inhibition of dynamin completely blocks compensatory synaptic vesicle endocytosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE clathrin; hippocampal; vesicle recycling; kiss-and-run ID RETINAL BIPOLAR CELLS; KISS-AND-RUN; HIPPOCAMPAL SYNAPSES; NERVE-TERMINALS; SUSTAINED STIMULATION; MEMBRANE RETRIEVAL; RAPID ENDOCYTOSIS; CHROMAFFIN CELLS; FUSION PORES; EXOCYTOSIS AB The ability of synapses to sustain signal propagation relies on rapid recycling of transmitter-containing presynaptic vesicles. Clathrin- and dynamin-mediated retrieval of vesicular membrane has an undisputed role in synaptic vesicle recycling. There is also evidence for other modes of vesicle retrieval, including bulk retrieval and the so-called kiss-and-run recycling. Whether dynamin in required for these other modes of synaptic vesicle endocytosis remains unclear. Here, we have tested the role of dynamin in synaptic vesicle endocytosis by using a small molecule called dynasore, which rapidly inhibits the GTPase activity of dynamin with high specificity. Endocytosis after sustained or brief stimuli was completely and reversibly blocked by dynasore in cultured hippocampal neurons expressing the fluorescent tracer synaptopHluorin. By contrast, dynasore had no effect on exocytosis. In the presence of dynasore, low-frequency stimulation led to sustained accumulation of synaptopHluorin and other vesicular proteins on the surface membrane at a rate predicted from net exocytosis. These vesicular components remained on surface membranes even after the stimulus was terminated, suggesting that all endocytic events rely on dynamin during low-frequency activity as well as in the period after it. Ultrastructural analysis revealed a reduction in the density of synaptic vesicles and the presence of endocytic structures only at synapses that were stimulated in the presence of dynasore. In sum, our data indicate that dynamin is essential for all forms of compensatory synaptic vesicle endocytosis including any kiss-and-run events. C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Murthy, VN (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. EM vnmurthy@fas.harvard.edu FU NIGMS NIH HHS [GM075252, R01 GM075252]; NINDS NIH HHS [R01 NS039059, NS39059] NR 50 TC 143 Z9 148 U1 0 U2 6 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 NOV 21 PY 2006 VL 103 IS 47 BP 17955 EP 17960 DI 10.1073/pnas.0606212103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 111PG UT WOS:000242464900068 PM 17093049 ER PT J AU Cannon, CP AF Cannon, Christopher P. TI Integrating platelet monitoring into clinical practice - Introduction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material C1 Harvard Univ, TIMI Study Grp, Sch Med, Brigham & Womens Hosp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. RP Cannon, CP (reprint author), Harvard Univ, TIMI Study Grp, Sch Med, Brigham & Womens Hosp,Cardiovasc Div,Dept Med, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 20 PY 2006 VL 98 IS 10 SU S BP 1N EP 1N DI 10.1016/j.amjcard.2006.10.004 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 135LA UT WOS:000244153900001 ER PT J AU Wiviott, SD AF Wiviott, Stephen D. TI Clopidogrel response variability, resistance, or both? SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; PLATELET-AGGREGATION; ANTIPLATELET THERAPY; STENT THROMBOSIS; PRASUGREL CS-747; DRUG-RESISTANCE; UNSTABLE ANGINA; INTERINDIVIDUAL VARIABILITY AB Dual antiplatelet therapy represents an important advance for patients with established cardiovascular disease. Variable platelet response and potential resistance to therapy have emerged with aspirin and clopidogrel. There is no clear and accepted definition of clopidogrel resistance, but patients with lower responses to clopidogrel are at risk for ischemic events, particularly when they undergo percutaneous coronary intervention. Inconsistent nomenclature about this lower response has led to confusion about its potential clinical importance. The concern about nomenclature is less important than answers to key questions such as its mechanisms, how and in whom to measure platelet function, what levels of inhibition are associated with failure of therapy, what levels are adequate for improved clinical outcomes, and in what ways therapy could be altered in patients with lower responses to improve measures of platelet function and clinical outcomes. One option may be to target more aggressive intervention (higher loading and maintenance doses of clopidogrel or alternative agents) to specific patients who are at greater risk and/or least responsive to standard therapies. Clinically useful risk stratification requires an easily performed and reproducible measure of platelet, aggregation, as well as standardized definitions of response that correlate with clinical outcomes. Point-of-care assays of platelet function may ultimately improve the ability of clinicians to modify therapy on the basis of response. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div,TIMI Study Grp, Boston, MA 02115 USA. RP Wiviott, SD (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div,TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM swiviott@partners.org NR 57 TC 24 Z9 24 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 20 PY 2006 VL 98 IS 10 SU S BP 18N EP 24N DI 10.1016/j.amjcard.2006.09.010 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 135LA UT WOS:000244153900005 PM 17097413 ER PT J AU Cannon, CP McLean, DS AF Cannon, Christopher P. McLean, Dalton S. TI Critical pathways using platelet testing to potentially optimize the use of oral antiplatelet therapy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; ST-SEGMENT ELEVATION; ASSOCIATION TASK-FORCE; MYOCARDIAL-INFARCTION; RANDOMIZED-TRIAL; CLOPIDOGREL PRETREATMENT; CARDIOVASCULAR-DISEASE; P2Y(12) ANTAGONIST; ASPIRIN RESISTANCE; AMERICAN-COLLEGE AB Although monitoring anticoagulation is standard practice, monitoring antiplatelet therapy has not yet widely been adopted as a means of assessing antithrombotic response. However, bedside devices have recently become available that facilitate more rapid assessment of antithrombotic response, allowing this information to be developed into a critical pathway. Three major opportunities exist for oral antiplatelet therapy: (1) optimizing the dose of aspirin for long-term therapy; (2) optimizing the dose of clopidogrel, especially in percutaneous coronary intervention, acutely and during long-term therapy; and (3) evaluating the level of platelet inhibition before coronary artery bypass grafting or other major surgery. Several critical pathways are proposed that may assist clinicians in trying to ensure adequate platelet inhibition in these important clinical situations. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,TIMI Study Grp, Boston, MA 02115 USA. Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. RP Cannon, CP (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org NR 25 TC 6 Z9 6 U1 1 U2 2 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 NOV 20 PY 2006 VL 98 IS 10 SU S BP 33N EP 38N DI 10.1016/j.amjcard.2006.09.012 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 135LA UT WOS:000244153900007 PM 17097416 ER PT J AU Larsen, KE Benn, SC Ay, I Chian, RJ Celia, SA Remington, MP Bejarano, M Liu, MQ Ross, J Carmillo, P Sah, D Phillips, KA Sulzer, D Pepinsky, RB Fishman, PS Brown, RH Francis, JW AF Larsen, Kristin E. Benn, Susanna C. Ay, Ilknur Chian, Ru-Ju Celia, Samuel A. Remington, Mary P. Bejarano, Michelle Liu, Meiqin Ross, Joshua Carmillo, Paul Sah, Dinah Phillips, Kester A. Sulzer, David Pepinsky, R. Blake Fishman, Paul S. Brown, Robert H., Jr. Francis, Jonathan W. TI A glial cell line-derived neurotrophic factor (GDNF): tetanus toxin fragment C protein conjugate improves delivery of GDNF to spinal cord motor neurons in mice SO BRAIN RESEARCH LA English DT Article DE protein delivery; glial cell line-derived neurotrophic factor; tetanus toxin fragment C; motor neuron; neuroprotection; retrograde transport ID AMYOTROPHIC-LATERAL-SCLEROSIS; RETROGRADE AXONAL-TRANSPORT; CENTRAL-NERVOUS-SYSTEM; MIDBRAIN DOPAMINERGIC-NEURONS; PLACEBO-CONTROLLED TRIAL; GROWTH-FACTOR-I; TETANUS TOXIN; IMMUNOHISTOCHEMICAL LOCALIZATION; INDUCED DEGENERATION; PARKINSON-DISEASE AB Glial cell line-derived neurotrophic factor (GDNF) has shown robust neuroprotective and neuroreparative activities in various animal models of Parkinson's Disease or amyotrophic lateral sclerosis (ALS). The successful use of GDNF as a therapeutic in humans, however, appears to have been hindered by its poor bioavailability to target neurons in the central nervous system (CNS). To improve delivery of exogenous GDNF protein to CNS motor neurons, we employed chemical conjugation techniques to link recombinant human GDNF to the neuronal binding fragment of tetanus toxin (tetanus toxin fragment C, or TTC). The predominant species present in the purified conjugate sample, GDNF:TTC, had a molecular weight of approximately 80 kDa as determined by non-reducing SDS-PAGE. Like GDNF, addition of GDNF:TTC to culture media of neuroblastoma cells expressing GFR alpha-1/c-RET produced a dose-dependent increase in cellular phospho-c-RET levels. Treatment of cultured midbrain dopaminergic neurons with either GDNF or the conjugate similarly promoted both DA neuron survival and neurite outgrowth. However, in contrast to mice treated with GDNF by intramuscular injection, mice receiving GDNF:TTC revealed intense GDNF immunostaining associated with spinal cord motor neurons in fixed tissue sections. That GDNF:TTC provided neuroprotection of axotomized motor neurons in neonatal rats further revealed that the conjugate retained its GDNF activity in vivo. These results indicate that TTC can serve as a non-viral vehicle to substantially improve the delivery of functionally active growth factors to motor neurons in the mammalian CNS. (c) 2006 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Boston, MA 02129 USA. New York State Psychiat Inst & Hosp, Dept Neurosci, New York, NY 10032 USA. Columbia Univ, Dept Neurol, New York, NY 10032 USA. Columbia Univ, Dept Psychiat, New York, NY 10032 USA. Baltimore Vet Affairs Med Ctr, Res Serv, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. BiogenIdec Inc, Cambridge, MA 02142 USA. RP Francis, JW (reprint author), Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Bldg 114,16th St,Room 3003, Boston, MA 02129 USA. EM jwfrancis@partners.org FU NINDS NIH HHS [R01 NS038679] NR 72 TC 24 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 20 PY 2006 VL 1120 BP 1 EP 12 DI 10.1016/j.brainres.2006.08.079 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 108HZ UT WOS:000242232200001 PM 17020749 ER PT J AU Strong, CD Wertz, PW Wang, CW Yang, F Meltzer, PS Andl, T Millar, SE Ho, IC Pai, SY Segre, JA AF Strong, Cristina de Guzman Wertz, Philip W. Wang, Chenwei Yang, Fan Meltzer, Paul S. Andl, Thomas Millar, Sarah E. Ho, I-Cheng Pai, Sung-Yun Segre, Julia A. TI Lipid defect underlies selective skin barrier impairment of an epidermal-specific deletion of Gata-3 SO JOURNAL OF CELL BIOLOGY LA English DT Article ID STEM-CELL NICHE; TRANSCRIPTION FACTOR; PERMEABILITY BARRIER; ATOPIC-DERMATITIS; GAUCHER-DISEASE; REGULATES DIFFERENTIATION; ANTIMICROBIAL PEPTIDES; CAENORHABDITIS-ELEGANS; TARGETED DISRUPTION; CORNIFIED ENVELOPE AB Skin lies at the interface between the complex physiology of the body and the external environment. This essential epidermal barrier, composed of cornified proteins encased in lipids, prevents both water loss and entry of infectious or toxic substances. We uncover that the transcription factor GATA-3 is required to establish the epidermal barrier and survive in the ex utero environment. Analysis of Gata-3 mutant transcriptional profiles at three critical developmental stages identifies a specific defect in lipid biosynthesis and a delay in differentiation. Genomic analysis identifies highly conserved GATA-3 binding sites bound in vivo by GATA-3 in the first intron of the lipid acyltransferase gene AGPAT5. Skin from both Gata-3-/- and previously characterized barrier-deficient Kruppel-like factor 4-/- newborns up-regulate antimicrobial peptides, effectors of innate immunity. Comparison of these animal models illustrates how impairment of the skin barrier by two genetically distinct mechanisms leads to innate immune responses, as observed in the common human skin disorders psoriasis and atopic dermatitis. C1 NHGRI, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Iowa, Iowa City, IA 52242 USA. Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. RP Segre, JA (reprint author), NHGRI, Bethesda, MD 20892 USA. EM jsegre@nhgri.nih.gov NR 55 TC 42 Z9 43 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 20 PY 2006 VL 175 IS 4 BP 661 EP 670 DI 10.1083/jcb.200605057 PG 10 WC Cell Biology SC Cell Biology GA 109ER UT WOS:000242291200015 ER PT J AU Hanna, N Lilenbaum, R Ansari, R Lynch, T Govindan, R Janne, PA Bonomi, P AF Hanna, Nasser Lilenbaum, Rogerio Ansari, Rafat Lynch, Thomas Govindan, Ramaswamy Jaenne, Pasi A. Bonomi, Philip TI Phase II trial of cetuximab in patients with previously treated non-small-cell lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Meeting of the International-Association-for-the-Study-of-Lung-Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN SP Int Assoc Study Lung Canc ID GROWTH-FACTOR RECEPTOR; MONOCLONAL-ANTIBODY CETUXIMAB; PLATINUM-BASED CHEMOTHERAPY; TYROSINE KINASE INHIBITOR; SUPPORTIVE CARE; GEFITINIB; MULTICENTER; COMBINATION; MUTATIONS; DOCETAXEL AB Purpose To determine the efficacy of cetuximab in patients with recurrent or progressive non-small-cell lung cancer (NSCLC) after receiving at least one prior chemotherapy regimen. Patients and Methods This was an open-label, phase II study of patients with epidermal growth factor receptor (EGFR) -positive and EGFR-negative advanced NSCLC with Eastern Cooperative Oncology Group performance status 0 to 1. Patients received cetuximab 400 mg/m(2) intravenously (IV) during 120 minutes on week 1 followed by weekly doses of cetuximab 250 mg/m(2) IV during 60 minutes. A cycle was considered as 4 weeks of treatment and therapy was continued until disease progression or intolerable toxicities. The primary end point was to assess response rate. Secondary end points included an estimation of time to progression and survival. Results Patient and disease characteristics (n = 66) included EGFR-positive status (n = 60); EGFR-negative status (n = 6); number of prior regimens (one, n = 28; two, n = 27; ! three, n = 11); male (n 41); female (n = 25); adenocarcinoma (n = 36), and smoking status (never, In = 13; former, n 45; current, In = 8). Grade 3/4 toxicities included acne-like rash (6.1 %), anaphylactic reactions (1.5%), and diarrhea (1.5%). The response rate for all patients (n = 66) was 4.5% (95% Cl, 0.9% to 12.7%) and the stable disease rate was 30.3% (95% Cl, 19.6% to 42.9%). The response rate for patients with EGFR-positive tumors (n = 60) was 5% (95% Cl, 1.0% to 13.9%). The median time to progression for all patients was 2.3 months (95% Cl, 2.1 to 2.6 months) and median survival time was 8.9 months (95% Cl, 6.2 to 12.6 months). Conclusion Although the response rate with single-agent cetuximab in this heavily pretreated patient population with advanced NSCLC was only 4.5%, the disease control rates and overall survival seem comparable to that of pemetrexed, docetaxel, and erlotinib in similar groups of patients. C1 Indiana Univ, Indianapolis, IN USA. Michiana Oncol Hematol, South Bend, IN USA. Mt Sinai Canc Ctr, Miami Beach, FL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Washington Univ, St Louis, MO USA. Rush Med Coll, Chicago, IL 60612 USA. RP Hanna, N (reprint author), 535 Barnhill Dr,RT 473, Indianapolis, IN 46202 USA. EM nhanna@iupui.edu NR 26 TC 136 Z9 140 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 20 PY 2006 VL 24 IS 33 BP 5253 EP 5258 DI 10.1200/JCO.2006.08.2263 PG 6 WC Oncology SC Oncology GA 109XL UT WOS:000242342800011 PM 17114658 ER PT J AU Mack, JW Wolfe, J Grier, HE Cleary, PD Weeks, JC AF Mack, Jennifer W. Wolfe, Joanne Grier, Holcombe E. Cleary, Paul D. Weeks, Jane C. TI Communication about prognosis between parents and physicians of children with cancer: Parent preferences and the impact of prognostic information SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LIFE DECISION-MAKING; OF-LIFE; BAD-NEWS; PATIENT COMMUNICATION; PALLIATIVE CARE; END; DIAGNOSIS; ATTITUDES; HOPE; ONCOLOGISTS AB Purpose Concerns about the harms of prognostic information, including distress and loss of hope, cause some physicians to avoid frank disclosure. We aimed to determine parent preferences for prognostic information about their children with cancer and the results of receiving such information. Patients and Methods We surveyed 194 parents of children with cancer (overall response rate, 70%), treated at the Dana-Farber Cancer Institute and Children's Hospital (Boston, VIA) and the children's physicians. Our main outcome measure was parent rating of prognostic information as extremely or very upsetting. Results The majority of parents desired as much information about prognosis as possible (87%) and wanted it expressed numerically (85%). Although 36% of parents found information about prognosis to be extremely or very upsetting, those parents were more likely to want additional information about prognosis than those who were less upset (P =.01). Parents who found information upsetting were no less likely to say that knowing prognosis was important (P =.39), that knowing prognosis helped in decision making (P =.40), or that hope for a cure kept them going (P =.72). Conclusion Although many parents find prognostic information about their children with cancer upsetting, parents who are upset by prognostic information are no less likely to want it. The upsetting nature of prognostic information does not diminish parents' desire for such information, its importance to decision making, or parents' sense of hope. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Mack, JW (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM Jennifer_mack@dfci.harvard.edu FU AHRQ HHS [T32 HS00063] NR 54 TC 85 Z9 86 U1 2 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 20 PY 2006 VL 24 IS 33 BP 5265 EP 5270 DI 10.1200/JCO.2006.06.5326 PG 6 WC Oncology SC Oncology GA 109XL UT WOS:000242342800013 PM 17114660 ER PT J AU Chen, AB D'Amico, AV Neville, BA Earle, CC AF Chen, Aileen B. D'Amico, Anthony V. Neville, Bridget A. Earle, Craig C. TI Patient and treatment factors associated with complications after prostate brachytherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol ID INFLAMMATORY-BOWEL-DISEASE; BEAM RADIATION-THERAPY; QUALITY-OF-LIFE; TRANSPERINEAL BRACHYTHERAPY; RECTAL COMPLICATIONS; COMORBIDITY INDEX; SEED IMPLANTATION; ERECTILE FUNCTION; CANCER; CARCINOMA AB Purpose To assess the prevalence and predictors population-based sample of older men. of complications after prostate brachytherapy in a Patients and Methods We analyzed claims for Medicare-enrolled men older than age 65 years living in Surveillance, Epidemiology, and End Results (SEER) surveillance areas diagnosed with prostate cancer from 1991 to 1999 who underwent brachytherapy as initial treatment. Results There were 5,621 men who had brachytherapy with at least 2 years of follow-up. A complication diagnosis or invasive procedure occurred in 54.5% of men within 2 years, with 14.1 % undergoing an invasive procedure. Urinary, bowel, and erectile morbidity rates were 33.8%, 21.0%, and 16.7%, respectively, and invasive procedure rates were 10.3%, 0.8%, and 4.0%, respectively. On multivariable analysis, combined urinary diagnoses and invasive procedures (obstruction, incontinence, bleeding, fistula) were associated with older age (P<.01), nonwhite race (odds ratio [OR], 1.30; P =.01), low income (OR, 1.74; P <.01), external-beam radiotherapy (EBRT; OR, 0.85; P=.01), androgen deprivation (OR, 1.31; P <.01), later year of brachytherapy (OR, 1.03/yr; P=.02), higher Charlson comorbidity score (P <.01), and prior transurethral resection of the prostate (OR, 1.65; P <.01). Bowel morbidity (bleeding/proctitis, injury) was associated with older age (P =.04), EBRT (OR, 1.46; P <.01), later year (OR, 1.04/yr; P <.01), higher Charlson score (P =.01), and inflammatory bowel disease (OR, 2.60; P <.01). Erectile morbidity was associated with younger age (P <.01), nonwhite race (OR, 1.37; P <.01), AD (OR, 1.18; P =.04), and later year (OR, 1.08/yr; P <.01). Invasive procedure rates declined with later year of brachytherapy (OR, 0.93/yr, P <.01). Conclusion Morbidity after prostate brachytherapy was common, though invasive procedures were required infrequently. Invasive procedures for complications declined during the 1990s, suggesting technical improvement with experience. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Harvard Radiat Oncol Program, Boston, MA 02115 USA. RP Earle, CC (reprint author), Dana Farber Canc Ctr, Ctr Outcomes & Policy Res, 44 Binney St,454-STE 21-24, Boston, MA 02115 USA. EM craig_earle@dfci.harvard.edu OI Chen, Aileen/0000-0002-5385-3360 NR 37 TC 58 Z9 61 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 20 PY 2006 VL 24 IS 33 BP 5298 EP 5304 DI 10.1200/JCO.2006.07.9954 PG 7 WC Oncology SC Oncology GA 109XL UT WOS:000242342800018 PM 17114664 ER PT J AU Chien, AJ Goss, PE AF Chien, Amy Jo Goss, Paul E. TI Aromatase inhibitors and bone health in women with breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID POSTMENOPAUSAL WOMEN; MINERAL DENSITY; OVARIECTOMIZED RATS; ADJUVANT TAMOXIFEN; RANDOMIZED-TRIAL; OSTEOCLAST DIFFERENTIATION; OSTEOPROTEGERIN LIGAND; BIOCHEMICAL MARKERS; VERTEBRAL FRACTURES; AMERICAN-SOCIETY C1 Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Dept Internal Med, 55 Fruit St,Cox Bldg,Room 640, Boston, MA 02114 USA. EM ajchien@partners.org; pgoss@partners.org NR 81 TC 61 Z9 64 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 20 PY 2006 VL 24 IS 33 BP 5305 EP 5312 DI 10.1200/JCO.2006.07.5382 PG 8 WC Oncology SC Oncology GA 109XL UT WOS:000242342800019 PM 17114665 ER PT J AU Tolaney, SM Partridge, AH Sheib, RG Burstein, HJ Winer, EP AF Tolaney, Sara M. Partridge, Ann H. Sheib, Rochelle G. Burstein, Harold J. Winer, Eric P. TI Pneumocystis carinii pneumonia during dose-dense chemotherapy for breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CORTICOSTEROID-THERAPY C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Tolaney, SM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 13 TC 8 Z9 9 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 20 PY 2006 VL 24 IS 33 BP 5330 EP 5331 DI 10.1200/JCO.2006.08.1083 PG 2 WC Oncology SC Oncology GA 109XL UT WOS:000242342800023 PM 17114668 ER PT J AU Wang, Q Tang, XN Wang, LZ Yenari, MA Ying, WH Goh, BC Lee, HS Wilder-Smith, EP Wong, PT AF Wang, Qing Tang, Xian Nan Wang, Lingzhi Yenari, Midori A. Ying, Weihai Goh, Boon-Cher Lee, How-Sung Wilder-Smith, Einar P. Wong, Peter T. TI Effects of high dose of simvastatin on levels of dopamine and its reuptake in prefrontal cortex and striatum among SD rats SO NEUROSCIENCE LETTERS LA English DT Article DE hydroxymethylglutaryl-coenzyme reductase inhibitors; simvastatin; reuptake; DA; rat striatum; prefrontal cortex ID D-2 RECEPTOR EXPRESSION; PARKINSONS-DISEASE; STATINS; STRESS; BRAIN; ATORVASTATIN; RELEASE; NEUROTRANSMITTERS; NORADRENALINE; INVOLVEMENT AB Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin increased dopamine receptors in the rat prefrontal cortex [Q. Wang, W.L. Ting, H. Yang, P.T. Wong, High doses of sirrvastatin upregulate dopamine D, and D, receptor expression in the rat prefrontal cortex: possible involvement of endothelial nitric oxide synthase, Br. J. Pharmacol. 144 (2005) 933-939] and restored its downregulation in a model of Parkinson's disease (PD) [Q. Wang, P.H. Wang, C. McLachlan, P.T. Wong, Simvastatin reverses the downregulation of dopamine D1 and D2 receptor expression in the prefrontal cortex of 6-hydroxydopamine-induced Parkinsonian rats, Brain Res. 1045 (2005) 229-233]. Here we explore the effects of simvastatin treatment on tissue dopamine content and reuptake. Sprague-Dawley rats were given simvastatin (1 and 10mgkg-1 day', p.o.) for 4 weeks. Brain tissue from prefrontal cortex and striaturn were taken out for dopamine content and its reuptake. Using high-performance liquid chromatographic-mass spectrometer (HPLC-MS), simvastatin (10 mg kg(-1) day(-1)) was found to increase dopamine content by 110% in the striaturn, but decreased by 76% in the prefrontal cortex compared with the saline treated group. Dopamine (DA) reuptake was unchanged in both brain regions. These results suaaest that chronic treatment with hiah dose of simvastatin may affect DA tissue level in prefrontal cortex and striaturn without changing on DA reuptake. This may have important clinical implications in psychiatric and striatal doparninergic disorders. (c) 2006 Elsevier Ireland Ltd. All ri-hts reserved. C1 Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore 117597, Singapore. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Natl Univ Singapore Hosp, Yong Loo Lin Sch Med, Div Neurol, Singapore 119074, Singapore. RP Wang, Q (reprint author), Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore 117597, Singapore. EM denniswq@yahoo.com OI Wilder-Smith, Einar/0000-0003-3402-7503 NR 38 TC 14 Z9 14 U1 0 U2 2 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 NOV 20 PY 2006 VL 408 IS 3 BP 189 EP 193 DI 10.1016/j.neulet.2006.09.009 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 104LB UT WOS:000241958800007 PM 16996211 ER PT J AU Cannon, CP Curtis, SP FitzGerald, GA Krum, H Kaur, A Bolognese, JA Reicin, AS Bombardier, C Weinblatt, ME van der Heijde, D Erdmann, E Laine, L AF Cannon, Christopher P. Curtis, Sean P. FitzGerald, Garret A. Krum, Henry Kaur, Amarjot Bolognese, James A. Reicin, Alise S. Bombardier, Claire Weinblatt, Michael E. van der Heijde, Desiree Erdmann, Erland Laine, Loren CA MEDAL Steering Comm TI Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison SO LANCET LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COX-2 INHIBITORS; GASTRODUODENAL ULCERS; MYOCARDIAL-INFARCTION; CLINICAL-TRIAL; DOUBLE-BLIND; PREVENTION; RISK; CYCLOOXYGENASE; VALDECOXIB AB Background Cyclo-oxygenase-2 (COX-2) selective inhibitors have been associated with an increased risk of thrombotic cardiovascular events in placebo-controlled trials, but no clinical trial has been reported with the primary aim of assessing relative cardiovascular risk of these drugs compared with traditional non-steroidal anti-inflammatory drugs (NSAIDs). The MEDAL programme was designed to provide a precise estimate of thrombotic cardiovascular events with the COX-2 selective inhibitor etoricoxib versus the traditional NSAID diclofenac. Methods We designed a prespecified pooled analysis of data from three trials in which patients with osteoarthritis or rheumatoid arthritis were randomly assigned to etoricoxib (60 mg or 90 mg daily) or diclofenac (150 mg daily). The primary hypothesis stated that etoricoxib is not inferior to diclofenac, defined as an upper boundary of less than 1.30 for the 95% CI of the hazard ratio for thrombotic cardiovascular events in the per-protocol analysis. Intention-to-treat analyses were also done to assess consistency of results. These trials are registered at http://www. clinicaltrials.gov with the numbers NCT00092703, NCT00092742, and NCT00250445. Findings 34701 patients (24913 with osteoarthritis and 9787 with rheumatoid arthritis) were enrolled. Average treatment duration was 18 months (SD 11.8). 320 patients in the etoricoxib group and 323 in the diclofenac group had thrombotic cardiovascular events, yielding event rates of 1.24 and 1.30 per 100 patient-years and a hazard ratio of 0.95 (95% CI 0.81-1.11) for etoricoxib compared with diclofenac. Rates of upper gastrointestinal clinical events (perforation, bleeding, obstruction, ulcer) were lower with etoricoxib than with diclofenac (0.67 vs 0.97 per 100 patient-years; hazard ratio 0.69 [0.57-0.83]), but the rates of complicated upper gastrointestinal events were similar for etoricoxib (0.30) and diclofenac (0.32). Interpretation Rates of thrombotic cardiovascular events in patients with arthritis on etoricoxib are similar to those in patients on diclofenac with long-term use of these drugs. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Dept Med, Los Angeles, CA USA. Univ Penn, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. Monash Univ, Dept Med, Melbourne, Vic 3004, Australia. Univ Toronto, Dept Med, Div Rheumatol, Toronto, ON, Canada. Univ Hlth Network, Toronto, ON, Canada. Univ Hosp Maastricht, Dept Internal Med, Div Rheumatol, Maastricht, Netherlands. Univ Cologne, Med Clin 3, Cologne, Germany. Merck Res Labs, Rahway, NJ USA. RP Cannon, CP (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA. EM cpcannon@partners.org RI FitzGerald, Garret/A-4222-2010 NR 53 TC 247 Z9 261 U1 0 U2 6 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 18 PY 2006 VL 368 IS 9549 BP 1771 EP 1781 DI 10.1016/S0140-6736(06)69666-9 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 108FJ UT WOS:000242225400030 PM 17113426 ER PT J AU Hartong, DT Berson, EL Dryja, TP AF Hartong, Dyonne T. Berson, Eliot L. Dryja, Thaddeus P. TI Retinitis pigmentosa SO LANCET LA English DT Review ID BARDET-BIEDL-SYNDROME; CGMP-GATED CHANNEL; RETINALDEHYDE-BINDING PROTEIN; PHOTORECEPTOR CELL-DEATH; MEDIATED GENE-TRANSFER; SYNDROME TYPE-II; ABNORMAL FUNDUS AUTOFLUORESCENCE; LEBER CONGENITAL AMAUROSIS; KEARNS-SAYRE SYNDROME; USHER-SYNDROME TYPE-1 AB Hereditary degenerations of the human retina are genetically heterogeneous, with well over 100 genes implicated so far. This Seminar focuses on the subset of diseases called retinitis pigmentosa, in which patients typically lose night vision in adolescence, side vision in young adulthood, and central vision in later life because of progressive loss of rod and cone photoreceptor cells. Measures of retinal function, such as the electroretinogram, show that photoreceptor function is diminished generally many years before symptomic night blindness, visual-field scotomas, or decreased visual acuity arise. More than 45 genes for retinitis pigmentosa have been identified. These genes account for only about 60% of all patients; the remainder have defects in as yet unidentified genes. Findings of controlled trials indicate that nutritional interventions, including vitamin A palmitate and omega-3-rich fish, slow progression of disease in many patients. Imminent treatments for retinitis pigmentosa are greatly anticipated, especially for genetically defined subsets of patients, because of newly identified genes, growing knowledge of affected biochemical pathways, and development of animal models. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Dryja, TP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, 243 Charles St, Boston, MA 02114 USA. EM thaddeus_dryja@meei.harvard.edu FU NEI NIH HHS [EY00169, EY08683] NR 262 TC 1040 Z9 1074 U1 24 U2 171 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 18 PY 2006 VL 368 IS 9549 BP 1795 EP 1809 DI 10.1016/S0140-6736(06)69740-7 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 108FJ UT WOS:000242225400034 PM 17113430 ER PT J AU Margolis, SS Perry, JA Forester, CM Nutt, LK Guo, YX Jardim, MJ Thomenius, MJ Freel, CD Darbandi, R Ahn, JH Arroyo, JD Wang, XF Shenolikar, S Nairn, AC Dunphy, WG Hahn, WC Virshup, DM Kornbluth, S AF Margolis, Seth S. Perry, Jennifer A. Forester, Craig M. Nutt, Leta K. Guo, Yanxiang Jardim, Melanie J. Thomenius, Michael J. Freel, Christopher D. Darbandi, Rashid Ahn, Jung-Hyuck Arroyo, Jason D. Wang, Xiao-Fan Shenolikar, Shirish Nairn, Angus C. Dunphy, William G. Hahn, William C. Virshup, David M. Kornbluth, Sally TI Role for the PP2A/B56 delta phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis SO CELL LA English DT Article ID PROTEIN PHOSPHATASE-2A; CHECKPOINT CONTROL; CELL-GROWTH; IN-VITRO; PHOSPHORYLATION; KINASE; 2A; SUBUNIT; BINDING; CHK1 AB DNA-responsive checkpoints prevent cell-cycle progression following DNA damage or replication inhibition. The mitotic activator Cdc25 is suppressed by checkpoints through inhibitory phosphorylation at Ser287 (Xenopus numbering) and docking of 14-3-3. Ser287 phosphorylation is a major locus of G2/M checkpoint control, although several checkpoint-independent kinases can phosphorylate this site. We reported previously that mitotic entry requires 14-3-3 removal and Ser287 dephosphorylation. We show here that DNA-responsive checkpoints also activate PP2A/B56 delta phosphatase complexes to dephosphorylate Cdc25 at a site distinct from Ser287 (T138), the phosphorylation of which is required for 14-3-3 release. However, phosphorylation of T138 is not sufficient for 14-3-3 release from Cdc25. Our data suggest that creation of a 14-3-3 "sink," consisting of phosphorylated 14-3-3 binding intermediate filament proteins, including keratins, coupled with reduced Cdc25-14-3-3 affinity, contribute to Cdc25 activation. These observations identify PP2A/B56 delta as a central checkpoint effector and suggest a mechanism for controlling 14-3-3 interactions to promote mitosis. C1 Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. Univ Utah, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT 84112 USA. Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10021 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Pfizer Global Res & Dev, Ann Arbor, MI 48105 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. MIT, Boston, MA 02115 USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. RP Kornbluth, S (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. EM kornb001@mc.duke.edu RI Virshup, David/C-1449-2009; OI Virshup, David/0000-0001-6976-850X; Arroyo, Jason/0000-0002-5674-6739; Nairn, Angus/0000-0002-7075-0195 FU NCI NIH HHS [P01 CA050661, P01 CA050661-190009, P01 CA073992, P01 CA50661]; NIDA NIH HHS [P01 DA010044]; NIGMS NIH HHS [R01 GM 070891, R01 GM 067225, R01 GM067225, R01 GM067225-03] NR 37 TC 121 Z9 125 U1 2 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 17 PY 2006 VL 127 IS 4 BP 759 EP 773 DI 10.1016/j.cell.2006.10.035 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 109TB UT WOS:000242330600022 PM 17110335 ER PT J AU Martin, BK Breitner, JCS Evans, D Lyketsos, CG Meinert, CL AF Martin, Barbara K. Breitner, John C. S. Evans, Denis Lyketsos, Constantine G. Meinert, Curtis L. CA ADAPT Res Grp TI Cardiovascular and cerebrovascular events in the randomized, controlled Alzheimer's disease Anti-inflammatory Prevention Trial (ADAPT) SO PLOS CLINICAL TRIALS LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; RHEUMATOID-ARTHRITIS; CYCLO-OXYGENASE-2 INHIBITORS; SELECTIVE INHIBITORS; RISK; DRUGS; CELECOXIB; CYCLOOXYGENASE-2; ROFECOXIB; NAPROXEN AB Objectives: The Alzheimer's Disease Anti-inflammatory Prevention Trial ( ADAPT) was designed to evaluate the conventional NSAID naproxen sodium and the selective COX-2 inhibitor celecoxib for primary prevention of Alzheimer's dementia ( AD). On 17 December 2004, after the Adenoma Prevention with Celecoxib (APC) trial reported increased cardiovascular risks with celecoxib, the ADAPT Steering Committee suspended treatment and enrollment. This paper reports on cardiovascular and cerebrovascular events in ADAPT. Design: ADAPT is a randomized, placebo-controlled, parallel chemoprevention trial with 1 - 46 mo of follow-up. Setting: The trial was conducted at six field sites in the United States: Baltimore, Maryland; Boston, Massachusetts; Rochester, New York; Seattle, Washington; Sun City, Arizona; and Tampa, Florida. Participants: The 2,528 participants were aged 70 y and older with a family history of AD. Interventions: Study treatments were celecoxib ( 200 mg b. i. d.), naproxen sodium ( 220 mg b. i. d.), and placebo. Outcome measures: Outcome measures were deaths, along with nonfatal myocardial infarction (MI), stroke, congestive heart failure (CHF), transient ischemic attack (TIA), and antihypertensive treatment recorded from structured interviews at scheduled intervals. Cox proportional hazards regression was used to analyze these events individually and in several composites. Results: Counts ( with 3-y incidence) of participants who experienced cardiovascular or cerebrovascular death, MI, stroke, CHF, or TIA in the celecoxib-, naproxen-, and placebo-treated groups were 28/717 (5.54%), 40/713 (8.25%), and 37/1070 (5.68%), respectively. This yielded a hazard ratio (95% confidence interval [ CI]) for celecoxib of 1.10 (0.67 - 1.79) and for naproxen of 1.63 (1.04 - 2.55). Antihypertensive treatment was initiated in 160/440 (47.43%), 147/427 (45.00%), and 164/644 (34.08%). This yielded hazard ratios (CIs) of 1.56 for celecoxib (1.26 - 1.94) and 1.40 for naproxen (1.12 - 1.75). Conclusions: For celecoxib, ADAPT data do not show the same level of risk as those of the APC trial. The data for naproxen, although not definitive, are suggestive of increased cardiovascular and cerebrovascular risk. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA. RP Martin, BK (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. EM bmartin@jhsph.edu NR 30 TC 6 Z9 6 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1555-5887 J9 PLOS CLIN TRIALS JI PLos Clin. Trials PD NOV 17 PY 2006 VL 1 IS 7 AR e33 DI 10.1371/journal.pctr.0010033 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 150ST UT WOS:000245239000001 ER PT J AU Mora, JR Iwata, M Eksteen, B Song, SY Junt, T Senman, B Otipoby, KL Yokota, A Takeuchi, H Ricciardi-Castagnoli, P Rajewsky, K Adams, DH von Andrian, UH AF Mora, J. Rodrigo Iwata, Makoto Eksteen, Bertus Song, Si-Young Junt, Tobias Senman, Balimkiz Otipoby, Kevin L. Yokota, Aya Takeuchi, Hajime Ricciardi-Castagnoli, Paola Rajewsky, Klaus Adams, David H. von Andrian, Ulrich H. TI Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells SO SCIENCE LA English DT Article ID A-DEFICIENT RATS; T-CELLS; IMMUNOGLOBULIN-A; IMMUNE-SYSTEM; RECEPTOR; INTERLEUKIN-6; RESPONSES; LYMPHOCYTES; SPECIFICITY; EXPRESSION AB Normal intestinal mucosa contains abundant immunoglobulin A (IgA) - secreting cells, which are generated from B cells in gut-associated lymphoid tissues (GALT). We show that dendritic cells ( DC) from GALT induce T cell - independent expression of IgA and gut-homing receptors on B cells. GALT-DC-derived retinoic acid (RA) alone conferred gut tropism but could not promote IgA secretion. However, RA potently synergized with GALT-DC-derived interleukin-6 (IL-6) or IL-5 to induce IgA secretion. Consequently, mice deficient in the RA precursor vitamin A lacked IgA-secreting cells in the small intestine. Thus, GALT-DC shape mucosal immunity by modulating B cell migration and effector activity through synergistically acting mediators. C1 Ctr Blood Res, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Tokushima Bunri Univ, Fac Pharmaceut Sci, Sanuki, Kagawa 7692193, Japan. Univ Birmingham, MRC, Ctr Immune Regulat, Birmingham B15 2TT, W Midlands, England. Univ Milano Bicocca, Dept Biosci & Biotechnol, Milan, Italy. RP Mora, JR (reprint author), Ctr Blood Res, Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM mora@cbr.med.harvard.edu; uva@cbr.med.harvard.edu RI Adams, David/C-9092-2009; Castagnoli, Paola/E-8288-2010; von Andrian, Ulrich/A-5775-2008; OI ADAMS, David/0000-0001-6776-0336 FU Medical Research Council [G0601816]; NHLBI NIH HHS [HL54936, HL56949, HL62524]; NIAID NIH HHS [AI-061663, R37 AI054636] NR 28 TC 512 Z9 540 U1 2 U2 24 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 NOV 17 PY 2006 VL 314 IS 5802 BP 1157 EP 1160 DI 10.1126/science.1132742 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 105PW UT WOS:000242045800048 PM 17110582 ER PT J AU Yoshimoto, G Miyamoto, T Iino, T Kikushige, S Niiro, H Iwasaki, H Harada, M Akashi, K AF Yoshimoto, Goichi Miyamoto, Toshihiro Iino, Tadafumi Kikushige, Shikane Niiro, Hiroaki Iwasaki, Hiromi Harada, Mine Akashi, Koichi TI Anti-apoptotic MCL-1 plays a critical role in maintenance of normal and malignant human hematopoietic stem cells through FLT3 signaling. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Kyushu Univ, Grad Sch Med Sci, Dept Med & Biosystem Sci, Fukuoka 812, Japan. Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 812, Japan. Harvard Med Sch, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 11 BP 8A EP 8A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000012 ER PT J AU Richardson, P Soiffer, RJ Antin, JH Jin, Z Kurtzberg, J Martin, PL Steinbach, G Murray, KF Vogelsang, GB Chen, A Krishnan, A Kernan, NA Avigan, D Spitzer, TR Warren, D Revta, C Wei, LJ Iacobelli, M McDonald, GB Guinan, EC AF Richardson, Paul Soiffer, R. J. Antin, J. H. Jin, Z. Kurtzberg, J. Martin, P. L. Steinbach, G. Murray, K. F. Vogelsang, G. B. Chen, A. Krishnan, A. Kernan, N. A. Avigan, D. Spitzer, T. R. Warren, D. Revta, C. Wei, L. J. Iacobelli, M. McDonald, G. B. Guinan, E. C. TI Defibrotide (DF) for the treatment of severe veno-occlusive disease (sVOD) and multi-organ failure (MOF) post SCT: Final results of a multi-center, randomized, dose-finding trial. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Childrens Hosp, Dana Farber Canc Inst, Harvard Sch Publ Hlth, BIDMC, Boston, MA 02115 USA. Columbia Univ, New York, NY 10027 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Johns Hopkins Univ, Johns Hopkins Oncol Ctr, Baltimore, MD 21218 USA. City Hope Canc Ctr, Duarte, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY USA. NR 0 TC 2 Z9 2 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 NOV 16 PY 2006 VL 108 IS 11 MA 43 BP 17A EP 18A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440000044 ER PT J AU Sarantopoulos, S Stevenson, KE Kim, HT Bhuiya, NS Cutler, CS Soiffer, RJ Antin, JH Ritz, J AF Sarantopoulos, Stefanie Stevenson, Kristen E. Kim, Haesook T. Bhuiya, Nazmim S. Cutler, Corey S. Soiffer, Robert J. Antin, Joseph H. Ritz, Jerome TI BAFF/Blys levels correlate with disease activity and alter peripheral B cell subsets in patients with chronic GVHD. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 41 BP 17A EP 17A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000042 ER PT J AU Lee, S Joffe, S Artz, A Champlin, R Davies, S Jagasia, M Keman, NA Soiffer, RJ Eapen, M AF Lee, Stephanie Joffe, Steven Artz, Andrew Champlin, Richard Davies, Stella Jagasia, Madan Keman, Nancy A. Soiffer, Robert J. Eapen, Mary TI Differences in medical decision making in adult and pediatric hematopoietic stem cell transplantation (HCT). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA USA. Dana Farber Canc Inst, Boston, MA USA. Univ Chicago, Chicago, IL 60637 USA. MD Anderson Canc Ctr, Houston, TX USA. Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. Vanderbilt Univ, Med Ctr, Nashville, TN 37240 USA. Mem Sloan Kettering Canc Ctr, New York, NY USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 74 BP 26A EP 26A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000075 ER PT J AU Mukherjee, S Raje, N Patel, C Vallet, S Aronson, J Chhetri, S Mitsiades, C Hideshima, T Anderson, KC Scadden, DT AF Mukherjee, Siddhartha Raje, Noopur Patel, Chirayu Vallet, Sonia Aronson, Joshua Chhetri, Shweta Mitsiades, Constantine Hideshima, Teru Anderson, Kenneth C. Scadden, David T. TI Bortezomib induces proliferation of mesenchymal progenitor cells and promotes differentiation towards osteoblastic lineage. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Ctr Regenerat Med Technologies, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 3 Z9 4 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 NOV 16 PY 2006 VL 108 IS 11 MA 88 BP 30A EP 30A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000089 ER PT J AU Morel, P Duhamel, A Gobbi, P Dimopoulos, M Dhodapkar, M Mccoy, J Ocio, E Garcia-Sanz, R Treon, S Leblond, V Kyle, R Barlogie, B Merlini, G AF Morel, Pierre Duhamel, Alain Gobbi, Paolo Dimopoulos, Meletios Dhodapkar, Madhav Mccoy, Jason Ocio, Enrique Garcia-Sanz, Ramon Treon, Steven Leblond, Veronique Kyle, Robert Barlogie, Bart Merlini, Giampaolo TI International prognostic scoring system (IPSS) for waldenstrom's macroglobulinemia (WM). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Hop Schaffner, Lens, France. Fac Med, CERIM, Lille, France. IRCCS, Policlin San Matteo, Pavia, Italy. Univ Athens, Sch Med, GR-10679 Athens, Greece. Spanish Grp Study Waldenstrom Macroglobulinaemia, Salamanca, Spain. Dana Farber Canc Inst, Boston, MA USA. Hop Pitie, Paris, France. Mayo Clin, Rochester, MN USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. RI Merlini, Giampaolo/A-3817-2008; Duhamel, Alain/B-8624-2011; Duhamel, Alain/A-4899-2013 OI Merlini, Giampaolo/0000-0001-7680-3254; NR 0 TC 8 Z9 9 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 NOV 16 PY 2006 VL 108 IS 11 MA 127 BP 42A EP 42A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000128 ER PT J AU Van Ness, BG Crowley, JC Ramos, C Grindle, SM Hoering, A Haessler, J Jacobus, S Durie, BG Katz, M Rajkumar, VS Barlogie, B Johnson, DC Morgan, GJ AF Van Ness, Brian G. Crowley, John C. Ramos, Christine Grindle, Suzanne M. Hoering, Antje Haessler, Jeff Jacobus, Susanna Durie, Brian G. Katz, Michael Rajkumar, Vincent S. Barlogie, Bart Johnson, David C. Morgan, Gareth J. TI SNP associations with event free survival in myeloma from two phase III clinical trials using the bank on a cure chip. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Minnesota, Ctr Canc, Minneapolis, MN 02115 USA. Canc Res & Biostat, Seattle, WA 90048 USA. Dana Farber Canc Inst, Boston, MA USA. Cedars Sinai Med Ctr, Inst Canc Res, Los Angeles, CA 72205 USA. Mayo Clin, Rochester SW3 6JB, MN USA. Univ Arkansas Med Sci, Little Rock, AR USA. Inst Canc Res, London, England. RI Johnson, David/A-3907-2011 OI Johnson, David/0000-0003-0887-3343 NR 0 TC 1 Z9 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 131 BP 43A EP 43A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000132 ER PT J AU Stone, RM Fischer, T Paquette, R Schiller, G Schiffer, CA Ehninger, G Cortes, J Kantarjian, H DeAngelo, DA Massimini, G Li, XM Phillips, P Giles, F AF Stone, Richard M. Fischer, Thomas Paquette, Ronald Schiller, Gary Schiffer, Charles A. Ehninger, Gerhard Cortes, Jorge Kantarjian, Hagop DeAngelo, Daniel A. Massimini, Georgio Li, Xiaoming Phillips, Penny Giles, Francis TI Phase IB study of PKC412, an oral FLT3 kinase inhibitor, in sequential and simultaneous combinations with daunorubicin and cytarabine (DA) induction and high-dose cytarabine consolidation in newly diagnosed adult patients (pts) with acute myeloid leukemia (AML) under age 61. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Mainz Klinikum, Mainz, Germany. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Karmanos Canc Inst, Detroit, MI USA. Univ Klinikum Carl Gustav Carus, Dresden, Germany. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Novartis Oncol, E Hanover, NJ USA. Novartis Oncol, Basel, Switzerland. NR 0 TC 15 Z9 15 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 NOV 16 PY 2006 VL 108 IS 11 MA 157 BP 50A EP 51A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440000158 ER PT J AU DeAngelo, DJ Amrein, PC Kovacsovics, TJ Klisovic, RB Powell, BL Cooper, M Webb, IJ Stone, RM AF DeAngelo, Daniel J. Amrein, Philip C. Kovacsovics, Tibor J. Klisovic, Rebecca B. Powell, Bayard L. Cooper, Michael Webb, Iain J. Stone, Richard M. TI Phase 1/2 study of tandutinib (MLN518) plus standard induction chemotherapy in newly diagnosed acute myelogenous leukemia (AML). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97201 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. RI Klisovic, Rebecca/E-3401-2011 NR 0 TC 9 Z9 11 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 NOV 16 PY 2006 VL 108 IS 11 MA 158 BP 51A EP 51A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000159 ER PT J AU Motto, DG Zhu, GJ Wagner, DD Ginsburg, D AF Motto, David G. Zhu, Guojing Wagner, Denisa D. Ginsburg, David TI A threshold level of von Willebrand Factor is required for disease pathogenesis in a mouse model of TTP. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Iowa, Iowa City, IA USA. Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 177 BP 56A EP 57A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440000178 ER PT J AU Gazda, H Grabowska, A Long, L Latawiec, E Schneider, H Lipton, J Machos, A Atsidaftos, E Ball, S Orfali, K Niewiadomska, E Da Costa, L Tchernia, GJ Niemeyer, CM Meerpohl, J Stahl, J Schratt, G Glader, B Nathan, DG Beggs, AH Sieff, CA AF Gazda, Hanna Grabowska, Agnieszka Long, Lilia Latawiec, Elzbieta Schneider, Hal Lipton, Jeffrey Machos, Adrianna Atsidaftos, Eva Ball, Sarah Orfali, Karen Niewiadomska, Edyta Da Costa, Lydie Tchernia, Gilbert Jean Niemeyer, Charlotte Marie Meerpohl, Joerg Stahl, Joachim Schratt, Gerhard Glader, Bertil Nathan, David G. Beggs, Alan H. Sieff, Colin A. TI Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Childrens Hosp, Div Pediat Hematol, Div Genet, Program Genom, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Meerpohl, Joerg/J-4224-2013 OI Meerpohl, Joerg/0000-0002-1333-5403 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 181 BP 58A EP 58A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000182 ER PT J AU Lin, Y Means, T Alyea, EP Canning, CM Soiffer, RJ Ritz, J Wu, CJ AF Lin, Yun Means, Terry Alyea, Edwin P. Canning, Christine M. Soiffer, Robert J. Ritz, Jerome Wu, Catherine J. TI Effective graft-versus-leukemia responses are associated with the presence of nucleic acid-immunoglobulin complexes that stimulate TLR8 and TLR9. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 188 BP 60A EP 60A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000189 ER PT J AU Shao, CH Head, JF Seaton, BA Gilbert, GE AF Shao, Chenghua Head, James F. Seaton, Barbara A. Gilbert, Gary E. TI Crystal structure of the C2 domain of lactadherin and computational docking of phosphatidyl-L-serine. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Boston Univ, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 195 BP 62A EP 62A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000196 ER PT J AU Goerge, T Barg, A Schnaeker, EM Luger, TA Steinhoff, M Schneider, SW AF Goerge, Tobias Barg, Alexej Schnaeker, Eva-Maria Luger, Thomas A. Steinhoff, Martin Schneider, Stefan W. TI Tumor-endothelial MMP1/PAR1 crosstalk promotes formation of ULVWF-Strings on human endothelium. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Munster, Dept Dermatol, Munster, NRW, Germany. Harvard Med Sch, CBR Inst, Dept Pathol, Boston, MA USA. RI Steinhoff, Martin/F-6312-2013 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3945 BP 63B EP 63B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440400226 ER PT J AU Andersson, KL Warth, JA AF Andersson, Karin L. Warth, James A. TI Spontaneous resolution of ITP in two elderly patients. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Faulkner Hosp, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3959 BP 67B EP 67B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440400240 ER PT J AU Watanabe, N Han, J Lim, CJ Soriani, A Puzon-McLaughlin, W LaFuente, EM Boussiotis, VA Ginsberg, MH Shattil, SJ AF Watanabe, Naohide Han, Jaewon Lim, C. James Soriani, Alessandra Puzon-McLaughlin, Wilma LaFuente, Esther M. Boussiotis, Vassiliki A. Ginsberg, Mark H. Shattil, Sanford J. TI On the yellow brick road to platelet GP IIb-IIIa (Integrin alpha IIb beta 3) activation. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Calif San Diego, La Jolla, CA 92093 USA. Massachusetts Gen Hosp, Hematol Oncol & Transplantat Biol Res Ctr, Boston, MA 02114 USA. RI Lafuente, Esther M/K-5684-2014; Lim, Chinten James/G-3777-2013 OI Lafuente, Esther M/0000-0001-8466-1022; Lim, Chinten James/0000-0001-6381-7585 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 211 BP 67A EP 67A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000212 ER PT J AU Chen, L Juszczynski, P Hitoshi, Y Chen, W Kutok, JL Shipp, MA AF Chen, Linfeng Juszczynski, Przemyslaw Hitoshi, Yasumichi Chen, Wen Kutok, Jeffery L. Shipp, Margaret A. TI Tonic B-cell receptor signaling promotes the survival of diffuse large B-cell lymphomas: Identification of SYK as a rational treatment target. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Rigel Inc, San Francisco, CA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 226 BP 71A EP 71A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000227 ER PT J AU Hunter, Z Leleu, X Hatjiharissi, E Santos, D Xu, L Ho, A Bakthavachalam, V Moreau, AS O'Connor, K Soumerai, J Patterson, C Ghobrial, I Hamilton, S Verselis, S Fox, E Treon, S AF Hunter, Zachary Leleu, Xavier Hatjiharissi, Evdoxia Santos, Daniel Xu, Lian Ho, Alan Bakthavachalam, Vinod Moreau, Anne-Sophie O'Connor, Kelly Soumerai, Jacob Patterson, Christopher Ghobrial, Irene Hamilton, Susanna Verselis, Sigitas Fox, Edward Treon, Steven TI IgA and IgG hypogammaglobulinemia are associated with mutations in the APRIL/BLYS receptor TACI in Waldenstrom's macroglobulinemia (WM). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. Dana Farber Canc Inst, Mol Diagnost Core, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 1 Z9 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 228 BP 71A EP 71A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000229 ER PT J AU Parekh, S Polo, J Juszczynski, P Lev, P Ranuncolo, S Cattoretti, G Shaknovich, R Shipp, M Melnick, A AF Parekh, Samir Polo, Jose Juszczynski, Przemyslaw Lev, Paola Ranuncolo, Stella Cattoretti, Georgio Shaknovich, Rita Shipp, Margaret Melnick, Ari TI BCL6 programs lymphoma cells for survival and differentiation through distinct biochemical mechanisms, both of which can be therapeutically targeted. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Albert Einstein Coll Med, Dept Mol Biol, Bronx, NY 10467 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Columbia Univ, Inst Canc Genet, New York, NY USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 225 BP 71A EP 71A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000226 ER PT J AU Mufti, G Bagg, A Hasserjian, R Bain, B Kuter, D Dreiling, L Nichol, J AF Mufti, Ghulam Bagg, Adam Hasserjian, Robert Bain, Barbara Kuter, David Dreiling, Lyndah Nichol, Janet TI Bone marrow reticulin in patients with immune thrombocytopenic purpura. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Kings Coll Hosp London, Dept Haematol Med, London, England. Hosp Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. St Marys Hosp, London, England. Clin Dev, Amagen Inc, Thousand Oaks, CA USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 3982 BP 73B EP 73B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440400263 ER PT J AU Chai, L Cui, W Ma, Y Yang, JC Kong, N Kao, G Silberstein, L AF Chai, Li Cui, Wei Ma, Yupo Yang, Jianchang Kong, Nikki Kao, Grace Silberstein, Leslie TI Constitutive expression of SALL4B in mice confers properties of leukemic stem cells to committed hematopoietic progenitors. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Brigham & Womens Hosp, Childrens Hosp, Dana Farber Canc Inst, Joint Program Transfus Med, Boston, MA 02115 USA. Nevada Canc Inst, Div Lab Med, Las Vegas, NV USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 240 BP 75A EP 75A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000241 ER PT J AU Runnels, JM Pitsillides, C Spencer, JA Fujisaki, J Ngo, H Hatjiharissi, E Leleu, X Moreau, AS Jia, XY Hideshima, T Munshi, N Anderson, KC Lin, CP Ghobrial, I AF Runnels, Judith M. Pitsillides, Costas Spencer, Joel A. Fujisaki, Joji Ngo, Hai Hatjiharissi, Evdoxia Leleu, Xavier Moreau, Anne-Sophie Jia, Xiaoying Hideshima, Teru Munshi, Nikhil Anderson, Kenneth C. Lin, Charles P. Ghobrial, IreneM. TI A novel real-time in vivo homing model of multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Adv Microscopy Core, Boston, MA 02114 USA. RI Spencer, Joel/A-4590-2013 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 242 BP 76A EP 76A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000243 ER PT J AU Armand, P Kim, HT DeAngelo, DJ Ho, VT Cutler, CS Stone, RM Ritz, J Alyea, EP Antin, JH Soiffer, RJ AF Armand, Philippe Kim, Haesook T. DeAngelo, Daniel J. Ho, Vincent T. Cutler, Corey S. Stone, Richard M. Ritz, Jerome Alyea, Edwin P. Antin, Joseph H. Soiffer, Robert J. TI Impact of cytogenetics and prior therapy on outcome of AML and MDS after allogeneic transplantation. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 259 BP 80A EP 81A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440000260 ER PT J AU Fukata, M Ishikawa, F Shimazu, H Nakamura, R Shimoda, K Akashi, K Leonard, SD Harada, M AF Fukata, Mitsuhiro Ishikawa, Fumihiko Shimazu, Hideki Nakamura, Ryu Shimoda, Kazuya Akashi, Koichi Leonard, Shultz D. Harada, Mine TI Highly purified hematopoietic stem cell can generate cardiomyocytes via myeloid progenitors through cell fusion. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Kyushu Univ, Grad Sch Med Sci, Dept Med & Biosystemic Sci, Fukuoka, Japan. Res Unit Human Disease Model, Yokohama, Kanagawa, Japan. Carl Zeiss Japan, Tokyo, Japan. Kyushu Univ Hosp, Ctr Cell & Mol Med, Fukuoka 812, Japan. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Jackson Lab, Bar Harbor, ME 04609 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 279 BP 86A EP 86A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000280 ER PT J AU Savage, KJ Vose, JM Harris, NL AF Savage, Kerry J. Vose, Julie M. Harris, Nancy Lee CA International T-Cell Lymphoma Proj TI Survival analysis of anaplastic large cell lymphoma, systemic and cutaneous-types: Report from the international T-cell lymphoma project. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Nebraska Med Ctr, Omaha, NE USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 293 BP 90A EP 90A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000294 ER PT J AU Rosovsky, RP Wen, P Kesari, S Van Cott, EM Kuter, DJ AF Rosovsky, Rachel P. Wen, Patrick Kesari, Samosh Van Cott, Elizabeth M. Kuter, David J. TI The identification of hypercoagulable markers in patients with malignant gliomas and venous thromboembolism. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 1 Z9 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 4097 BP 104B EP 104B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440400378 ER PT J AU Pikman, Y Levine, RL Lee, BH Tothova, Z Mercher, T Wadleigh, M Lee, SJ Gilliland, DG Wernig, G AF Pikman, Y. Levine, R. L. Lee, B. H. Tothova, Z. Mercher, T. Wadleigh, M. Lee, S. J. Gilliland, D. G. Wernig, G. TI Comparative analysis of the constitutively active MPLW515L and JAK2V617F alleles in a murine bone marrow transplant model of myeloproliferative disease. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Brigham & Womens Hosp, Harvard Med Sch, Boston, MA 02115 USA. Dana Farber Canc Inst, Havard Med Sch, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RI Mercher, Thomas/J-2446-2014 OI Mercher, Thomas/0000-0003-1552-087X NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 378 BP 116A EP 116A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000379 ER PT J AU Graham, GJ Tanaka, E De Grand, AM Laurence, RG Hoshino, K Hajjar, RJ Frangioni, JV Flaumenhaft, R AF Graham, Gwenda J. Tanaka, Eiichi De Grand, Alec M. Laurence, Rita G. Hoshino, Kozo Hajjar, Roger J. Frangioni, John V. Flaumenhaft, Robert TI Real-time imaging of platelet-rich thrombi in thick-walled blood vessels using near-infrared fluorescence light. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Beth Israel Deaconess Med Ctr, Div Hemostasis & Thrombosis, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 NOV 16 PY 2006 VL 108 IS 11 MA 383 BP 118A EP 118A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000384 ER PT J AU Italiano, J Richardson, JL Folkman, J Klement, G AF Italiano, Joseph Richardson, Jennifer L. Folkman, Judah Klement, Giannoula TI Blood platelets organize pro- and anti-angiogenic factors into separate, distinct alpha granules: Implications for the regulation of angiogenesis. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 3 Z9 4 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 NOV 16 PY 2006 VL 108 IS 11 MA 393 BP 120A EP 121A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440000394 ER PT J AU Richardson, P Chanan-Khan, AA Lonial, S Krishnan, A Alsina, M Carroll, M Adler, K Cropp, G Mitsiades, C Johnson, R Hannah, A Anderson, KC AF Richardson, Paul Chanan-Khan, Asher Alban Lonial, Sagar Krishnan, Amrita Alsina, Melissa Carroll, Michael Adler, Karen Cropp, G. Mitsiades, C. Johnson, Robert Hannah, Alison Anderson, Kenneth C. TI A multicenter phase 1 clinical trial of tanespimycin (KOS-953) + bortezomib (BZ): Encouraging activity and manageable toxicity in heavily pre-treated patients with relapsed refractory multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Hematol, Boston, MA 02115 USA. Roswell Pk Canc Ctr, Buffalo, NY USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. Arizona Canc Ctr, Tucson, AZ USA. Kosan Biosci Inc, Hayward, CA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 406 BP 124A EP 125A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440000407 ER PT J AU Richardson, PG Jagannath, S Avigan, DE Alsina, M Schlossman, RL Mazumder, A Munshi, NC Ghobrial, I Doss, D McKenney, ML Farrell, MG Warren, DL Lunde, LE Gourley, B Vaccaro, S Delaney, C Pountney, S Mitsiades, CS Hideshima, T Byrne, C Knight, R Birner, A Myers, T Weller, E Anderson, KC AF Richardson, Paul G. Jagannath, S. Avigan, D. E. Alsina, M. Schlossman, R. L. Mazumder, A. Munshi, N. C. Ghobrial, I. Doss, D. McKenney, M. L. Farrell, M. G. Warren, D. L. Lunde, L. E. Gourley, B. Vaccaro, S. Delaney, C. Pountney, S. Mitsiades, C. S. Hideshima, T. Byrne, C. Knight, R. Birner, A. Myers, T. Weller, E. Anderson, K. C. TI Lenalidomide plus bortezomib (Rev-Vel) in relapsed and/or refractory multiple myeloma (MM): Final results of a multicenter phase 1 trial. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. Celgene Corp, Summit, NJ USA. Millennium Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 5 Z9 5 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 NOV 16 PY 2006 VL 108 IS 11 MA 405 BP 124A EP 124A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000406 ER PT J AU Bashey, A Medina, B Corringham, S Pasek, M Carrier, E Streicher, H Lowy, I Mason, JR Soiffer, RJ Ball, ED AF Bashey, Asad Medina, Bridget Corringham, Sue Pasek, Mildred Carrier, Ewa Streicher, Howard Lowy, Israel Mason, James R. Soiffer, Robert J. Ball, Edward D. TI Phase I study of ipilimumab (neutralizing monoclonal anti-CTLA4 antibody) to treat relapse of malignancy after allogeneic hematopoietic stem cell transplantation: Evidence of tumor regression without induction of GVHD. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. NCI, Pharmaceut Management Branch, Bethesda, MD 20892 USA. Medarex Inc, Bloomsbury, NJ USA. Scripps Clin, La Jolla, CA USA. Northside Hosp, BMT Grp Georgia, Atlanta, GA USA. Dana Farber Canc Inst, Hematol Malignancies Program, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 410 BP 125A EP 126A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440000411 ER PT J AU Kantarjian, HM Sawyers, C Hochhaus, A Schiffer, CA Guilhot, F Niederwieser, DW Gambacorti, C Stone, RM Fischer, T Goldman, J Krahnke, T Mone, M Talpaz, M Druker, BJ AF Kantarjian, Hagop M. Sawyers, Charles Hochhaus, Andreas Schiffer, Charles A. Guilhot, Francois Niederwieser, Dietger W. Gambacorti, Carlo Stone, Richard M. Fischer, Thomas Goldman, John Krahnke, T. Mone, M. Talpaz, Moshe Druker, Brian J. TI Six year follow-up results of a phase II study of imatinib in late chronic phase (L-CP) chronic myeloid leukemia (CML) post interferon-a (IFN) Refractoriness/Intolerance. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 MD Anderson Canc Ctr, Houston, TX USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Heidelberg, D-6800 Mannheim, Germany. Karmanos Canc Inst, Detroit, MI USA. CHU La Miletrie, Poitiers, France. Univ Leipzig, D-7010 Leipzig, Germany. Inst Natl Tumori, Milan, Italy. Dana Farber Canc Inst, Boston, MA USA. Univ Mainz, D-6500 Mainz, Germany. NHLBI, Bethesda, MD 20892 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RI Sawyers, Charles/G-5327-2016 NR 0 TC 2 Z9 2 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 NOV 16 PY 2006 VL 108 IS 11 MA 428 BP 130A EP 131A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440000429 ER PT J AU Tothova, Z Kollipara, R Huntly, BJ Lee, BH Castrillon, DH Passegue, EA Cullen, DE McDowell, EP Lazo-Kallanian, S Williams, IR DePinho, R Gilliland, DG AF Tothova, Zuzana Kollipara, Ramya Huntly, Brian J. Lee, Benjamin H. Castrillon, Diego H. Passegue, Emmanuelle A. Cullen, Dana E. McDowell, Elizabeth P. Lazo-Kallanian, Suzan Williams, Ifor R. DePinho, RonaldA. Gilliland, D. Gary TI FoxO are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Brigham & Womens Hosp, Harvard Med Sch, Howard Hughes Med Inst, Dept Genet, Boston, MA USA. Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Dept Med Genet, Boston, MA USA. Univ Cambridge, Dept Haematol, Cambridge, England. Univ Calif San Francisco, Dev & Stem Cell Biol Program, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Dept Med Oncol & Hematol Neoplasia, Boston, MA 02115 USA. Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 439 BP 134A EP 134A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000440 ER PT J AU Li, XA Xiong, JW Shelley, CS Park, HY Arnaout, MA AF Li, Xiangen Xiong, Jing-wei Shelley, Carl Simon Park, HeiYoung Arnaout, M. Amin TI The transcription factor ZBP-89 controls generation of the hematopoietic lineage in zebrafish and mouse embryonic stem cells. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Harvard Med Sch, Charlestown, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 441 BP 135A EP 135A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000442 ER PT J AU Mullally, A Li, C Kim, H Mohseni, M Alyea, EP Antin, JH Soiffer, RJ Ritz, J AF Mullally, Ann Li, Cheng Kim, Haesook Mohseni, Mehrdad Alyea, Edwin P. Antin, Joseph H. Soiffer, Robert J. Ritz, Jerome TI Genome wide single nucleotide polymorphism typing for identification of putative minor histocompatibility antigens in graft versus host disease. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostatist & Computat Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 447 BP 136A EP 136A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000448 ER PT J AU Juszczynski, P Ouyang, J Kutok, JL Monti, S Chen, W Dal Cin, P Abramson, JS Takeyama, K Golub, TR Aster, JC Rabinovich, GA Shipp, MA AF Juszczynski, Przemyslaw Ouyang, Jing Kutok, Jeffery L. Monti, Stefano Chen, Wen Dal Cin, Paola Abramson, Jeremy S. Takeyama, Kunihiko Golub, Todd R. Aster, Jon C. Rabinovich, Gabriel A. Shipp, Margaret A. TI Hodgkin's lymphoma Reed Sternberg cells over express the T-Cell inhibitory carbohydrate-binding lectin, galectin 1: Role of AP-1 and likely mechanism of tumor immune escape. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Buenos Aires, Buenos Aires, DF, Argentina. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 469 BP 142A EP 142A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000470 ER PT J AU Kuter, D Bussel, J George, J Aledort, L Lichtin, A Lyons, R Nieva, J Wasser, J Bourgeois, E Kappers-Klunne, M Lefrere, F Schipperus, M Kelly, R Christal, J Guo, M Nichol, J AF Kuter, David Bussel, James George, James Aledort, Louis Lichtin, Alan Lyons, Roger Nieva, Jorge Wasser, Jeffrey Bourgeois, Emanuelle Kappers-Klunne, Mies Lefrere, Francois Schipperus, Martin Kelly, Reggie Christal, Jenny Guo, Matthew Nichol, Janet TI Long-term dosing of AMG 531 in thrombocytopenic patients with immune thrombocytopenic purpura: 48-week update. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Boston, MA 10029 USA. Weill Cornell Med Ctr, New York, NY 44195 USA. Univ Oklahoma, Oklahoma City, OK USA. Mt Sinai Hosp, New York, NY USA. Cleveland Clin Fdn, Cleveland, OH USA. Assoc So Tex, San Antonio, TX USA. Scripps Clin, La Jolla, CA USA. DeQuattro Commun Canc Ctr, Manchester, CT USA. CHRU, Lille, France. Erasmus MC, Rotterdam, Netherlands. Hop Necker Enfants Malad, Paris, France. Haga Ziekenhuis, The Hague, Netherlands. Amgen Inc, Thousand Oaks, CA USA. NR 0 TC 8 Z9 9 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 NOV 16 PY 2006 VL 108 IS 11 MA 476 BP 144A EP 144A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000477 ER PT J AU Desjardins, RE Tempel, DL Lucek, R Kuter, DJ AF Desjardins, Robert E. Tempel, Donna L. Lucek, Rudolph Kuter, David J. TI Single and multiple oral doses of AKR-501 (YM477) increase the platelet count in healthy volunteers. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 AkaRx Inc, Paramus, NJ USA. Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Med Oncol, Boston, MA USA. NR 0 TC 15 Z9 15 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 NOV 16 PY 2006 VL 108 IS 11 MA 477 BP 145A EP 145A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000478 ER PT J AU Zhang, JL Crumpacker, CS Scadden, DT AF Zhang, Jie Lin Crumpacker, Clyde S. Scadden, David T. TI Primitive hematopoietic cells resist HIV-1 infection via P21Waf1/Cip1/sdi1. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol ID P21(CIP1/WAF1) C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA USA. Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. NR 2 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 490 BP 149A EP 149A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000491 ER PT J AU Kim, HS Wiernik, PH Tallman, MS Gallagher, RE AF Kim, Haesook Wiernik, Peter H. Tallman, Martin S. Gallagher, Robert E. TI Common gene expression changes in matched pretreatment and relapse samples from eastern cooperative oncology group acute promyelocytic leukemia (APL) patients treated on the chemotherapy (C) or all-Trans retinoic acid (ATRA)-containing (A) randomization arms of protocol E2491. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Albert Einstein Canc Ctr, Bronx, NY 02115 USA. Dana Farber Canc Inst, Boston, MA USA. New York Med Coll, Sch Med, Bronx, NY 60611 USA. Northwestern Univ, Chicago, IL USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 4311 BP 156B EP 156B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440400590 ER PT J AU Zhou, DC Thompson, R Kim, HS Greally, J Gallagher, R AF Zhou, Da-Cheng Thompson, Reid Kim, Haesook Greally, John Gallagher, Robert TI Lack of increased gene promoter methylation at relapse in acute promyelocytic leukemia (APL). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Albert Einstein Canc Ctr, Bronx, NY 02115 USA. Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 4315 BP 157B EP 157B PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440401002 ER PT J AU Bernal, F Walensky, LD Tyler, AF Korsmeyer, SJ Verdine, GL AF Bernal, Federico Walensky, Loren D. Tyler, Andrew F. Korsmeyer, Stanley J. Verdine, Gregory L. TI Selective targeting of the p53-hDM2 interaction using hydrocarbon-stapled p53 peptides. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 525 BP 159A EP 159A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000526 ER PT J AU Yang, G Huang, SC Benz, EJ AF Yang, Guang Huang, Shu-Ching Benz, Edward J. TI Protein 4.1R exon 16 splicing mediated by regulated expression of RBM9 and PTB during erythroid differentiation. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 538 BP 162A EP 162A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000539 ER PT J AU Nakase, K Cheng, JH Zhu, Q Marasco, WA AF Nakase, Koichi Cheng, Jihua Zhu, Quan Marasco, Wayne A. TI Transcriptional regulation of the SHP-1, a candidate tumor suppressor gene in hematological malignancies. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Med Sch, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 4346 BP 165B EP 165B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440401033 ER PT J AU Boshkov, L Chien, G Van Winkle, D Furnary, AP Wu, YX Grunkemeier, G Morris, CD AF Boshkov, Lynn Chien, Grace Van Winkle, Donna Furnary, Antony P. Wu, Yingxing Grunkemeier, Gary Morris, Cynthia D. TI Prestorage leukoreduction of transfused red cells is associated with significant ongoing 2-12 month survival benefit in cardiac surgery patients. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Providence St Vincents Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Providence St Vincents Med Ctr, Med Data Res Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV 16 PY 2006 VL 108 IS 11 BP 174A EP 174A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000579 ER PT J AU Cutler, CS Kim, HT Ho, VT Koreth, J Alyea, EP Soiffer, RJ Antin, JH AF Cutler, Corey S. Kim, Haesook T. Ho, Vincent T. Koreth, John Alyea, Edwin P. Soiffer, Robert J. Antin, Joseph H. TI Prognostic impact of elevated serum ferritin in patients undergoing myeloablative stem cell transplantation. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 595 BP 179A EP 180A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440000596 ER PT J AU Ballen, KK Cutler, C Spitzer, TR Yeap, B McAfee, S Dey, BR Attar, E Haspel, RL Alyea, E Ho, V Soiffer, RJ Antin, JH AF Ballen, Karen K. Cutler, Corey Spitzer, Thomas R. Yeap, Beow McAfee, Steve Dey, Bimalangshu R. Attar, Eyal Haspel, Richard L. Alyea, Edwin Ho, Vincent Soiffer, Robert J. Antin, Joseph H. TI Outcomes of 40 adult patients after double cord blood transplantation using a reduced intensity chemotherapy conditioning regimen. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 605 BP 182A EP 183A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440000606 ER PT J AU Polo, JM Juszczynski, P Cerchietti, L Monti, S Ye, K Shipp, MA Melnick, AM AF Polo, Jose M. Juszczynski, Przemyslaw Cerchietti, Leandro Monti, Stefano Ye, Kenny Shipp, Margaret A. Melnick, Ari M. TI A BCL6 target gene signature predicts the biological behavior and classification of diffuse large B-cell lymphoma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Albert Einstein Coll Med, Bronx, NY 10467 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Broad Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 616 BP 186A EP 186A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000617 ER PT J AU Blotta, S Yasui, H Tassone, P Bellucci, R Tai, YT Prabhala, R Shammas, MA Tagliaferri, P Podar, K Neri, PE Fulciniti, M Munshi, V Chauhan, D Hideshima, T Venuta, S Ritz, J Anderson, KC Munshi, NC AF Blotta, Simona Yasui, Hiroshi Tassone, Pierfrancesco Bellucci, Roberto Tai, Yu-Tzu Prabhala, Rao Shammas, Masood A. Tagliaferri, Pierosandro Podar, Klaus Neri, Paola E. Fulciniti, Mariateresa Munshi, Vidit Chauhan, Dharminder Hideshima, Teru Venuta, Salvatore Ritz, Jerome Anderson, Kenneth C. Munshi, Nikhil C. TI Identification of novel antigens nvith induced immune response in MGUS. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Harvard Med Sch, Boston, MA USA. Harvard Med Sch, VA Boston Healthcare Syst, Boston, MA USA. Univ Magna Graecia & Canc Ctr, Catanzaro, Italy. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 655 BP 197A EP 197A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000656 ER PT J AU Prabhala, RH Neri, P Fulciniti, M Therrien, VA Munshi, V Driscoll, JJ Shammas, MA Hideshima, T Daley, JF Anderson, KC Munshi, NC AF Prabhala, Rao H. Neri, Paola Fulciniti, Mariateresa Therrien, Vanessa A. Munshi, Vidit Driscoll, James J. Shammas, Masood A. Hideshima, Tern Daley, John F. Anderson, Kenneth C. Munshi, Nikhil C. TI Myeloma microenvironment controls T regulatory cell activity: Potential target for therapeutic interventions. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 VA Boston Healthcare Syst, West Roxbury, MA USA. Harvard Med Sch, DFCI, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 659 BP 198A EP 198A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000660 ER PT J AU Saito, N Ishikawa, F Shimoda, K Yoshida, S Saito, Y Kawano, N Shulz, LD Akashi, K Harada, M AF Saito, Noriyuki Ishikawa, Fumihiko Shimoda, Kazuya Yoshida, Shuro Saito, Yoriko Kawano, Noriaki Shulz, Leonard D. Akashi, Koichi Harada, Mine TI Xenotransplantation of primary CD34+CD38 - Hematopoietic stem cells results in an in vivo model of idiopathic myelofibrosis. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Kyushu Univ, Grad Sch Med, Dept Med & Biosyst Sci, Fukuoka 812, Japan. RIKEN Res Ctr Allergy & Immunol, Yokohama, Kanagawa, Japan. Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RI 石川, 文彦/L-4488-2014 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 666 BP 200A EP 200A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000667 ER PT J AU Bergmeier, W Goerge, T Wang, HW Cifuni, SM Crittenden, JR Graybiel, AM Wagner, DD AF Bergmeier, Wolfgang Goerge, Tobias Wang, Hong-Wei Cifuni, Stephen M. Crittenden, Jill R. Graybiel, Ann M. Wagner, Denisa D. TI Mice lacking the signaling molecule, CalDAG-GEFI, represent a mouse model for leukocyte adhesion deficiency type III. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 CBR Inst Biomed Res, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 674 BP 202A EP 202A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000675 ER PT J AU Feusner, J Kim, H Gregory, J Alonzo, T Woods, W Weinstein, H Tallman, M AF Feusner, James Kim, Haesook Gregory, John Alonzo, Todd Woods, William Weinstein, Howard Tallman, Martin TI Obesity in newly diagnosed childhood acute promyelocytic leukemia. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Childrens Oncol Grp, Operat Off, Arcadia, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Sch Med, Chicago, IL USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 4494 BP 202B EP 202B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440401178 ER PT J AU Saito, Y Attar, E Jana, S Dombkowski, D Janzen, V Lee, BC Morrison, AD Abuin, A Pickering, S Livi, GP Adams, GB Scadden, DT AF Saito, Yoriko Attar, Eyal Jana, Samyukta Dombkowski, David Janzen, Viktor Lee, Byeong-Chel Morrison, Alastair D. Abuin, Alejandro Pickering, Sue Livi, George P. Adams, Gregor B. Scadden, David T. TI Nucleotide receptor P2Y14 modulates hematopoietic stem cell response to tissue injury altering stem cell preservation and tissue recovery. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. Univ Pittsburgh, Sch Med, Ctr Canc, Pittsburgh, PA USA. GlaxoSmithKline Res & Dev Ltd, Essex Jct, VT USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 679 BP 204A EP 204A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000680 ER PT J AU Chen, Z Balduinui, A Conti, MA Adelstein, RS Shivdasani, RA AF Chen, Zhao Balduinui, Alessandra Conti, Mary Anne Adelstein, Robert S. Shivdasani, Ramesh A. TI Loss of non-muscle myosin heavy chain IIA function does not restrict megakaryocyte maturation or spontaneous platelet release and likely affects non-cell-autonomous aspects of thrombopoiesis. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pavia, I-27100 Pavia, Italy. NHLBI, Natl Inst Hlth, Mol Cardiol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 701 BP 210A EP 210A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000702 ER PT J AU Quintas-Cardama, A Tong, WG Manshouri, T Cools, J Gilliland, DG Kantarjian, HM Cortes, J Garcia-Manero, G AF Quintas-Cardama, Alfonso Tong, Weigang Manshouri, Taghi Cools, Jan Gilliland, D. Gary Kantarjian, Hagop M. Cortes, Jorge Garcia-Manero, Guillermo TI Frequency of NUP214-ABL1 oncogene in patients with T-cell acute lymphoblastic leukemia (TALL) and analysis of the activity of imatinib and nilotinib in NUP214-ABL1-expressing T-ALL cell lines. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 MD Anderson Canc Ctr, Houston, TX USA. Flanders Interuniv Inst Biotechnol, Louvain, Belgium. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 710 BP 213A EP 213A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000711 ER PT J AU Walensky, LD Pitter, K Morash, JG Verdine, GL Korsmeyer, SJ Orkin, SH AF Walensky, Loren D. Pitter, Kenneth Morash, Joel G. Verdine, Gregory L. Korsmeyer, Stanley J. Orkin, Stuart H. TI Anti-leukemic potency of stapled BH3 helices correlates with their capacity for bifunctional activation of apoptotic pathways. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 NOV 16 PY 2006 VL 108 IS 11 MA 711 BP 213A EP 214A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440000712 ER PT J AU Fiore, LD Fallon, A Young, M Lawler, EV Brophy, MT AF Fiore, Louis D. Fallon, Amy Young, Melissa Lawler, Elizabeth V. Brophy, Mary T. TI The risk of venous thromboembolism following hospitalization in medical patients without cancer. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Massachusetts Vet Epidemiol Res & Informat Ctr, Dept Vet Affairs, Cooperat Studies Program, Boston, MA USA. VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 714 BP 214A EP 214A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000715 ER PT J AU Giles, F Morariu-Zamfir, R Lambert, J Verstovsek, S Thomas, D Ravandi, F Deangelo, D AF Giles, Francis Morariu-Zamfir, Rodica Lambert, John Verstovsek, Srdan Thomas, Deborah Ravandi, Farhad Deangelo, Dan TI Phase I study of AVE9633, an antiCD33-maytansinoid immunoconjugate, administered as an intravenous infusion in patients with refractory/relapsed CD33-positive acute myeloid leukemia (AML). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 MD Anderson Canc Ctr, Houston, TX USA. Sanofi Aventis, Paris, France. ImmunoGen Inc, Cambridge, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 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 NOV 16 PY 2006 VL 108 IS 11 MA 4548 BP 216B EP 216B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440401232 ER PT J AU Stegmaier, K Corsello, SM Ross, KN Golub, TR AF Stegmaier, Kimberly Corsello, Steven M. Ross, Kenneth N. Golub, Todd R. TI Modulating AML1-ETO with signature-based small molecule library screening. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, MIT, Broad Inst, Canc Program, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 729 BP 219A EP 219A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440000730 ER PT J AU Faber, J Krivtsov, AV Stubbs, MC Wright, R van den Heuvel-Eibrink, M Kung, AL Zwaan, CM Armstrong, SA AF Faber, Jorg Krivtsov, Andrei V. Stubbs, Matthew C. Wright, Renee van den Heuvel-Eibrink, Marry Kung, Andrew L. Zwaan, Christian M. Armstrong, Scott A. TI HoxA9 knockdown inhibits proliferation and induces cell death in human MLL-Rearranged leukemias. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Med Sch, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Sophia Childrens Univ Hosp, Dept Pediat Oncol, Erasmus MC, Rotterdam, Netherlands. RI Faber, Joerg/G-4549-2010 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 734 BP 220A EP 221A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440000735 ER PT J AU Krause, DS Lazarides, K von Andrian, UH Van Ellen, RA AF Krause, Daniela S. Lazarides, Katherine von Andrian, Ulrich H. Van Ellen, Richard A. TI CD44 is selectively required for the homing and engraftrnent of BCR-ABL-expressing leukemic stem cells. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Tufts Univ, New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. Harvard Med Sch, CBR Inst Biomed Res, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 743 BP 223A EP 223A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001003 ER PT J AU Cutler, C Li, SL Ho, V Koreth, J Alyea, E Soiffer, RJ Antin, JH AF Cutler, Corey Li, Shuli Ho, Vincent Koreth, John Alyea, Edwin Soiffer, Robert J. Antin, Joseph H. TI Long-term outcome of methotrexate-free GVHD prophylaxis using sirolimus and tacrolimus in matched related (MRD) and unrelated donor (URD) peripheral blood stem cell transplantation (PBSCT). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 757 BP 227A EP 227A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001017 ER PT J AU Hsieh, JJ Takeda, S Chen, DY Westergard, TD Fisher, JK Rubens, JA Sasagawa, S Kan, JT Korsmeyer, SJ Cheng, EH AF Hsieh, James J. Takeda, Shugaku Chen, David Y. Westergard, Todd D. Fisher, Jill K. Rubens, Jeffrey A. Sasagawa, Satoru Kan, Jason T. Korsmeyer, Stanley J. Cheng, Emily H. TI Proteolysis of MLL family proteins is essential for Taspase1-orchestrated cell cycle progression. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Washington Univ, St Louis, MO USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 769 BP 231A EP 231A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001029 ER PT J AU Maeda, T Merghoub, T Dong, L Maeda, M Hobbs, R Zakrzewski, J van den Brink, M Shigematsu, H Akashi, K Zelent, A Teruya-Feldstein, J Cattoretti, G Pandolfi, PP AF Maeda, Takahiro Merghoub, Taha Dong, Lin Maeda, Manami Hobbs, Robin Zakrzewski, Johannes van den Brink, Marcel Shigematsu, Hirokazu Akashi, Koichi Zelent, Arthur Teruya-Feldstein, Julie Cattoretti, Giorgio Pandolfi, Pier Paolo TI LRF/Pokemon plays a pivotal role in B versus T lymphoid lineage fate decision at the early lymphoid progenitor stage by opposing Notch1 signaling. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Mem Sloan Kettering Canc Ctr, Canc Biol & Genet, New York, NY 10021 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Inst Canc Res, Leukaemia Res Fund Ctr, London SW3 6JB, England. Columbia Univ, Inst Canc Genet, New York, NY USA. RI Cattoretti, Giorgio/H-2340-2011 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 778 BP 233A EP 234A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440001038 ER PT J AU Wu, L Maillard, I Nakamura, M Pear, WS Griffin, JD AF Wu, Lizi Maillard, Ivan Nakamura, Makoto Pear, Warren S. Griffin, James D. TI The MAML1 transcriptional co-activator is required for the development of marginal zone B cells. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Abramson Family Canc Res Inst, Dept Pathol, Philadelphia, PA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 777 BP 233A EP 233A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001037 ER PT J AU Mizuno, SI Ozawa, H Shigematsu, H Arinobu, Y Yong, C Iino, T Akashi, K AF Mizuno, Shin-ichi Ozawa, Hidetoshi Shigematsu, Hirokazu Arinobu, Yojiro Yong, Chong Iino, Tadafumi Akashi, Koichi TI Notch1 expression is regulated at translational level by 3'UTR region in hematopoietic stem cell development. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 782 BP 234A EP 235A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440001042 ER PT J AU Raffel, GD Mercher, T Shigematsu, H Williams, IR Cullen, DE Akashi, K Bernard, OA Gilliland, DG AF Raffel, Glen D. Mercher, Thomas Shigematsu, Hirokazu Williams, Ifor R. Cullen, Dana E. Akashi, Koichi Bernard, Olivier A. Gilliland, D. Gary TI Ott1(Rbm15) is essential for pre-B differentiation and has an inhibitory role in myeloid and megakaryocytic lineages. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Beth Israel Deaconess Med Ctr, Harvard Med Sch, Div Hematol Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Emory Univ, Sch Med, Dept Pathol, Atlanta, GA USA. Univ Paris 05, INSERM, E0210, Paris, France. Harvard Med Sch, Howard Hughes Med Inst, Boston, MA USA. RI Mercher, Thomas/J-2446-2014 OI Mercher, Thomas/0000-0003-1552-087X NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 784 BP 235A EP 235A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001044 ER PT J AU Kriangkum, J Taylor, BJ Treon, SP Mant, MJ Reiman, T Belch, AR Pilarski, LM AF Kriangkum, Jitra Taylor, Brian J. Treon, Steven P. Mant, Michael J. Reiman, Tony Belch, Andrew R. Pilarski, Linda M. TI Molecular characterization of clonotypic VDJ sequences in waldenstrom's macroglobulinemia suggests independent transformation events in the development of biclonal B cells. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Alberta, Cross Canc Inst, Edmonton, AB, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Alberta, Edmonton, AB, Canada. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 4624 BP 237B EP 237B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440401308 ER PT J AU Rajkumar, SV Jacobus, S Callander, N Fonseca, R Vesole, D Greipp, P AF Rajkumar, S. Vincent Jacobus, Susanna Callander, Natalie Fonseca, Rafael Vesole, David Greipp, Philip TI A randomized phase III trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4AO3): A trial coordinated by the Eastern Cooperative Oncology Group. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Mayo Clin, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Wisconsin, Madison, WI USA. Mayo Clin, Scottsdale, AZ USA. St Vincents Hosp, New York, NY USA. NR 0 TC 21 Z9 21 U1 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 799 BP 239A EP 240A PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440001059 ER PT J AU Leleu, X Xu, LA Hunter, ZR Jia, XY Moreau, AS Ho, AW Hatjiharissi, E N'Go, H Santos, DD O'Connor, K Manning, R Soumerai, J Patterson, C Ghobrial, IM Treon, SP AF Leleu, Xavier Xu, Lian Hunter, Zachary R. Jia, Xiaoying Moreau, Anne-Sophie Ho, Allen W. Hatjiharissi, Evdoxia N'Go, Hai Santos, Daniel D. O'Connor, Kelly Manning, Robert Soumerai, Jacob Patterson, Christopher Ghobrial, Irene M. Treon, Steven P. TI Endoplasmic reticulum stress is a target for therapy in Waldenstrom's macroglobutinemia (WM). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Ctr waldenstroms Macroglobulinemia, Boston, MA 02115 USA. CHRU, Serv Malad Sang & Lab Immunol, Lille, France. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 4641 BP 241B EP 241B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440401325 ER PT J AU Leleu, X Xu, LA Hunter, ZR Moreau, AS Jia, XY O'Sullivan, G Bakthavachalam, V Ho, AW Hatjiharissi, E N'Go, HT Santos, DD O'Connor, K Manning, R Soumerai, J Patterson, C Ghobrial, IM Treon, SP AF Leleu, Xavier Xu, Lian Hunter, Zachary R. Moreau, Anne-Sophie Jia, Xiaoying O'Sullivan, Garrett Bakthavachalam, Vinod Ho, Allen W. Hatjiharissi, Evdoxia N'Go, Hai T. Santos, Daniel D. O'Connor, Kelly Manning, Robert Soumerai, Jacob Patterson, Christopher Ghobrial, Irene M. Treon, Steven P. TI Abnormal expression of TRAF adapter, proteins in waldenstrom's macroglobulinemia. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Bing Ctr Waldenstorms Macroglobulinemia, Boston, MA 02115 USA. CHRU, Serv Malad Sang & Lab Immunol, Lille, France. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 4640 BP 241B EP 241B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440401324 ER PT J AU Ngo, HT Leleu, X Moreau, AS Hatjiharissi, E Jia, ZY O'Sullivan, G Runnels, J Villarreal, R Hunter, Z Treon, S Hideshima, T Anderson, K Ghobrial, I AF Ngo, Hai T. Leleu, Xavier Moreau, Anne-Sophie Hatjiharissi, Evodoxia Jia, Xiaoying O'Sullivan, Garrett Runnels, Judith Villarreal, Rose Hunter, Zachary Treon, Steven Hideshima, Teru Anderson, Kenneth Ghobrial, Irene TI Analysis of chemokine and adhesion markers in waldenstrom macroglobulinemia. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. CHRU, Serv Maladies Sang, Lille, France. CHRU, Lab Immunol, Lille, France. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 4653 BP 244B EP 244B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440401337 ER PT J AU Brown, JR Phillips, KS Neuberg, D Raderschall, E Freedman, AS AF Brown, Jennifer R. Phillips, Kimberly S. Neuberg, Donna Raderschall, Elke Freedman, Arnold S. TI Prevalence of familial lymphoproliferative malignancy in a prospectively screened cohort of patients with lymphoproliferative disorders. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 818 BP 246A EP 246A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001078 ER PT J AU Abramson, JS Chen, W Takahashi, H Juszczynski, P Kutok, JL Shipp, MA AF Abramson, Jeremy S. Chen, Wen Takahashi, Hidenobu Juszczynski, Przemyslaw Kutok, Jeffery L. Shipp, Margaret A. TI Heat shock protein 90 (HSP90) is a rational therapeutic target in diffuse large B-cell lymphoma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 829 BP 249A EP 249A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001089 ER PT J AU Stemberg, DW Ray, A Lee, BH Adelsperger, J Duclos, N McDonwell, E Haq, N Imbach, P Ohmori, O Honda, T Warmuth, M Fabbro, D Griffin, JD Roesel, J AF Stemberg, David W. Ray, Arghya Lee, Benjamin H. Adelsperger, Jennifer Duclos, Nicole McDonwell, Elizabeth Haq, Naznin Imbach, Patricia Ohmori, Osamu Honda, Toshiyuki Warmuth, Markus Fabbro, Doriano Griffin, James D. Roesel, Johannes TI Inhibition of the NPM-ALK fusion tyrosine kinase in hematopoietic neoplasia by the small molecule tyrosine kinase antagonist TAE684. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Mt Sinai Sch Med, Div Hematol & Oncol, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Novartis Pharma AG, Basel, Switzerland. Tsukuba Res Inst, Novartis Pharma KK, Tsukuba, Ibaraki, Japan. Dept Pharmacol, Kinase Lead Discovery, San Diego, CA USA. Genom Inst Novartis Res Fdn, Dept Med Chem, San Diego, CA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 828 BP 249A EP 249A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001088 ER PT J AU Nardi, V Raz, T Chao, XY Wu, CJ Stone, R Galinsky, I Wadleigh, M Deininger, MWN Church, G Zhu, J Daley, GQ AF Nardi, Valentina Raz, Tal Chao, Xinyu Wu, Catherine J. Stone, Richard Galinsky, Ilene Wadleigh, Martha Deininger, Michael W. N. Church, George Zhu, Jun Daley, George Q. TI Monitoring imatinib resistance with a "Polony" assay: Towards tailored therapy of chronic myelogenous leukemia (CML). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Childrens Hosp Boston, Boston, MA USA. Duke Univ, Inst Sci Genome & Policy, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Ctr Hematol Malignancies, Portland, OR 97201 USA. Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 837 BP 251A EP 252A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440001097 ER PT J AU Neri, P Kumar, S Fulciniti, M Vallet, S Chhetri, S Yasui, H Tai, YT Chauhan, D Hideshima, T Tassone, P Venuta, S Munshi, NC Anderson, KC Raje, N AF Neri, Paola Kumar, Shaji Fulciniti, Mariateresa Vallet, Sonia Chhetri, Shweta Yasui, Hiroshi Tai, Yu-Tzu Chauhan, Dharminder Hideshima, Teru Tassone, Pierfrancesco Venuta, Salvatore Munshi, Nikhil C. Anderson, Kenneth C. Raje, Noopur TI The in vivo activity of neutralizing B cell-activating factor (BAFF) antibody in the treatment of multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. VA Boston Healthcare Syst, Boston, MA USA. Univ Magna Graecia, Ctr Canc, Catanzaro, Italy. Mayo Clin, Div Hematol, Rochester, MN USA. RI Kumar, Shaji/A-9853-2008 OI Kumar, Shaji/0000-0001-5392-9284 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 843 BP 253A EP 253A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001103 ER PT J AU Adams, GB Alley, IR Chabner, KT Chung, UI Marsters, ES Weinstein, LS Kronenberg, HM Scadden, DT AF Adams, Gregor B. Alley, Ian R. Chabner, Karissa T. Chung, Ung-il Marsters, Emily S. Weinstein, Lee S. Kronenberg, Henry M. Scadden, David T. TI Hematopoietic stem cell engraftment in bone marrow is dependent upon G(s)alpha. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Tokyo Univ Hosp, Div Tissue Engn, Tokyo 113, Japan. NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 857 BP 257A EP 257A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001117 ER PT J AU Janzen, V Fleming, HE Waring, MT Milne, CD Scadden, DT AF Janzen, Viktor Fleming, Heather E. Waring, Michael T. Milne, Craig D. Scadden, David T. TI Multifunctional role of caspase-3 in regulating hematopoietic stem cells. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Ctr Regenerat Med, Harvard Stem Cell Inst, Boston, MA 02114 USA. Univ Toronto, Hlth Network, Dept Immunol, Toronto, ON, Canada. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 861 BP 258A EP 258A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001121 ER PT J AU Haining, WN Ebert, B Subramanian, A Wherry, EJ Evans, J Mak, R Rivoli, S Angelosanto, J Pretz, J Kaech, S Ahmed, R Nadler, LM Golub, TR AF Haining, W. Nicholas Ebert, Benjamin Subramanian, Aravind Wherry, E. John Evans, John Mak, Raymond Rivoli, Stephen Angelosanto, Jill Pretz, Jennifer Kaech, Susan Ahmed, Rafi Nadler, Lee M. Golub, Todd R. TI All memory lymphocytes share a common differentiation program. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. MIT, Broad Inst Harvard, Cancer Program, Cambridge, MA 02139 USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. Yale Univ, New Haven, CT USA. Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 865 BP 259A EP 259A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001125 ER PT J AU Appleman, LJ Chemova, I Li, LQ Boussiotis, V AF Appleman, Leonard J. Chemova, Irene Li, Lequn Boussiotis, Vassiliki TI CD28 costimulation induces transcription of SKP2 and CKS1, the substrate recognition components of the Skp1-cullin-F-box ubiquitin ligase, SCFSkp2. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 869 BP 260A EP 260A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001129 ER PT J AU Galardy, PJ D'Andrea, AD Ploegh, HL AF Galardy, Paul J. D'Andrea, Alan D. Ploegh, Hidde L. TI The IL-2 induced de-ubiquitinating enzyme, DUB-2, is a nuclear-cytoplasmic shuttle which requires catalytic activity for nuclear localization. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Mayo Clin, Div Pediat Hematol Oncol, Rochester, MN USA. Mayo Clin Coll Med, Dept Biochem & Mol Biol, Rochester, MN USA. Dana Farber Canc Inst, Div Radiat & Canc Biol, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 868 BP 260A EP 260A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001128 ER PT J AU Li, LQ Iwamoto, Y Berezovskaya, A Boussiotis, VA AF Li, Lequn Iwamoto, Yoshiko Berezovskaya, Alla Boussiotis, Vassiliki A. TI A novel p27(kip1)-Smad3 regulated pathway is involved in induction of T cell tolerance. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 867 BP 260A EP 260A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001127 ER PT J AU Grabowski, EF Nestoridi, E Bussel, JB AF Grabowski, Eric F. Nestoridi, Eirini Bussel, James B. TI Active site-inhibited rFVIIa (ASIS) blocks platelet adhesion/aggregation on intact endothelium activated with TNF alpha and Shiga toxin-1. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Thrombosis Lab, Boston, MA USA. Cornell Univ, Presbyterian Hosp, Weill Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 898 BP 269A EP 270A PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440001158 ER PT J AU Conley, P Jurek, M Stephens, G He, M Finn, A Gold, H Romanko, K Gretler, D Phillips, D Andre, P AF Conley, Pamela Jurek, Marzena Stephens, Gillian He, Ming Finn, Alok Gold, Herman Romanko, Kevin Gretler, Daniel Phillips, David Andre, Patrick TI A novel pharmacodynamic perfusion chamber assay reveals superior and unique antithrombotic activities of a direct-acting P2Y(12) antagonist, PRT128, relative to clopidogrel. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Portola Pharmaceut Inc, Biol, San Francisco, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 900 BP 270A EP 270A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001160 ER PT J AU Jia, XY Leleu, X Moreau, AS Hatjiharisi, E Ngo, H O'Sullivan, G McMillin, D Treon, S Mitsiades, C Hideshima, T Palladino, M Anderson, K Chauban, D Ghobrial, I AF Jia, Xiaoying Leleu, Xavier Moreau, Anne-Sophie Hatjiharisi, Evdoxia Ngo, Hai O'Sullivan, Garrett McMillin, Douglas Treon, Steven Mitsiades, Constantine Hideshima, Teru Palladino, Michael Anderson, Kenneth Chauban, Dharminder Ghobrial, Irene TI The proteasome inhibitor NPI-0052 in combination with bortezomib induces antitumor activity in Waldenstrom macroglobulinemia. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. CHRU, Lab Immunol, Serv Maladies Sang, Lille, France. Nereus Pharmaceut, San Diego, CA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 4746 BP 270B EP 270B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440401430 ER PT J AU Patterson, CJ Moreau, AS Leleu, X Soumerai, J Hunter, Z Hatjiharissi, E Xu, L Treon, S AF Patterson, Christopher J. Moreau, Anne Sophie Leleu, Xavier Soumerai, Jacob Hunter, Zachary Hatjiharissi, Evdoxia Xu, Lian Treon, Steven TI Abnormalities in lipoprotein metabolism provide insight into novel therapeutic approaches for Waldenstrom's macroglobulinemia (WM). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 2 Z9 2 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 NOV 16 PY 2006 VL 108 IS 11 MA 4749 BP 270B EP 270B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440401433 ER PT J AU Bradner, JE Greenberg, EF Schreiber, SL Mazitschek, R AF Bradner, James E. Greenberg, Edward F. Schreiber, Stuart L. Mazitschek, Ralph TI Design and characterization of a novel, reverse prodrug histone deacetylase inhibitor for cutaneous T-Cell Lymphoma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 MIT, Broad Inst Harvard, Chem Biol Program, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. RI Mazitschek, Ralph/E-3741-2013 OI Mazitschek, Ralph/0000-0002-1105-689X NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 4759 BP 272B EP 273B PN 2 PG 2 WC Hematology SC Hematology GA 111GW UT WOS:000242440401443 ER PT J AU Grabowski, EF Bussel, JB AF Grabowski, Eric F. Bussel, James B. TI Pediatric experience with fondaparinux in deep venous thrombosis. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Presbyterian Hosp, Weill Med Coll, New York, NY USA. NR 0 TC 6 Z9 6 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 NOV 16 PY 2006 VL 108 IS 11 MA 916 BP 274A EP 275A PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440001176 ER PT J AU Chen, L Juszczynski, P Takeyama, K Aguiar, RCT Shipp, MA AF Chen, Linfeng Juszczynski, Przemyslaw Takeyama, Kunihiko Aguiar, Ricardo C. T. Shipp, Margaret A. TI Protein tyrosine phosphatase receptor-type O truncated (PTPROT) regulates SYK phosphorylation, proximal B-cell receptor signaling and cellular proliferation. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 933 BP 279A EP 279A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001193 ER PT J AU Yagasaki, H Yoshida, N Hirano, N Nishio, N Wang, Y Takahashi, Y Kojima, S AF Yagasaki, Hiroshi Yoshida, Nao Hirano, Naoto Nishio, Nobuhiro Wang, Yue Takahashi, Yoshiyuki Kojima, Seiji TI Presence of HLA-DR15, a minor PNH clone, or an aplastic anemia - Associated autoantibody do not predict a favorable response to immunosuppressive therapy in children with aplastic anemia. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Nagoya Univ, Aichi, Japan. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 984 BP 294A EP 294A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001244 ER EF